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674d4a9b7be152b1d0a40a3d | 10.26434/chemrxiv-2024-kssns | A new method for the production of 1,1-diphenylalkanes based on Ta-mediated arylation of aldehydes using benzene | It was first discovered that the reaction between alkyl-substituted aldehydes and benzene, when treated with the TaCl5-Mg reagent system, results in the highly selective formation of 1,1-diphenyl alkanes with a high yield (87-90%). The reaction of p-methoxybenzaldehyde and benzene in the presence of TaCl5 and Mg leads to the quantitative formation of triphenylmethane | Azat M. Gabdullin; Aidar B. Yulbarisov; Rita N. kadikova; Ilfir R. Ramazanov | Organic Chemistry | CC BY 4.0 | CHEMRXIV | 2024-12-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/674d4a9b7be152b1d0a40a3d/original/a-new-method-for-the-production-of-1-1-diphenylalkanes-based-on-ta-mediated-arylation-of-aldehydes-using-benzene.pdf |
60c743f4bb8c1a35f23da3f8 | 10.26434/chemrxiv.9706040.v1 | Effect of H Adsorption on the Magnetic Properties of an Fe Island on a W(110) Surface | <p>Low-dimensional materials, such as ultrathin films, nanoislands and wires, are actively being researched due to their interesting magnetic properties and possible technological applications for example in high density data storage. Results of calculations of an Fe nanoisland on a W(110) support are presented here with particular focus on the effect of hydrogen adsorption on its magnetic properties. This is an important consideration since hydrogen is present even under ultra-high vacuum conditions. The calculations are based on density functional theory within the generalized gradient approximation. The adsorption of H atoms is found to strongly decrease the magnetic moment of the Fe atoms they are bound to, down to less than a half in some cases as compared with the clean Fe island. The results show that it may be important to take the presence of hydrogen into account in measurements of magnetic properties of nanoislands.</p> | Marko Melander; Hannes Jonsson | Magnetic Materials; Nanostructured Materials - Materials; Nanostructured Materials - Nanoscience; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2019-08-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c743f4bb8c1a35f23da3f8/original/effect-of-h-adsorption-on-the-magnetic-properties-of-an-fe-island-on-a-w-110-surface.pdf |
634837d586473a184f11bf60 | 10.26434/chemrxiv-2022-gkwnf | Effect of Stacking Interactions on Charge Transfer States in Photoswitches Interacting with Ion Channels | The activity of ion channels can be reversibly photo-controlled via the binding of molecular photoswitches, often based on an azobenzene scaffold, in their internal cavity. Those azobenzene derivatives mainly interact non-covalently with aromatic residues via stacking interactions. In the present work, the effect of face-to-face and t-shaped stacking interactions on the excited state electronic structure of azobenzene and p-diaminoazobenzene integrated into the NaV1.4 channel is investigated via quantum mechanics/molecular mechanics calculations combined with classical molecular dynamics. The formation of a charge transfer state, characterized by electron transfer from aromatic protein residues to the photoswitches, is observed. This state is strongly red shifted when the interaction takes place in a face-to-face orientation, and electron donating groups are present on the aromatic ring of the aminoacids but not on the photoswitches. The low-energy charge transfer state can interfere with the photoisomerization process after excitation to the bright state and lead to the formation of radical species, which can permanently damage the protein and the surrounding environment | Vito Federico Palmisano; Shirin Faraji; Juan Jose Nogueira | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/634837d586473a184f11bf60/original/effect-of-stacking-interactions-on-charge-transfer-states-in-photoswitches-interacting-with-ion-channels.pdf |
60c747b9702a9b4b9118ae32 | 10.26434/chemrxiv.11770437.v1 | Low Temperature Calorimetry Coupled with Molecular Simulations for an In-Depth Characterization of the Guest-Dependent Compliant Behaviour of MOFs | In this study adsorption microcalorimetry is employed to monitor the adsorption of four probes (argon, oxygen, nitrogen and carbon monoxide) on a highly flexible mesoporous metal-organic framework (DUT-49, DUT = Dresden University of Technology), precisely measuring the differential enthalpy of adsorption alongside high-resolution isotherms. This experimental approach combined with force field Monte Carlo simulations reveals distinct pore filling adsorption behaviours for the selected probes, with argon and oxygen showing abrupt adsorption in the open pore form of DUT-49, in contrast with the gradual filling for nitrogen and carbon monoxide. A complex structural transition behaviour of DUT-49 observed upon nitrogen adsorption is elucidated through an isotherm deconvolution in order to quantify the fraction of the open pore, contracted pore and intermediate pore forms that coexists at a given gas pressure. Finally, the heat flow measured during the guest-induced structural contraction of DUT-49 allowed an exploration of complex open-contracted pore transition energetics, leading to a first assessment of the energy required to induce this spectacular structural change. | Paul Iacomi; Bin Zheng; Simon Krause; Stefan Kaskel; Guillaume Maurin; Philip L. Llewellyn | Hybrid Organic-Inorganic Materials; Interfaces; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-01-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c747b9702a9b4b9118ae32/original/low-temperature-calorimetry-coupled-with-molecular-simulations-for-an-in-depth-characterization-of-the-guest-dependent-compliant-behaviour-of-mo-fs.pdf |
60dc2226bc1d6ec732cd3261 | 10.26434/chemrxiv-2021-m8sr9-v2 | Anti-Fouling Performance of Mixed Matrix PVDF Membranes with Mono-Hydroxyl Poly(dimethylsiloxane) (PDMS-OH) Grafted Silica Nanoparticles | In this study, we investigate the use of surface-modified silica nanoparticles to improve the anti-fouling performance of PVDF ultrafiltration membranes. Here, fouling resistant nanoparticles were prepared by grafting monohydroxy-polydimethylsiloxane onto the surface of silica nanoparticles using Steglich esterification. The mixed matrix PVDF membranes were prepared at a range of nanoparticle concentrations (0, 1.6, 3.2, 6.3, and 11.8%) to understand how PDMS modified silica content affected membrane performance. The resulting hybrid membranes were characterised using a range of techniques including scanning electron microscopy (SEM), water contact angle (CA), porosity, and pore size measurements, in order to determine how morphological features of the nanocomposite membranes affected fouling and pure water flux. Embedding silica nanoparticles resulted in a significant reduction in membrane fouling, including lower protein adsorption and a flux recovery ratio of 97 %. Although water flux was reduced by the addition of nanoparticles, the change in the porosity, mean pore size and the hydrophilicity of the membrane caused the rejection rate to be increased significantly. Together, these results are of particular benefit to the ultrafiltration industry, where improved antifouling and flux recovery can help reduce operating and maintenance costs in these membrane processes.<br /><br /> | MUAYAD AL-SHAELI; Stefan J. D. Smith; Shanxue Jiang; Huanting Wang; Kaisong Zhang; Bradley P. Ladewig | Materials Science; Chemical Engineering and Industrial Chemistry; Composites; Nanostructured Materials - Materials; Water Purification; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60dc2226bc1d6ec732cd3261/original/anti-fouling-performance-of-mixed-matrix-pvdf-membranes-with-mono-hydroxyl-poly-dimethylsiloxane-pdms-oh-grafted-silica-nanoparticles.pdf |
646a04a9f2112b41e9e99cc4 | 10.26434/chemrxiv-2023-fc8q9-v2 | Hydrophobic Hydration of the Hydrocarbon Adamantane in Amorphous Ice | Hydrophobic molecules are by definition difficult to hydrate. Previous studies in the area of hydrophobic hydration have therefore often relied on using amphiphilic molecules where the hydrophilic part of a molecule enabled the solubility in liquid water. Here we show that the hydrophobic adamantane (C10H16) molecule can be fully hydrated through vapour codeposition with water onto a cryogenic substrate at 80 K resulting in the matrix isolation of adamantane in amorphous ice. Using neutron diffraction in combination with the isotopic substitution method and the empirical potential structure refinement technique, we find that the first hydration shell of adamantane is well structured consisting of a hydrogen-bonded cage of 28 water molecules that is also found in cubic structure II clathrate hydrates. The four hexagonal faces of the 51264 cage are situated above the four methine (CH) groups of adamantane whereas the methylene (CH2) groups are positioned below the edges of two adjoining pentagonal faces. The oxygen atoms of the 28 water molecules can be categorised on the basis of symmetry equivalences as twelve A, twelve B and four C oxygens. The water molecules of the first hydration shell display orientations consistent with those expected for a clathrate-hydrate-type cage, but also unfavourable ones with respect to the hydrogen bonding between the water molecules. Annealing the samples at 140 K, which is just below the crystallisation temperature of the matrix, removes the unfavourable orientations and leads to a slight increase of the structural order of the first hydration shell. The very closest water molecules display a tendency for their dipole moments to point towards the adamantane which is attributed to steric effects. Other than this, no significant polarisation effects are observed which is consistent with weak interactions between adamantane and the amorphous ice matrix. FT-IR spectroscopy shows that the incorporation of adamantane into amorphous ice leads to a weakening of the hydrogen bonds. In summary, the matrix-isolation of the highly symmetric adamantane in amorphous ice provides an interesting test case for hydrophobic hydration. Studying the structure and spectroscopic properties of water at the interface with hydrophobic hydrocarbons is also relevant for astrophysical environments, such as comets or the interstellar medium, where amorphous ice and hydrocarbons have been shown to coexist in large quantities. | Sukhpreet Talewar; Luis Carlos Pardo; Thomas Headen; Siriney Halukeerthi; Bharvi Chikani; Alexander Rosu-Finsen; Christoph Salzmann | Physical Chemistry; Earth, Space, and Environmental Chemistry; Space Chemistry; Interfaces; Physical and Chemical Properties | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/646a04a9f2112b41e9e99cc4/original/hydrophobic-hydration-of-the-hydrocarbon-adamantane-in-amorphous-ice.pdf |
61c2a0b97f367e29da5bd056 | 10.26434/chemrxiv-2021-x3849 | Sporopollenin-inspired design and synthesis of robust materials | Sporopollenin is a mechanically robust and chemically inert biopolymer that constitutes the outer protective exine layer of plant spores and pollen grains. Recent investigation of the molecular structure of pine sporopollenin revealed unique monomeric units and inter-unit linkages distinct from other previously known biopolymers, which could be harnessed for new material design. Here, we report the bioinspired synthesis of a series of sporopollenin analogues. This exercise confirms large portions of the previously proposed pine sporopollenin structural model, while the measured chemical, thermal, and mechanical properties of the synthetic sporopollenins indicate favorable attributes of a new kind of robust material. This study explores a new design framework of robust materials inspired by natural sporopollenins, and provides insights and reagents for future elucidation and engineering of sporopollenin biosynthesis in plants. | Christopher Glinkerman; Shaoting Lin; Jiahua Ni; Fu-Shuang Li; Xuanhe Zhao; Jing-Ke Weng | Materials Science; Polymer Science; Biopolymers; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-12-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61c2a0b97f367e29da5bd056/original/sporopollenin-inspired-design-and-synthesis-of-robust-materials.pdf |
60c74e7f4c8919046bad3a3f | 10.26434/chemrxiv.12765956.v1 | Role of Thr199 Residue in Human β-Carbonic Anhydrase-II pH-Dependent Activity Elucidated by Microsecond Simulation Analysis | Carbonic anhydrases catalyze the reversible hydration of carbon dioxide to form bicarbonate, a reaction required for many functions such as carbon assimilation, pH acid–base homeostasis, respiration and photosynthesis via zinc-hydroxide mechanism for carbon dioxide hydration. In earlier studies, it was revealed that Carbonic anhydrases are inactive at pH 7.5 and active at pH 8.4. This steep pH dependence for its activity led us to design this work in order to understand its mode of action at atomic level detailing. In our microsecond simulation based analysis, it was revealed that the interaction between Glu106 and Thr199 plays a critically important role in its activity. Thr199 co-ordinated loop movement was observed to be acting as a lid, with ‘open’ and ‘close’ mechanism for substrate entry to the core of the catalytic site, where Zn-ion resides and executes its carbon dioxide hydration mechanism. On the other hand, decline in the total secondary structural elements percentage in the protein was observed in correspondence to the pH condition change. Especially, α-helices between Thr125-Gly145 and Val150-Lys170 residues were noticed to be losing their structural integrity responsible for formation of dimer and tetramers. In conclusion, our analysis showed that the interaction between Glu106 and Thr199 is crucial for maintaining the structural integrity of the Thr199 corodinated loop, responsible for allowing substrate towards catalytic site. | Pulala Raghuveer Yadav; Hussain Syed; Pavan Kumar Pindi | Biochemistry; Bioinformatics and Computational Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74e7f4c8919046bad3a3f/original/role-of-thr199-residue-in-human-carbonic-anhydrase-ii-p-h-dependent-activity-elucidated-by-microsecond-simulation-analysis.pdf |
62c706cafb6381baabd02693 | 10.26434/chemrxiv-2022-7xp7g | Thermal Transport in Citrate-Capped Gold Interfaces using a Polarizable Force Field | The interfacial thermal conductance from solvated gold nanostructures capped with sodium citrate was determined using reverse nonequilibrium molecular dynamics (RNEMD) methods. The surfaces of spherical nanoparticles and the (111) surfaces of fcc gold slabs were modeled using the density readjusting embedded atom method (DR-EAM) as well as with the standard embedded atom method (EAM), and the effects of polarizability on the binding preferences of citrate were determined. We find that the binding configurations of citrate depend significantly on gold surface curvature and are not strongly influenced by surface polarizability. The interfacial thermal conductance was also determined for the spherical nanoparticles and (111) surfaces, and we find that applying DR-EAM increases the interfacial thermal conductance for systems with spherical nanoparticles much more sharply than for systems with (111) surfaces. Through analysis of excess charge density near the interface, we find that inclusion of polarizability has a larger impact on image charge creation in nanospheres than it does for the planar (111) interfaces. This effectively increases the interaction strength to polar species in the solvent, yielding larger interfacial thermal conductance estimates for the nanospheres. | Sydney A. Shavalier; J. Daniel Gezelter | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Transport phenomena (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2022-07-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62c706cafb6381baabd02693/original/thermal-transport-in-citrate-capped-gold-interfaces-using-a-polarizable-force-field.pdf |
618bee3fda150640969d2ff2 | 10.26434/chemrxiv-2021-sv16l-v2 | Direct Synthesis and Applications of Solid Silylzinc Reagents | The increased synthetic utility of organosilanes motivates researchers to develop a milder and more practical synthetic methods. Silylzinc reagents, which are typically the most functional group tolerant, are notoriously difficult to synthesize because they are obtained by a pyrophoric reaction of silyllithium, particularly Me3 SiLi itself prepared by the reaction of MeLi and disilane. Furthermore, the dissolved LiCl in silylzinc may have a detrimental effect. A synthetic method that can avoid silyllithium and involves a direct synthesis of silylzinc reagents from silyl halides is arguably the simplest and economical strategy. We describe for the first time, the direct synthesis of PhMe2 SiZnI and Me3 SiZnI reagents by employing a coordinating TMEDA ligand, as well as single crystal XRD structures. Importantly, they can be obtained as solid and stored for longer periods of time. We demonstrate their significance in cross-coupling of various free alkyl/aryl/alkenyl carboxylic acids with broader functional group tolerance and API derivatives. The general applicability and efficiency of solid Me3 SiZnI are shown in a wide variety of reactions including alkylation, arylation, allylation, 1,4-addition, acylation and more. | Ramesh Rasappan; Revathi Chandrasekaran; Feba Thomas Pulikkottil; Krishna Suresh | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/618bee3fda150640969d2ff2/original/direct-synthesis-and-applications-of-solid-silylzinc-reagents.pdf |
60c74ebd337d6ceb61e2801a | 10.26434/chemrxiv.12407105.v2 | Deciding Between One-Step and Two-Step Irreversible Inhibition Mechanisms on the Basis of “Kobs” Data: A Statistical Approach | Covalent (irreversible) enzyme inhibitors are an
important group of actual or potential therapeutics. For example, Aspirin is an
irreversible inhibitor of the cyclooxygenase enzyme. Evaluating covalent inhibitors in the drug discovery
is exceptionally challenging, because their overall inhibitory potency consists
of two separate but intertwined contributions: (1) initial binding affinity and
(2) chemical reactivity. It is
especially difficult to reliably asses the kinetic mechanism of
inhibition. This paper describes an
objective statistical approach that can be used to decide between two alternate
kinetic mechanisms of covalent enzyme inhibition, from kinetic experiments
based on the standard "kobs" method [Copeland (2013) "Evaluation
of Enzyme Inhibitors in Drug Discovery", section 9.1]. The two
alternatives are either a two-step kinetic mechanism, which involves a
reversibly formed noncovalent intermediate, or a one-step kinetic mechanism, proceeding
in a single bimolecular step. The proposed
statistical toolkit uses four independent methods to arrive at a reliable
mechanistic conclusion. The results are illustrated
by using recently published experimental data on the inhibition of two
different protein kinases by the experimental drugs ibrutinib (PCI-32765) and
acalabrutinib [Hopper <i>et al.</i> (2020) <i>J. Pharm. Exp. Therap.</i> <b>372</b>, 331–338]. | Petr Kuzmic | Biochemistry; Biophysics; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ebd337d6ceb61e2801a/original/deciding-between-one-step-and-two-step-irreversible-inhibition-mechanisms-on-the-basis-of-kobs-data-a-statistical-approach.pdf |
65bbc654e9ebbb4db9741f5c | 10.26434/chemrxiv-2024-pjh9z | Improving Gas Adsorption Modeling for MOFs by Local Calibration of Hubbard U Parameters | While computational screening with density functional theory (DFT) is frequently employed for the screening of metal-organic frameworks (MOFs) for gas separation and storage, commonly applied generalized gradient approximations (GGAs) exhibit self-interaction errors, that hinder predictions of adsorption energies. We investigate the Hubbard U parameter to augment DFT calculations for full periodic MOFs, targeting a more precise modeling of gas molecule–MOF interactions, specifically for N2, CO2, and O2. We introduce a calibration scheme for the U parameter, which is tailored for each MOF, by leveraging higher-level calculations on the secondary building unit (SBU) of the MOF. When applied to the full periodic MOF, the U parameter calibrated against hybrid HSE06 calculations of SBUs successfully reproduces hybrid-quality calculations of the adsorption energy of the periodic MOF. The mean absolute deviation (MAD) of adsorption energies reduces from 0.13 eV for a standard GGA treatment to 0.06 eV with the calibrated U, demonstrating the utility of the calibration procedure when applied to the full MOF structure. Furthermore, attempting to use CCSD(T) calculations of isolated SBUs for this calibration procedure shows varying degrees of success in predicting the experimental heat of adsorption. It improves accuracy for N2 adsorption for cases of overbinding, whereas its impact on CO2 is minimal, and ambiguities in spin state assignment hinder consistent improvements of O2 adsorption. Our findings emphasize the limitations of cluster models and advocate the use of full periodic MOF systems with a calibrated U parameter, providing a more comprehensive understanding of gas adsorption in MOFs. | Yeongsu Cho; Heather Kulik | Theoretical and Computational Chemistry; Materials Science; Inorganic Chemistry; Nanostructured Materials - Materials; Computational Chemistry and Modeling; Theory - Computational | CC BY 4.0 | CHEMRXIV | 2024-02-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65bbc654e9ebbb4db9741f5c/original/improving-gas-adsorption-modeling-for-mo-fs-by-local-calibration-of-hubbard-u-parameters.pdf |
60c73eda0f50dbe50c3956f9 | 10.26434/chemrxiv.7137680.v1 | A Biopolymer Based 3D Printable Hydrogel for Toxic Metal Adsorption from Water | <div><div><div><p>Herein, we describe a 3D<br />printable hydrogel that is capable of<br />removing toxic metal pollutants from water<br />solutions. To achieve this, shear-thinning<br />hydrogels were prepared by blending<br />chitosan with diacrylated Pluronic F-127 (F127-DA) which allows for UV curing after printing. Several hydrogel compositions were tested for their ability to absorb common metal pollutants such as lead, copper, cadmium and mercury, as well as for their printability. These hydrogels displayed excellent metal adsorption with some examples capable of up to 95% metal removal within 30 min. We show that 3D printed hydrogel structures that would be difficult to fabricate by conventional manufacturing methods, can adsorb metal ions significantly faster than solid objects, owing to their higher accessible surface areas.</p></div></div></div> | Gayan A. Appuhamillage; Danielle Berry; Candace Benjamin; Michael A. Luzuriaga; John C. Reagan; Jeremiah J. Gassensmith; Ron Smaldone | Composites; Materials Processing; Biopolymers; Hydrology and Water Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2018-09-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73eda0f50dbe50c3956f9/original/a-biopolymer-based-3d-printable-hydrogel-for-toxic-metal-adsorption-from-water.pdf |
