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66a45c0c01103d79c5d19fb0 | 10.26434/chemrxiv-2024-jrfqg-v2 | Correcting dispersion corrections with density-corrected DFT | Almost all empirical parameterizations of dispersion corrections in DFT use only energy errors, thereby mixing functional and density-driven errors. We introduce density and dispersion-corrected DFT (D2C-DFT), a dual-calibration approach that accounts for density delocalization errors when parametrizing dispersion interactions. We simply exclude density-sensitive reactions from the training data. We find a significant reduction in both errors and variation among several semilocal functionals and their global hybrids when tailored dispersion corrections are employed with Hartree-Fock densities. | Minhyeok Lee; Byeongjae Kim; Mingyu Sim; Mihira Sogal; Youngsam Kim; Hayoung Yu; Kieron Burke; Eunji Sim | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a45c0c01103d79c5d19fb0/original/correcting-dispersion-corrections-with-density-corrected-dft.pdf |
64b57dbfae3d1a7b0de01219 | 10.26434/chemrxiv-2023-6ttgx | Mechanistic Centrality of Boron-Containing Complexes in α-Hydroxy C–H Alkylation of Alcohols Promoted by Photoredox and Hydrogen Atom Transfer Catalysis | Selective α-hydroxy C–H alkylation of alcohols can be achieved using boronic acid, photoredox, and hydrogen atom transfer (HAT) catalysis. The key intermediate undergoing HAT is pro-posed to be a tetracoordinate boron-ate complex, formed from diol substrate, boronic acid and bound quinuclidine, which also serves as the HAT catalyst. Our studies reveal electron-poor boronic acids result in increased reaction efficiency. Calculated BDEs demonstrate this electronic trend is not due to modulating bond strengths in the boron-substrate complexes, although bond weakening is observed. Electron-poor boronic acids lead to a more dynamic equilibrium between different species, which we propose to be a contributing factor to overall increased alkylation rates. | Seth Cowan; Anas Ansari; Matthew Ross; Courtney Glenn; Margaret Hilton | Organic Chemistry; Catalysis; Organometallic Chemistry; Physical Organic Chemistry; Photocatalysis; Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64b57dbfae3d1a7b0de01219/original/mechanistic-centrality-of-boron-containing-complexes-in-hydroxy-c-h-alkylation-of-alcohols-promoted-by-photoredox-and-hydrogen-atom-transfer-catalysis.pdf |
66480dcc418a5379b096205f | 10.26434/chemrxiv-2024-vlq7m-v2 | A decarbonized vinyl chloride synthesis via selective oxidative coupling of methyl chloride | Selective coupling of C1 platform molecules to C2 olefins is a cornerstone for establishing a sustainable chemical industry based on non petroleum sources. Vinyl chloride (C2H3Cl), one of top commodity petrochemicals, is commercially produced from coal or oil derived C2 hydrocarbon (acetylene and ethylene) feedstocks with a high carbon footprint. Here, we report a decarbonized vinyl chloride synthesis via selective oxidative coupling of methyl chloride. This is enabled by a solid catalyst, featuring tungstate sub nanoclusters embedded in a zirconia matrix, which effectively captures CH2Cl radicals homogeneously generated in CH3Cl oxy pyrolysis and selectively couples them into C2H3Cl. In situ synchrotron based vacuum ultraviolet photoionization mass spectrometry provides direct experimental evidence of the homogeneous heterogeneous reaction mechanism. The process achieves methyl chloride conversion of 10 – 65% with a high vinyl chloride selectivity (60 – 75%) at a reaction temperature (600 – 750 °C), which is much lower than the traditional pyrolysis (> 850 °C). It also delivers a stable performance (at a vinyl chloride yield of ca. 30%) with no deactivation observed during a 50 hour test. Furthermore, combining with reaction of methanol and HCl to produce methyl chloride, we establish a methanol to vinyl chloride (MTV) route with the potential for significant reductions in climate change impact (24%) and cost (38%) compared to the state of the art ethylene based balanced process. A more remarkable 237% reduction in climate change impacts can be anticipated in the future oriented green scenario for MTV process primarily attributed to the utilization of renewable C1 feedstocks that results in negative net contributions to the overall impacts. | Yue Wang; Shihui Zou; Abhinandan Nabera; Yang Pan; Xutao Chen; Kunkun Wei; Jingbo Hu; Yilin Zhao; Chengyuan Liu; Juanjuan Liu; Yong Wang; Gonzalo Guillén-Gosálbez; Javier Pérez-Ramírez; Jie Fan | Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66480dcc418a5379b096205f/original/a-decarbonized-vinyl-chloride-synthesis-via-selective-oxidative-coupling-of-methyl-chloride.pdf |
678282146dde43c9081e2700 | 10.26434/chemrxiv-2025-72jhl | Actinide 5f Occupations: The Case of PuO2 | In actinide chemistry, the formal number of open‐shell 5f electrons, n(open), is a well‐defined quantity with an integer value. The effective 5f occupation, n(f), additionally takes donation and back‐donation into account, generally has a non‐integer value, and varying numerical definitions. The present study explores the important distinction between n(f) and n(open) in actinide chemistry with the example of PuO2, by using electronic structure methods with a relativistic Hamiltonian in combination with experimental Pu M5‐edge high energy resolution X‐ray absorption and emission spectroscopic data. The total donation to the metal in PuO2 is between 3.1 and 2.4 electrons, depending on the type of calculation, most of which is to the Pu 6d and 5f shells. The donation into 5f is sensitive to the approximations in the electronic structure model but likely amounts to 1.6/0.8 electrons when the diffuse regions of the 5f shell are included/excluded. Valence band resonant inelastic X‐ray scattering (VB‐RIXS) experiments demonstrate that Pu 5f electron density is present in the valence band; thus, there is a clear experimental signature of covalent bonding in PuO2. Pu M5‐edge and M3‐edge high energy resolution X‐ray absorption near edge structure (HR‐XANES) for Pu3+ and Pu4+ in aqueous solution are compared to PuO2 showing that Pu in PuO2 has n(f) closer to Pu4+(aq). | Ashima Bajaj; Harry Ramanantoanina; Bianca Schacherl; Sven Schenk; Tim Prüßmann; Agost Tasi; David Fellhauer; Alaina Thompson; Jeff Terry; Xiaoyu Wang; Eva Zurek; Tonya Vitova; Paul S. Bagus; Jochen Autschbach | Inorganic Chemistry; Lanthanides and Actinides | CC BY 4.0 | CHEMRXIV | 2025-01-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/678282146dde43c9081e2700/original/actinide-5f-occupations-the-case-of-pu-o2.pdf |
64a46e6b9ea64cc1676f2ba8 | 10.26434/chemrxiv-2023-j1n1p | Room-Temperature Multiple Phosphorescence from Functionalized Corannulenes: Temperature Sensing and Afterglow Organic Light-Emitting Diode | Corannulene-derived materials have been extensively explored in energy storage and solar cells, but, however, are rarely documented as emitters in light-emitting sensors and organic light-emitting diodes (OLEDs), due to low exciton utilization. Here, we report a family of multi-donor and acceptor (multi-D-A) motifs, TCzPhCor, TDMACPhCor, and TPXZPhCor, using corannulene as the acceptor and carbazole (Cz), 9,10-dihydro-9,10-dimethylacridine (DMAC), and phenoxazine (PXZ) as the donor, respectively. By decorating corannulene with different donors, multiple phosphorescence is realized. Theoretical and photophysical investigations reveal that TCzPhCor shows room-temperature phosphorescence (RTP) from the lowest-lying T1; however, for TDMACPhCor, dual RTP originating from a higher-lying T1 (T1H) and a lower-lying T1 (T1L) can be observed, while for TPXZPhCor, T1H-dominated RTP occurs resulting from a stabilized high-energy T1 geometry. Benefiting from the high-temperature sensitivity of TPXZPhCor, high color-resolution temperature sensing is achieved. Besides, due to degenerate S1 and T1H states of TPXZPhCor, the first corannulene-based solution-processed afterglow organic light-emitting diodes (OLEDs) is investigated. The afterglow OLED with TPXZPhCor shows a maximum external quantum efficiency (EQEmax) and a luminance (Lmax) of 3.3% and 5167 cd m-2, respectively, which is one of the most efficient afterglow RTP OLEDs reported to date. | Changfeng Si; Tao Wang; Abhishek Kumar Gupta; David Cordes; Alexandra Slawin; Jay Siegel; Eli Zysman-Colman | Physical Chemistry; Organic Chemistry; Organic Compounds and Functional Groups; Physical Organic Chemistry; Spectroscopy (Physical Chem.); Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2023-07-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a46e6b9ea64cc1676f2ba8/original/room-temperature-multiple-phosphorescence-from-functionalized-corannulenes-temperature-sensing-and-afterglow-organic-light-emitting-diode.pdf |
641d99d2647e3dca996f9dc7 | 10.26434/chemrxiv-2023-wsh0x | Phase stability and thermal expansion of ZnO solid solutions with 3d transition metal oxides synthesized at high pressure | Phase stability and thermal expansion of rock-salt Me1-xZnxO (Me = Ni2+, Co2+, Fe2+, Mn2+) solid solutions synthesized at high pressures and high temperatures have been studied by synchrotron X ray diffraction in a wide (0.1 ≤ x ≤ 0.8) concentration range. At ambient pressure rs-Me1-xZnxO solid solutions were found kinetically stable up to 670-1100 K depending on the composition and type of Me2+ cation. Temperature-induced decomposition of the single-phase rock-salt solid solutions lead in most cases to the formation of a mixture of two solid solutions, with cubic and wurtzite structures. Oxidation of the Me2+ cation (Co, Mn) by atmospheric oxygen can result in formation of mixed higher oxides of these metals. In all the systems studied, the rock-salt solid solutions show a linear temperature dependence of the thermal expansion, but for the compositions with the highest ZnO content, deviations from the linear dependence are observed. | Petr S. Sokolov; Andrey N. Baranov; Vladimir L. Solozhenko | Inorganic Chemistry; Solid State Chemistry; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2023-03-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/641d99d2647e3dca996f9dc7/original/phase-stability-and-thermal-expansion-of-zn-o-solid-solutions-with-3d-transition-metal-oxides-synthesized-at-high-pressure.pdf |
63975ccbcfb5ffb3896873d8 | 10.26434/chemrxiv-2022-q2zxh | An aluminium imide as a transfer agent for the [NR]2- function via metathesis chemistry | The reactions of a terminal aluminium imide with a range of oxygen-containing substrates have been probed with a view to developing its use as a novel main group transfer agent for the [NR]2- fragment. We demonstrate transfer of the imide moiety to [N2], [CO] and [Ph(H)C] units driven thermodynamically by Al-O bond formation. N2O reacts rapidly to generate the organoazide DippN3 (Dipp = 2,6-iPr2C6H3), while CO2 (under dilute reaction conditions) yields the corresponding isocyanate, DippNCO. Mechanistic studies, using both experimental and quantum chemical techniques, identify a carbamate complex K2[(NON)Al{k2-(N,O)-N(Dipp)CO2}]2 (formed via [2+2] cycloaddition) as an intermediate in the formation of DippNCO, and also in an alternative reaction leading to the generation of the amino-dicarboxylate complex K2[(NON)Al{k2-(O,O')-(O2C)2N(Dipp)}] (via the take-up of a second equivalent of CO2). In the case of benzaldehyde, a similar [2+2] cycloaddition process generates the metallacyclic hemi-aminal complex, Kn[(NON)Al{k2-(N,O)-(N(Dipp)C(Ph)(H)O}]n. Extrusion of the imine, PhC(H)NDipp, via cyclo-reversion is disfavoured thermally, due to the high energy of the putative aluminium oxide co-product, K2[(NON)Al(O)]2. However, addition of CO2 allows the imine to be released, driven by the formation of the thermodynamically more stable aluminium carbonate co-product, K2[(NON)Al(k2-(O,O')-CO3)]2. | Andreas Heilmann; Petra Vasko; Jamie Hicks; Jose Goicoechea; Simon Aldridge | Inorganic Chemistry; Organometallic Chemistry; Main Group Chemistry (Inorg.); Main Group Chemistry (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63975ccbcfb5ffb3896873d8/original/an-aluminium-imide-as-a-transfer-agent-for-the-nr-2-function-via-metathesis-chemistry.pdf |