651720e4006594091222700c | 10.26434/chemrxiv-2023-f5ll4 | Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as orthodisubstituted benzene bioisosteres with improved biological activity | 1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are becoming increasingly popular building blocks in medicinal chemistry since they are saturated bioisosteres of orthosubstituted phenyl rings. Here we have developed the first enantioselective catalytic strategy based on a Lewis acid-catalyzed [2+2] photocycloaddition to obtain these motifs as enantioenriched scaffolds, providing an efficient approach for their incorporation in a variety of drug analogues. The bioisostere-containing drugs have been evaluated in cancer cell viability studies, observing that in some cases the biological activity of the two enantiomers is highly different. This showcases that the control of the absolute configuration and tridimensionality of the drug analogue has a large impact on its bioactivity, highlighting the need for stereoselective methods towards the construction of the bicyclo[2.1.1]hexane core. | Pablo Garrido-Garcia; Irene Quiros; Paula Milan-Rois; Alvaro Somoza; Israel Fernandez; Thomas Rigotti; Mariola Tortosa | Organic Chemistry; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/651720e4006594091222700c/original/enantioselective-photocatalytic-synthesis-of-bicyclo-2-1-1-hexanes-as-orthodisubstituted-benzene-bioisosteres-with-improved-biological-activity.pdf |
64da574a69bfb8925aedbb97 | 10.26434/chemrxiv-2023-ff8dr | Chemical Kinetics in Microdroplets | Micron-sized compartments play significant roles in driving heterogeneous transformations within atmospheric and biochemical systems as well as providing vehicles for drug delivery and novel reaction environments for the synthesis of industrial chemicals. Many reports now indicate that reaction kinetics are accelerated under micro-confinement; for example in sprays, thin films, droplets, aerosols, and emulsions. These observations are dramatic, posing a challenge to our understanding of chemical reaction mechanisms with potentially significant practical consequences for predicting the complex chemistry in natural systems. Here we introduce the idea of “kinetic confinement,” which is intended to provide a conceptual backdrop for understanding when and why microdroplet reaction kinetics differ from their macroscale analogs. | Kevin Wilson; Alexander Prophet | Physical Chemistry; Nanoscience; Earth, Space, and Environmental Chemistry; Chemical Kinetics; Interfaces; Physical and Chemical Processes | CC BY NC ND 4.0 | CHEMRXIV | 2023-08-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64da574a69bfb8925aedbb97/original/chemical-kinetics-in-microdroplets.pdf |
60c73ea00f50db9df73956c2 | 10.26434/chemrxiv.7076462.v1 | Strongly Coloured Thiocyanate Frameworks with Perovskite-Analogue Structures | We report the first examples of thiocyanate-based analogues of the cyanide Prussian blue compounds, MIII[Bi(SCN)6], M= Fe, Cr, Sc. These compounds adopt the primitive cubic pcu topology and show strict cation order. Optical absorption measurements show these compounds have band gaps within the visible and near IR region, suggesting that they may be useful for photocatalytic applications. We also show that Cr[Bi(SCN)6] can reversibly uptake water into its framework structure pointing towards the possibility of using these frameworks for host/guest chemistry.<br /> | Matthew Cliffe; Evan Keyzer; Matthew Dunstan; Shahab Ahmad; Michael F. L. De Volder; Felix Deschler; Andrew
J. Morris; Clare P. Grey | Hybrid Organic-Inorganic Materials; Optical Materials; Coordination Chemistry (Inorg.); Theory - Computational | CC BY 4.0 | CHEMRXIV | 2018-09-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73ea00f50db9df73956c2/original/strongly-coloured-thiocyanate-frameworks-with-perovskite-analogue-structures.pdf |
60d2fcebe21133fa5de05ee7 | 10.26434/chemrxiv-2021-llnkr | Syntheses of Hydrocarbazole Derivatives via Brønsted acid-Initiated Diels-Alder Cycloaddition/retro-Michael Addition Cascade Reaction of Azepino[4,5-b]indoles and Acrolein | A unique approach to hydrocarbazoles bearing an all-carbon quaternary center at C4a position was developed via a Brønsted acid-initiated Diels-Alder cycloaddition/retro-Michael addition cascade process from facilely prepared azepino[4,5-b]indoles and commercially available acrolein. The method provided a range of hydrocarbazoles in good to excellent yields. The practi-cality of this transformation was demonstrated by scale-up experiment and various transformations to several hydrocarbazole derivatives. | Fukai Xie; Xiang Li; Liangyu Xu; Jun Ma; Lei Sun; Bo Zhang; Bin Lin; Maosheng Cheng; Yongxiang Liu | Organic Chemistry; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60d2fcebe21133fa5de05ee7/original/syntheses-of-hydrocarbazole-derivatives-via-br-nsted-acid-initiated-diels-alder-cycloaddition-retro-michael-addition-cascade-reaction-of-azepino-4-5-b-indoles-and-acrolein.pdf |
62968576195959f961bc1cd0 | 10.26434/chemrxiv-2022-s0319 | New Synthetic Route to Water Soluble Prism[5]arene Hosts and their Molecular Recognition Properties | We report that the direct macrocyclization of naphthalene monomers (N1 and N3) bearing ethyl ester functional groups delivers prism[5]arene derivatives (H1E and H3E) which can be deprotected to yield water soluble prism[5]arenes (H1 and H3). 1H NMR spectroscopy showed that dicationic guests G1 – G9 bind with the hydrophobic cores buried inside the anisotropic magnetically shielding cavity. Isothermal titration calorimetry measurements showed that H1 and H3 are high affinity hosts in PBS buffered water with Ka values exceeding 109 M-1 for G9. The complexation events are driven by the non-classical hydrophobic effect, CH•••p interactions, and electrostatic interactions. Host H1 displays somewhat higher affinity toward a common guest than WP6 but is significantly less potent than P6AS. Nevertheless, H1 and H3 should be considered alongside other high affinity hosts for a variety of chemical and biological applications. | Canjia Zhai; Lyle Isaacs | Organic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-06-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62968576195959f961bc1cd0/original/new-synthetic-route-to-water-soluble-prism-5-arene-hosts-and-their-molecular-recognition-properties.pdf |
650661c0b338ec988a9b5358 | 10.26434/chemrxiv-2023-2fs8n | Total Synthesis of Aleutianamine | ABSTRACT: Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC50 = 25 nM against PANC-1, making it a potential candi-date for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic car-bonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product. | Hao Yu; Zachary Sercel; Samir Rezgui; Jonathan Farhi; Scott Virgil ; Brian Stoltz | Organic Chemistry; Natural Products; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/650661c0b338ec988a9b5358/original/total-synthesis-of-aleutianamine.pdf |
64c9cef09ed5166e93e2bf2a | 10.26434/chemrxiv-2023-vmhtd | Inactivation of human coronaviruses using an automated room disinfection device | The emergence of more virulent and epidemic strains of viruses, especially with the current COVID-19 pandemic, makes it more important than ever to improve methods of decontamination. The use of vapour dispersion devices or “foggers” have played a critical role in rapidly applying disinfectants over large areas or complex surfaces to prevent the spread of pathogens. The objective of this study was to evaluate the potential of on-demand production of chlorine species to inactivate human coronaviruses. The commercial prototype disinfection unit was provided by Unipolar Water Technologies. The Unipolar device generates active chlorine species using an electrochemical reaction and dispenses the disinfectant vapour onto surfaces with an aspirator. The minimum effective concentration and exposure time of disinfectant were evaluated on human hepatoma (Huh7) cells using 50% tissue culture infectious dose (TCID50) assay and human coronavirus 229E (HCoV-229E), a surrogate for pathogenic human coronaviruses. We showed that chlorine species generated in the Unipolar device inactivates HCoV-229E at ≥ 400 parts per million active chlorine concentration with a 5 min exposure time. Importantly, no toxic effect was observed on Huh7 cells for any of the active chlorine concentrations and contact times tested. | Nicholas Lundquist; Legesse Kifelew; Sait Elmas; Zhongfan Jia; Peter Speck; Justin Chalker | Biological and Medicinal Chemistry; Inorganic Chemistry; Electrochemistry; Cell and Molecular Biology; Drug Discovery and Drug Delivery Systems | CC BY NC 4.0 | CHEMRXIV | 2023-08-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64c9cef09ed5166e93e2bf2a/original/inactivation-of-human-coronaviruses-using-an-automated-room-disinfection-device.pdf |
60c742514c89195465ad2424 | 10.26434/chemrxiv.7628939.v4 | Predicting the Strength of Stacking Interactions Between Heterocycles and Aromatic Amino Acid Side Chains | Despite the ubiquity of stacking interactions between
heterocycles and aromatic amino acids in biological systems, our ability to
predict their strength, even qualitatively, is limited. Based on rigorous <i>ab initio</i> data, we have devised a simple predictive model of the
strength of stacking interactions between heterocycles commonly found in biologically
active molecules and the amino acid side chains Phe, Tyr, and Trp. This model provides reliable predictions of
the stacking ability of a given heterocycle based on readily-computed
heterocycle descriptors, obviating the need for quantum chemical computations
of stacked dimers. We show that the values
of these descriptors, and therefore the strength of stacking interactions with
aromatic amino acid side chains, follow simple predictable trends and can be modulated
by changing the number and distribution of heteroatoms within the heterocycle. This
provides a simple conceptual model for understanding stacking interactions in protein
binding sites and tuning the strength of stacking interactions in drug design. | Andrea
N. Bootsma; Analise C. Doney; Steven Wheeler | Physical Organic Chemistry; Supramolecular Chemistry (Org.); Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2019-05-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742514c89195465ad2424/original/predicting-the-strength-of-stacking-interactions-between-heterocycles-and-aromatic-amino-acid-side-chains.pdf |
6327c4550e3c6ae0971f7da2 | 10.26434/chemrxiv-2022-pdmdr | Postmortem skeletal muscle metabolism of farm animals approached with metabolomics | Skeletal muscle metabolism regulates homeostatic balance in animals. The metabolic impact persists even after farm animal skeletal muscle is converted to edible meat through postmortem rigor mortis and aging. Muscle metabolites resulting from animal growth and postmortem storage have a significant impact on meat quality, including flavor and color. Metabolomics studies of postmortem muscle aging have identified metabolisms that contain signatures inherent to muscle properties and the altered metabolites by physiological adaptation, with glycolysis as the pivotal metabolism in postmortem aging. In addition to major postmortem metabolisms, such as amino acid generation, metabolomics has played a role in mining relevant postmortem metabolisms and pathways that have recently been revealed, such as the citrate cycle and mitochondrial metabolism. This leads to a deeper understanding of the mechanisms underlying the generation of key compounds that are associated with meat quality. Genetic background, feeding strategy, and muscle type primarily determine skeletal muscle properties in live animals and affect post-mortem muscle metabolism. With comprehensive metabolite detection, metabolomics is also beneficial for exploring biomarker candidates that could be useful to monitor meat production and predict the quality traits. The present review focuses on advances in farm animal muscle metabolomics, especially postmortem muscle metabolism associated with genetic factors and muscle type. | Susumu Muroya | Agriculture and Food Chemistry; Food | CC BY 4.0 | CHEMRXIV | 2022-09-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6327c4550e3c6ae0971f7da2/original/postmortem-skeletal-muscle-metabolism-of-farm-animals-approached-with-metabolomics.pdf |
6511fc0c60c37f4f76723cc5 | 10.26434/chemrxiv-2023-4wkf8-v2 | Anion-templated synthesis of a switchable fluorescent [2]catenane with sulfate sensing capability | Anion templation strategies have facilitated the synthesis of various catenane and rotaxane hosts capable of strong and selective binding of anions in competitive solvents. However, this approach has primarily relied on positively charged precursors, limiting the structural diversity and the range of potential applications of the anion-templated mechanically interlocked molecules. Here we demonstrate the synthesis of a rare electroneutral [2]catenane using a powerful, doubly charged sulfate template and a complementary diamidocarbazole-based hydrogen bonding precursor. Owing to the unique three-dimensional hydrogen bonding cavity and the embedded carbazole fluorophores, the resulting catenane receptor functions as a sensitive fluorescent turn-ON sensor for the highly hydrophilic sulfate, even in the presence of large excess of water. Importantly, the [2]catenane exhibits enhanced binding affinity and selectivity for sulfate over its parent macrocycle and other acyclic diamidocarbazole-based receptors. We demonstrate also, for the first time, that the co-conformation of the catenane may be controlled by reversible acid/base induced protonation and deprotonation of the sulfate anionic template. This approach pioneers a new strategy to induce molecular motion of interlocked components using switchable anionic templates. | Krzysztof M. Bąk; Bartosz Trzaskowski; Michał J. Chmielewski | Organic Chemistry; Physical Organic Chemistry; Supramolecular Chemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-09-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6511fc0c60c37f4f76723cc5/original/anion-templated-synthesis-of-a-switchable-fluorescent-2-catenane-with-sulfate-sensing-capability.pdf |
66b48c5f01103d79c52e7146 | 10.26434/chemrxiv-2024-rk92s | Zigzag-type N-Heterocyclic Aromatic Belts | Zigzag aromatic hydrocarbon belts, ultrashort segments of zigzag carbon nanotubes, have been fascinating chemistry community for more than a half century because of their aesthetically appealing molecular nanostructures and tantalizing applications. Precise introduction of heteroatoms of distinct electronegativity and electronic configuration can create various heterocyclic aromatic nanobelts with novel physical and chemical properties. Here, we report the synthesis of unprecedented zigzag-type N-heterocyclic aromatic belts, belt[n]pyrrole[n]pyridines (n = 6 - 8), from multiple intramolecular Caryl-Caryl homocoupling reactions of readily available azacalix[n](3,5-dibromopyridine)s. These compounds adopt globally -conjugated belt structures and displayed unique photophysical and electrochemical properties. The spherical frustum cavity of belt[8]pyrrole[8]pyridine was used as the outstanding host to form a very stable 2:1 encapsulation complex with buckminsterfullerene. This work opens a new avenue to the rational design and efficient synthesis of aromatic belts of distinct topological structures and tailor-made properties which are invaluable in applications in materials and supramolecular chemistry. | Jia-Hui Chen; Shuo Tong; Mei-Xiang Wang | Organic Chemistry | CC BY 4.0 | CHEMRXIV | 2024-08-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66b48c5f01103d79c52e7146/original/zigzag-type-n-heterocyclic-aromatic-belts.pdf |
626a9fc2d048ed1492544d2e | 10.26434/chemrxiv-2022-tjrtf | Adsorption Free Energy Predicts Amyloid Protein Nucleation Rates | Primary nucleation is the fundamental event that initiates the conversion of proteins from their normal physiological forms into pathological amyloid aggregates associated with the onset and development of disorders including systemic amyloidosis, as well as the neurodegenerative conditions Alzheimer's and Parkinson's diseases. It has become apparent that the presence of surfaces can dramatically modulate nucleation. However, the underlying physico-chemical parameters governing this process have been challenging to elucidate, with interfaces in some cases having been found to accelerate aggregation, while in others they can inhibit the kinetics of this process. Here, we show through kinetic analysis that for three different fibril-forming proteins, interfaces affect the aggregation reaction mainly through modulating the primary nucleation step. Moreover, we show through direct measurements of the Gibbs free energy of adsorption, combined with theory and coarse-grained computer simulations, that overall nucleation rates are suppressed at high and at low surface interaction strengths, but significantly enhanced at intermediate strengths, and we verify these regimes experimentally. Taken together, these results provide a quantitative description of the fundamental process which triggers amyloid formation and shed light on the key factors that control this process. | Zenon Toprakcioglu; Ayaka Kamada; Thomas Michaels; Mengqi Xie; Johannes Krausser; Jiapeng Wei; Andela Saric; Michele Vendruscolo; Tuomas Knowles | Physical Chemistry; Biological and Medicinal Chemistry; Biophysical Chemistry; Chemical Kinetics; Self-Assembly | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/626a9fc2d048ed1492544d2e/original/adsorption-free-energy-predicts-amyloid-protein-nucleation-rates.pdf |
60c73d3b0f50db95e539542e | 10.26434/chemrxiv.5519074.v1 | Molecular level investigation of the role of peptide interactions in the glyphosate analytics | <p>The
detection of the herbicide glyphosate (GLP) in environmental samples is most
often conducted after derivatizing the target molecule with the chromophore 9-fluorenylmethyloxycarbonyl
chloride (FMOC-Cl). However, this method is sensitive to all primary and
secondary amines, which can occur in the sample matrix as well. In order to
quantify the interference of primary and secondary amines on GLP detection, we
have used the oligo peptide pentaglycine (PG) as an
example. PG has been added
to the derivatization solution of GLP at different constant concentration
levels and UV extinction coefficients have been determined. Data analysis supported
by quantum chemical modeling of the GLP–PG, FMOC–GLP, and FMOC–PG complexation reactions
facilitated the identification of two interfering impacts of PG on GLP
derivatization: (i) increase of the signal due to its reaction with FMOC-Cl
leading to an overestimation of GLP concentration and (ii) decrease of GLP
recovery due to complex formation and therefore inhibition of GLP
derivatization, which leads to an underestimation.</p> | Ashour A. Ahmed; Peter Gros; Oliver Kühn; Peter Leinweber | Soil Science | CC BY NC ND 4.0 | CHEMRXIV | 2017-10-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d3b0f50db95e539542e/original/molecular-level-investigation-of-the-role-of-peptide-interactions-in-the-glyphosate-analytics.pdf |
66a9ece55101a2ffa8ab891e | 10.26434/chemrxiv-2024-m02f1-v2 | Si–Al Pitzer dataset: Consistent set of Pitzer activity model interaction parameters of Al and Si species, for modelling cements in saline systems with THEREDA | The Si and Al thermodynamic data and Pitzer interaction parameters (IPs) from THEREDA were re-evaluated to extend the applicability of the database for modeling cementitious systems from low to highly saline environments. This study involved reassessing the standard reference thermodynamic data for Si and Al aqueous species and relevant solids (quartz, gibbsite, boehmite) and producing a new consistent set of polythermal Pitzer interaction parameters for Si and Al species within the oceanic salt system Al–Si–Ca–Mg–Na–K–Cl–SO4–CO3–H2O. Experimental data done for a range of compositions and temperatures were used optimize the interaction parameters and their temperature coefficients. In the absence of data, estimation methods using analogous species or correlations with the SIT aqueous activity model parameters were applied. For Si in acidic to neutral pH regions, interaction parameters for Si(OH)4(aq) were determined from extensive binary and ternary experimental data. The formation constant for the first silicic acid hydrolysis and its temperature dependence were assessed, while the second hydrolysis species required estimation methods due to limited data. Interaction parameters with K+ were estimated, and the effect of Ca and Mg at high pH was accounted for using complexes between Si and alkaline earth metals. At high Si concentrations, polymeric species impact aqueous Si speciation. Due to limited data, selecting the silica tetramer (Si4O8(OH)44–) and its binary IPs sufficed to reproduce amorphous Si solubility data in NaCl solutions. For Al, standard thermodynamic properties of ions, hydrolyzed species, and hydroxide phases were derived using gibbsite solubility measurements. No temperature coefficients were required for interactions in the Al–Cl–H2O system, yielding similar results in ternary and quaternary systems. Complexes between aluminum and sulfate were accounted for by the β(2) interaction parameter. At intermediate pH, few measurements exist to derive IPs for hydrolyzed aluminum species, with only Cl– interactions derived. Al(OH)3(aq) IPs were assumed similar to Si(OH)4(aq). At high pH, extensive gibbsite solubility data enabled consistent IPs for the Na–K–Cl–OH–Al(OH)4 system. Potential IPs with Ca2+ and Mg2+ were not selected due to precipitation of hydrates in cementitious systems and the use complexes instead. Ternary IPs with SO42– and CO32– were estimated using OH– as an analog for Al(OH)4–. This provided satisfactory predictions from gibbsite solubility measurements in Na2CO3 and Na2SO4 solutions. No significant Si and Al interactions were expected in high pH cement system due to the low Si concentration maintained by cement phases like C–S–H or M–S–H precipitation. The updated Pitzer model for Si and Al aqueous speciation was compared with independent data on cement hydrate phases and solutions in moderate concentrations up to 85 °C, showing good performance. Additional testing against salt-rich systems and further investigations are recommended. The fitted, estimated, and fixed parameter values were documented, and the updated dataset was implemented in THEREDA (https://www.thereda.de/) for use in calculations. | George Dan Miron | Inorganic Chemistry; Earth, Space, and Environmental Chemistry; Environmental Science; Geochemistry; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a9ece55101a2ffa8ab891e/original/si-al-pitzer-dataset-consistent-set-of-pitzer-activity-model-interaction-parameters-of-al-and-si-species-for-modelling-cements-in-saline-systems-with-thereda.pdf |