60c73d51bb8c1a33803d9737 | 10.26434/chemrxiv.5664853.v1 | Peptidomics analysis of potato protein hydrolysates: post-translational modifications and peptide hydrophobicity | Post-translational modifications (PTMs) often <a></a><a>occur in proteins</a>
and play a regulatory role in protein function. However, the role of PTMs in
food-derived peptides remains largely unknown. The shotgun peptidomics strategy
was employed to identify PTMs in peptides from potato protein hydrolysates. Various
hydrophobicity-inducing PTMs were found to be located in different potato
peptides, <i>e.g</i>. acetylation of lysine,
N-terminal of proteins and peptides, C-terminal amidation, asparagine/glutamine
deamidaiton, methylation and trimethylation, methionine oxidation, and
N-terminal pyro-glutamate formation. Some of the PTMs are likely formed by
chemical reactions that occur during isolation and proteolytic processing of
potato proteins. The PTMs enhance peptide hydrophobicity, which can improve
bioactivity, decrease solubility and increase the bitterness of peptides. This is
the first report that food-derived peptides are widely modified by various PTMs
associated with hydrophobicity-inducing structural changes. This finding will
enhance understanding of the behaviour of bioactive peptides in biological
matrices. | Shixiang Yao; Chibuike Udenigwe | Food | CC BY NC ND 4.0 | CHEMRXIV | 1970-01-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d51bb8c1a33803d9737/original/peptidomics-analysis-of-potato-protein-hydrolysates-post-translational-modifications-and-peptide-hydrophobicity.pdf |
6703af9751558a15ef581f40 | 10.26434/chemrxiv-2024-rjdlq-v2 | Microscopic Mechanism of Water-Assisted Diffusional Phase Transitions in Inorganic Metal Halide Perovskites | The stability of perovskite materials is profoundly influenced by the presence of moisture in the surrounding environment. While it is well-established that water triggers and accelerates the black-yellow phase transition, leading to the degradation of the photovoltaic properties of perovskites, the underlying microscopic mechanism remains elusive. In this study, we employ classical molecular dynamics simulations to examine the role of water molecules in the yellow-black phase transition in a typical inorganic metal halide perovskite, CsPbI3. We have demonstrated, through interfacial energy calculations and classical nucleation theory, that the phase transition necessitates a crystal-amorphous-crystal two-step pathway, rather than the conventional crystal-crystal mechanism. Simulations for CsPbI3 nanowires show that water molecules in the air can enter the amorphous interface between the black and yellow regions. The phase transition rate markedly increases with the influx of interfacial water molecules, which enhance ion diffusivity by reducing the diffusion barrier, thereby expediting the yellow-black phase transition in CsPbI3. We propose a general mechanism through which solvent molecules can greatly facilitate phase transitions that otherwise have prohibitively high transition energies. | Jialin Liu; Xiangming Hao; Marijn van Huis; Zhaochuan Fan | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Statistical Mechanics; Structure; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2024-10-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6703af9751558a15ef581f40/original/microscopic-mechanism-of-water-assisted-diffusional-phase-transitions-in-inorganic-metal-halide-perovskites.pdf |
66522708418a5379b045c817 | 10.26434/chemrxiv-2024-bgpj2-v2 | Formulating reduced density gradient approaches
for noncovalent interactions | This work elucidates several forms of reduced electron density gradient (RDG) to describe non-covalent interactions (NCIs). By interpreting the RDG as a local-moment function, we systematically leveraged Weizacker's and Fermi's local moments. This resulted in high-fidelity RDG representations consistent with the NCI analysis. In addition, the RDG version derived from the Lagrangian kinetic energy density is conveniently normalized. These results suggest the non-existence of a particular RDG formulation when performing NCI analysis. Thus, an in-depth examination of the theoretical foundations connecting the RDG function with the nature of non-covalent interactions is necessary. | Cristian Guerra ; José Burgos; Leandro Ayarde-Henríquez; Eduardo Chamorro | Physical Chemistry; Quantum Mechanics | CC BY NC 4.0 | CHEMRXIV | 2024-05-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66522708418a5379b045c817/original/formulating-reduced-density-gradient-approaches-for-noncovalent-interactions.pdf |
60c740a2702a9b986218a107 | 10.26434/chemrxiv.7782797.v1 | Solvent Molecules Play a Role in an SNAr Reaction | <p>Reaction
between 4-nitrobenzonitrile and sodium methoxide (MeONa) exhibits unexpectedly low
conversion and puzzling kinetics behavior, which is in sharp contrast to the
prediction that reaction would be rapid and thorough made by density functional
theory (DFT) calculations under implicit solvation. Free energy surfaces (FES)
obtained by explicit solvation model including 62 solvent molecules differ
greatly from those with implicit solvation. The real nucleophile is not methoxide<sup>
</sup>anion but methanol-methoxide complex, and it is the entropy effect due to
solvent molecules that modifies the FES. It is the first work revealing the
significant modification of FES by explicit solvation for small molecule
reactions.</p> | Yumiao Ma | Solvates; Computational Chemistry and Modeling; Theory - Computational; Quantum Computing | CC BY NC ND 4.0 | CHEMRXIV | 2019-03-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c740a2702a9b986218a107/original/solvent-molecules-play-a-role-in-an-sn-ar-reaction.pdf |
60c750e1bb8c1a88533dbb9d | 10.26434/chemrxiv.13093529.v1 | Indol-2-Ylidene (IdY): A New Ambiphilic N-Heterocyclic Carbene Derived from Indole | The ambiphilic
N-heterocyclic carbene ligand, indol-2-ylidene (IdY, <b>A</b>), is described. A series of indolenium precursors (<b>2a</b>-<b>f</b>)
were prepared on a gram scale in good yields. Trapping experiments with
elemental selenium, [RhCl(cod)]<sub>2</sub> and CuCl lead to IdY-supported
materials, respectively. Computational and spectroscopic studies revealed the
ambiphilicity of IdY. The copper complexes (<b>6</b>) show high percent buried volume (%V<sub>bur</sub> = 58.1) and
allow for carboboration of terminal alkynes within 30 minutes as synthetically
useful yields and high regioselectivity. | Hyunho Kim; Minseop Kim; Hayoung Song; Eunsung Lee | Ligands (Inorg.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-10-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c750e1bb8c1a88533dbb9d/original/indol-2-ylidene-id-y-a-new-ambiphilic-n-heterocyclic-carbene-derived-from-indole.pdf |
60c74ebdbdbb89f8a7a39c10 | 10.26434/chemrxiv.12546698.v2 | NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy | Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination. | zhihong sun; Guanjun Deng; Xinghua Peng; Xiuli Xu; Lanlan Liu; Zhen Xu; Yifan Ma; Pengfei Zhang; Ping Gong; Lintao Cai | Aggregates and Assemblies; Biocompatible Materials; Biological Materials; Biodegradable Materials; Imaging Agents; Drug delivery systems; Imaging; Nanostructured Materials - Nanoscience; Bioengineering and Biotechnology; Drug Discovery and Drug Delivery Systems; Self-Assembly; Robotics | CC BY NC ND 4.0 | CHEMRXIV | 2020-08-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74ebdbdbb89f8a7a39c10/original/nir-active-nanoterminator-with-mature-dendritic-cell-acitivities-for-immuno-priming-mild-photothermal-cancer-therapy.pdf |
6213c090bd05a03d6b0ec67e | 10.26434/chemrxiv-2022-g2pv8 | Controlled Assembly of AIE Active Bolaamphiphilic Macromolecules into Luminescent Organic Nanoparticles Optimized for Two-Photon Microscopy in vivo | The (Z) and (E) isomers of an extended tetraphenylethylene-based chromophore with optimized two-photon induced luminescence properties are separated and functionalized with water-solubilizing pendant polymer groups, promoting their self-assembly in physiological media in the form of small, colloidal stable organic nanoparticles. The two resulting fluorescent suspensions are then evaluated as potential two-photon luminescent contrast agents for intravital epifluorescence and two-photon fluorescence microscopy. Comparisons with previously reported works involving similar fluorophores devoid of polymer side chains illustrate the benefits of the later functionalization regarding the control of the self-assembly of the nano-objects, and ultimately their biocompatibility towards the imaged organism. | Jean Rouillon; Laamia Ali; Kamel Hadj-Kaddour; Raphaël Marie-Luce; Mélanie Onofre; Sandrine Denis-Quanquin; Marion Jean; Muriel Albalat; Nicolas Vanthuyne; Guillaume Micouin; Akos Banyasz; Magali Gary-Bobo; Cyrille Monnereau; Chantal Andraud | Polymer Science; Nanoscience; Polymer scaffolds | CC BY NC 4.0 | CHEMRXIV | 2022-02-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6213c090bd05a03d6b0ec67e/original/controlled-assembly-of-aie-active-bolaamphiphilic-macromolecules-into-luminescent-organic-nanoparticles-optimized-for-two-photon-microscopy-in-vivo.pdf |
60ff21a77bf0c9c5f860fc29 | 10.26434/chemrxiv-2021-t8vdn | Cis-Divacant Octahedral Fe(II) in a Dimensionally Reduced Family of 2-(Pyridin-2-yl)pyrrolide Complexes | Four-coordinate transition metal complexes can adopt a diverse array of coordination geometries, with square planar and tetra- hedral coordination being the most prevalent. Previously, we reported the synthesis of a trinuclear Fe(II) complex, Fe3TPM2, supported by a three-fold symmetric 2-pyridylpyrrolide ligand (i.e., tris(5-(pyridin-2-yl)-1H-pyrrol-2-yl)methane), that featured a rare cis-divacant octahedral (CDO) geometry at each Fe(II) center. Here, a series of truncated 2-pyridylpyrrolide ligands is described that support mono- and binuclear Fe(II) complexes that also exhibit CDO geometries. Metallation of tetradentate ligand bis(5-(pyridin-2-yl)-1H-pyrrol-2-yl)methane (H2BPM) in THF results in a binuclear complex Fe2(BPM)2(THF)2 in which both Fe(II) ions are octahedrally coordinated. The coordinated THF solvent ligands are labile: THF dissociation leads to Fe2(BPM)2, which features five-coordinate Fe(II) ions. The Fe–Fe distance in these binuclear complexes can be elongated by ligand methylation. Metalation of bis(5-(6-methylpyridin-2-yl)-1H-pyrrol-2-yl)methane (H2BPMMe) in THF leads to the formation of four-coordinate, CDO Fe(II) centers in Fe(BPMMe)2. Further ligand truncation affords bidentate ligands 2- (1H-pyrrol-2-yl)pyridine (PyrPyrrH) and 2-methyl-6-(1H-pyrrol-2-yl)pyridine (PyrMePyrrH). Metalation of these ligands in THF affords six-coordinate complexes Fe(PyrPyrr)2(THF)2 and Fe(PyrMePyrr)2(THF)2. Dissociation of labile solvent ligands provides access to four- coordinate Fe(II) complexes. Ligand disproportionation at Fe(PyrPyrr)2 results in the formation of Fe(PyrPyrr)3 and Fe(0). Ligand methyl- ation suppresses this disproportionation and enables isolation of Fe(PyrMePyrr)2, which is rigorously CDO. Complete ligand truncation, by separating the 2-pyridylpyrrolide ligands into the constituent monodentate pyridyl and pyrrolide donors, affords Fe(Pyr)2(Pyrr)2 in which the Fe(II) is tetrahedrally coordinated. Computational analysis indicates that the potential energy surface that dictates the coordination geometry in this family of four-coordinate complexes is fairly flat in the vicinity of CDO coordination. These synthetic studies provide the structural basis to explore the implications of CDO geometry on Fe-catalyzed reactions. | Sung-Min Hyun; Kaleb Reid; Shaik Waseem Vali; Paul Lindahl; David Powers | Inorganic Chemistry; Organometallic Chemistry; Coordination Chemistry (Inorg.); Transition Metal Complexes (Inorg.); Ligand Design | CC BY NC ND 4.0 | CHEMRXIV | 2021-07-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60ff21a77bf0c9c5f860fc29/original/cis-divacant-octahedral-fe-ii-in-a-dimensionally-reduced-family-of-2-pyridin-2-yl-pyrrolide-complexes.pdf |
60c748dd4c89192806ad2fc7 | 10.26434/chemrxiv.11816739.v2 | Frozen-Density Embedding Based Many-Body Expansions | <div>Fragmentation methods allow for the accuratequantum-chemical treatment of large molecular clusters and materials. Here, we explore the combination of two complementary approaches to the development of such fragmentation methods: the many-body expansion (MBE) on the one hand and subsystem density-functional theory (DFT) or frozen-density embedding (FDE) theory on the other hand. First, we assess potential benefits of using FDE to account of the environmentin the subsystem calculation performed within the MBE. Second, we use subsystem DFT to derive a density-based MBE, in which a many-body expansion of the electron density is used to calculate the systems' total energy. This provides a correctionto the energies calculated with a conventional, energy-based MBE that only depends on the subsystem's electron densities. For the test case of clusters of water and of aspirin, we show that such a density-based MBE converges faster than the conventional energy-based MBE. For our test cases, truncation errors in the interaction energies are below chemical accuracy already with a two-body expansion. The density-based MBE thus provides a promising avenue for accurate quantum-chemical calculation of molecular clusters and materials.</div> | Daniel Schmitt-Monreal; Christoph R. Jacob | Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c748dd4c89192806ad2fc7/original/frozen-density-embedding-based-many-body-expansions.pdf |
63e3884f5c37ece322bace9c | 10.26434/chemrxiv-2023-kplr0 | Continuous Molecular Monitoring of Human Dermal Interstitial Fluid with Microneedle-Enabled Electrochemical Aptamer Sensors. | The ability to continually collect diagnostic information from the body during daily activity has revolutionized the monitoring of health and disease. Much of this monitoring, however, has been of physical vital signs, with the monitoring of molecular markers having been limited to glucose, primarily due to the lack of other medically relevant molecules for which continuous measurements are possible in bodily fluids. Electrochemical aptamer sensors, however, have a recent history of successful in-vivo demonstrations in rat animal models. Herein, we present the first report of real-time human molecular data collected using such sensors, successfully demonstrating their ability to measure the concentration of phenylalanine in dermal interstitial fluid after an oral bolus. To achieve this, we used a device that employs three hollow microneedles to couple interstitial fluid to an ex-vivo, phenylalanine-detecting sensor. The resulting architecture achieves good precision over the physiological concentration range and clinically relevant, 20 min time lag times. By also demonstrating 90 day dry room-temperature shelf-storage, the reported work also reaches another important milestone in moving such sensors to the clinic. While the devices demonstrated are not without remaining challenges, the results at minimum provide a simple method by which aptamer sensors can be quickly moved into human subjects testing. | Mark Friedel; Benjamin Werbovetz; Amy Drexelius; Kevin Plaxco; Jason Heikenfeld | Biological and Medicinal Chemistry; Analytical Chemistry; Electrochemical Analysis; Bioengineering and Biotechnology | CC BY 4.0 | CHEMRXIV | 2023-02-09 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63e3884f5c37ece322bace9c/original/continuous-molecular-monitoring-of-human-dermal-interstitial-fluid-with-microneedle-enabled-electrochemical-aptamer-sensors.pdf |
640adf040e6a36faba0c2820 | 10.26434/chemrxiv-2023-hwjg0 | Characterizing Surface Ice-philicity Using
Molecular Simulations and Enhanced Sampling | The formation of ice, which plays an important role in diverse contexts, ranging from cryopreservation to atmospheric science, is often mediated by solid surfaces. Although surfaces that interact favorably with ice (relative to liquid water) can facilitate ice formation by lowering nucleation barriers, the molecular characteristics that confer a surface with "ice-philicity" are complex and incompletely understood. To address this challenge, here we introduce a robust and computationally effcient method for characterizing surface ice-philicity, which combines molecular simulations and enhanced sampling techniques to quantify the free energetic cost of increasing surface-ice contact at the expense of surface-water contact. Using this method to characterize the ice-philicity of a family of model surfaces that are latticed matched with ice but vary in their polarity, we find that the non-polar surfaces are moderately ice-phobic, whereas the polar surfaces are highly ice-philic. In contrast, for surfaces that display no complementarity to the ice lattice, we find that ice-philicity is independent of surface polarity and that both non-polar and polar surfaces are moderately ice-phobic. Our work thus provides a prescription for quantitatively characterizing surface ice-philicity and sheds light on how ice-philicity is infuenced by lattice matching and polarity. | Sean Marks; Zachariah Vicars; Aniket Thosar; Amish Patel | Theoretical and Computational Chemistry; Materials Science; Coating Materials; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2023-03-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/640adf040e6a36faba0c2820/original/characterizing-surface-ice-philicity-using-molecular-simulations-and-enhanced-sampling.pdf |
66311276418a5379b01b5cde | 10.26434/chemrxiv-2024-53dsj | Application of Polymer Brush-Shells on Nanoparticles for Controlling Interaction with Serum | The interaction of nanoparticles (NPs) with biological environments triggers the formation of a protein corona (PC), which significantly influences their behaviour in vivo. This review explores the evolving understanding of PC formation, focusing on the opportunity for decreasing or suppressing protein-NP interactions by macromolecular engineering of NP shells. The functionalization of NPs with a dense, hydrated polymer brush-shell is a powerful strategy to impart stealth properties in order to elude recognition by the immune system. While poly(ethylene glycol) (PEG) has been extensively used for this purpose, concerns regarding its stability and immunogenicity have prompted exploration of alternative polymers. The stealth properties of brush shells can be enhanced by tailoring functionalities and structural parameters, including molar mass, grafting density and polymer topology. Determining correlations between these parameters and biopassivity has enabled to obtain polymer-grafted NPs with high colloidal stability and prolonged circulation time in biological media. | Carlos Pavón; Edmondo M. Benetti; Francesca Lorandi | Polymer Science; Nanoscience; Polymer brushes; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-05-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66311276418a5379b01b5cde/original/application-of-polymer-brush-shells-on-nanoparticles-for-controlling-interaction-with-serum.pdf |
63be1c8eee6f18dfa69bbdf4 | 10.26434/chemrxiv-2023-6dh2q | Holistic Prediction of Nucleophilicity and Electrophilicity Based on a Machine Learning Approach | Nucleophilicity and electrophilicity dictate the reactivity of polar organic reactions. In the past decades, Mayr et al. established a quantitative scale for nucleophilicity (N) and electrophilicity (E), which proved to be useful tools for the rationalization of chemical reactivity. In this study, a holistic prediction model was developed through a machine-learning approach. rSPOC, an ensemble molecular representation with structural, physicochemical, and solvent features, was developed for this purpose. With 1115 nucleophiles, 285 electrophiles and 22 solvents, the dataset was currently the largest one for reactivity prediction. The rSPOC model trained with the Extra Trees algorithm showed high accuracy in predicting Mayr’s N and E parameters with R2 of 0.96 and 0.92, MAE of 0.99 and 1.47, respectively. Furthermore, the practical applications of the model, for instance, nucleophilicity prediction of NAD(P)H and a series of enamines showed potential in predicting molecules with unknown reactivity within seconds. An online prediction platform (http://isyn.luoszgroup.com/) was constructed based on the current model, which is available free to the scientific community. | Yidi Liu; Qi Yang; Junjie Cheng; Long Zhang; Sanzhong Luo; Jin-Pei Cheng | Theoretical and Computational Chemistry; Organic Chemistry; Physical Organic Chemistry; Machine Learning | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63be1c8eee6f18dfa69bbdf4/original/holistic-prediction-of-nucleophilicity-and-electrophilicity-based-on-a-machine-learning-approach.pdf |
67920ada6dde43c908f688f6 | 10.26434/chemrxiv-2025-d2zc8 | China's rise in the chemical space and the decline of US influence | At the turn of the 21st century, China has achieved a spectacular surge in the scientific arena. However, little is known about its role in the material core of chemistry, encoded in the chemical space, which spans the discovery of chemicals. Here we show, by analysing the chemical space between 1996 and 2022, that its expansion has been dominated by China ever since 2013. Chinese dominance occurs at different levels, from organic to rare-earth chemistry, but is less dramatic in organometallic chemistry. We also found that Chinese dominance is mainly the product of the country’s own efforts, rather than the result of international collaboration. China’s surge mainly comes at the expense of the contribution of the US. Interestingly, the US share of the chemical space is more dependent on international collaboration, which mainly occurs with China. We also observe the emergent role of India. We believe these results provide a contemporary account of the geopolitics of the chemical space, which may constitute the basis for future national and international science policies, as well as research and development agendas. | Marisol Bermúdez-Montaña; Angel Garcia-Chung; Peter F. Stadler; Jürgen Jost; Guillermo Restrepo | Earth, Space, and Environmental Chemistry; Chemical Education; Chemical Education - General; Environmental Science; Geochemistry; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2025-01-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67920ada6dde43c908f688f6/original/china-s-rise-in-the-chemical-space-and-the-decline-of-us-influence.pdf |
60c74d18ee301ce3a1c7a1c0 | 10.26434/chemrxiv.11764368.v2 | Fluorescence lifetime predicts performance of voltage sensitive fluorophores in cardiomyocytes and neurons | <p></p><p>Voltage imaging with
fluorescent indicators offers a powerful complement to traditional electrode or
Ca<sup>2+</sup>-imaging approaches for monitoring electrical activity. Small
molecule fluorescent indicators present the unique opportunity for exquisite
control over molecular structure, enabling detailed investigations of
structure/function relationships. In this paper, we tune the conjugation
between aniline donors and aromatic π
systems within the context of photoinduced electron transfer (PeT) based
voltage indicators. We describe the design and synthesis of four new
voltage-sensitive fluorophores (VoltageFluors, or VFs). Three of these dyes
have higher relative voltage sensitivities than the previously-reported
indicator, VF2.1.Cl. We pair these new indicators with existing VFs to
construct a library of voltage indicators with varying degrees of conjugation
between the aniline nitrogen lone pair and the aromatic π system. Using a combination of steady-state and
time-resolved fluorescence spectroscopy, cellular electrophysiology, fluorescence
lifetime imaging microscopy (FLIM), and functional imaging in mammalian neurons
and human cardiomyocytes, we
establish a detailed link between the photophysical properties of VF dyes and
their ability to report on membrane potential dynamics with high signal-to-noise.