6125e1e2fa49ac53ca5a24d5 | 10.26434/chemrxiv-2021-02c1d | Engineering transient dynamics of artificial cells by stochastic distribution of enzymes | Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors. | Jan C. van Hest; Shidong Song; Alexander Mason; Richard Post; Marco de Corato; Rafael Mestre; Amy Yewdall; Shoupeng Cao; Remco van der Hofstad; Samuel Sanchez; Loai Abdelmohsen | Nanoscience; Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6125e1e2fa49ac53ca5a24d5/original/engineering-transient-dynamics-of-artificial-cells-by-stochastic-distribution-of-enzymes.pdf |
61d33656d6dcc267874e59e0 | 10.26434/chemrxiv-2021-djd3d-v2 | Group Contribution and Machine Learning Approaches to Predict Abraham Solute Parameters, Solvation Free Energy, and Solvation Enthalpy | We present a group contribution method (SoluteGC) and a machine learning model (SoluteML) to predict the Abraham solute parameters, as well as a machine learning model (DirectML) to predict solvation free energy and enthalpy at 298 K. The proposed group contribution method uses atom-centered functional groups with corrections for ring and polycyclic strain whilst the machine learning models adopt a directed message passing neural network. The solute parameters predicted from SoluteGC and SoluteML are used to calculate solvation energy and enthalpy via linear free energy relationships. Extensive data sets containing 8366 solute parameters, 20253 solvation free energies, and 6322 solvation enthalpies are compiled in this work to train the models. The three models are each evaluated on the same test sets using both random and substructure-based solute splits for solvation energy and enthalpy predictions. The results show that the DirectML model is superior to the SoluteML and SoluteGC models for both predictions and can provide accuracy comparable to that of advanced quantum chemistry methods. Yet, even though the DirectML model performs better in general, all three models are useful for various purposes. Uncertain predicted values can be identified by comparing the 3 models, and when the 3 models are combined together, they can provide even more accurate predictions than any one of them individually. Finally, we present our compiled solute parameter, solvation energy, and solvation enthalpy databases (SoluteDB, dGsolvDBx, dHsolvDB) and provide public access to our final prediction models through a simple web-based tool, software package, and source code. | Yunsie Chung; Florence H. Vermeire; Haoyang Wu; Pierre J. Walker; Michael H. Abraham; William H. Green | Theoretical and Computational Chemistry; Chemical Engineering and Industrial Chemistry; Computational Chemistry and Modeling; Machine Learning; Thermodynamics (Chem. Eng.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61d33656d6dcc267874e59e0/original/group-contribution-and-machine-learning-approaches-to-predict-abraham-solute-parameters-solvation-free-energy-and-solvation-enthalpy.pdf |
65ef1cc766c1381729bf4810 | 10.26434/chemrxiv-2024-5w8m4 | A solid Xantphos macroligand based on porous organic polymers for the catalytic hydrogenation of CO2 | Porous organic polymers enable a novel approach to incorporate Xantphos into a solid macroligand. Immobilizing a ruthenium complex on the Xantphos network results in an excellent catalyst for the hydrogenation of CO2 to formic acid. Recycling experiments indicate a minor partial degradation of the heterogenous catalyst after a certain induction period, which is referred to its structural changes. | Arne Nisters; Torsten Gutmann; Sun-Myung Kim; Jan Philipp Hofmann; Marcus Rose | Materials Science; Catalysis; Catalysts; Heterogeneous Catalysis; Nanocatalysis - Reactions & Mechanisms; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2024-03-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65ef1cc766c1381729bf4810/original/a-solid-xantphos-macroligand-based-on-porous-organic-polymers-for-the-catalytic-hydrogenation-of-co2.pdf |
66d01f23a4e53c4876fa0215 | 10.26434/chemrxiv-2024-ldpx6 | Local dynamics control the C–CX3 (X = H and F) bond photodissociation in acetylacetones | The primary photodissociation events of acetylacetone and its fluorinated analogs reveal that the translational energy distribution profiles of the CH3 and CF3 radicals follow a barrier-impulsive model for the C–C bond cleavage. Analysis based on the one-dimensional potential energy surfaces in the T1 state as well as dynamics simulations using on-the-fly semi-empirical potentials suggest that the C–C bond cleavage with OH in syn orientation, in general, is accompanied by proton migration. Interestingly, the near identical fragment translational energy distribution profiles of CH3 radical release from acetylacetone and trifluoroacetylacetone, as well as CF3 radical release from trifluoroacetylacetone and hexafluoroacetylacetone, suggest that the dynamics of formation of CH3 / CF3 radicals in acetylacetones appears to be independent of nature of the substituent on the other end of the molecule and the behaviour is akin to “let not thy left hand know what thy right hand doeth.” In the case of acetylacetones the C–C bond cleavage is governed by the local intramolecular vibrational redistribution (IVR) is either statistical or non-statistical along the ‘complex’ reaction coordinate yielding CF3 and CH3 radicals, respectively, and remains non-statistical over the entire molecular framework. | Prahlad Roy Chowdhury; Basudha Deb; Monali Kawade; Amit Kumar Paul; G Naresh Patwari | Physical Chemistry; Photochemistry (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66d01f23a4e53c4876fa0215/original/local-dynamics-control-the-c-cx3-x-h-and-f-bond-photodissociation-in-acetylacetones.pdf |
628bdf0787d01f534defa1c5 | 10.26434/chemrxiv-2022-351l7 | Multifunctional Charge and Hydrogen-Bond Effects of Second-Sphere Imidazolium Pendants Promote Capture and Electrochemical Reduction of CO2 in Water Catalyzed by Iron Porphyrins | Microenvironments tailored by multifunctional secondary coordination sphere groups can enhance catalytic performance at primary metal active sites in natural systems. Here, we capture this biological concept in synthetic systems by developing a family of iron porphyrins decorated imidazolium (im) pendants for the electrochemical CO2 reduction reaction (CO2RR), which promotes multiple synergistic effects to enhance CO2RR and enables the disentangling of second-sphere contributions that stem from each type of interaction. Fe-ortho-im(H), which poises imidazolium units featuring both positive charge and hydrogen-bond capabilities proximal to the active iron center, increases CO2 binding affinity by 25-fold and CO2RR activity by 2,000-fold relative to the parent Fe tetraphenylporphyrin (Fe-TPP), achieving turnover frequencies (TOF) exceeding 109 s-1 with >95% Faradaic efficiency for CO product. Owing to these dual, synergistic second-sphere enhancements, this catalyst also retains high activity and selectivity for homogeneous CO2RR in aqueous media. Notably, the observed TOF value for Fe-ortho-im(H) is 14,000-fold higher than the Fe-para-im(H) positional analog, but only 40-fold higher than the Fe-ortho-im(Me) congener that retains the proximal positive charge but lacks the C2-H hydrogen-bonding moiety, revealing that through-space charge effects have a greater impact on catalytic CO2RR performance compared to hydrogen bonding in this context. This work emphasizes the use of second-sphere pendants that can promote multiple synergistic effects as a design strategy for achieving CO2 reduction catalysis in water. | Mina R Narouz; Patricia De La Torre; Lun An; Christopher J Chang | Inorganic Chemistry; Catalysis; Energy; Electrocatalysis; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/628bdf0787d01f534defa1c5/original/multifunctional-charge-and-hydrogen-bond-effects-of-second-sphere-imidazolium-pendants-promote-capture-and-electrochemical-reduction-of-co2-in-water-catalyzed-by-iron-porphyrins.pdf |
60c751a34c8919b6e3ad3fdd | 10.26434/chemrxiv.12601883.v3 | Impedimetric Characterization of Bioelectronic Nano-Antennae | <p>The merging of electronics with biology at the nanoscale holds considerable promise for sensing and modulating cellular behavior. Advancing our understanding of nano-bioelectronics will facilitate development and enable applications in biosensing, tissue engineering and bioelectronic medicine. However, studies investigating the electrical effects when merging wireless conductive nanoelectrodes with biology are lacking. Consequently, a new tool is required to develop a greater understanding of the bioelectrical effects of merging conductive nanoparticles with biology. Herein, this challenge is addressed by developing an impedimetric method to evaluate bipolar electrochemical systems (BESs) that could act as nano-antennas. A theoretical framework is provided, using impedance to determine if conductive nanoparticles can be polarized and used to drive current. It is then demonstrated that 125 nm Au nanoparticle bipolar electrodes (BPEs) could be sensed in the presence of biology when incorporated intracellularly at 500 mg/ml, using water and PBS as electrolytes. These results highlight how nanoscale BPEs act within biological systems and characterize their behavior in electric fields. This research will impact on the rational design of using BPE systems in biology for both sensing and actuating applications.</p> | Andie Robinson; Akhil Jain; Ruman Rahman; Sidahmed Abayzeed; Richard Hague; Frankie Rawson | Electrochemical Analysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751a34c8919b6e3ad3fdd/original/impedimetric-characterization-of-bioelectronic-nano-antennae.pdf |
60c74fc4f96a002eb6287ce8 | 10.26434/chemrxiv.12937304.v1 | nm-Resolution Functional Pattern Transfer to an Amorphous Elastomeric Material | Here, we show that striped monolayers of diyne amphiphiles, assembled on graphite and photopolymerized, can be covalently transferred to polydimethylsiloxane (PDMS), an elastomer common in applications including microfluidics, soft robotics, wearable electronics, and cell culture. This process creates precision polymer films < 1 nm thick, with 1-nm-wide functional patterns, that control interfacial wetting, reactivity, and adsorption of flexible, ultranarrow inorganic nanowires. The polydiacetylenes exhibit polarized fluorescence emission, revealing polymer location, orientation, and environment, and resist engulfment, a common problem in PDMS functionalization. These findings illustrate a route for controlling surface chemistry well below the length scale of heterogeneity in an amorphous material. | Tyson C Davis; Jeremiah O. Bechtold; Anni Shi; Erin N. Lang; Anamika Singh; Shelley Claridge | Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-11 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74fc4f96a002eb6287ce8/original/nm-resolution-functional-pattern-transfer-to-an-amorphous-elastomeric-material.pdf |
67c762506dde43c9087fdcf6 | 10.26434/chemrxiv-2025-nkgp3 | Water-Soluble Integral Membrane Protein Nanoparticles | Helical integral membrane proteins are assumed to require a lipid bilayer or model membrane (e.g. detergent micelles) to prevent aggregation and precipitation in aqueous solution. Here, we show that this is not always true and that single-span helical integral membrane proteins are capable of forming stable but reversible protein nanoparticle assemblies (detergent-limited particles — DLPs) when purified after removal of lipid and all or nearly all detergent. Residual detergent in DLPs is not exchangeable with the surrounding solution. This work focuses on DLPs formed by the transmembrane C-terminal domain of the human amyloid precursor protein (C99), although evidence of DLP formation by other membrane proteins is provided. Size exclusion chromatography, light scattering and electron microscopy showed that C99-DLPs are spherical with modest polydispersity (7-16 monomers) and are stable for months in solution. C99-DLPs revert to traditional protein-detergent complexes upon addition of detergent. Circular dichroism and 2D IR spectroscopies revealed that β-sheet content is significantly higher in C99-DLPs than that of C99 in detergent micelles. C99-DLPs were taken up by mammalian cells, trafficked to a perinuclear location and appeared to accumulate in or next to LC3B-positive punctae, which likely are stalled autophagosomes. C99-DLPs appeared to remain intact in cells as there was no evidence of protein degradation over a period of days. This work challenges the broad assumption that native single-span membrane proteins always require either a bilayer or membrane mimetic to prevent aggregation / precipitation from solutions. It also shows that protein nanoparticles are not always easily degraded by cellular proteases. | Ricardo Capone; James Hutchison; Amanda Cao; Geoffrey Li; James Hayes; Oliver Chalkley; Michael Goodman; Manuel Castro; William Weeks; Sivaraja Vaithiyalingam; Qiangjun Zhou; Charles Sanders; Lauren Buchanan | Physical Chemistry; Biological and Medicinal Chemistry; Nanoscience; Biochemistry; Biophysics | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67c762506dde43c9087fdcf6/original/water-soluble-integral-membrane-protein-nanoparticles.pdf |
6735144df9980725cf195ee7 | 10.26434/chemrxiv-2023-rtpsz-v2 | An Automated On-The-Fly Optimization of Resource Allocation for High-Throughput Protein-Ligand Binding Free Energy Simulations | Molecular dynamics simulations to compute protein to small molecule binding free energies are becoming a valuable tool in the early stages of drug discovery. However, their cost and complexity are often prohibitive for high-throughput studies. Herein, we present an automated workflow for the thermodynamic integration scheme with the “on-the-fly” optimization of computational resource allocation for each λ-window of both relative and absolute binding free energy simulations. This iterative workflow utilizes automatic equilibration detection and convergence testing via the Jensen-Shannon distance to determine optimal simulation stopping points in an entirely data-driven manner. We benchmark our workflow on the well-characterized systems cyclin-dependent kinase 2 and T4 Lysozyme L99A/M102Q mutant, as well as the more flexible SARS-CoV-2 papain-like protease. We demonstrate that this proposed protocol can achieve over an 85% reduction in computational expense while maintaining similar levels of accuracy when compared to other benchmarking protocols. We examine the performance of this protocol on both small and large molecular transformations. The cost accuracy tradeoff of repeated runs is also investigated. | S. Benjamin Koby; Evgeny Gutkin; Shree Patel; Maria Kurnikova | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling; Theory - Computational | CC BY NC 4.0 | CHEMRXIV | 2024-11-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6735144df9980725cf195ee7/original/an-automated-on-the-fly-optimization-of-resource-allocation-for-high-throughput-protein-ligand-binding-free-energy-simulations.pdf |
60c73cbf567dfe070bec3566 | 10.26434/chemrxiv.14679624.v1 | 3D Printed Multi Functional Ti6Al4V Based Hybrid Scaffold for the Management of Osteosarcoma | <p>2.1.1 Preparation of drug-laden Gel/HA composite</p>
<p>Alendronate
(ALN), is a commonly used bisphosphonate drug for osteoporosis management and bone
regeneration. <sup>[33] </sup>However, direct
loading of ALN onto Gel often results in burst drug release due to the fast Gel
degradation <i>in vivo</i>. In
contrast, degradable HA microsphere is an excellent drug delivery vehicle,
which can provide sustained/controlled drug release as well as promoting osteoblasts mineralization/maturation (due to slow release of Ca<sup>2+</sup>
and PO<sub>4</sub><sup>3-</sup>). <sup>[34]</sup> To prepare the ALN-laden HA microspheres/Gel
composite (ALN-HA/Gel), HA microspheres were first synthesized following established procedure.<sup> [35]</sup> 0.5 g ALN was then added into 50 mL aqueous dispersion containing 2.0 g
HA microspheres. After mixing using shaking incubator under 37 ℃ for
48 h, ALN-HA were collected by centrifugation and vacuum dried
at 40 ℃ for 24 h. ALN concentration in the supernatant solution was evaluated
by UV-vis spectroscopy. The drug-laden Gel/ALN-HA can be obtained by
dispersing 3.0g ALN-HA
microspheres in 50 mL deionized water, followed by addition of 8.0 g Gel, and
stirred magnetically at 1000 rpm under 50 ℃ for 1 h.</p>
<p>2.1.2 Preparation of 3D printed
Ti6Al4V scaffolds</p>
<p>3D
printed Ti6Al4V scaffolds (named as Ti) were manufactured by electron beam
melting (EBM) facility in-house. The lattice structure was designed by
computer-assisted design (CAD) software (Magics, Materialise, Belgium) based on
a dodecahedron unit cell with strut diameter of 300 μm and porosity of 80%.
Cubic scaffolds (5mm × 5mm × 5mm) were used for <i>in vitro</i> testing and cylindrical scaffolds (Φ = 6mm, height = 6mm) were used for <i>in vivo</i>
experiments. All samples were thoroughly cleaned by sonication in acetone,
alcohol and deionized water for 30 min, respectively. The Ti scaffolds were subsequently
subjected to hydrothermal treatment.<sup> [36]</sup> Specifically, the
scaffolds were immersed in an aqueous solution (m(H<sub>2</sub>O<sub>2</sub>):m(H<sub>3</sub>PO<sub>4</sub>)
9:1) and placed in a Teflon-lined autoclave under 220 ℃ for 24 h. After the treatment, scaffolds were
washed with distilled water and dried in air at room temperature for 24 h. The
hydrothermally treated samples were named as HR-Ti.</p>
<p>2.1.3 Preparation of Gel/ALN-HA infused HR-Ti scaffold</p>
<p>The Gel/ALN-HA mixture was infused into the HR-Ti,
then the infused scaffolds were held at -80<a> </a>℃ overnight followed by freeze-drying at -40 ℃ for 48 h. After that, the infused scaffolds
were immersed in 100 mL ethanol containing 50mmol/L 1-ethyl-3-(3- (dimethylamino)
propyl) carbodiimide hydrochlorid (EDC∙HCl) and N-hydroxysuccinimide (NHS) at 4
℃ for 10
h to crosslink the Gel content. Afterwards, the scaffolds were washed three
times by ethanol and freeze-dried again. The final scaffolds were named as
Gel/ALN-HA/HR-Ti. For comparison, ALN/HR-Ti (without Gel and HA), Gel/ALN/HR-Ti
(without HA) and Gel/HA/HR-Ti (without ALN) were also prepared.</p> | Bianyun Cai; Leizhen Huang; Jingcheng Wang; dan Sun; Ce zhu; Yong Huang; Shujun Li; Zhijun Guo; Limin Liu; Ganjun Feng; Yubao Li; Li Zhang | Alloys; Biocompatible Materials; Biological Materials; Hybrid Organic-Inorganic Materials; Bioinorganic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73cbf567dfe070bec3566/original/3d-printed-multi-functional-ti6al4v-based-hybrid-scaffold-for-the-management-of-osteosarcoma.pdf |
645d709cf2112b41e96777e6 | 10.26434/chemrxiv-2023-h25dz | Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogs | Sulfonamides are one of the most important pharmacophores in medicinal chemistry and sulfonamide analogs have gained substantial interest in recent years. However, the protein interactions of sulfonamides and especially of their analogs are underexplored. Using FKBP12 as a model system, we describe the synthesis of optically pure sulfenamide, sulfinamide and sulfonimidamide analogs of a well characterized sulfonamide ligand. This allowed us to precisely determine the binding contributions of each sulfonamide oxygen atom and the consequence of nitrogen replacements. We also present high resolu-tion cocrystal structures of sulfonamide analogs buried in the pocket of a protein target. This revealed intimate contacts with the protein, including an unprecedented hydrogen bond acceptor of sulfonimidamides. The use of sulfonamide analogs ena-bled new exit vectors that allowed to remodel a subpocket in FKBP12. Our results illuminate the protein interaction potential of sulfonamides/sulfonamide analogs and will aid in their rational design. | Patrick Purder; Christian Meyners; Wisely Sugiarto; Jürgen Kolos; Frank Löhr; Jakob Gebel; Thomas Nehls; Volker Dötsch; Frederik Lermyte; Felix Hausch | Biological and Medicinal Chemistry; Biophysics; Drug Discovery and Drug Delivery Systems | CC BY NC 4.0 | CHEMRXIV | 2023-05-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/645d709cf2112b41e96777e6/original/deconstructing-protein-binding-of-sulfonamides-and-sulfonamide-analogs.pdf |
60c754d0842e650404db4222 | 10.26434/chemrxiv.13739320.v1 | Protein Conjugation with Triazolinediones: Switching from a General Tyrosine-Selective Labeling Method to a Highly Specific Tryptophan Bioconjugation Strategy | Selective labeling of tyrosine residues in
peptides and proteins can be achieved via a 'tyrosine-click' reaction with
triazolinedione reagents (TAD). We have found that tryptophan residues are in
fact often also labeled with this reagent. This off-target labeling is only
observed at very low levels in protein bioconjugation but remains under the
radar due to the low relative abundance of tryptophan compared to tyrosines in
natural proteins, and because of the low availability and accessibility of
their nucleophilic positions at the solvent-exposed protein surface. Moreover,
because TAD-Trp adducts are known to be readily thermoreversible, it can be
challenging to detect these physiologically stable but thermally labile
modifications using several MS/MS techniques. We have found that fully
solvent-exposed tryptophan side chains are kinetically favored over tyrosines
under almost all conditions, and this selectivity can even be further enhanced
by modifying the pH of the aqueous buffer to effect selective Trp-labeling.