Anilines with intermediate degrees of conjugation to the aromatic π system experience intermediate rates
of PeT and possess the highest absolute voltage sensitivities. Measured using FLIM in
patch-clamped HEK cells, we find that the absolute voltage sensitivity of
fluorescence lifetime (∆τ<sub>fl</sub> per mV) provides the best predictor of
dye performance in cellular systems.</p><br /><p></p> | Steven Boggess; Julia Lazzari-Dean; Benjamin Raliski; Dong Min Mun; Amy Li; Evan Miller | Physical Organic Chemistry; Microscopy; Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d18ee301ce3a1c7a1c0/original/fluorescence-lifetime-predicts-performance-of-voltage-sensitive-fluorophores-in-cardiomyocytes-and-neurons.pdf |
63d036e9246f165acccb9e7c | 10.26434/chemrxiv-2023-q6vd2-v2 | Toward routine Kohn-Sham inversion using the "Lieb-response" approach | Kohn-Sham inversion, in which the effective Kohn-Sham mean-field potential is found for a given density, provides insights into the nature of exact density functional theory (DFT) that can be exploited for the development of density functional approximations. Unfortunately, and despite significant and sustained progress in both theory and software libraries, KS inversion remains rather difficult in practice, and especially in finite basis sets. The present work presents a Kohn-Sham inversion method, dubbed the “Lieb-response” approach, that naturally works with existing Fock-matrix DFT infrastructure in finite basis sets, is numerically efficient, and directly provides meaningful matrix and energy quantities for pure-state and ensemble systems. Some additional work yields potentials. It thus enables the routine inversion of even difficult KS systems, as illustrated on a variety of problems within this work; and provides outputs that can be used for embedding schemes or machine learning of density functional approximations. The effect of finite basis sets on Kohn-Sham inversion is also analysed and investigated. | Tim Gould | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2023-01-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63d036e9246f165acccb9e7c/original/toward-routine-kohn-sham-inversion-using-the-lieb-response-approach.pdf |
6494b18b24989702c2ccd7e5 | 10.26434/chemrxiv-2022-zdpsh-v2 | The Catalytic Reaction of Cytochrome c Oxidase Probed by In Situ Gas Titrations and FTIR Difference Spectroscopy | Cytochrome c oxidase (CcO) is a transmembrane heme-copper metalloenzyme that catalyzes the reduction of O2 to H2O at the reducing end of the respiratory electron transport chain. To understand this reaction, we followed the conversion of CcO from Rhodobacter sphaeroides between several active-ready and carbon monoxide-inhibited states via attenuated total reflection Fourier-transform infrared (ATR FTIR) difference spectroscopy. Utilizing a novel gas titration setup, we prepared the mixed-valence, CO-inhibited R2CO state as well as the fully-reduced R4 and R4CO states and induced the “active ready” oxidized state OH. These experiments are performed in the dark yielding FTIR difference spectra exclusively triggered by exposure to O2, the natural substrate of CcO. Our data demonstrate that the presence of CO at heme a3 does not impair the catalytic oxidation of CcO when the cycle starts from the fully-reduced states. Interestingly, when starting from the R2CO state, the release of the CO ligand upon purging with inert gas yield a product that is indistinguishable from photolysis-induced states. The observed changes at heme a3 in the catalytic binuclear center (BNC) result from the loss of CO and are unrelated to electronic excitation upon illumination. Based on our experiments, we re-evaluate the assignment of marker bands that appear in time-resolved photolysis and perfusion-induced experiments on CcO. | Federico Baserga; Julian Storm; Ramona Schlesinger; Joachim Heberle; Sven Stripp | Physical Chemistry; Biological and Medicinal Chemistry; Catalysis; Biocatalysis; Biophysical Chemistry; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-23 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6494b18b24989702c2ccd7e5/original/the-catalytic-reaction-of-cytochrome-c-oxidase-probed-by-in-situ-gas-titrations-and-ftir-difference-spectroscopy.pdf |
60c757f89abda2499bf8e817 | 10.26434/chemrxiv.14474373.v1 | Quantum Control for Trapped Particles at Matter Surface | In this theoretic work, trapped particles at matter surface to be considered as target
system of quantum control. At the framework of variational method in Hilbert space, it
would be quite interesting for us to explore particles which is trapped via optical lattice or
other kinds of constraints at a matter surface (metal, crystal). The aim of this task is to
survey theoretical control for quantum particles as they are appeared and trapped at matter
surface (cf. [1]). The physical background of this work is laying on the specified particles
motion or reaction under a certain chemical surface. As is well known, one can move a
particle at surface smoothly through a point force above it or according to a proper angle,
such quantum mechanical motion had already been achieved by the IBM team several years
ago.
At the viewpoint of quantum control, what is theoretic support? Can we make these
control theoretically, computationally or experimentally? In fact, free trapped particles had
been considered by scientists and researchers at worldwide scale. The most exciting things in
this study is to take particle as target as it constrained on a surface. Theoretically, this work
is to describe quantum control system consisting of time-varying Schrodinger equation at
physical constraints condition. Then to apply control theory to quantum system of trapped particles, find and characterize optimal quantum control. Further, to compose optimality
system (Euler-Lagrange system). Comprising of control free trapped particle, this work is
focusing on control taking place at matter surface (on it particle is trapped), that is, try to
discuss the external force constrain (e.g. optical lattice) and surface constrain are acting at
particle together.
Amazing result is desired in control of different multi-forces as control inputs, what
would be happened as a particle changing its position, displacement or status under trapped
situation? can we make a trapped chemical quantum well, or a physical optical lattice which
worked using external force? what is extension of such kind of works at a variety of fields?
whether the general quantum control is worked in this case? It is the purpose to solve
these mysteries in this work, and report the initial conclusion of theoretic aspect for trapped
particle at matter surface. | Quan-Fang Wang | Quantum Mechanics; Surface | CC BY NC ND 4.0 | CHEMRXIV | 2021-04-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c757f89abda2499bf8e817/original/quantum-control-for-trapped-particles-at-matter-surface.pdf |
67b9529bfa469535b963aa6c | 10.26434/chemrxiv-2025-7jc1f | Extended Cycling Stability in an Anodeless Solid-State Battery at Ambient Pressure and Temperature Enabled by a Corroded, Reactive Interphase | Solid-state Li-ion batteries in the ‘anodeless’ configuration can lead to a significant increase in volumetric energy density compared to their liquid-electrolyte based counterparts. However, challenges related to the electrochemical stability of highly Li+ -conductive solid-state electrolytes need to be resolved to improve cyclability. Herein, we present a scalable, solution-phase interfacial engineering approach to generate a porous surface layer on the Cu current collector via a corrosion reaction involving the controlled hydrolysis of LiPF6 salt in EC-DEC at elevated temperatures. The optimal corrosion protocol results in a uniform reaction depth on the Cu foil with a reaction layer comprising of fluorides and oxides of Cu and Li. Subsequently, through a series of conversion reactions in a Li metal half-cell with Li1.3Al0.3Ti1.7(PO4)3 (LATP) as the solid-electrolyte, these F- and O-species on the porous interphase layer generated from Cu corrosion converted to lithium fluoride and lithium oxide, respectively, with the concomitant reduction of Cu(II) to its metallic form throughout the thickness of the interface layer. The reactive interphases are characterized with SEM, EDX, XPS and atom probe tomography along with electrochemical measure- ments to understand the composition, distribution, evolution and charge transfer properties during cycling. The unique interfacial microstructure consisting of a dense, well-adhered passivation layer resulted in a significantly improved coulombic efficiency of Li plating/stripping beyond 90% in an anodeless solid- state cell at ambient pressure and temperature. | Piyali Pahari; Srinivasan Ramakrishnan | Energy; Energy Storage | CC BY NC ND 4.0 | CHEMRXIV | 2025-02-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67b9529bfa469535b963aa6c/original/extended-cycling-stability-in-an-anodeless-solid-state-battery-at-ambient-pressure-and-temperature-enabled-by-a-corroded-reactive-interphase.pdf |
61b91129d6dcc22e97384a6f | 10.26434/chemrxiv-2021-r1cmw | Towards autonomous analysis of Chemical Exchange Saturation Transfer experiments using Deep Neural Networks | Macromolecules often exchange between functional states on timescales that can be accessed with NMR spectroscopy and many NMR tools have been developed to characterise the kinetics and thermodynamics of the exchange processes, as well as the structure of the conformers that are involved. However, analysis of the NMR data that report on exchanging macromolecules often hinges on complex least-squares fitting procedures as well as human experience and intuition, which, in some cases, limits the widespread use of the methods. The applications of deep neural networks (DNNs) and artificial intelligence have increased significantly in the sciences, and recently, specifically, within the field of biomolecular NMR, where DNNs are now available for tasks such as the reconstruction of sparsely sampled spectra, peak picking, and virtual decoupling. Here we present a DNN for the analysis of chemical exchange saturation transfer (CEST) data reporting on two- or three-site chemical exchange involving sparse state lifetimes of between approximately 3 - 60 ms, the range most frequently observed via experiment. The work presented here focuses on the 1H CEST class of methods that are further complicated, in relation to applications to other nuclei, by anti-phase features. The developed DNNs accurately predict the chemical shifts of nuclei in the exchanging species directly from anti-phase 1HN CEST profiles, along with an uncertainty associated with the predictions. The performance of the DNN was quantitatively assessed using both synthetic and experimental anti-phase CEST profiles. The assessments show that the DNN accurately determines chemical shifts and their associated uncertainties. The DNNs developed here do not contain any parameters for the end-user to adjust and the method therefore allows for autonomous analysis of complex NMR data that report on conformational exchange. | Gogulan Karunanithy; Tairan Yuwen; Lewis E Kay; D Flemming Hansen | Theoretical and Computational Chemistry; Physical Chemistry; Biological and Medicinal Chemistry; Biochemistry; Biophysics; Artificial Intelligence | CC BY NC ND 4.0 | CHEMRXIV | 2021-12-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61b91129d6dcc22e97384a6f/original/towards-autonomous-analysis-of-chemical-exchange-saturation-transfer-experiments-using-deep-neural-networks.pdf |
60c73e10469df4660ef427d5 | 10.26434/chemrxiv.6291671.v1 | Two Consecutive Magneto-Structural Gas-Solid Transformations with Single-Crystal Retention in Non-Porous Molecular Materials | <p>Modification of the magnetic properties in a solid-state material upon external stimulus has attracted much attention in the recent years for their potential applications as switches and sensors. Within the field of coordination polymers, gas sorption studies typically focus on porous solids, with the gas molecules accommodating in the channels. Here we present a 1D non-porous coordination polymer capable of incorporating HCl gas molecules, which not only causes a reordering of its atoms in the solid state but also provokes dramatic changes in the magnetic behaviour. Subsequently, a further solid-gas transformation can occur with the extrusion of HCl gas molecules causing a second structural rearrangement which is also accompanied by modification in the magnetic path between the metal centres. Unequivocal evidence of the two-step magnetostructural transformation is provided by X-ray single-crystal diffraction.</p> | Julia Miguel-Donet; Javier López-Cabrelles; Nestor Calvo Galve; Eugenio Coronado; Guillermo Minguez Espallargas | Hybrid Organic-Inorganic Materials; Coordination Chemistry (Inorg.); Magnetism | CC BY NC ND 4.0 | CHEMRXIV | 2018-05-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73e10469df4660ef427d5/original/two-consecutive-magneto-structural-gas-solid-transformations-with-single-crystal-retention-in-non-porous-molecular-materials.pdf |
67964b23fa469535b9ee14cb | 10.26434/chemrxiv-2025-q1q5x | Unraveling the Hidden Pathway of Catalyst‐Free Direct Photochemical Conversion of Sulfides to Sulfoxides: A Universal Pathway Under UVA Radiation | Selective conversion of sulfides to sulfoxides is an important class of chemical transformation having tremendous importance in medicinal chemistry. However, the primary process associated with the photoexcitation during the direct photochemical conversion of sulfides to sulfoxides is poorly understood and misrepresented in the literature. Herein, we discover a hidden pathway responsible for the efficient and selective conversion of sulfides to sulfoxides in the absence of any photocatalysts (PCs) or photosensitizers (PSs) under UVA illumination (λex = 370 nm). We show that this hidden pathway directly generates singlet oxygen (a1Δg,1O2) via solvent‐oxygen (X3Σg–,3O2) charge transfer (CT) excitation under ambient conditions without the need of any additional PCs or PSs. Our experimental and computational findings reveal that the 1O2 generated via CT excitation efficiently and selectively oxidizes sulfides to sulfoxides via the generation of persulfoxide intermediates with an excellent yields, fast kinetics, and broad substrate scope. In addition, we found that the presence of marginal amount of water favors faster kinetics and prevents overoxidation to sulfones due to the stabilization of the sulfoxide products via specific hydrogen‐bonding interactions. Finally, we demonstrate that the present hidden pathway is equally efficient and operational for other classes of photoredox reactions under UVA illumination; and thus, making this pathway a universal route for efficient and sustainable photoredox conversions under ambient conditions. | Shivendra Singh; Supritam Datta; Souvik Manna; Biswarup Pathak; Tushar Kanti Mukherjee | Organic Chemistry; Catalysis; Photochemistry (Org.); Photocatalysis; Redox Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67964b23fa469535b9ee14cb/original/unraveling-the-hidden-pathway-of-catalyst-free-direct-photochemical-conversion-of-sulfides-to-sulfoxides-a-universal-pathway-under-uva-radiation.pdf |
632a83a52984c92eb566bbf0 | 10.26434/chemrxiv-2022-1q37t | Prediction of Multiple Hydrogen Ligation at a Vanadium(II) Site in a Metal-Organic Framework | Densifying hydrogen in a metal-organic framework (MOF) at moderate pressures can circumvent challenges associated with high-pressure compression. The highly tunable structural and chemical composition in MOFs affords vast possibilities to optimize binding interactions.
At the heart of this search are the nanoscale characteristics of molecular adsorption at the binding site(s). Using density functional theory (DFT) to model binding interactions of hydrogen to the exposed metal site of cation-exchanged MFU-4l, we predict multiple hydrogen ligation of H2 at the first coordination sphere of V(II) in V(II)-exchanged MFU-4l.
We find that the strength of this binding between the metal site and \ce{H2} molecules can be tuned by altering the halide counterion adjacent to the metal site and that the fluoride-containing node affords the most favourable interactions for high-density H2 storage. Using energy decomposition analysis, we delineate electronic contributions that enable multiple hydrogen ligation and demonstrate its benefits for hydrogen adsorption and release at modest pressures. | Romit Chakraborty; Kurtis M. Carsch; David E. Jaramillo; Yuto Yabuuchi; Hiroyasu Furukawa; Jeffrey R. Long; Martin Head-Gordon | Theoretical and Computational Chemistry; Energy; Computational Chemistry and Modeling; Energy Storage; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2022-09-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/632a83a52984c92eb566bbf0/original/prediction-of-multiple-hydrogen-ligation-at-a-vanadium-ii-site-in-a-metal-organic-framework.pdf |
66291db091aefa6ce14ffe93 | 10.26434/chemrxiv-2024-0ppxl | Mixing order asymmetry in nanoparticle-polymer complexation and precipitation revealed by isothermal titration calorimetry | In recent years, there has been a renewed interest in complex coacervation, driven by concerted efforts to offer novel experimental and theoretical insights into electrostatic charge-induced association. While previous studies have primarily focused on polyelectrolytes, proteins or surfactants, our work explores the potential of using cerium (CeO2) and iron (γ-Fe2O3) oxide nanoparticles (NPs) to develop innovative nanomaterials. By combining various charged species, such as polyelectrolytes, charged neutral block copolymers and coated NPs, we study a wide variety of complexation patterns and compare them using isothermal titration calorimetry, light scattering and microscopy. These techniques confirm that the titration of oppositely charged species occurs in two steps: the formation of polyelectrolyte complexes and subsequent phase (or microphase) separation, depending on the system studied. Across all examined cases, the entropic contribution to the total free energy surpasses the enthalpic contribution, in agreement with counterion release mechanisms. Furthermore, our investigation reveals a consistent asymmetry in the reaction enthalpy associated with the secondary process, with exothermic profiles observed upon the addition of cationic species to anionic ones and endothermic profiles in the reverse case. | Leticia Vitorazi; Jean-Francois Berret | Physical Chemistry; Polymer Science; Nanoscience | CC BY NC ND 4.0 | CHEMRXIV | 2024-04-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66291db091aefa6ce14ffe93/original/mixing-order-asymmetry-in-nanoparticle-polymer-complexation-and-precipitation-revealed-by-isothermal-titration-calorimetry.pdf |
60c756f9337d6c205ce28f53 | 10.26434/chemrxiv.14225942.v2 | On the Acid Sites of Phosphorous Modified Zeosils | The acid sites of phosphorus-containing zeosils were probed through a combination of solid acid characterization, density functional theory calculations, and kinetic interrogations, establishing their weakly Brønsted acidic character. Due to the disparity in acid-site strength, P-zeosils catalyzed the probe chemistry of isopropanol dehydration slower than aluminosilicate zeolites by an order of magnitude on an active site basis. Propene selectivity during isopropanol dehydration remained 20-30% higher than that of aluminosilicates, illustrating the distinct nature of the weakly acidic phosphorus active sites that favored unimolecular dehydration routes. Regardless of the confining siliceous environment, the nature of phosphorous active sites was unchanged, indicated by identical apparent uni- and bi-molecular dehydration energy barriers. Kinetic isotope experiments with deuterated isopropanol feeds implicated an E2-type elimination to propene formation on phosphorus-containing materials. Comparison of KIEs between phosphorus-containing zeosils and aluminosilicates pointed to an unchanged isopropanol dehydration mechanism, with changes in apparent energetic barriers attributed to weaker binding on phosphorous-active sites that lead to a relatively destabilized alcohol dimer adsorbate. Both ex-situ alkylamine Hofmann elimination and in-situ pyridine titration characterization methods exhibited phosphorous acid site counts dependent on probe molecules identity and/or concentration, underpinning the limitations of extending common characterization techniques for Brønsted-acid catalysis to weakly acidic materials. | Gaurav Kumar; Limin Ren; Yutong Pang; Xinyu Li; Han Chen; Jason Gulbinski; Paul Dauenhauer; Michael Tsapatsis; Omar Abdelrahman | Acid Catalysis; Heterogeneous Catalysis | CC BY NC ND 4.0 | CHEMRXIV | 2021-03-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c756f9337d6c205ce28f53/original/on-the-acid-sites-of-phosphorous-modified-zeosils.pdf |