This new site-selective bioconjugation method does not rely on unnatural amino
acids and has been demonstrated for peptides and for recombinant proteins.
Thus, the TAD-Tyr click reaction can be turned into a highly site-specific
labeling method for tryptophan. | Klaas Decoene; Kamil Unal; An Staes; Kris Gevaert; Johan M. Winne; Annemieke Madder | Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c754d0842e650404db4222/original/protein-conjugation-with-triazolinediones-switching-from-a-general-tyrosine-selective-labeling-method-to-a-highly-specific-tryptophan-bioconjugation-strategy.pdf |
620ce5e9bd05a0a6b708da1e | 10.26434/chemrxiv-2022-m1mk5 | Graph-Based Molecular Pareto Optimisation | Computer-assisted design of small molecules has experienced a resurgence in academic and indus-
trial interest due to the widespread use of data-driven techniques such as deep generative models.
While the ability to generate molecules that fulfill required chemical properties is encouraging, the
use of deep learning models requires significant, if not prohibitive, amounts of data and computa-
tional power. At the same time, open-sourcing of more traditional techniques such as graph-based
genetic algorithms for molecular optimisation [Jensen, Chem. Sci., 2019, 12, 3567-3572] has shown
that simple and training-free algorithms can be efficient and robust alternatives. Further research
alleviated the common genetic algorithm issue of evolutionary stagnation by enforcing molecular
diversity during optimisation [Van den Abeele, Chem. Sci., 2020, 42, 11485-11491]. The crucial
lesson distilled from the simultaneous development of deep generative models and advanced genetic
algorithms has been the importance of chemical space exploration [Aspuru-Guzik, Chem. Sci., 2021,
12, 7079-7090]. For single-objective optimisation problems, chemical space exploration had to be
discovered as a usable resource but in multi-objective optimisation problems, an exploration of trade-
offs between conflicting objectives is inherently present. In this paper we provide state-of-the-art
and open-source implementations of two generations of graph-based non-dominated sorting genetic
algorithms (NSGA-II, NSGA-III) for molecular multi-objective optimisation. In addition, we provide
the results of a series of benchmarks for the inverse design of small molecule drugs for both the
NSGA-II and NSGA-III algorithms. | Jonas Verhellen | Theoretical and Computational Chemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2022-02-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/620ce5e9bd05a0a6b708da1e/original/graph-based-molecular-pareto-optimisation.pdf |
673a21d07be152b1d063f922 | 10.26434/chemrxiv-2024-5pdjx | Investigating the presence of different catalysts and their effect on the rate of decomposition of hydrogen peroxide at various temperatures, analyzed through the change in oxygen volume in controlled laboratory conditions. | The decomposition of hydrogen peroxide (H2O2) is a vital concept in various engineering and environmental procedures. Catalysts such as MnO2, PbO2, and Fe2O3 can significantly influence the rate of reactions; temperature also plays a vital role in the effectiveness of these catalysts. This paper will explore the question of “How does the presence of different catalysts [MnO2, PbO2, Fe2O3] affect the rate of decomposition of hydrogen peroxide (H2O2) at various temperatures (30°C, 60°C, 90°C) under controlled laboratory conditions”. By investigating the impact of different catalysts (MnO2, PbO2, Fe2O3) on the decomposition rate of hydrogen peroxide at various temperatures (30°C, 60°C, 90°C), this paper aims to provide insights into optimizing this reaction for practical applications in fields of chemical and mechanical engineering. Optimizing industrial reactions to improve efficiency, reduce costs, and minimize environmental impact. Understanding how different catalysts and temperatures affect the decomposition of hydrogen peroxide will help in designing more efficient catalytic processes and further expand my interest in chemical and mechanical engineering. The research and experimentation of these reactions allow me to further gain an understanding of my future profession in the optimization of reactions in my field of study.
| Evan Trinh; Kevin Trinh | Catalysis | CC BY 4.0 | CHEMRXIV | 2024-11-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/673a21d07be152b1d063f922/original/investigating-the-presence-of-different-catalysts-and-their-effect-on-the-rate-of-decomposition-of-hydrogen-peroxide-at-various-temperatures-analyzed-through-the-change-in-oxygen-volume-in-controlled-laboratory-conditions.pdf |
658de2e266c13817293b8174 | 10.26434/chemrxiv-2023-hfntq | Chemical Proteomics-based Target Prioritization through a Residue Agnostic Ligandability Assessment Platform | The landscape of drug discovery is undergoing a transformative phase with the influx of structural biology and omics data. Identifying optimal drug targets amid this data surge presents a multifaceted challenge. Covalent inhibitors, once undervalued, now hold substantial promise, especially targeted covalent inhibitors (TCIs), effectively engaging 'undruggable' proteins and overcoming resistance mechanisms. Existing ML software can proficiently model covalent ligands but lack comprehensive utility across large chemoproteomics sites. Challenges persist in predicting and assessing cryptic ligandable sites and sites beyond cysteine, demanding advanced computational tools. As cysteine-ligandable proteins represent only ~20% of the quantifiable proteome, there is a requirement for ligandability mapping of other nucleophilic amino acids. This study introduces a pioneering computational pipeline leveraging an AI-based ligandable predictor for meticulous evaluation of chemical proteomics-based reactive sites. The pipeline offers a scalable framework to assess covalent ligandability on a large scale, filter out improbable hits and systematically evaluate potential drug targets. Our work addresses covalent drug design challenges through a pipeline that fills crucial gaps in predicting cryptic ligandable and covalent sites in addition to cysteines to foster more efficient drug discovery methodologies. | Fettah Erdogan; Raiyan Chowdhury; Serap Beldar; Tom Bobby Chandy; Rebecca G. Allan; Elvin D. de Araujo; Patrick T. Gunning | Biological and Medicinal Chemistry; Biochemistry; Bioinformatics and Computational Biology; Chemical Biology | CC BY 4.0 | CHEMRXIV | 2023-12-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/658de2e266c13817293b8174/original/chemical-proteomics-based-target-prioritization-through-a-residue-agnostic-ligandability-assessment-platform.pdf |
669e65de5101a2ffa894f26e | 10.26434/chemrxiv-2024-f0rjq | A long fluorescence lifetime probe for labeling of Gram-negative bacteria | Bacterial resistance, primarily stemming from misdiagnosis, misuse, and overuse of antibacterial medications in humans and animals is a pressing issue. To address this, we hereby focused on developing a fluorescent probe for the detection of bacteria, with a unique feature — an exceptionally long fluorescence lifetime — to overcome autofluorescence limitations in biological samples. The polymyxin-based probe (ADOTA-PMX) selectively targets Gram-negative bacteria and used the red-emitting fluorophore azadioxatriangulenium (with a reported fluorescent lifetime of 19.5 ns). Evaluation of ADOTA-PMX's bacterial labeling efficacy revealed strong specificity for Gram-negative bacteria and full spectral fluorescence lifetime imaging microscopy demonstrated the potential of ADOTA-PMX for bacterial imaging applications. The probe exhibited a lifetime of 4.5 ns when bound to bacteria possibly indicating interactions with the bacterial outer membrane. Furthermore, the fluorescence lifetime measurements of ADOTA-PMX labelled bacteria could be performed using a bench-top fluorimeter without the need of sophisticated microscopes. This study represents the first targeted probe for fluorescence lifetime imaging, offering sensitivity crucial for detecting Gram-negative bacteria and enabling multiplexing via fluorescence lifetime imaging. | Assel Baibek; Zuzanna Konieczna; Muhammed Üçüncü; Zainab S. Alghamdi; Richa Sharma; Mathew Horrocks; Mark Bradley | Biological and Medicinal Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/669e65de5101a2ffa894f26e/original/a-long-fluorescence-lifetime-probe-for-labeling-of-gram-negative-bacteria.pdf |
65f41bce9138d2316182d09f | 10.26434/chemrxiv-2024-p5qcr | A Martini-based coarse-grained soil organic matter model derived from atomistic simulations | The significance of soil organic matter (SOM) in environmental contexts, particularly its role in pollutant adsorption, has prompted increased utilization of molecular simulations to understand microscopic interactions. This study introduces a coarse-grained SOM model, parametrized within the framework of the versatile Martini 3 force field. Utilizing systems generated by the Vienna Soil Organic Matter Modeler 2, which constructs humic substance systems from a fragment database, we employed Swarm-CG to parametrize the fragments and subsequently assembled them into macromolecules. Direct Boltzmann Inversion (DBI) facilitated the determination of bonded parameters between fragments. The parametrization yielded favorable agreement in the radius of gyration and solvent-accessible surface area. Transfer free energies exhibited a strong correlation with hexadecane-water and chloroformwater values, albeit deviations were noted for octanol-water values. Comparing densities of modeled Leonardite Humic Acid (LHA) systems at coarse-grained and atomistic levels revealed promising agreement, particularly at higher water concentrations. The DBI approach effectively reproduced average values of bonded interactions between fragments. Radial distribution functions between carboxylate groups and calcium ions partially concurred, yet limitations arose in reproducing certain peaks due to fixed bead sizes. Detailed analysis of atomistic systems elucidated different configurations between groups, further explaining discrepancies. The present contribution provides a comprehensive insight into the properties, strengths, and weaknesses of the coarse-grained SOM model, serving as a foundation for future investigations encompassing pollutant interactions and varied SOM compositions. | Lorenz Dettmann; Oliver Kuehn; Ashour Ahmed | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2024-03-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65f41bce9138d2316182d09f/original/a-martini-based-coarse-grained-soil-organic-matter-model-derived-from-atomistic-simulations.pdf |
646ced16ccabde9f6e3c1467 | 10.26434/chemrxiv-2023-n4jrp-v2 | Environmental and Nuclear Quantum Effects on Double Proton Transfer in Guanine-Cytosine Base Pair | In the present work, we investigate the double proton transfer (DPT) tautomerization process in Guanine-Cytosine (GC) DNA base pairs. In particular, we study the influence of the biological environment on the mechanism, the kinetics and thermodynamics of such DPT. To this end, we present a molecular dynamics (MD) study in the tight-binding density functional theory framework, and compare the reactivity of the isolated GC dimer with that of the same dimer embedded in a small DNA structure. The impact of nuclear quantum effects (NQEs) is also evaluated using Path Integral based MD. Results show that in the isolated dimer, the DPT occurs via a concerted mechanism, while in the model biological environment, it turns into a step-wise process going through an intermediate structure. One of the water molecules in the vicinity of the proton transfer sites plays an important role as it changes H-bond pat- tern during the DPT reaction. The inclusion of NQEs has the effect of speeding up the tautomeric-to-canonical reaction, reflecting the destabilization of both the tautomeric and intermediate forms. | Federica Angiolari; Simon Huppert; Fabio Pietrucci; Riccardo Spezia | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/646ced16ccabde9f6e3c1467/original/environmental-and-nuclear-quantum-effects-on-double-proton-transfer-in-guanine-cytosine-base-pair.pdf |
635b264331107283fff2fb4c | 10.26434/chemrxiv-2021-66w4j-v8 | Second-order Phase Transition Behavior behind Polymer Glass Transition | Glass transition has similarity to the second-order phase transition in temperature dependent changes in entropy, non-Arrhenius viscosity, and heat capacity of glass forming materials. However, it has primarily been considered to be not phase transition. Recent single-molecule spectroscopy developments prompted re-investigating glass transition at the nanometer scale probing resolution, showing that glass transition includes phenomena similar to the second-order phase transition. They are characterized by microscopic collective polymer motion and discontinuous changes in temperature dependent relaxation times, the latter of which resembles the critical slowing down of second-order phase transitions, within a temperature window above the polymer calorimetric glass transition temperature. Simultaneous collective motion and critical slowing down occurrences disclose that the second-order phase transition hides behind polymer glass transition.
| Mitsuru Ishikawa; Taihei Takahashi; Yu-ichiro Hayashi; Maya Akashi; Takayuki Uwada | Physical Chemistry; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-10-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/635b264331107283fff2fb4c/original/second-order-phase-transition-behavior-behind-polymer-glass-transition.pdf |
67d1d0116dde43c9088f3846 | 10.26434/chemrxiv-2025-2mrbb-v2 | Comparing Massively-Multitask Regression Algorithms for Drug Discovery | Massively-Multitask Regression Models (MMRMs) trained on millions of compounds and many thousands of assays can predict bioactivity with accuracy comparable to 4-concentration IC50 experiments. Recent advances in hardware and algorithms have produced a variety of methods for multitask modeling. This report compares the performance of six MMRM algorithms: Profile-QSAR (pQSAR), Alchemite, a meta learner (MetaNN), a multitask feed-forward neural network (MT-DNN), Bayesian factorization with side information (Macau) and Inductive Matrix Completion (IMC). To ensure a fair comparison, each was trained by an expert, in several cases an author, of each method. All used the same sets of 159 kinase and 4276 diverse ChEMBL assays, employing the same realistically novel training/test set splits. MMRMs generally performed much better than a benchmark of single-task random forest regression models for our use case of virtually screening the compound collection on which the models were trained. The comparison was complicated, because methods that train all models simultaneously must leave out the test-set measurements for all assays to avoid test-set leakage, here 75% of measurements. MMRMs which train models one-at-a-time need only leave out data for each assay as it is trained, training on 99+% of data. This does not affect the accuracy of the final production models trained on 100% of data but does affect evaluation of how the final models will perform. The comparisons, therefore, included 3 training/test set collections: “all-out” models that leave out all test sets during training; “one-out” models where practical; and “subset-out” models, which only built models for about 10% of kinase assays or 1% of diverse assays, but could thus train evaluation models on about 90% or 99% of the measurements respectively. Many methods achieve similar accuracy. However, models trained on only 75% of the data performed much worse than those trained on 99+%. This indicates that all-out models seriously underestimate the performance of the final production models. Subset-out models were closer to one-out. A compromise method is to assess performance of the final models by multiple subset-out models, a more practicable computation for 1000s of assays. MMRMs demonstrated little advantage over single-task models for “cold-start” predictions on our novel test-set compounds not only unlike the specific assay’s training set, but also never tested on any of the other multitask supporting assays. Instead, the accuracy advantage was mainly from imputations within these sparse assay collections, compounds unlike the training set for the assay of interest, but with some measurements on other assays. This implies that MMRMs are best suited for hit-finding, off-target, promiscuity, mechanism-of-action, polypharmacology or drug repurposing prediction of compounds from the source used to train the overall multitask model. They have little advantage over single-task models, at much higher cost, for virtual screening of vendor archives or exploratory generative chemistry. Given that accuracy of the final models is often comparable between several of the algorithms, the paper concludes with a detailed discussion of other practical pros and cons of each method that might help choose which method to employ. | Eric Martin; Xiang-Wei Zhu; Patrick Riley; Steven Kearnes; Ekaterina A Sosnina; Li Tian; Zijian Wang ; Ying Wei; Thomas M Whitehead; Gareth J Conduit; Matthew D Segall | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d1d0116dde43c9088f3846/original/comparing-massively-multitask-regression-algorithms-for-drug-discovery.pdf |
67d9982581d2151a02dfe38c | 10.26434/chemrxiv-2025-htc0s | Synthesis of oxasilolanes by TBAT-catalyzed hydroxyl-directed hydrosilylation | The reaction of allylic and homoallylic styrenyl alcohols with diphenylsilane and catalytic tetrabutylammonium difluorotriphenylsilicate (TBAT) produces 5- and 6-membered ring oxasilolanes respectively. Differing substitution at the carbinol position, phenyl ring, and carbon-carbon double bond were all found to have significant impacts on both yield and diastereoselectivity. A mechanism is proposed involving fluoride-promoted intramolecular hydrosilylation and formation of an intermediate benzylic anion, followed by cyclization and oxasilolane formation. | Tess Billmire; Adam Jones; Sarah Maffett; Gregory O'Neil | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Stereochemistry | CC BY NC ND 4.0 | CHEMRXIV | 2025-03-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d9982581d2151a02dfe38c/original/synthesis-of-oxasilolanes-by-tbat-catalyzed-hydroxyl-directed-hydrosilylation.pdf |
60c74f964c89195593ad3c08 | 10.26434/chemrxiv.12923684.v1 | Virtual Screening of Some Antivirals That Can Be Repurposed As Potential Effective Drugs against SARS-CoV-2 | <p>SARS-CoV-2 has triggered a big epidemic among people around the world and it is the newest
in the sequence to be prevalent among other infectious diseases. Drug repurposing concept has
been utilized effectively for numerous viral infections. Considering the situation and the urgency,
the idea of drug repurposing for coronavirus infection (COVID-19) is also being studied.