614d312a39ef6a8aa728168e | 10.26434/chemrxiv-2021-fgcts | Preparation of LDO@TiO2 core-shell nanosheets for enhanced photocatalytic degradation of organic pollutions | TiO2-based nanosheets materials with core-shell structure are expected to be one of the promising photocatalysts to degradation of organic pollutions. However, it is a challenge to synthesis of TiO2 shell on functional core materials by desired nucleation and growth process. Layered double hydroxides (LDHs) are considered as ideal platforms to in-situ grow TiO2 and further serve as additional components to construct heterojunction to improve the separation of photo-generated charge carriers. In this work, we report the design and fabrication of anatase TiO2 coated ZnAl-layered double oxide (LDO@TiO2) nanosheets, which involves the in-situ growth of TiO2 on ZnAl-LDH followed by a subsequent calcination treatment. The resulting LDO@TiO2 photocatalyst gives typical core-shell nanosheets morphology with mesoporous structure, which exhibiting excellent photodegradation and mineralization efficiency for organic pollutions. | Can Wang; Ruikang Zhang; Yucong Miao; Qihui Xue; Borong Yu; Yuanzhe Gao; Zhan-gang Han; Mingfei Shao | Catalysis; Photocatalysis; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-09-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/614d312a39ef6a8aa728168e/original/preparation-of-ldo-ti-o2-core-shell-nanosheets-for-enhanced-photocatalytic-degradation-of-organic-pollutions.pdf |
638fa9f0b103af8c5e0d8c59 | 10.26434/chemrxiv-2022-khw4t | High entropy alloy nanoparticle formation at low temperatures | Entropy-driven formation of high entropy alloy (HEA) nanoparticles from metal precursors requires high temperatures and controlled cooling rates. However, several proposed HEA nanoparticle synthesis strategies avoid the high-temperature regime. In our work, we address the question of how single-phase HEA nanoparticles can form at low temperatures. Investigating a system of five noble metal single source precursors, we combine in situ X-ray powder diffraction with multi-edge X-ray absorption spectroscopy to demonstrate that the formation of single-phase nanoparticles is governed by stochastic principles and the inhibition of precursor mobility during the formation process. The proposed formation principle is supported by simulations of the nanoparticle formation in a randomized process, rationalizing the experimentally found differences between two-element and multi-element metal precursor mixtures. | Rebecca Pittkowski; Christian M. Clausen; Qinyi Chen; Dragos Stoian; Wouter van Beek; Jan Bucher; Rahel L. Welten; Nicolas Schlegel; Jette K. Mathiesen; Tobias M. Nielsen; Asger W. Rosenkranz; Espen D. Bøjesen; Jan Rossmeisl; Kirsten M. Ø. Jensen; Matthias Arenz | Materials Science; Catalysis; Nanoscience; Alloys | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/638fa9f0b103af8c5e0d8c59/original/high-entropy-alloy-nanoparticle-formation-at-low-temperatures.pdf |
65aa7e8d66c1381729cfc36b | 10.26434/chemrxiv-2024-d7fxg | Copper-Catalyzed Perarylation of Cyclopentadiene:
Synthesis of Hexaarylcyclopentadienes | While hexaphenylsilacyclopentadiene (hexaphenylsilole) is viewed as an archetypal Aggregation-Induced Emission (AIE) luminogen, its isostructural hydrocarbon surrogate hexaphenylcyclopentadiene has strikingly never been investigated in this context, most probably due to a lack of synthetic availability. Herein, we report a straightforward synthesis of hexaphenylcyclopentadiene, via the direct perarylation of cyclopentadiene upon copper(I) catalysis under microwave activation, with the formation of six new C-C bonds in a single synthetic operation. Using zirconocene dichloride as a convenient source of cyclopentadiene and a variety of aryl iodides as coupling partners, this copper-catalyzed cross-coupling reaction gave rise to a series of unprecedented hexaarylcyclopentadienes, displaying promising properties as AIE luminogens. In addition, these propeller-shaped perarylcyclopentadienes are direct precursors of π-extended conjugated polycyclic compounds, and their cyclodehydrogenation under Scholl reaction conditions yielded helicenic 17,17-diarylcyclopenta[l,l’]diphenanthrenes. These structurally complex polyannelated fluorene derivatives can now be prepared in only two synthetic steps from cyclopentadiene for applications as organic semiconductors or fluorophores. | Yohan Gisbert; Pablo Simón Marqués; Caterina Baccini; Seifallah Abid; Nathalie Saffon-Merceron; Gwénaël Rapenne; Claire Kammerer | Physical Chemistry; Organic Chemistry; Catalysis; Organic Compounds and Functional Groups; Homogeneous Catalysis; Physical and Chemical Properties | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65aa7e8d66c1381729cfc36b/original/copper-catalyzed-perarylation-of-cyclopentadiene-synthesis-of-hexaarylcyclopentadienes.pdf |
67793db8fa469535b9bde6e3 | 10.26434/chemrxiv-2025-bdnwm | Replacing a Cereblon Ligand by a DDB1 and CUL4 Associated Factor 11 (DCAF11) Recruiter Converts a Selective Histone Deacetylase 6 PROTAC into a pan-degrader | Proteolysis-targeting chimeras (PROTACs) have recently gained popularity as targeted protein degradation (TPD) promises to overcome the limitations of occupancy-driven pharmacology. However, most degraders rely on a small number of E3 ligases. In this study, we present the first-in-class histone deacetylase (HDAC) PROTACs recruiting the DDB1- and CUL4- associated factor 11 (DCAF11). We established a synthesis route entirely on solid-phase to prepare a set of eleven degraders. The long and flexible spacer bearing FF2039 (1j) showed significant HDAC1 and 6 degradation in combination with cytotoxicity against the multiple myeloma cell line MM.1S. Further investigations revealed that 1j was also able to degrade HDAC isoforms of class I, IIa and IIb. Compared to our previously published cereblon-recruiting HDAC6 selective PROTAC A6, we succesfully transformed the selective degrader into a pan-HDAC degrader by switching the recruited E3 ligase. A detailed profiling of the anticancer properties of 1j demonstrated its significant antiproliferative activity against both hematological and solid cancer cell lines, driven by cell cycle arrest and apoptosis induction. | Felix Feller; Heiko Weber; Martina Miranda; Irina Honin; Maria Hanl; Finn Kristian Hansen | Biological and Medicinal Chemistry | CC BY 4.0 | CHEMRXIV | 2025-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67793db8fa469535b9bde6e3/original/replacing-a-cereblon-ligand-by-a-ddb1-and-cul4-associated-factor-11-dcaf11-recruiter-converts-a-selective-histone-deacetylase-6-protac-into-a-pan-degrader.pdf |
60c74f884c891946fcad3c06 | 10.26434/chemrxiv.12918959.v1 | Impact of Electron Beam Irradiation on Thermoplastic Polyurethanes Unraveled by Thermal Field-Flow Fractionation | The impact of electron beam irradiation on thermoplastic polyurethane material was studied for both an aliphatic and an aromatic polyurethane with equal amount of hard and soft segments. Irradiation doses up to 300 kGy at room temperature and at 100 °C were applied. Changes in chemical structure, molar mass and size were assessed using infrared spectroscopy, differential scanning calorimetry, size exclusion chromatography and thermal field flow fractionation. Material alterations were correlated with trends regarding to degradation, crosslinking or branching changes. Thereby, limits of characteri-zation by size exclusion chromatography are addressed and amended by thermal field-flow fractionation studies. In addition, a thermophoretic analysis has been carried out complementary to the portfolio of analytical methods applied in this work. | Martin Geisler; Tuhin Subhra Pal; Kerstin Arnhold; Mikhail Malanin; Michael Thomas Müller; Brigitte Voit; Jürgen Pionteck; Albena Lederer | Separation Science; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-09-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74f884c891946fcad3c06/original/impact-of-electron-beam-irradiation-on-thermoplastic-polyurethanes-unraveled-by-thermal-field-flow-fractionation.pdf |
60c75540bb8c1a93af3dc395 | 10.26434/chemrxiv.14058332.v1 | Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes | We report the facile
production of ArCF<sub>2</sub>X and ArCX<sub>3 </sub>from ArCF<sub>3</sub>
using catalytic iron(III)halides, which constitutes the first iron-catalyzed
halogen exchange for non-aromatic CF bonds. Theoretical calculations suggest direct activation of C–F bonds
by iron coordination. ArCX<sub>3</sub> and ArCF<sub>2</sub>X products of the reaction are synthetically valuable due to
their diversification potential. In particular, bromo-, chloro-, and
iododifluoromethyl arenes (ArCF<sub>2</sub>Br, ArCF<sub>2</sub>Cl, ArCF<sub>2</sub>I,
respectively) provide access to a myriad of difluoromethyl arene derivatives
(ArCF<sub>2</sub>R). To optimize for mono-halogen exchange, a statistical
method called Design of Experiments was used. Optimized parameters were
successfully applied to electron rich and electron deficient aromatic
substrates, and to the late stage diversification of flufenoxuron, a commercial
insecticide. | Andreas Dorian; Emily Landgreen; Hayley Petras; James Shepherd; Florence Williams | Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Bond Activation; Main Group Chemistry (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75540bb8c1a93af3dc395/original/iron-catalyzed-halogen-exchange-of-trifluoromethyl-arenes.pdf |
65d6133666c13817292b8f94 | 10.26434/chemrxiv-2024-18d58-v2 | Design of 2D nanomaterials (photo-)electrocatalysts for biomass valorization coupled with H2 production | Electrocatalytic water splitting driven by renewable energy is a promising strategy for sustainable hydrogen production. However, the slow oxygen evolution reaction (OER) kinetics severely limit the rate of the hydrogen evolution reaction (HER) and the overall energy conversion efficiency of the water electrolyzer. To overcome this challenge, hybrid water electrolysis systems have been developed which replace the sluggish OER with thermodynamically and kinetically favorable biomass (photo-)electro-oxidation. In addition, these system allow for the simultaneous production of value-added chemical products. This review highlights the design strategies related to the host structure remodeling and structure assembly design of two-dimensional (2D) nanomaterial-based (photo)electrocatalysts, as well as their wide application in hybrid water electrolysis. Moreover, the current challenges and emerging strategies for the development of advanced (photo-)electrocatalysts and industrial-scale systems are emphasized. | Bahareh Feizi Mohazzab; Kiarash Torabi; Dandan Gao | Catalysis; Electrocatalysis; Heterogeneous Catalysis; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-02-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65d6133666c13817292b8f94/original/design-of-2d-nanomaterials-photo-electrocatalysts-for-biomass-valorization-coupled-with-h2-production.pdf |
60c74888842e655375db2be7 | 10.26434/chemrxiv.11918406.v1 | Microfluidic Microbioreactor to Reduce the Cost and Speed Up Optimisation of Protein Production | Here, we demonstrate a low-cost polymer microfluidic microbioreactor
with a working volume of 1 mL, integrated with optical sensors for pH, oxygen
and cell density, and maintained at constant set temperature for the
optimisation of recombinant protein production from <i>Pichia pastoris</i>. Oxygen is transferred from a headspace enclosure,
formed using inkjet 3D printing, through
a gas-permeable membrane within the microbioreactor with a K<sub>L</sub>a<sub> </sub>of
90 at 1500 rpm. A pressurised fluid driving system is used with
flow rates controllable to 0.7 µL/min with fluid switching from four reservoirs performed off the microfluidic
microbioreactor element so that this can be produced at low cost using high
replication techniques. | Mayur Parekh; abdulaziz ali; Simon Bateson; Fathi Abugchem; Leon Pybus; Christopher Lennon; Zulfiqur Ali | Analytical Chemistry - General; Bioengineering and Biotechnology; Cell and Molecular Biology | CC BY NC ND 4.0 | CHEMRXIV | 2020-03-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74888842e655375db2be7/original/microfluidic-microbioreactor-to-reduce-the-cost-and-speed-up-optimisation-of-protein-production.pdf |
669c0e9d01103d79c5b46d7b | 10.26434/chemrxiv-2024-2h0fw | AlzyFinder Platform: A web-based tool for machine-learning based virtual screening and network pharmacology | Alzheimer’s disease (AD), a prevalent neurodegenerative disorder, presents significant challenges in drug development due to its multifactorial nature. The AlzyFinder Platform presented here addresses this by providing a comprehensive, free web-based tool for ligand-based virtual screening and network pharmacology, specifically targeting over 85 key proteins implicated in AD. Utilizing advanced machine learning models, AlzyFinder facilitates the identification of potential multitarget ligands and their systemic therapeutic impacts. The platform's user-friendly interface allows for various input methods, including SMILES format and a molecular editor. AlzyFinder outputs interaction data in multiple formats (tables, heatmaps, and interactive Ligand-Protein Interaction networks) enhancing the visualization and analysis of drug-protein interactions. Key machine learning models employed by AlzyFinder, were meticulously trained and validated using robust methodologies, ensuring high predictive accuracy. Machine Learning models were built with XGBoost algorithm, optimized through Optuna and evaluated based on balanced accuracy, precision, and F1 score metrics. A unique soft-voting ensemble approach further refines the classification process, integrating the strengths of individual models. Validation included extensive testing with active, inactive, and decoy molecules, demonstrating the platform’s efficacy in distinguishing active compounds.
AlzyFinder’s innovative approach extends beyond traditional virtual screening by incorporating network pharmacology analysis, thus providing insights into the systemic actions of drug candidates. This feature allows for the exploration of ligand-protein and protein-protein interactions and their extensions, offering a comprehensive view of potential therapeutic impacts. As the first open-access platform of its kind, AlzyFinder stands as a valuable resource for the AD research community, available at http://www.alzyfinder-platform.udec.cl with supporting data and scripts accessible via GitHub https://github.com/ramirezlab/AlzyFinder. In this work as case of study we screened 5 molecules recently reported as active compounds against five key AD targets. We observe that AlzyFinder was able to accurately predict (with a probability greater than 0.70) all five molecules as true positives.
| Jessica Valero-Rojas; Camilo Ramírez; Laura Pacheco-Paternina; Paulina Valenzuela-Hormazabal; Paula Santana; Janneth González; Tatiana Gutiérrez-Bunster; Alejandro Valdés-Jiménez; David Ramírez | Theoretical and Computational Chemistry | CC BY 4.0 | CHEMRXIV | 2024-07-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/669c0e9d01103d79c5b46d7b/original/alzy-finder-platform-a-web-based-tool-for-machine-learning-based-virtual-screening-and-network-pharmacology.pdf |
66f98014cec5d6c14299e69b | 10.26434/chemrxiv-2024-02ctf | Intermolecular Formal [8+3] Cycloaddition of Azaheptafulvene with Bicyclo[1.1.0]butanes Promoted by Lewis Acids | Azaheptafulvenes reacting with bicyclo[1.1.0]butanes (BCBs) through FeCl3 or Sc(OTf)3-promoted formal [8+3] cycloaddition reactions to furnish Nitrogen-containing polycyclic compounds has been developed for the first time. This new reaction tolerated a wide range of azaheptafulvenes and BCBs. Furthermore, the amplification experiments and synthetic transformations of the cycloaddition compounds further highlighted its practicality. | Shi-Wu Li; Shijie Zhu; Jiaojiao Lei | Organic Chemistry; Organic Synthesis and Reactions; Stereochemistry | CC BY 4.0 | CHEMRXIV | 2024-10-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66f98014cec5d6c14299e69b/original/intermolecular-formal-8-3-cycloaddition-of-azaheptafulvene-with-bicyclo-1-1-0-butanes-promoted-by-lewis-acids.pdf |
60c74c1cee301cbd28c79fe3 | 10.26434/chemrxiv.12430082.v1 | A manganese(II)-Based Responsive Contrast Agent Detects Glucose- Stimulated Zinc Secretion from the Mouse Pancreas and Prostate by MRI. | A Mn(II)-based zinc-sensitive MRI contrast agent, Mn(PyC3A)-BPEN, was prepared and
characterized and the agent was used in imaging experiments to detect
glucose-stimulated zinc secretion (GSZS) from the mouse pancreas and prostate <i>in vivo</i>. Thermodynamic and kinetic
stability tests showed that Mn(PyC3A-BPEN) has superior kinetic inertness
compared to Gd(DTPA), is less susceptible to transmetallation in the presence
of excess Zn<sup>2+</sup>
ions, and less susceptible to transchelation by albumin. In comparison with other gadolinium-based
zinc sensors bearing a single zinc binding moiety, Mn(PyC3A-BPEN) appears to be a reliable alternative for imaging b-cell function in the pancreas and
glucose-stimulated zinc secretion from prostate cells. | Sara Chirayil; Veronica Clavijo-Jordan; Andre F. Martins; Namini Paranawithana; James Soundrarajan; Dean Sherry | Bioinorganic Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74c1cee301cbd28c79fe3/original/a-manganese-ii-based-responsive-contrast-agent-detects-glucose-stimulated-zinc-secretion-from-the-mouse-pancreas-and-prostate-by-mri.pdf |
60c75338bb8c1a55243dbfd7 | 10.26434/chemrxiv.13129910.v3 | Resolving impurities in atomic layer deposited aluminum nitride through low cost, high efficiency precursor design | Synthesis, characterization, and use of an amidoalane precursor for the deposition of high-quality and low-impurity aluminum nitride films by atomic layer deposition. This study highlights the importance of smart precursor design in order to deposit high-quality thin films at low cost and high efficiency. | Sydney Buttera; Polla Rouf; Petro Deminskyi; Nathan O'Brien; Henrik Pedersen; Sean Barry | Thin Films; Main Group Chemistry (Inorg.); Physical and Chemical Processes; Surface; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-12-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75338bb8c1a55243dbfd7/original/resolving-impurities-in-atomic-layer-deposited-aluminum-nitride-through-low-cost-high-efficiency-precursor-design.pdf |
60c74bff567dfeca0bec508b | 10.26434/chemrxiv.12410093.v1 | Synthesis of Decaarylanthracene with Nine Different Substituents | A synthesis of decaarylanthracene with nine different substituents has been accomplished by a coupling/ring-transformation strategy. The oxidation of tetraarylthiophenes with four different substituents to the corresponding thiophene <i>S</i>-oxides, and a [4+2] cycloaddition with a double benzyne precursor afforded a multiply arylated naphthalene derivative. Subsequently, the naphthalene derivative was converted into a naphthalyne, and then a [4+2] cycloaddition of another thiophene <i>S</i>-oxide provided decaarylanthracenes with nine different aryl groups. | Takashi Asako; Shin Suzuki; Shuhei Tanaka; Eisuke Ota; Junichiro Yamaguchi | Organic Synthesis and Reactions | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-03 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74bff567dfeca0bec508b/original/synthesis-of-decaarylanthracene-with-nine-different-substituents.pdf |
65507c892c3c11ed713c746b | 10.26434/chemrxiv-2023-b786t | Quantitative Measurement of Cation-Mediated Adhesion of DNA to Anionic Surfaces | Anionic polyelectrolytes, such as DNA, are attracted to anionic surfaces in the presence of multivalent cations. A major barrier toward molecular-level understanding of these attractive interactions is the paucity of measurements of the binding strength. Here, atomic force microscopy-based single molecule force spectroscopy was used to quantify the binding free energy of double-stranded DNA to an anionic surface, with complementary density functional theory calculations of the binding energies of metal ion-ligand complexes. The results support both electrostatic attraction and ion-specific binding. Our study suggests that the correlated interactions between counterions are responsible for attraction between DNA and an anionic surface, but the strength of this attraction is modulated by the identity of the metal ion. We propose a mechanism in which the strength of metal-ligand binding, as well as the preference for particular binding sites, influence both the concentration dependence and the strength of the DNA-surface interactions. | Xian Hao; Qufei Gu; Christine Isborn; Makenzie Long; Tao Ye | Materials Science; Nanostructured Materials - Materials | CC BY NC ND 4.0 | CHEMRXIV | 2023-11-16 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/65507c892c3c11ed713c746b/original/quantitative-measurement-of-cation-mediated-adhesion-of-dna-to-anionic-surfaces.pdf |
60c74da3842e658310db34d4 | 10.26434/chemrxiv.12501734.v2 | Unraveling the SARS-CoV-2 Main Protease Mechanism Using Multiscale DFT/MM Methods | <p>We present a detailed theoretical analysis of the reaction mechanism of proteolysis catalyzed by the main protease of SARS-CoV-2. Using multiscale simulation methods, we have characterized the interactions stablished by a peptidic substrate in the active site and then we have explored the free energy landscape associated to the acylation and de-acylation steps of the proteolysis reaction, characterizing the transition states of the process. Our mechanistic proposals can explain most of the experimental observations made on the highly similar ortholog protease of SARS-CoV. We point out to some key interactions that may facilitate the acylation process and thus can be crucial in the design of more specific and efficient inhibitors of the main protease activity. In particular, from our results, the P1’ residue can be a key factor to improve the thermodynamics and kinetics of the inhibition process.</p> | Carlos A. Ramos-Guzmán; J. Javier Ruiz-Pernía; Iñaki Tuñón | Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74da3842e658310db34d4/original/unraveling-the-sars-co-v-2-main-protease-mechanism-using-multiscale-dft-mm-methods.pdf |
60c7597c0f50dbd5443986ba | 10.26434/chemrxiv.14703450.v1 | Mixed-Metal Cu-Zn Thiocyanate Coordination Polymers with Melting Behavior, Glass Transition, and Tunable Electronic Properties | <p>The
solid-state mechanochemical reactions under ambient conditions of CuSCN and Zn(SCN)<sub>2</sub>
resulted in two novel materials: partially Zn-substituted <i>α</i>-CuSCN and a
new phase Cu<sub>x</sub>Zn<sub>y</sub>(SCN)<sub>x+2y</sub>. The reactions take
place at the labile S-terminal, and both products show melting and glass
transition behaviors. The optical band gap and solid-state ionization potential
can be adjusted systematically by adjusting the Cu:Zn ratio. Density functional
theory calculations also reveal that the Zn-substituted CuSCN structure
features a complementary electronic structure of Cu 3<i>d</i> states at the valence
band maximum (VBM) and Zn 4<i>s</i> states at the conduction band minimum
(CBM). This work shows a new route to develop semiconductors based on
coordination polymers which are becoming technologically relevant for
electronic and optoelectronic applications.</p> | Chayanit Wechwithayakhlung; Suttipong Wannapaiboon; Sutassana Na-Phattalung; Phisut Narabadeesuphakorn; Similan Tanjindaprateep; Saran Waiprasoet; Satoshi Horike; Pichaya Pattanasattayavong | Coordination polymers; Coordination Chemistry (Inorg.); Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7597c0f50dbd5443986ba/original/mixed-metal-cu-zn-thiocyanate-coordination-polymers-with-melting-behavior-glass-transition-and-tunable-electronic-properties.pdf |