Screening with molecular docking method for 29 antiviral drugs was performed against SARSCoV-2 primary protease proteins (MPP), spike ecto-domain, spike receptor binding domain,
Nsp9 RNA binding protein,and HR2 domain. Among these drugs, Indinavir, Sorivudine,
Cidofovir and Darunavir show minimum docking scores with all key proteins in terms of least
binding energy. For ADME (Absorption, Distribution, Metabolism, and Excretion) analysis, the
top 4 drug candidates were further used to examine their drug profiles for suitability against
SARS-CoV-2. The toxicity testing of top drug candidates showed no significant carcinogenic,
mutagenic or skin irritating impacts. Indinavir may possess some complexity to heart. In
addition, the drug similarity prediction revealed several approved structural analogues such as
Telbivudine, Tenofovir, Amprenavir, Fosamprenavir etc which also could be used to treat viral
infections. The study may speed up the findings of therapeutics against SARS-CoV-2. <br /></p> | Mohammad Rejaur Rahman; Anik Banik; Ishtiak Malique Chowdhury; Emran Sajib; Sanchita Sarkar | Bioinformatics and Computational Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems; Microbiology | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f964c89195593ad3c08/original/virtual-screening-of-some-antivirals-that-can-be-repurposed-as-potential-effective-drugs-against-sars-co-v-2.pdf |
62d6a28efe12e33b24a9c7da | 10.26434/chemrxiv-2022-5sqh3 | Mechanical Interlocking Enhances the Electrocatalytic Oxygen Reduction Activity and Selectivity of Molecular Copper Complexes | Efficient O2 reduction reaction (ORR) for selective H2O generation enables advanced fuel cell technology. Non-precious metal (NPM) catalysts are viable and attractive alternatives to state-of-the-art Pt-based materials that are expensive. Cu complexes inspired by Cu-containing O2 reduction enzymes in nature have yet to reach their desired ORR catalytic performance. Here, the concept of mechanical interlocking is introduced to the ligand architecture to enforce dynamic spatial restriction on the Cu coordination site unachievable using other structural means. The utility of the kinetic effects from mechanical bond in transition metal catalysis is just about to emerge, and here the catenane ligands govern the O2 adduct binding mode, thereby steering the selectivity to generate H2O as the major product via the 4e– pathway, rivaling the selectivity of Pt. The kinetic effects from the interlocked catenane ligand also promotes product elimination and boosts the onset potential by 130 mV, the mass activity by 1.8 times, and the turnover frequency (TOF) by 1.5 folds as compared to the non-interlocked counterpart. Our Cu catenane complex represents one of the first examples to take advantage of mechanical interlocking to afford electrocatalysts with enhanced activity and selectivity. The mechanistic insights gained through this integrated experimental and theoretical study are envisioned to be of practical value not just to the area of ORR energy catalysis, but also with broad implications on interlocked metal complexes that are of critical importance to the general fields in redox reactions involving proton-coupled electron transfer (PCET) steps | Xiaoyong Mo; Yulin Deng; Samuel Kin-Man Lai; Xutao Gao; Hung-Ling Yu; Kam-Hung Low; Heng-Liang Wu; Ho Yu Au-Yeung; Edmund Chun Ming Tse | Inorganic Chemistry; Catalysis; Energy; Bioinorganic Chemistry; Supramolecular Chemistry (Inorg.); Electrocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2022-07-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62d6a28efe12e33b24a9c7da/original/mechanical-interlocking-enhances-the-electrocatalytic-oxygen-reduction-activity-and-selectivity-of-molecular-copper-complexes.pdf |
62070e98bd05a04ae103fa7e | 10.26434/chemrxiv-2022-d8sgv | A Co-Axial Microtubular Flow Battery Cell with Ultra-high Volumetric Power Density | Volumetric power density is a key factor determining flow batteries' footprint, capital cost and ability to handle uneven energy resource distributions. While significant progress has been made on flow battery materials and electrochemistry to improve energy density, conventional flow battery assemblies based on planar cell configuration exhibit low packing efficiencies and membrane surface area per volume of the cell, thus resulting in low volumetric power density. Here, we introduce a co-axial microtubular (CAMT) flow battery cell that significantly improves the volumetric power density. This cell design overcomes the intrinsic power limit of planar cell configuration and is suitable for all mainstream flow battery chemistries. Using zinc-iodide chemistry as a demonstration, our CAMT cell shows peak charge and discharge power densities of 1322 W/Lcell and 306.1 W/Lcell compared to average charge and discharge power densities of < 60 W/Lcell and 45 W/Lcell of conventional planar flow battery cells. In addition, the battery can cycle for more than 220 hours, corresponding to > 2,500 cycles at off-peak conditions. Furthermore, we have also demonstrated that the CAMT cell is compatible with zinc-bromide, quinone-bromide, and all-vanadium chemistries. The CAMT flow cell represents a device-level innovation to enhance the volumetric power of flow batteries, and potentially reduce the size and cost of the cells and the entire flow battery. The CAMT design can potentially be applied to other electrochemical systems and lead to a paradigm shift in flow battery fundamental study and commercialization. | Yutong Wu; Fengyi Zhang; Ting Wang; Po-Wei Huang; Haochen Yang; Alexandros Filippas; Yanghang Huang; Chao Wang; Huitian Liu; Xing Xie; Ryan Lively; Nian Liu | Energy; Chemical Engineering and Industrial Chemistry; Reaction Engineering; Energy Storage; Power | CC BY NC ND 4.0 | CHEMRXIV | 2022-02-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62070e98bd05a04ae103fa7e/original/a-co-axial-microtubular-flow-battery-cell-with-ultra-high-volumetric-power-density.pdf |
635fe071ecdad5194ef45d24 | 10.26434/chemrxiv-2022-7x7f7 | Illuminating the Human Metabolome: Selective Detection of Multiple Metabolites in Unaltered Biofluids via Hyperpolarisation-Enhanced NMR Spectroscopy | Detecting and identifying individual metabolites in biological mixtures constitutes a challenge in analytical research. In this context, nuclear magnetic resonance (NMR) has proven to be powerful providing precise qualitative and quantitative information non-invasively. However, NMR is inherently insensitive and lacks selectivity regarding the analysis of molecular targets in complex mixtures. Here, we present a method that circumvents these shortcomings performing photo-chemically induced dynamic nuclear polarisation (photo-CIDNP) on unmodified biofluids, i.e. human urine and serum. We demonstrate that photo-CIDNP on biofluids is feasible, can be performed straightforwardly in the native aqueous medium at physiological concentrations, and acts as a spectral filter highlighting a clinically relevant metabolite subset. The method is compatible with standard metabolomics protocols and holds great promise for in-depth studies for use in metabolomics and other areas of analytical research. | Lars Kuhn; Stefan Weber; Joachim Bargon; Teodor Parella; Míriam Pérez-Trujillo | Analytical Chemistry; Spectroscopy (Anal. Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-11-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/635fe071ecdad5194ef45d24/original/illuminating-the-human-metabolome-selective-detection-of-multiple-metabolites-in-unaltered-biofluids-via-hyperpolarisation-enhanced-nmr-spectroscopy.pdf |
64ef73cadd1a73847fd6b37f | 10.26434/chemrxiv-2023-59xhv | Designing Electrocatalysts for Hydrogen Evolution in Saline Electrolyte Using Rapid Synthesis on Carbon Paper Supports | Generating hydrogen from brackish or seawater could enable flexible energy generation, de-centralized electricity storage, and decreased reliance on energy-intensive water purification for hydrogen evolution reaction (HER). Platinum is often the most effective electrocatalyst for HER, however, it is not as stable or efficient in nonideal electrolytes, such as seawater or non-acidic media. In this work, we investigate the activity and stability of binary electrocatalysts in brackish and neutral electrolytes. Using a rapid carbon-paper-based electrochemical synthesis method, we systematically assessed 45 unary and binary electrocatalysts. Four standout binary electrocatalyst materials were identified that showed either comparable or superior activity and stability to Pt in saline-containing electrolyte. Most notably, the 1Ni:1Pt electrocatalyst had a similar overpotential (60 mV) to a Pt control (50 mV), but with greater stability. Finally, we show that this carbon-paper-based synthesis method is scalable for synthesizing and assessing electrocatalysts. This work provides important insight both for rapid synthesis and comparison of new electrocatalysts, but also for the specific goal of performing HER in non-ideal aqueous conditions. | Connor Sullivan; Sangmin Jeong; Melissa King; Michael Ross | Catalysis; Nanoscience; Nanocatalysis - Catalysts & Materials; Electrocatalysis; Heterogeneous Catalysis; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-08-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64ef73cadd1a73847fd6b37f/original/designing-electrocatalysts-for-hydrogen-evolution-in-saline-electrolyte-using-rapid-synthesis-on-carbon-paper-supports.pdf |
60c7534e842e65c454db3f3f | 10.26434/chemrxiv.12973178.v2 | Methylguanidinium at the Air/Water Interface: A Simulation Study with the Drude Polarizable Force Field | <div>Methylguanidinium is an important molecular ion which also serves as the model compound for arginine side chain. We studied the structure and dynamics of methylguanidium ion at the air/water interface by molecular dynamics simulations employing the Drude polarizable force field. We found out that methylguanidinium accumulate on the interface with a majority adopting tilted conformations. We also demonstrated that methylguanidinium and guanidinium ions have different preference towards the air/water interface. Our results illustrate the importance to explicitly include the electronic polarization effects in modeling interfacial properties.</div><div><br /> </div> | Jian Zhu; Jing Huang | Theory - Computational; Interfaces | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7534e842e65c454db3f3f/original/methylguanidinium-at-the-air-water-interface-a-simulation-study-with-the-drude-polarizable-force-field.pdf |
60c74d32337d6cfc0fe27d5a | 10.26434/chemrxiv.12546596.v2 | Aniline-Containing Derivatives of Parthenolide: Synthesis and Anti-Chronic Lymphocytic Leukaemia Activity | A protocol for squaric acid-catalysed 1,4-addition of aniline derivatives to parthenolide is identified, developed and disclosed.<br /> | Alex Quy; Xingjian Li; Louise Male; Tatjana Stankovic; Angelo Agathanggelou; John Fossey | Natural Products; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d32337d6cfc0fe27d5a/original/aniline-containing-derivatives-of-parthenolide-synthesis-and-anti-chronic-lymphocytic-leukaemia-activity.pdf |
66ba644a5101a2ffa81dc23b | 10.26434/chemrxiv-2024-sl7t4 | Imaging and Simulation of Surface Plasmon Polaritons on Layered 2D MXenes | Two-dimensional transition metal carbides and nitrides, commonly known as MXenes, are a novel class of 2D materials with high free carrier densities, making them highly attractive candidates for plasmonic 2D materials. In this study, we use multiphoton photoemission electron microscopy (nP-PEEM) to directly image the plasmonic near fields of multilayers of the prototypical MXene, Ti3C2Tx, with mixed surface terminations (Tx = F, O, and OH). Photon-energy dependent nP-PEEM reveals a dispersive surface plasmon polariton between 1.4 eV and 1.9 eV on MXene flakes thicker than 30 nm and waveguide modes above 1.9 eV. Combining experiments with finite difference time domain (FDTD) simulations, we reveal the emergence of a visible surface plasmon polariton in MXenes, opening avenues for exploration in polaritonic phenomena in MXenes in the visible portion of the electromagnetic spectrum. | Janek Rieger; Atreyie Ghosh; Joseph Spellberg; Calvin Raab; Aishani Mohan; Prakriti Joshi; Sarah King | Physical Chemistry; Materials Science; Quasiparticles and Excitations; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ba644a5101a2ffa81dc23b/original/imaging-and-simulation-of-surface-plasmon-polaritons-on-layered-2d-m-xenes.pdf |
641f2c8391074bccd045cb35 | 10.26434/chemrxiv-2023-z28f4 | Evaluation of autophagy inhibition to combat cancer: (vanadium complex)–protein interactions, parameterization, and validation of a new force field | Autophagy has drawn attention from the scientific community, mainly because of its significant advantages over chemotherapeutic processes. One of these advantages is its direct action on cancer cells, avoiding possible side effects, unlike chemotherapy, which reaches tumor cells and affects healthy cells in the body, leading to a great loss in the quality of life of patients. In this way, it is known that vanadium complex (VC) [VO(oda)(phen)] has proven inhibition effect on autophagy process in pancreatic cancer cells. Keeping that in mind, Molecular Dynamics (MD) simulations can be considered excellent strategies to investigate the interaction of metal complexes and their biological targets. However, simulations of this type are strongly dependent on the appropriate choice of force field (FF). Therefore, this work proposes the development of AMBER FF parameters for VC, having a minimum energy structure as a starting point, obtained through DFT calculations with B3LYP/def2-TZVP level of theory plus ECP for the vanadium atom. An MD simulation in vacuum was performed to validate the developed FF. From the structural analyses, satisfying values of VC bond lengths and angles were obtained, where a good agreement with the experimental data and the quantum reference was found. The RMSD analysis showed an average of only 0.3%. Finally, we performed docking and MD (120 ns) simulations with explicit solvent between VC and PI3K. Overall, our findings encourage new parameterizations of metal complexes with significant biological applications, as well as allow to contribute to the elucidation of the complex process of autophagy. | Taináh Santos; Camila Tavares; Ander Pereira; Elaine Cunha; Teodorico Ramalho | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/641f2c8391074bccd045cb35/original/evaluation-of-autophagy-inhibition-to-combat-cancer-vanadium-complex-protein-interactions-parameterization-and-validation-of-a-new-force-field.pdf |
60c742ec702a9b7c5918a502 | 10.26434/chemrxiv.8850296.v1 | Suzuki-Miyaura Cross-Coupling Towards 4-Amino Biphenyl Intermediates | The preparation of biphenyl derivatives bearing amino groups via direct cross-coupling reaction is being widely explored due to its importance for many branches of the chemical industry. One of the necessary components for such a transformation are halogenated arenes. In order to make the process more economical, we focus on inexpensive and easily available aryl chlorides which usually are not considered reagents of choice for catalytic couplings. In the following short communication, we report the results of the coupling of relatively unreactive chloroaniline with a fluorinated phenylboronic acid leading to the corresponding aminobiphenyl.<br /> | Tomasz Jastrząbek; Artur Ulikowski; Rafał Lisiak | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2019-07-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c742ec702a9b7c5918a502/original/suzuki-miyaura-cross-coupling-towards-4-amino-biphenyl-intermediates.pdf |
60c7537a567dfe4d06ec5e95 | 10.26434/chemrxiv.13480434.v1 | Semi-Automated Optimization of the CHARMM36 Lipid Force Field to Include Explicit Treatment of Long-Range Dispersion | The development of the CHARMM lipid force field (FF) can be traced back to the early 1990s with its current
version denoted CHARMM36 (C36). The parametrization of C36 utilized high-level quantum mechanical data
and free energy calculations of model compounds before parameters were manually adjusted to yield agreement
with experimental properties of lipid bilayers. While such manual fine-tuning of FF parameters is based
on intuition and trial-and-error, automated methods can identify beneficial modifications of the parameters via
their sensitivities and thereby guide the optimization process. This paper introduces a semi-automated approach
to reparametrize the CHARMM lipid FF with consistent inclusion of long-range dispersion through the LennardJones particle-mesh Ewald (LJ-PME) approach. The optimization method is based on thermodynamic
reweighting with regularization with respect to the C36 set. Two independent optimizations with different
topology restrictions are presented. Targets of the optimizations are primarily liquid crystalline phase properties
of lipid bilayers and the compression isotherm of monolayers. Pair correlation functions between water and lipid
functional groups in aqueous solution are also included to address headgroup hydration. While the physics of the
reweighting strategy itself is well understood, applying it to heterogeneous, complex anisotropic systems poses
additional challenges. These were overcome through careful selection of target properties and reweighting
settings allowing for the successful incorporation of the explicit treatment of long-range dispersion, and we denote
the newly optimized lipid force field as C36/LJ-PME. The current implementation of the optimization protocol
will facilitate the future development of the CHARMM and related lipid force fields.<br /> | Yalun Yu; Andreas Kramer; Andrew Simmonett; Rick Venable; Alex MacKerell; Jeffery Klauda; Richard W. Pastor; Bernard Brooks | Biophysical Chemistry; Interfaces; Physical and Chemical Properties | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7537a567dfe4d06ec5e95/original/semi-automated-optimization-of-the-charmm36-lipid-force-field-to-include-explicit-treatment-of-long-range-dispersion.pdf |
663e18b1418a5379b0ef3ff8 | 10.26434/chemrxiv-2024-pjktp | Understanding the Redox Chemistry of β-diketiminate Supported Aluminium Complexes | Recent years have seen a renaissance in main group chemistry, owing in part to the success of some of their lower oxidation species to mimic useful transition metal behaviour. Whilst reversible redox events have been observed within the p-block, discrete redox events that would enable facile bond activations and catalysis is still generally the domain of transition metals. This study reports a combined electrochemical and synthetic investigation probing the redox chemistry available to aluminium supported by the common β-diketiminate ligand. The key finding here is that reduction from Al(III) to Al(I) occurs in a stepwise manner via an Al(II) intermediate. Though the highly reactive nature of Al(I) induces an electrochemical-chemical (EC) reaction, reversible redox processes are observed in the individual steps [Al(III) ↔ Al(II) and Al(II) ↔ Al(I)]. Importantly, this work provides new insight into the electron transfer processes available to aluminium, essential towards building bona fide redox-based catalytic cycles to compete with those of transition metals. | Madeleine Bell; Fáinché Murphy; Brian McMillan; Catherine Weetman | Inorganic Chemistry; Organometallic Chemistry; Electrochemistry - Organometallic; Main Group Chemistry (Organomet.) | CC BY 4.0 | CHEMRXIV | 2024-05-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/663e18b1418a5379b0ef3ff8/original/understanding-the-redox-chemistry-of-diketiminate-supported-aluminium-complexes.pdf |
6310ef00faf4a413f5035664 | 10.26434/chemrxiv-2022-hrc86 | Host polarity invariant TADF rISC mediated through vibronic coupling of two CT triplet states in Novel Hybrid Sulfone-Triarylboron Acceptor donor TADF molecules with ultra-long fluorescent lifetimes | Insert abstract text here. 10H-Dibenzo[b,e][1,4]thiaborinine 5,5-dioxide (SO2B) - a new high triplet (T1 = 3.05 eV) strongly electron-accepting boracycle - was successfully utilised in TADF emitters PXZ-Dipp-SO2B and CZ-Dipp-SO2B. We demonstrate the near complete separation of HOMO and LUMO leading to a low oscillator strength of the S1→S0 CT transition, resulting in very long ca. 83 ns and 400 ns prompt fluorescence lifetime for CZ-Dipp-SO2B and PXZ-Dipp-SO2B respectively, but retaining near unity photoluminescence quantum yield. Devices based on CZ-Dipp-SO2B have high EQE = 23.3% and maximum luminance of 18600 cd m-2 with low efficiency roll off at high brightness. For CZ-Dipp-SO2B rISC is mediated through the vibronic coupling of two CT states, without involving the 3LE, resulting in remarkable rISC rate invariance to environmental polarity and polarizability whilst giving near 100% IQE. This new form of rISC allows stable OLED performance to be achieved in different host environments. | Mateusz Urban; Paulina Marek-Urban; Krzysztof Durka; Sergiusz Lulinski; Piotr Pander; Andrew Monkman | Organic Chemistry; Materials Science; Organic Synthesis and Reactions; Dyes and Chromophores; Optical Materials; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6310ef00faf4a413f5035664/original/host-polarity-invariant-tadf-r-isc-mediated-through-vibronic-coupling-of-two-ct-triplet-states-in-novel-hybrid-sulfone-triarylboron-acceptor-donor-tadf-molecules-with-ultra-long-fluorescent-lifetimes.pdf |
60f8289fc0c36e0b6ccbd6ad | 10.26434/chemrxiv-2021-vdnql | Synthetic Studies on the Indane SHIP1 Agonist AQX-1125. | A new synthetic route to the SHIP1 agonist AQX-1125 has been developed. This sequence utilizes a hydroxy-acid intermediate which allows for ready differentiation of the C6 and C7 positions. The role of the C17 alkene in the biological activity of the system is also investigated, and this functional group is not required for SHIP1 agonist activity. | Otto Dungan; Shawn Dormann; Sandra Fernandes-Denney; Brian Duffy; Daniel Effiong; William Kerr; John Chisholm | Biological and Medicinal Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2021-07-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60f8289fc0c36e0b6ccbd6ad/original/synthetic-studies-on-the-indane-ship1-agonist-aqx-1125.pdf |
656856c729a13c4d4754c0ae | 10.26434/chemrxiv-2023-j3cl3-v2 | Breakdown of Langmuir Adsorption Isotherm in Small Closed Systems | For more than a century, monolayer adsorptions in which adsorbate molecules and adsorbing sites behave ideally have been successfully described by Langmuir adsorption isotherm. For example, the amount of adsorbed material, as a function of concentration of the material which is not adsorbed, obeys Langmuir's equation. In this paper we argue this relation is valid only for macroscopic (large enough) systems. However, when particle numbers of adsorbate molecules and/or adsorbing sites are small, Langmuir's model fails to describe the chemical equilibrium of the system. This is because the kinetics of forming, or the probability of observing, occupied sites arises from two-body interactions, and as such, ought to include cross-correlations between particle numbers of the adsorbate and adsorbing sites. The effect of these correlations, as reflected by deviations in predicting composition when correlations are ignored, increases with decreasing particle numbers and becomes substantial when only few adsorbate molecules, or adsorbing sites, are present in the system. In addition, any change that augments the fraction of occupied sites at equilibrium (e.g., smaller volume, lower temperature, or stronger adsorption energy) further increases the discrepancy between observed properties of small systems and those predicted by Langmuir's theory. In contrast, for large systems these cross-correlations become negligible, and therefore when expressing properties involving two-body processes, it is possible to consider independently the concentration of each component. By applying statistical mechanics concepts, we derive a general expression of the equilibrium constant for adsorption. It is also demonstrated that in ensembles in which total numbers of particles are fixed, the magnitudes of fluctuations in particle numbers alone, can predict the average chemical composition of the system. Moreover an alternative adsorption equation, predicting the average fraction of occupied sites from the value of the equilibrium constant, is proposed. All derived relations and predictions were tested against results obtained by Monte Carlo simulations. | Ronen Zangi | Theoretical and Computational Chemistry; Physical Chemistry; Nanoscience; Chemical Kinetics; Interfaces; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/656856c729a13c4d4754c0ae/original/breakdown-of-langmuir-adsorption-isotherm-in-small-closed-systems.pdf |
66ced2d520ac769e5f16bbd7 | 10.26434/chemrxiv-2024-hrv2f | Ligand-Enabled Ni-Catalyzed Dicarbofunctionalization of Alkenyl Alcohols | Here, an alcohol-directed 1,2-dicarbofunctionalization of alkenyl alcohols has been realized with aryl/alkenyl boronic acids and alkyl halides as the coupling partners. This reaction was enabled by a commercially available bulky 3-amyl β-diketone (Amacac) ligand, that enhancing the reactivity and suppressing many competitive processes. With alcohol as a weak native directing group, this protocol delivers 1,2-arylalkylated and 1,2-alkenylalkylated alcohols with high efficiency, high regioselectivities, a broad substrate scope, and exceptional functional group tolerance. Notably, this methodology facilitates the modular synthesis of biologically active compounds and key alcohol-containing synthetic intermediates. Preliminary mechanistic studies shed light on the neutral coordination of alcohol functionality to nickel catalyst and the origin of regioselectivity. | Li-Qin She; Dao-Ming Wang; Yichen Wu; Peng Wang | Organic Chemistry; Catalysis; Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY NC 4.0 | CHEMRXIV | 2024-08-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ced2d520ac769e5f16bbd7/original/ligand-enabled-ni-catalyzed-dicarbofunctionalization-of-alkenyl-alcohols.pdf |
60c74a16ee301c2b8cc79bbc | 10.26434/chemrxiv.12155076.v1 | A Deep-Learning Approach Toward Rational Molecular Docking Protocol Selection | While a plethora of different protein-ligand docking protocols have been developed over the past twenty years, their performances greatly depend on the provided input protein-ligand pair. In this work we have developed a machine-learning model that uses a combination of convolutional and fully-connected neural networks for the task of predicting the performance of several popular docking protocols given a protein structure and a small compound. We also rigorously evaluate the performance of our model using a widely available database of protein-ligand complexes and different types of data splits. We further open-source all code related to this study so that potential users can make informed guesses on which protocol is best suited for their particular protein-ligand pair. | Jose Jimenez-Luna; Alberto Cuzzolin; Giovanni Bolcato; Mattia Sturlese; Stefano Moro | Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence | CC BY NC ND 4.0 | CHEMRXIV | 2020-04-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74a16ee301c2b8cc79bbc/original/a-deep-learning-approach-toward-rational-molecular-docking-protocol-selection.pdf |
6166f4f92aca5388986252d3 | 10.26434/chemrxiv-2021-23rr0-v2 | Tuning dynamic DNA- and peptide-driven self-assembly in DNA-peptide conjugates | DNA-peptide conjugates offer an opportunity to marry the benefits of both biomolecules, such as the high level of control and programmability found with DNA and the chemical diversity and biological stability of peptides. These hybrid systems offer great potential in fields such as therapeutics, nanotechnology, and robotics to name a few. Using the first DNA-β-turn peptide conjugate, we present three studies designed to investigate the self-assembly of DNA-peptide conjugates over a period of 28 days. Time-course studies, such as these have not been previously conducted for DNA-peptide conjugates, although they are common in pure peptide assembly, for example in amyloid research. By using aging studies to assess the structures produced, we gain insights into the dynamic nature of these systems. The first study explores the influence varying amounts of DNA-peptide conjugates have on the self-assembly of our parent peptide. Study 2 explores how DNA and peptide can work together to change the structures observed during aging. Study 3 investigates the presence of orthogonality within our system by switching the DNA and peptide control on and off independently. These results show that two orthogonal self-assemblies can be combined and operated either independently or in tandem within a single macromolecule, with both spatial and temporal effects upon the resultant nanostructures. | Emerald Taylor; Akiko Sato; Prashant Gudeangadi; David Beal; James Hopper; Michael Reithofer; Christopher Serpell | Polymer Science; Nanoscience; Biopolymers; Nanostructured Materials - Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2021-10-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6166f4f92aca5388986252d3/original/tuning-dynamic-dna-and-peptide-driven-self-assembly-in-dna-peptide-conjugates.pdf |
60c73e994c89192f28ad1e0e | 10.26434/chemrxiv.5590876.v3 | Post-synthetic ligand exchange in zirconium-based metal-organic frameworks: beware of the defects! | <p>Post-synthetic ligand exchange in the prototypical zirconium-based metal-organic framework UiO-66 was investigated by in situ solution <sup>1</sup>H nuclear magnetic resonance. Samples of UiO-66 having different degrees of defectivity were exchanged using solutions of several terephthalic acid analogues in a range of conditions. Linker exchange only occurred in defect-free UiO-66, whereas monocarboxylates grafted at defective sites were found to be preferentially exchanged with respect to terephthalic acid over the whole range of conditions investigated. A 1:1 exchange ratio between the terephthalic acid analogue and modulator was observed, providing evidence that the defects had missing-cluster nature. Ex situ characterisation of the MOF powders after exchange corroborated these findings and evidenced that the physical-chemical properties of the MOF depend on whether the functionalisation occurs at defective sites or on the framework. N<sub>2</sub> sorption analysis showed that, upon exchange, defective samples underwent significant decrease of surface area and disappearance of large pores, associated with the presence of missing-cluster defects in the starting material. CO<sub>2 </sub>sorption studies displayed the different impact of pure defect functionalisation and pure framework functionalisation on isosteric heat of adsorption and CO<sub>2</sub>/N<sub>2</sub> selectivity.</p> | Marco Taddei; Russell J. Wakeham; Athanasios Koutsianos; Enrico Andreoli; Andrew R. Barron | Coordination Chemistry (Inorg.); Solid State Chemistry; Spectroscopy (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2018-06-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73e994c89192f28ad1e0e/original/post-synthetic-ligand-exchange-in-zirconium-based-metal-organic-frameworks-beware-of-the-defects.pdf |
63a418f6a2da4bc77c0ce4a0 | 10.26434/chemrxiv-2022-sw7x6 | Total Synthesis of (+)-Coriamyrtin via a Desymmetric Strategy of a 1,3-Cyclopentanedione Moiety | This paper describes the total synthesis of (+)-coriamyrtin, a picrotoxane-type sesquiterpene. The natural product is widely known as a neurotoxin of the Coriariaceae family and bears a highly functionalized cis-hydrindane skeleton. Despite being biologically and synthetically attractive molecule, only two examples of the total synthesis are reported to date. Our synthetic strategy involves the highly stereoselective construction of the cis-hydrindane skeleton via the desymmetric strategy of a 1,3-cyclopentanedione moiety using an intramolecular aldol reaction and elaborate functionalization of the cyclopentane ring in the bicyclic structure for the formation of the 1,3-diepoxide moiety of coriamyrtin. Our method could be applied to synthesize various natural products with similar bicyclic skeletons and to expand neurobiological studies using synthesized products. | Kazutada Ikeuchi; Shota Haraguchi; Ryo Fujii; Hidetoshi Yamada; Takahiro Suzuki; Keiji Tanino | Organic Chemistry; Natural Products | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63a418f6a2da4bc77c0ce4a0/original/total-synthesis-of-coriamyrtin-via-a-desymmetric-strategy-of-a-1-3-cyclopentanedione-moiety.pdf |
637b9a1556c6f45c707625ff | 10.26434/chemrxiv-2022-2s4zc | In silico Evaluation of the Thr58-associated Conserved Water with KRAS Switch-II Pocket Binders | The KRAS switch-II pocket (SII-P) has proven to be one of the most successful tools for targeting KRAS with small-molecules to date. This has been demonstrated with several KRAS(G12C) targeting covalent inhibitors, already resulting in one FDA-approved drug. Several earlier stage compounds have been also reported to engage KRAS SII-P with other position 12 mutants, including G12D, G12S and G12R. A highly conserved water molecule exists in the KRAS SII-P, linking the Thr58 of switch-II and Gly10 of beta1-sheet. This conserved water is also present in the co-crystal structures of most of the disclosed small-molecule inhibitors but is only displaced by a handful of SII-P binders. Here we evaluated the conserved water molecule energetics by the WaterMap for the SII-P binders with publicly disclosed structures and studied the water behavior in the presence of selected inhibitors by microsecond timescale molecular dynamics (MD) simulations using two water models (total simulation time of 120 μs). Our data reveals the high-energy nature of this hydration site when co-existing with a SII-P binder, and that there is a preference for a single isolated hydration site in this location within the most advanced compounds. Furthermore, the water displacement is suboptimal and only achieved with a few disclosed compounds. These results suggest that this conserved water should be considered more central when designing new inhibitors, especially in the design of non-covalent inhibitors targeting the SII-P. | Renne Leini; Tatu Pantsar | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling | CC BY 4.0 | CHEMRXIV | 2022-11-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/637b9a1556c6f45c707625ff/original/in-silico-evaluation-of-the-thr58-associated-conserved-water-with-kras-switch-ii-pocket-binders.pdf |
6661b2a491aefa6ce1ea8a1d | 10.26434/chemrxiv-2024-82q4c-v2 | In situ complexation of sgRNA and Cas12a improves the performance of a one-pot RPA–CRISPR-Cas12 assay | Due to their ability to selectively target pathogen-specific nucleic acids, CRISPR-Cas systems are increasingly being employed as diagnostic tools. “One pot” assays that combine nucleic acid amplification and CRISPR-Cas systems (NAAT–CRISPR-Cas) in a single step have emerged as one of the most popular CRISPR-Cas biosensing formats. However, operational simplicity comes at a cost, with one-pot assays typically being less sensitive than corresponding two-step NAAT–CRISPR-Cas assays and often failing to detect targets at low concentrations. It is thought that these performance reductions result from the competition between the two enzymatic processes driving the assay, namely Cas-mediated cis-cleavage and polymerase-mediated amplification of the target DNA. Herein, we describe a novel one-pot RPA–Cas12a assay that circumvents this issue by leveraging in situ complexation of the target-specific sgRNA and Cas12a to purposefully limit the concentration of active Cas12a during the early stages of the assay. Using a clinically relevant assay against a DNA target for HPV-16, we show how this in situ format reduces competition between target cleavage and amplification and engenders significant improvements in detection limit when compared to the traditional one-pot assay format, even in patient-derived samples. Finally, to gain further insight into the assay, we use experimental data to formulate a mechanistic model describing the competition between the Cas enzyme and nucleic acid amplification. These findings suggest that purposefully limiting cis-cleavage rates of Cas proteins is a viable strategy for improving the performance of one-pot NAAT–CRISPR-Cas assays. | Jake M. Lesinski; Thomas Moragues; Prerit Mathur; Yang Shen; Carolina Paganini; Léonard Bezinge; Bo Verberckmoes; Bodine Van Eenooghe; Stavros Stavrakis; Andrew J. deMello; Daniel A. Richards | Biological and Medicinal Chemistry; Analytical Chemistry; Biochemical Analysis; Bioengineering and Biotechnology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6661b2a491aefa6ce1ea8a1d/original/in-situ-complexation-of-sg-rna-and-cas12a-improves-the-performance-of-a-one-pot-rpa-crispr-cas12-assay.pdf |
60c74125469df42657f42db5 | 10.26434/chemrxiv.7966706.v1 | Expanding Reactivity in DNA-Encoded Library Synthesis via Reversible Binding of DNA to an Inert Quaternary Ammonium Support | Herein, we present the adaptation of reversible adsorption to solid support (RASS) for a DEL setting, which allows
reactions to be performed in organic solvents at near anhydrous conditions
opening previously inaccessible chemical reactivities to DEL. The RASS approach
enabled the rapid development of C(sp<sup>2</sup>)-C(sp<sup>3</sup>)
decarboxylative cross-couplings with broad substrate scope, an electrochemical
amination (the first electrochemical synthetic transformation performed in a DEL
context), and improved reductive amination conditions. We believe that RASS will offer expedient access to new DEL reactivities,
expanded chemical space, and ultimately more drug-like libraries. | Dillon T. Flood; Shota Asai; Xuejing Zhang; Jie Wang; Leonard Yoon; Zoë C. Adams; Blythe C. Dillingham; Brittany Sanchez; Julien C. Vantourout; Mark E. Flanagan; David W. Piotrowski; Paul Richardson; Samantha Green; Ryan Shenvi; Jason Chen; Phil Baran; Philip Dawson | Bioorganic Chemistry; Combinatorial Chemistry; Organic Synthesis and Reactions; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2019-04-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74125469df42657f42db5/original/expanding-reactivity-in-dna-encoded-library-synthesis-via-reversible-binding-of-dna-to-an-inert-quaternary-ammonium-support.pdf |
64103da17290f69f8ef4d44f | 10.26434/chemrxiv-2023-6fxzk | Characterization of sulfur/carbon copolymer cathodes for Li-S batteries: a combined experimental and ab initio Raman spectroscopy study | Optimization of lithium-sulfur batteries highly depends on exploring and characterizing new cathode materials. Sulfur/carbon copolymers have recently attracted much attention as an alternative class of cathodes to replace crystalline sulfur. In particular, poly(sulfur-n-1,3-diisopropenylbenzene) (S/DIB) has been under considerable experimental and theoretical investigations, promising a good performance in mitigating the so-called shuttle effect. Here, combining ab initio Raman spectroscopy simulations with experimental measurements, we show that S/DIB copolymers containing short and long sulfur chains are distinguishable based on their Raman activity in 400-500 1/cm. This frequency range corresponds to S--S stretching vibrations and is only observed in the Raman spectra of those copolymers with longer sulfur chains. The results reported in this study have direct applications in identification and characterization of general sulfur/carbon copolymers with different sulfur contents. | Rana Kiani; Matthias Steimecke; Marah Alqaisi; Michael Bron; Daniel Sebastiani; Pouya Partovi-Azar | Physical Chemistry; Energy; Physical and Chemical Properties; Quantum Mechanics; Spectroscopy (Physical Chem.) | CC BY 4.0 | CHEMRXIV | 2023-03-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64103da17290f69f8ef4d44f/original/characterization-of-sulfur-carbon-copolymer-cathodes-for-li-s-batteries-a-combined-experimental-and-ab-initio-raman-spectroscopy-study.pdf |
610bead37117502613e332cb | 10.26434/chemrxiv-2021-v74sm-v3 | A simplistic computational procedure for the tunneling splittings caused by the proton transfer | In this manuscript we present an approach for computing tunneling splittings for large amplitude motions. <br />The core of the approach is a solution of an effective one-dimensional Schrödinger equation with an effective mass and an effective potential energy surface composed of electronic and harmonic zero-point vibrational energies of small amplitude motions in the molecule.<br />The method has been shown to work in cases of three model motions: nitrogen inversion in ammonia, single proton transfer in malonaldehyde, and double proton transfer in the formic acid dimer. In the current work we also investigate the performance of different DFT and post-Hartree-Fock methods for prediction of the proton transfer tunneling splittings, quality of the effective Schrödinger equation parameters upon the isotopic substitution, and possibility of a complete basis set (CBS) extrapolation for the resulting tunneling splittings.<br /> | Denis Tikhonov | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Quantum Mechanics; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/610bead37117502613e332cb/original/a-simplistic-computational-procedure-for-the-tunneling-splittings-caused-by-the-proton-transfer.pdf |
631a29133e2e36135a2f7230 | 10.26434/chemrxiv-2021-c93dp-v3 | Reversible microscale assembly of nanoparticles driven by the phase transition of a thermotropic liquid crystal | The arrangement of nanoscale building blocks into patterns with microscale periodicity is challenging to achieve via self-assembly processes. Here, we report on the phase transition-driven collective assembly of gold nanoparticles in a thermotropic liquid crystal. A temperature-induced transition from the isotropic to the nematic phase leads to the assembly of individual nanometre-sized particles into arrays of micrometre-sized aggregates, whose size and characteristic spacing can be tuned by varying the cooling rate. This fully reversible process offers hierarchical control over structural order on the molecular, nanoscopic, and microscopic level and is an interesting model system for the programmable patterning of nanocomposites with access to micrometre-sized periodicities. | Niamh Mac Fhionnlaoich; Stephen Schrettl; Nicholas B. Tito; Ye Yang; Malavika Nair; Luis A. Serrano; Kellen Harkness; Paulo Jacob Silva; Holger Frauenrath; W Craig Carter; Francesco Stellacci; Stefan Guldin | Physical Chemistry; Materials Science; Nanoscience; Liquid Crystals; Nanostructured Materials - Nanoscience; Self-Assembly | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/631a29133e2e36135a2f7230/original/reversible-microscale-assembly-of-nanoparticles-driven-by-the-phase-transition-of-a-thermotropic-liquid-crystal.pdf |
64111da1e53eff1af3229c51 | 10.26434/chemrxiv-2023-5mgm5 | 3D Print and Shrink Microfabrication of Polymer-derived Ceramics: Silicon oxycarbide Glass-Ceramic Microneedles and Microfluidics | Polymer-derived ceramics are advancing various sectors, such as health, defence, and aerospace, however, their manufacturing has been cumbersome, unsafe, and design-limited. Some efforts have been made to 3D print polymer-derived ceramics, however, the physio-chemical properties of those pre-ceramic resins have prevented their use in microfabrication and generating glass-ceramic phases. Here, a new pre-ceramic resin and microfabrication method, 3D print and shrink, has been developed to enable the fabrication of high-resolution glass-ceramic components. The resin utilises a binary thiol-acrylate based photocurable system, which has been optimised for high-resolution 3D printing and high isotropic shrinkage during pyrolysis, without incurring cracks or defects even at higher temperatures, as required for generating silicon oxycarbide glass-ceramics. The resin has also been found to overcome the limitations of oxygen inhibition and short shelf-life associated with their current acrylate and thiol-ene counterparts, respectively. The method has been validated for fabricating both positive and negative micro-features. A single-pixel resolution (ca. 30 um) has been maintained throughout the printing process, which has been further improved to a half-pixel resolution (ca. 15 um) in the sintered glass-ceramic, allowing 3D printing of a microneedle patch with ca. 28 um tips and a microfluidic distributor with ca. 250 um ID channels. | Ahmad Norouzi; Thomas Rodeman; Brett Paull; Vipul Gupta | Materials Science; Ceramics; Composites; Materials Processing; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64111da1e53eff1af3229c51/original/3d-print-and-shrink-microfabrication-of-polymer-derived-ceramics-silicon-oxycarbide-glass-ceramic-microneedles-and-microfluidics.pdf |
63eabe7a1d2d18406370e80d | 10.26434/chemrxiv-2023-1mnz4 | Tetra-tert-butyl-s-indacene is a Bond Localized C2h Structure: Even More Bad News for B3LYP | Whether tetra-tert-butyl-s-indacene (TtB-s-indacene) is a symmetric D2h structure or a bond alternating C2h structure remains a standing puzzle. Agreement between 1H NMR data and computed proton chemical shifts based on minima structures optimized at the M06-2X, B97X-D, and M11 levels confirm a bond localized C2h symmetryconsistent with its antiaromaticity. X-ray structures and computed B3LYP geometries of D2h TtB-s-indacene poorly reproduce experimental NMR data. The limitations and complications of using B3LYP geometries for interpreting the structures and paratropicities of -expanded antiaromatic systems are discussed. | Lucas J. Karas; Said Jalife; Renan Viesser; Joao Soares; Michael Haley; Judy Wu | Theoretical and Computational Chemistry; Physical Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Physical Organic Chemistry; Computational Chemistry and Modeling | CC BY NC 4.0 | CHEMRXIV | 2023-02-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63eabe7a1d2d18406370e80d/original/tetra-tert-butyl-s-indacene-is-a-bond-localized-c2h-structure-even-more-bad-news-for-b3lyp.pdf |
639c91d7e8047a61d0eb2d2f | 10.26434/chemrxiv-2022-6fcwk | Scalable High Tensile Modulus Composite Laminates Using Carbon Nanotube Yarns | A novel approach is established for fabricating high-strength and high-stiffness composite laminates with continuous carbon nanotube (CNT) yarns for scaled-up mechanical tests and potential engineering applications. Continuous CNT yarns with up to 80% degree of nanotube alignment and a unique self-assembled graphitic CNT packing result in their specific tensile strengths up to 1.9 N/tex. Unidirectional CNT yarn reinforced composite laminates with a CNT concentration of greater than 80 wt.% and minimal microscale voids are fabricated using filament winding and aerospace-grade resin matrices. A specific tensile strength of up to 1.71 GPa/(g cm-3) and a specific modulus of 256 GPa/(g cm-3) are realized; the specific modulus exceeds current state-of-the-art IM7, T1100G and even M60J unidirectional carbon fiber composite laminates. The results demonstrate an effective approach transferring high-strength CNT yarns into composites for applications that require specific tensile modulus properties that are significantly beyond state-of-the-art carbon fiber composites, and potentially open a new performance region in the Ashby chart for composite material applications. | Cecil Evers; Britannia Vondrasek; Claire Jolowsky; Jin Gyu Park; Michael Czabaj; Bailee Ku; Kaylee Thagard; Gregory Odegard; Zhiyong Liang | Materials Science; Nanoscience; Carbon-based Materials; Composites; Nanostructured Materials - Materials | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/639c91d7e8047a61d0eb2d2f/original/scalable-high-tensile-modulus-composite-laminates-using-carbon-nanotube-yarns.pdf |
63bf8597553889ce017dba45 | 10.26434/chemrxiv-2023-wmgwn | 68 million natural product-like compound database generated via molecular language processing | Natural products are a rich resource of bioactive compounds for valuable applications across multiple fields such as food, agriculture, medicine. For natural product discovery, high throughput in silico screening offers a cost-effective alternative to traditional resource-heavy assay-guided exploration of structurally novel chemical space. In this data descriptor, we report a characterized database of 68,113,839 natural product-like molecules generated using a recurrent neural network trained on known natural products, demonstrating a significant 167-fold expansion in library size over the currently estimated 406,919 natural products known. This study highlights the potential of using deep generative models to uncover novel natural product chemical space for high throughput in silico screening toward natural product discovery. | Dillon Tay Wei Peng; Naythan Yeo Zhen Xi; Krishnan Adaikkappan; Yee Hwee Lim; Shi Jun Ang | Theoretical and Computational Chemistry; Organic Chemistry; Natural Products; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63bf8597553889ce017dba45/original/68-million-natural-product-like-compound-database-generated-via-molecular-language-processing.pdf |
60c7543bee301c81c6c7af11 | 10.26434/chemrxiv.13633925.v1 | A Red Phosphorus-Graphite Anode for K-ion Batteries | <div><div><div><p>Red phosphorus (RP) is a promising anode material for potassium-ion batteries because of its theoretical capacity of 865mAhg–1 delivered at an average potential of 0.5V vs K+/K. However, its alloy reaction</p><p>to form KP entails a volume expansion of 162% resulting in severe stresses that lead to SEI and electrode fracture, loss of electric contact, and ultimately reduced cycle life. Moreover, its low electronic conductivity (10<sup>-14 </sup>Scm–1) limits rate capability. Here, we report a RP-graphite composite prepared by a two step ball milling procedure to control particle size and optimize carbon coating. Electrodes prepared with the composites achieve high capacity (723mAhg–1) at C/20 and retaining 75% at 5C. It also shows very good cycling stability, retaining more than 96% of the capacity after 100 cycles at 1C.</p></div></div></div> | Isaac Capone; Jack Aspinall; Hyeon Jeong Lee; Albert Xiao; Johannes Ihli; Mauro Pasta | Energy Storage | CC BY NC ND 4.0 | CHEMRXIV | 2021-01-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7543bee301c81c6c7af11/original/a-red-phosphorus-graphite-anode-for-k-ion-batteries.pdf |
6583d3be9138d231612aa6d5 | 10.26434/chemrxiv-2023-mmns2 | Studies on circular dichroism behaviors of aggregated poly(1,4-phenylene)s with head-to-tail regioregularity | Circular dichroism (CD) studies on poly(1,4-phenylene)s bearing a chiral side chain in the aggregated conditions were carried out. Little CD was observed in a solution form, while addition of a poor solvent into the polyphenylene solution induced aggregation and a strong CD was observed, accordingly. Applying the controlled degree of polymerization (DP) of poly(1,4-phenylene) in the use of bidentate diphosphine Chiraphos as a ligand for the nickel catalyst, the relationship of DP with CD strength was studied to reveal to show the highest CD at the DP = 84 (g<sub>abs<sub> = ca. 2 x 10<sup>–2<sup>). It was also found that the related aggregation was observed in good solvent 1,2-dichloroethane upon standing the solution at 4 °C for 3–23 days to observe g<sub>abs<sub> = ca. 10<sup>–1<sup>. Studies on the substituent effect of poly(1,4-phenylene) suggested that CD behaviors were dependent on the type of non-chiral substituent on the aromatic ring as well as the side-chain chirality. | Rikuya Tanaka; Seiha Yamaoka; Shuichi Ikeda; Kentaro Okano; Masaki Horie; Hideto Minami; Nozomu Suzuki; Atsunori Mori | Polymer Science; Conducting polymers; Organic Polymers; Polymerization catalysts; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6583d3be9138d231612aa6d5/original/studies-on-circular-dichroism-behaviors-of-aggregated-poly-1-4-phenylene-s-with-head-to-tail-regioregularity.pdf |
60c75358ee301c7390c7adac | 10.26434/chemrxiv.13480947.v1 | In-Situ Generation of N-Heteroaromatic Polymers: Metal-Free Polymerization and Multiple Functionalities | The
electron-deficient <i>N</i>-heteroaromatic polymers are crucial for the
high-tech applications of organic materials, especially in the electronic and
optoelectronic fields. Thus, the development of new polymerizations to afford
adaptable electron donating-accepting scaffolds in <i>N</i>-heteroaromatic
polymers is in high demand. Herein, metal-free multicomponent polymerizations
of diynes, diamines and glyoxylates are successfully developed for <i>in-situ</i>
generation of poly(quinoline)s with high molecular weights (<i>M</i><sub>w</sub>
up to 16 900) in nearly quantitative yields. By tuning the electron
distributions of the polymer backbones, the resulting poly(quinoline)s show
various aggregation-induced behaviors and photo-responsive abilities. The thin
films of these poly(quinoline)s can be readily fabricated into well-resolved
fluorescent photopatterns by photolithography techniques. They can be utilized
as fluorescent probes to visualize the morphologies of polymer materials
including spherulites and microphase separation of polymer blends. Their
nanoparticles demonstrate sensitive and highly selective fluorescence quenching
to hexavalent chromium ion Cr(VI), which provides access for the biological
imaging of Cr(VI) in unicellular <i>algae</i>. | YUBING HU; Neng Yan; XIAOLIN LIU; Lingyu Pei; Canbin Ye; Wen-Xiong Wang; Jacky W. Y. Lam; Ben Zhong Tang | Aggregates and Assemblies; Dyes and Chromophores; Optical Materials; Polymerization (Polymers) | CC BY NC ND 4.0 | CHEMRXIV | 2021-08-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75358ee301c7390c7adac/original/in-situ-generation-of-n-heteroaromatic-polymers-metal-free-polymerization-and-multiple-functionalities.pdf |
67589bd47be152b1d08d130a | 10.26434/chemrxiv-2024-bjv6f | Defect-enabled fast gas encapsulation into water lattices for innovative energy storage and decarbonization | Non-polar gases do not mix well with liquid water, but they can be incorporated massively in solid water lattices and create gas-carrying water structures called gas hydrates. Nature showcases this extraordinary gas/water incorporation through multi-trillion tones of methane solidified in natural hydrates on seafloors. Laboratory experiments successfully produced gas hydrates containing ~5 wt% of hydrogen, 15 wt% of methane, and 30 wt% of CO2. Such water-based gas carriers hold great promise for energy storage and CO2 sequestration, taking the advantages of water as a sustainable feedstock. However, the slow gas encapsulation in water lattices hinders real-world applications. We present a novel defect-engineering concept for tailoring gas uptake in water lattices. We elaborate microscopic views of dopant-induced defects in water lattices, reveal an intrinsic link between the engineered defects and gas encapsulation kinetics, and provide a path-opening concept of defect engineering for efficient gas encapsulation in solid water lattices for energy storage and decarbonization applications. | Ngoc Nguyen; Mirza Galib; Anh Nguyen; Praveen Linga | Energy; Chemical Engineering and Industrial Chemistry; Natural Resource Recovery; Energy Storage; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2024-12-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67589bd47be152b1d08d130a/original/defect-enabled-fast-gas-encapsulation-into-water-lattices-for-innovative-energy-storage-and-decarbonization.pdf |
66019cfb66c1381729c94e47 | 10.26434/chemrxiv-2024-t4x0n | TDDFT and the X-ray absorption spectrum of liquid water: finding the “best” functional | We investigate the performance of time-dependent density functional theory (TDDFT) for reproducing high-level reference X-ray absorption spectra of liquid water. For this, we apply the integrated absolute difference (IAD) metric, previously used for X-ray emission spectra of liquid water [J. Chem. Theory Comput. 19, 7333-7342 (2023)], in order to investigate which exchange-correlation (xc) functionals yield TDDFT spectra in best agreement to reference, as well as to investigate the suitability of IAD for XAS spectrum calculations. It is seen that long-range corrected xc-functionals are required to yield good agreement with reference coupled cluster (CC) and algebraic-diagrammatic construction (ADC) spectra, with 100% asymptotic Hartree−Fock exchange resulting in the lowest IADs. The xc-functionals with best agreement to reference have been adopted for larger water clusters, yielding results in line with recently published coupled cluster theory, but which still show some discrepancies in the relative intensity of the features compared to experiment. | Thomas Fransson; Lars Pettersson | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-03-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66019cfb66c1381729c94e47/original/tddft-and-the-x-ray-absorption-spectrum-of-liquid-water-finding-the-best-functional.pdf |
66a35dd0c9c6a5c07a01e071 | 10.26434/chemrxiv-2024-l3f1b | Bioorthogonal chemical engineering of rAAV capsid: Advancing gene therapy targeting using proteins | We report the chemical conjugation of recombinant Adeno Associated Virus (rAAV) capsid with various functionalities, including proteins, using a bioorthogonal strategy. rAAVs were azido-coated or DBCO-coated by chemically modifying lysine or tyrosine residues. Lysine residues were modified using a phenyl isothiocyanate anchor, and tyrosine residues using either an aryldiazonium salt or a N-methyl luminol derivative. We demonstrate anchor- dependent labelling levels, as observed with biochemical assays and mass spectrometry. Strain-promoted azide-alkyne cycloaddition (SPAAC) was then implemented and evaluated on the rAAV to append functionalities such as fluorescein, biotin and carbohydrates to the azido- coated capsids. We confirmed the efficiency of the bioorthogonal reaction and observed a stronger reactivity with dibenzylcyclooctyne (DBCO) compared to bicyclononyne (BCN). The optimized SPAAC reaction was finally used to label the viral vectors with two relevant nanobodies targeting specific immune cell receptors (CD62L and CD45). In vitro transduction assays conducted with one rAAV-nanobody conjugate demonstrated the promising targeting properties of these chemically modified vectors. Thus, we anticipate that this strategy will positively impact the field of rAAV capsid engineering and contribute in tissue-specific targeting for the optimisation of gene therapy treatments. | Maia Marchand; Sébastien Depienne; Mohammed Bouzelha; Karine Pavageau; Roxane Peumery; Denis Loquet; Dimitri Alvarez-Dorta; Mickaël Guilbaud; Mikaël Croyal; Aurélien Dupont; Oumeya Adjali; Sébastien G. Gouin; David Deniaud; Mathieu Mével | Biological and Medicinal Chemistry; Biochemistry; Bioengineering and Biotechnology; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a35dd0c9c6a5c07a01e071/original/bioorthogonal-chemical-engineering-of-r-aav-capsid-advancing-gene-therapy-targeting-using-proteins.pdf |
6255f29fed4d88c5b7084deb | 10.26434/chemrxiv-2022-0xf4t | Self-complementary Dimers Based on Zwitterionic Halogen Bond Donors | Even though halogen bonding is routinely used in crystal engineering and beyond, multipoint interactions are still quite rare. This applies in particular to self-complementary systems which incorporate both halogen bond donating and accepting moieties. Herein, we present the first homodimer based on a zwitterionic halogen bond donor in which a iodolium core acts as Lewis acidic unit and a sulfonate groups acts as Lewis base. Prior experiments with a carboxylate variant had indicated that it featured too strong coordination, leading to poor solubility. The sulfonate system, in contrast, resulted in a strongly bound dimer with halogen bond distances of 2.73 Å. We anticipate that this motif will form the basis for the further development of halogen-bonding-based linkers.
| Raffaella Papagna; Elric Engelage; Hermina Wieske; Mate Erdelyi; Stefan Huber | Organic Chemistry; Supramolecular Chemistry (Org.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-04-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6255f29fed4d88c5b7084deb/original/self-complementary-dimers-based-on-zwitterionic-halogen-bond-donors.pdf |
657b4ec6e9ebbb4db9e3af78 | 10.26434/chemrxiv-2023-x07wk | A Non-Steady-State Electric Circuit in Electrophoresis on Paper: Thermal Consideration of Electrophoretic Lateral-Flow Assays | Non-steady-state behaviors are not expected in electric circuits that lack significant capacitance, inductivity, and/or active feedback. Here, we report that electrophoresis on paper (used to conduct/enhance paper-based assays) can create a non-steady-state electric circuit. We studied electrophoresis on 4-mm wide nitrocellulose-membrane strips utilized in lateral-flow immunoassays; the voltage was applied to strip termini immersed in reservoirs with a running buffer. If the total supplied power exceeded approximately 0.5 W, neither the electric current nor the temperature map reached their steady states on a multi-minute time scale. The current grew slowly to its maximum and then slowly decreased, and the temperature map evolved slowly, with one or more hot spots appearing and disappearing gradually in different positions on the strip. The slow evolution of a temperature map led to the occurrence of a terminal hot spot in which the strip burned. No chaotic behavior was observed, i.e., time dependences of both the current and temperature map were reproducible. We analyzed major processes involved in paper-based electrophoresis and explained the non-steady-state behavior. Unlike ordinary electric circuits with metal conductors, paper-based electrophoresis involves two slow processes: (i) intense buffer evaporation from hot spots and (ii) buffer supply from the reservoirs by an interplay of the capillary penetration and the electroosmotic flow. These processes affect heat generation and/or dissipation on the strip and, accordingly, the resistivity profile along the strip. The slow evolution of the resistivity profile is responsible for the non-steady-state behavior. Our work is the first detailed and conclusive study of heat maps in electrophoretically-enhanced LFA. We demonstrate spatiotemporal temperature distribution, which emphasizes the need for the empirical study of thermal behaviors due to the inability to create predictive quantitative models of the complex interplay of multiple processes, including evaporation. | Nikita Ivanov; Vasily Panferov; Sergey Krylov | Analytical Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/657b4ec6e9ebbb4db9e3af78/original/a-non-steady-state-electric-circuit-in-electrophoresis-on-paper-thermal-consideration-of-electrophoretic-lateral-flow-assays.pdf |
63a66979dadddc70c8995480 | 10.26434/chemrxiv-2022-1snxw | Potential-Energy Surfaces Sampled in Cremer–Pople Coordinates and Represented by Common Force Field Functionals for Small-cyclic Molecules | The complex conformations of the cyclic moieties impact the physical and chemical properties of the molecules. In this work, we chose 22 molecules of four-, five-, and six-membered rings and performed a thorough conformational sampling using Cremer-Pople coordinates. We sampled hundreds or thousand of conformational structures including all well-known and many less well-known conformers for each molecule. We tried to represent the potential energy surfaces (PESs) by fitting the data to common analytical force field functional forms. Although the general features of PESs can be described by the essential force field functional forms, the accuracy of representation can be improved remarkably by including the torsion-bond and torsion-angle coupling terms. The best fit yields R-squared (R2) values close to 1.0 and mean absolute errors (MAEs) in energy less than 0.3 kcal/mol. | Evangelia Charvati; Huai Sun | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63a66979dadddc70c8995480/original/potential-energy-surfaces-sampled-in-cremer-pople-coordinates-and-represented-by-common-force-field-functionals-for-small-cyclic-molecules.pdf |
6724e6cbf9980725cfc9e07a | 10.26434/chemrxiv-2024-j9mcq | In situ study of ceria trapping Pt cluster under heating condition and the resulted strong metal‒support interaction effect in CO oxidation | The synergistic relationship between platinum (Pt) and ceria support is vital for advancing the innovative design of Pt/ceria catalyst, which extensively applied in the fields of energy conversion and environmental remediation. Through thermal treatment, A serial of Pt/ceria with different metal support interaction were obtained. Advanced analyses employing in situ transmission electron microscopy (TEM) and X-ray Photon-electron Spectroscopy (XPS) elucidated that these thermal methods provoke a marked affinity between the Pt clusters and ceria support. High-temperature treatment can result in partial encapsulation of Pt clusters by CeO2, enabling the Pt clusters to match to the CeO2 lattice. Notably, high-temperature treatments lead to the partial encapsulation of Pt clusters by CeO2, facilitating alignment of the Pt clusters with the CeO2 lattice. This results in the emergence of oxidized Pt (Pt4+), which replaces the initial metallic Pt0, embedding itself onto the ceria support and subsequently activating adjacent Ce atoms in proximity to Pt. This innovative structure creates more site for CO adsorption but with weaker adsorption energy, effectively eliminating CO poisoning on the Pt surface and enhancing O2 dissociative adsorption. Collectively, these modifications birth a catalyst exhibiting remarkable proficiency in low-temperature CO oxidation. | Liang Zhu; Yang Liu; Evgeny I. Vovk; Yilan Jiang; Danyu Wang; Zhehao Qiu; Junyu Lang; Yixiao Wang; Yong Yang | Catalysis; Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6724e6cbf9980725cfc9e07a/original/in-situ-study-of-ceria-trapping-pt-cluster-under-heating-condition-and-the-resulted-strong-metal-support-interaction-effect-in-co-oxidation.pdf |
65fd6700e9ebbb4db941ffa9 | 10.26434/chemrxiv-2024-4v9df | Automated Prediction of Ground State Spin for Transition Metal Complexes | Exploiting crystallographic data repositories for large-scale quantum chemical computations requires the rapid and accurate extraction of the molecular structure, charge and spin from the crystallographic information file. Here, we develop a general approach to assign the ground state spin of transition metal complexes, in complement to our previous efforts on determining metal oxidation states and bond order within the cell2mol software. Starting from a database of 31k transition metal complexes extracted from the Cambridge Structural Database with cell2mol, we construct the TM-GSspin dataset, which contains 2,032 mononuclear first row transition metal complexes and their computed ground state spins. TM-GSspin is highly diverse in terms of metals, metal oxidation states, coordination geometries, and coordination sphere compositions. Based on TM-GSspin, we identify correlations between structural and electronic features of the complexes and their ground state spins to develop a rule-based spin state assignment model. Leveraging this knowledge, we construct interpretable descriptors and build a statistical model achieving 97% cross-validated accuracy in predicting the ground state spin across the board. Our approach provides a practical way to determine the ground state spin of transition metal complexes directly from crystal structures without additional computations, thus enabling the automated use of crystallographic data for large-scale computations involving transition metal complexes. | Cho Yuri; Ruben Laplaza; Sergi Vela; Clémence Corminboeuf | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-03-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65fd6700e9ebbb4db941ffa9/original/automated-prediction-of-ground-state-spin-for-transition-metal-complexes.pdf |
62f508806948b9433fb482f8 | 10.26434/chemrxiv-2022-bt3p4 | In silico Investigation of phytochemicals from common medicinal plants as potential inhibitor of SARS-CoV-2 | In view of increasing threat of Covid-19 and due to the lack of any effective medicines, we have performed in silico studies of various SARS-CoV-2 proteins such as 6LU7, 6YWL, 2GTB, 6W02, 6W63 with active phytochemicals of some common medicinal plants such as aloevera, asafoetida, fennel, clove, cardamom, tamarind, coriander, camomile, and bryophyllum. Molecular docking was perfomed using UCSF Chimera 1.15 and docking was analysed by using Biovia Discovery Studio 2021. The reults shows that phytochemicals qurercetin, ferulic acid, salicylic acid, and eugenol can act as potential inhibitors of SARS-CoV-2. | Rajbir Kaur; Manpreet Kaur; Amanpreet Kaur; Harjinder Singh | Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2022-08-17 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62f508806948b9433fb482f8/original/in-silico-investigation-of-phytochemicals-from-common-medicinal-plants-as-potential-inhibitor-of-sars-co-v-2.pdf |
60c740a29abda27a80f8bd18 | 10.26434/chemrxiv.7777343.v1 | Thienopyrrolocarbazoles: New Building Blocks for Functional Organic Materials | The facile preparation of three regioisomeric
thienopyrrolocarbazoles applying a convenient C-H activation approach is
presented. Derived from indolo[3,2,1-<i>jk</i>]carbazole,
the incorporation of thiophene into the triarylamine framework significantly
impacted the molecular properties of the parent scaffold. The developed
thienopyrrolocarbazoles enrich the family of triarylamine donors and constitute
a novel building block for functional organic materials. | Dorian Bader; Johannes Fröhlich; Paul Kautny | Organic Compounds and Functional Groups; Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2019-02-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740a29abda27a80f8bd18/original/thienopyrrolocarbazoles-new-building-blocks-for-functional-organic-materials.pdf |
64df34ef00bbebf0e662b14b | 10.26434/chemrxiv-2023-gmd5q | Aligned Bioelectronic Polypyrrole/Collagen Constructs for Peripheral Nerve Interfacing | Electrical stimulation has shown promise in clinical studies to treat nerve injuries. This work aimed to create an aligned bioelectronic construct that can be used to bridge a nerve gap, directly interfacing with the damaged nerve tissue to support regeneration. The conductive three-dimensional bioelectronic scaffolds described herein are composite materials, comprised of conductive polypyrrole (PPy) nanoparticles embedded in an aligned collagen hydrogel. The bioelectronic constructs were seeded with dorsal root ganglion (DRG) derived primary rat neurons and electrically stimulated in vitro. The PPy loaded constructs supported a 1.7-fold increase in neurite length in comparison to control collagen constructs. Furthermore, upon electrical stimulation of the PPy-collagen construct, a 1.8-fold increase in neurite length was shown. This work illustrates the potential of bioelectronic constructs in neural tissue engineering and lays the groundwork for the development of novel bioelectronic materials for neural interfacing applications. | Ryan Trueman; Owein Guillemot-Legris; Henry Lancashire; Abijeet Mehta; Joshua Tropp; Rachel Daso; Jonathan Rivnay; Alethea Tabor; James Phillips; Bob Schroeder | Materials Science; Biocompatible Materials; Biological Materials; Materials Processing | CC BY NC 4.0 | CHEMRXIV | 2023-08-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64df34ef00bbebf0e662b14b/original/aligned-bioelectronic-polypyrrole-collagen-constructs-for-peripheral-nerve-interfacing.pdf |
615509329f1b4402dbda3106 | 10.26434/chemrxiv-2021-pq8v5-v2 | A Practical Guide to Analyzing and Reporting the Movement of Nanoscale Swimmers | The recent invention of nanoswimmers– synthetic, powered objects with characteristic lengths in the range of 10-500 nm - has sparked widespread interest among scientists and the general public. As more researchers from different backgrounds enter the field, the study of nanoswimmers offers new opportunities but also significant experimental and theoretical challenges. In particular, the accurate characterization of nanoswimmers is often hindered by strong Brownian motion, convective effects, and the lack of a clear way to visualize them. When coupled with improper experimental designs and imprecise practices in data analysis, these issues can translate to results and conclusions that are inconsistent and poorly reproducible. This Perspective follows the course of a typical nanoswimmer investigation from synthesis through to applications and offers suggestions for best practices in reporting experimental details, recording videos, plotting trajectories, calculating and analyzing mobility, eliminating drift, and performing control experiments, in order to improve the reliability of the reported results. | Wei Wang; Thomas Mallouk | Materials Science; Nanoscience; Nanostructured Materials - Materials; Nanodevices; Nanostructured Materials - Nanoscience; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-09-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/615509329f1b4402dbda3106/original/a-practical-guide-to-analyzing-and-reporting-the-movement-of-nanoscale-swimmers.pdf |
60c73db8bdbb89678aa37ccb | 10.26434/chemrxiv.6045422.v1 | A Paramedic Treatment for Modeling Explicitly Solvated Chemical Reaction Mechanisms | <div>
<div>
<div>
<p>We report a static quantum chemistry modeling treatment to study how solvent molecules affect chemical
reaction mechanisms without dynamics simulations. This modeling scheme uses a global optimization
procedure to identify low energy intermediate states with different numbers of explicit solvent molecules
and then the growing string method to locate sequential transition states along a reaction pathway. Testing
this approach on the acid-catalyzed Morita-Baylis-Hillman (MBH) reaction in methanol, we found a
reaction mechanism that is consistent with both recent experiments and computationally intensive
dynamics simulations with explicit solvation. In doing so, we explain unphysical pitfalls that obfuscate
computational modeling that uses microsolvated reaction intermediates. This new paramedic approach
can promisingly capture essential physical chemistry of the complicated and multistep MBH reaction
mechanism, and the energy profiles found with this model appear reasonably insensitive to the level of
theory used for energy calculations. Thus, it should be a useful and computationally cost-effective
approach for modeling solvent mediated reaction mechanisms when dynamics simulations are not
possible. </p>
</div>
</div>
</div> | Yasemin Basdogan; John Keith | Computational Chemistry and Modeling; Homogeneous Catalysis; Chemical Kinetics; Clusters; Solution Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2018-03-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73db8bdbb89678aa37ccb/original/a-paramedic-treatment-for-modeling-explicitly-solvated-chemical-reaction-mechanisms.pdf |
60c751cd567dfe27a0ec5b08 | 10.26434/chemrxiv.13146404.v2 | Data-science driven autonomous process optimization | <p>Autonomous
process optimization involves the human intervention-free exploration of a
range of pre-defined process parameters in order to improve responses such as
reaction yield and product selectivity. Utilizing off-the-shelf components, we
developed a closed-loop system capable of carrying out parallel autonomous
process optimization experiments in batch with significantly reduced cycle
times. Upon implementation of our system in the autonomous optimization of a
palladium-catalyzed stereoselective Suzuki-Miyaura coupling, we found that the
definition of a set of meaningful, broad, and unbiased process parameters was
the most critical aspect of a successful optimization. In addition, we found
that categorical parameters such as phosphine ligand were vital to determining
the reaction outcome. To date, categorical parameter selection has relied on
chemical intuition, potentially introducing an element of bias into the
experimental design. In seeking a systematic method for the selection of a
diverse set of phosphine ligands fully representative of the chemical space, we
developed a strategy that leveraged computed molecular descriptor clustering
analysis. This strategy allowed for the successful autonomous optimization of a
stereoselective Suzuki-Miyaura coupling between a vinyl sulfonate and an
arylboronic acid to selectively generate the <i>E</i>-product isomer in high
yield. </p> | Melodie Christensen; Lars Yunker; Folarin Adedeji; Florian Häse; Loic Roch; Tobias Gensch; Gabriel dos Passos Gomes; Tara Zepel; Matthew Sigman; Alan Aspuru-Guzik; Jason Hein | Stereochemistry; Machine Learning; Artificial Intelligence; Chemoinformatics - Computational Chemistry; Pharmaceutical Industry; Homogeneous Catalysis; Transition Metal Complexes (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-11-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c751cd567dfe27a0ec5b08/original/data-science-driven-autonomous-process-optimization.pdf |
63f6398032cd591f1251e140 | 10.26434/chemrxiv-2023-8hjqs-v2 | Cooperative taming of CS2/oxetane copolymerisation: Consequences of main-chain sulfuration on polymer properties and catalysis | CS2 promises easy access to degradable sulfur-rich polymers and insights into how main-group derivatisation affects polymer formation and properties, though its ring-opening copolymerisation is plagued by low linkage selectivity and small-molecule by-products. We demonstrate that a cooperative Cr(III)/K catalyst selectively delivers poly(dithiocarbonates) from CS2 and oxetanes while state-of-the-art strategies produce linkage scrambled polymers and heterocyclic by-products. The formal introduction of sulfur centres into the parent polycarbonates results in a net shift of the polymerisation equilibrium towards, and therefore facilitating, depolymerisation. During copolymerisation however the catalyst enables near quantitative generation of the metastable polymers in high sequence selectivity by limiting the lifetime of alkoxide intermediates. Furthermore, linkage selectivity is key to obtain semi-crystalline materials that can be moulded into self-standing objects. Our report demonstrates the potential of cooperative catalysis to produce previously inaccessible main-group rich materials with beneficial chemical and physical properties | Alex Plajer; Christoph Fornacon-Wood; Cesare Gallizioli; Merlin Stühler; Carsten Müller; Patrick Pröhm | Inorganic Chemistry; Catalysis; Polymer Science | CC BY 4.0 | CHEMRXIV | 2023-02-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63f6398032cd591f1251e140/original/cooperative-taming-of-cs2-oxetane-copolymerisation-consequences-of-main-chain-sulfuration-on-polymer-properties-and-catalysis.pdf |
671a577b98c8527d9e365cd3 | 10.26434/chemrxiv-2024-lg8l7 | Interoperable nanosafety data using semantic modeling and linked data knowledge graphs | The nanosafety domain has seen significant advancements in data generation and sharing, yet challenges remain in ensuring data interoperability and reuse. This article focuses on developing a semantic interoperability framework for nanosafety data to maximize the FAIRness (Findability, Accessibility, Interoperability, and Reusability) of existing and new datasets. The approach centers on creating the NanoLinks semantic model, which unifies diverse data modalities representation, such as cytotoxicity, transcriptomics, and physicochemical data. By leveraging established ontologies like the BioAssay Ontology (BAO), NanoParticle Ontology (NPO), Data Catalog vocabulary (DCAT) and the PROV-O ontology, NanoLinks facilitates the conversion of semi-structured data into Resource Description Framework (RDF) format using the RDF Mapping Language (RML). This transformation allows to generate machine-readable and interoperable datasets. Five datasets from the literature, spanning nanomaterial characteristics and biological assay data, were selected by the NanoSolveIT EU project partners for FAIRification. These datasets were converted into RDF format, hosted on Zenodo under a CC-BY 4.0 license, and integrated into a knowledge graph, NanoLinks-KG, following the linked-data best practices. The knowledge graph was validated for consistency and adherence to the semantic model using shape expressions (ShEx). The presented applications of this graph showcase the potential of querying interconnected datasets to derive insights and support integration with external resources such as AOP-Wiki and the NanoCommons knowledge base. One usage example given is the cross-dataset dose-response curve comparison of zinc oxide nanomaterials. The results demonstrate the successful application of semantic modeling and linked-data knowledge graphs to convert and integrate diverse nanosafety datasets, enhancing their interoperability, and promoting reuse. The developed framework advances the state of data sharing in the nanosafety community and demonstrates the potential of semantic technologies in facilitating comprehensive data analysis and novel discoveries in the field. | Ammar Ammar; Chris Evelo; Egon Willighagen | Nanoscience | CC BY 4.0 | CHEMRXIV | 2024-10-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/671a577b98c8527d9e365cd3/original/interoperable-nanosafety-data-using-semantic-modeling-and-linked-data-knowledge-graphs.pdf |
60c74fbc842e65c2d4db38df | 10.26434/chemrxiv.12935585.v1 | In Situ Formation of a Sub-Nanometer Iridium Phosphide Catalyst from Supported Organometallic Species | <p>While several metal phosphides have
attracted significant attention in the last several years due to their
potential use as photocatalytic and hydrotreating catalysts, iridium phosphide
has remained largely unexplored. In this work, silica-supported pincer-iridium
species are thermolyzed, resulting in deconstruction of the tridentate ligand
precursor and formation of a sub-nanometer iridium phosphide phase
characterized by <sup>31</sup>P magic angle spinning nuclear magnetic resonance
(<sup>31</sup>P-MAS-NMR), X-ray absorption spectroscopy (XAS), and high angle
annular dark field scanning transmission electron microscopy (HAADF-STEM). The
support material was found to play an active role in determining the product of
the surface thermolysis, with the silica supported material generating
phosphorus rich iridium phosphide nanoparticles. The resulting silica-supported
iridium phosphide phase is explored as a thermocatalyst for non-oxidative butane
dehydrogenation, achieving high initial reaction rates up to 900 mol<sub>butenes</sub> mol<sub>catalyst</sub><sup>-1</sup>
hr<sup>-1 </sup>and a terminal olefin selectivity of up to 70 %.</p> | Boris Sheludko; Evan Wegener; Gokhan Celik; A. Jeremy Kropf; Cristina Castro; Massimiliano Delferro; Alan Goldman; David Kaphan; Fuat E. Celik | Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74fbc842e65c2d4db38df/original/in-situ-formation-of-a-sub-nanometer-iridium-phosphide-catalyst-from-supported-organometallic-species.pdf |
643dae801d262d40eaa853f5 | 10.26434/chemrxiv-2023-wf0g1 | Linear Free Energy Relationships and Transition State Analysis of CO2 Reduction Catalysts Bearing Second Coordination Spheres with Tunable Acidity | The development of molecular catalysts for electrochemical CO2 reduction is a promising approach to the valorization of this stable small molecule. Drawing inspiration from enzymes, protic functional groups in the secondary coordination sphere (SCS) work in conjunction with an exogenous acid to relay proton equivalents to the active site of CO2 reduction. However, it is not well understood how the acidity of the SCS and exogenous acid together determine the kinetics of catalytic turnover. To gain insight into the relative contributions of proton transfer driving forces, we synthesized a series of iron tetraphenylporphyrin electrocatalysts bearing SCS amide groups of tunable pKa (17.6–20.0 in DMSO) and employed phenols of variable acidity (15.3–19.1) as exogenous acids. The modularity of this system allowed us to (1) evaluate contributions from proton transfer driving forces associated with either the SCS or exogenous acid, and (2) obtain mechanistic insights into CO2 reduction as a function of pKa. Plots of catalytic rate constants as a function of the various acidities reveal a series of linear free energy relationships: kinetics become increasingly sensitive to variations in SCS pKa when more acidic exogenous acids are used (0.82 ≥ Brønsted α ≥ 0.13), as well as to variations in exogenous acid pKa when acidity of the SCS is increased (0.62 ≥ Brønsted α ≥ 0.32). An Eyring analysis reveals that the rate-determining transition state is highly ordered and trends with SCS acidity (-88 ± 4 ≥ ΔSǂ ≥ -139 ± 3 J K-1 mol-1). These results are consistent with the proposal that SCS acidity modulates the degree of charge accumulation and solvation at the rate-limiting transition state. Together, this system provides key insights that enable optimization of catalytic activation barriers as a function of the acidity of all participants in a proton relay. The implications of this work can be used to guide rational design of electrocatalysts in which SCS acidity is considered in conjunction with that of the exogenous proton source. | Kaeden Teindl; Brian Patrick; Eva Nichols | Inorganic Chemistry; Catalysis; Kinetics and Mechanism - Inorganic Reactions; Electrocatalysis; Homogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/643dae801d262d40eaa853f5/original/linear-free-energy-relationships-and-transition-state-analysis-of-co2-reduction-catalysts-bearing-second-coordination-spheres-with-tunable-acidity.pdf |
620fa64ecbb4f43a3ec54ffb | 10.26434/chemrxiv-2022-bm5gq | Self-reporting styrylthiazolium photopharmaceuticals: mitochondrial localisation as well as SAR drive biological activity | Novel photoswitches with features complementary to the well-established azobenzenes are increasingly driving high-precision research in photopharmacology in cells and in vivo. Styrylthiazolium (StyTz) and styrylbenzothiazolium (StyBtz) are cellularly untested E/Z-isomerisation photoswitches which are nearly isosteric to azobenzenes, but have distinct photophysical and physicochemical properties: including ca. 60 nm red-shifted π→π* absorption, self-reporting fluorescence, Z→E relaxation that matches typical biological timescales, and good solubility due to their permanent positive charge. We here tested StyTz and StyBtz for their potential as photopharmaceutical scaffolds, by applying them to photocontrol the dynamics of the microtubule cytoskeleton. We observed light-specific disruption of microtubule network architecture and antiproliferative activity, with a structure-activity relationship matching expectations for tubulin inhibitors. However, while testing the lead StyBtz2 for its molecular mechanism of action, we found that it did not inhibit microtubule dynamics. We tracked its localisation in live cells by relying on its self-reporting fluorescence, observing accumulation of E-StyBtz2 into mitochondria; after several minutes of illumination it was then released into the cytosol concomitant with blebbing and cell death. We interpret this as light-dependent catastrophic rupturing of mitochondria on acute timescales. We conclude that StyTz/StyBtz can be interesting photopharmaceutical scaffolds for addressing mitochondrial, rather than cytosolic, targets. | Li Gao; Yvonne Kraus; Andrea Stegner; Thomas Wein; Constanze Heise; Leonie von Brunn; Elena Fajardo-Ruiz; Julia Thorn-Seshold; Oliver Thorn-Seshold | Biological and Medicinal Chemistry; Organic Chemistry; Bioorganic Chemistry; Photochemistry (Org.); Chemical Biology; Materials Chemistry | CC BY NC 4.0 | CHEMRXIV | 2022-02-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/620fa64ecbb4f43a3ec54ffb/original/self-reporting-styrylthiazolium-photopharmaceuticals-mitochondrial-localisation-as-well-as-sar-drive-biological-activity.pdf |
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