66a99d8501103d79c54aec7e | 10.26434/chemrxiv-2023-hs9n1-v2 | Design Green Chemicals by Predicting Vaporization Properties Using Explainable Graph Attention Networks | Computational predictions of vaporization properties aid the de novo design of green chemicals, including clean alternative fuels, working fluids for efficient thermal energy recovery, and polymers that are easily degradable and recyclable. Here, we developed chemically explainable graph attention networks to predict five physical properties pertinent to performance in utilizing renewable energy: heat of vaporization (HoV), critical temperature, flash point, boiling point, and liquid heat capacity. The predictive model for HoV was trained using ~150,000 data points, considering their uncertainties and temperature dependence. Next, this model was expanded to the other properties through transfer learning to overcome the limitations due to fewer data points (700-7,500). The chemical interpretability of the model was then investigated, demonstrating that the model explains molecular structural effects on vaporization properties. Finally, the developed predictive models were applied to design chemicals that have desirable properties as efficient and green working fluids, fuels, and polymers, enabling fast and accurate screening before experiments. | Yeonjoon Kim; Jaeyoung Cho; Hojin Jung; Lydia E. Meyer; Gina M. Fioroni; Christopher D. Stubbs; Keunhong Jeong; Robert L. McCormick; Peter C. St. John; Seonah Kim | Theoretical and Computational Chemistry; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-08-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a99d8501103d79c54aec7e/original/design-green-chemicals-by-predicting-vaporization-properties-using-explainable-graph-attention-networks.pdf |
61d385149efae7806e308f50 | 10.26434/chemrxiv-2021-cqh6c-v2 | Using Machine Learning to Greatly Accelerate
Path Integral Ab Initio Molecular Dynamics | Ab initio molecular dynamics (AIMD) has become one of the most popular and robust approaches for modeling complicated chemical, liquid, and material systems. However, the formidable computational cost often limits its widespread application in simulations of the largest scale
systems. The situation becomes even more severe in cases where the hydrogen nuclei may be better described as quantized particles using a path integral representation. Here, we present a computational approach that combines machine learning with recent advances in path integral
contraction schemes, and we achieve a two-orders-of-magnitude acceleration over direct path integral AIMD simulation while at the same time maintaining its accuracy. | Chenghan Li; Gregory A. Voth | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61d385149efae7806e308f50/original/using-machine-learning-to-greatly-accelerate-path-integral-ab-initio-molecular-dynamics.pdf |
60c74e45ee301c5b95c7a48d | 10.26434/chemrxiv.12727982.v1 | Cation Distributions and Magnetic Properties of Ferrispinel MgFeMnO4 | The research deals with spinel compounds MgFeMnO<sub>4</sub>, which is known as a cathode material of magnesium battery. It exhibits a cationic disordering in cubic spinel structure and ferrimagnetism at room-temperature. The experimental data is acquired using a combination of magnetization, Mössbauer spectroscopy measurements, powder diffractions and muon spin rotation, relaxation and resonance (μ<sup>+</sup>SR) techniques. <br /> | Nami Matsubara; Titus Masese; Emmanuelle Suard; Ola Kenji Forslund; Elisabetta Nocerino; rasmus palm; Zurab Guguchia; Daniel Andreica; Alexandra Hardut; Motoyuki Ishikado; Konstantinos Papadopoulos; Yasmine Sassa; Martin Månsson | Solid State Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74e45ee301c5b95c7a48d/original/cation-distributions-and-magnetic-properties-of-ferrispinel-mg-fe-mn-o4.pdf |
62b99b4d486c986797b59360 | 10.26434/chemrxiv-2022-gwf1r | Bulky Iridium NHC Complexes for Bright, Efficient Deep-Blue OLEDs | Four new deep-blue-emitting iridium(III) NHC complexes containing sterically demanding ligands have been synthesised. The four complexes showed bright, deep-blue emission, with emission maxima between 420 and 427 nm in both acetonitrile solution and 30 wt% doped films in TSPO1; the two meridional isomers showing photoluminescence quantum yields, ΦPL, in doped films of 80 and 89%. The two meridional isomers have been used to assess the impact of emitters containing bulky, sterically demanding ligands on the performance of organic light-emitting diodes (OLEDs). OLEDs employing a stepped doping profile with mer-Ir(tfpi_tmBn)3 as the emitter produced the highest performing devices in this study, with these devices exhibiting deep-blue [λEL = 429 nm, CIE = (0.16, 0.08)] emission and a maximum external quantum efficiency (EQEmax) of 14.9%, which decreased to 11.7% at 100 cd m-2. The performance of the OLEDs is amongst the highest efficiencies and lowest efficiency roll-offs reported for phosphorescent deep-blue OLEDs with CIEy ≤ 0.08, as required for commercial displays. | Campbell Mackenzie; Le Zhang; David Cordes; Alexandra Slawin; Ifor Samuel; Eli Zysman-Colman | Physical Chemistry; Inorganic Chemistry; Organometallic Chemistry; Coordination Chemistry (Organomet.); Ligand Design; Spectroscopy (Organomet.) | CC BY 4.0 | CHEMRXIV | 2022-06-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/62b99b4d486c986797b59360/original/bulky-iridium-nhc-complexes-for-bright-efficient-deep-blue-ole-ds.pdf |
679b0f11fa469535b9643ab7 | 10.26434/chemrxiv-2025-9hcdq | Development of Parallel On-the-Fly Crystal Algorithm for Reaction Discovery in Large and Complex Molecular Systems | The parallel on-the-fly Crystal algorithm is a new, efficient global search algorithm that has found utility in exploring the single-state potential energy surfaces and conical intersection seam spaces of a wide range of molecules in the gas phase. Despite its major developments, its application to complex molecular systems, especially in the condensed phase, remains challenging due to the high dimensionality of the configurational space. In this work, we address this challenge and extend its applicability to the reaction discovery of large, complex molecular photoswitches in the condensed phase. This is achieved by improved search algorithms that facilitate the exploration of a comparatively large Crystal configurational subspace while relaxing the other degrees of freedom. The new Crystal algorithm is applied to bilirubin and a next-generation class of molecular photoswitches in the vacuum and the aqueous solution environment in a quantum mechanics/molecular mechanics (QM/MM) setting. We designed an automatic and systematic workflow to discover previously unreported minima and low-energy reaction pathways and analyze them with a focus on the low-energy spectrum. Our findings reveal the algorithm's effectiveness in quickly exploring the configuration space, uncovering new product minima that are kinetically accessible, which provides new insights into the intricate chemical reactivities of these molecules. The results underscore the promising potential of parallelized global exploration methods in reaction discovery in biomolecular systems. | Ankit Pandey; Gustavo J. Costa; Alam Mushfiq; Bill Poirier; Ruibin Liang | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2025-01-31 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/679b0f11fa469535b9643ab7/original/development-of-parallel-on-the-fly-crystal-algorithm-for-reaction-discovery-in-large-and-complex-molecular-systems.pdf |
60c73e15469df44d8bf427f2 | 10.26434/chemrxiv.6394430.v1 | Design and Evaluation of Heterobivalent PAR1–PAR2 Ligands as Antagonists of Calcium Mobilization | A novel class of bivalent ligands targeting putative Protease-Activated Receptor (PAR) heteromers has been prepared based upon reported antagonists for the subtypes PAR1 and PAR2. Modified versions of the PAR1 antagonist RWJ-58259 containing alkyne adapters were connected via cycloaddition reactions to azide-capped polyethylene glycol (PEG) spacers attached to imidazopyridazine-based PAR2 antagonists. Initial studies of the PAR1–PAR2 antagonists indicated that they inhibited G alpha q-mediated calcium mobilization in endothelial and cancer cells driven by both PAR1 and PAR2 agonists. Compounds of this novel class hold promise for the prevention of restenosis, cancer cell metastasis, and other proliferative disorders.<br /> | Mark W. Majewski; Disha M. Gandhi; Ricardo Rosas; Chris Dockendorff | Bioorganic Chemistry; Organic Synthesis and Reactions; Cell and Molecular Biology; Chemical Biology; Drug Discovery and Drug Delivery Systems | CC BY NC ND 4.0 | CHEMRXIV | 2018-06-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73e15469df44d8bf427f2/original/design-and-evaluation-of-heterobivalent-par1-par2-ligands-as-antagonists-of-calcium-mobilization.pdf |
6538115dc3693ca993085415 | 10.26434/chemrxiv-2023-cmws5 | To flame-seal or not to the NMR tubes: The role of liquid-vapor equilibria on the accuracy of variable temperature experiments. | In NMR experiments, it is crucial to control the temperature of the sample, especially when measuring kinetic parameters. Usually, it takes two to five minutes for the temperature of the sample inside the NMR probe to stabilize at a fixed value set for the experiment. However, in some cases, the NMR sample tubes are flame-sealed, such as when working with volatile solvents, atmosphere-sensitive samples, or calibration samples for long-term use. When these samples are placed inside the NMR probe, the spectrometer controls the lower portion (liquid phase) of the NMR sample tube with a gas flow at a fixed temperature, while the upper portion (vapor) is at ambient temperature. This probe design creates a unique temperature gradient across the sample, leading to vapor pressure build-up, particularly inside a sealed NMR tube. By analyzing the temperature-dependent line shape changes of a chemical exchange process, we report that under standard experimental conditions, the sample temperature can take up to two to three hours (instead of minutes) to stabilize. The time scale of the liquid-vapor equilibrium process is much slower, with a half-life exceeding 35 minutes, in contrast to the two-minute duration required to obtain each spectrum. As a result, each spectrum represents the time-averaged status of the double bond rotation observable from the liquid phase of the sample. This phenomenon is exclusively due to the liquid-vapor equilibrium process of the flame-sealed NMR tube and is not observable otherwise. | Derek Morrelli; santanu Maitra; Krish Krishnan | Physical Chemistry; Analytical Chemistry; Physical and Chemical Properties; Spectroscopy (Physical Chem.); Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2023-10-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6538115dc3693ca993085415/original/to-flame-seal-or-not-to-the-nmr-tubes-the-role-of-liquid-vapor-equilibria-on-the-accuracy-of-variable-temperature-experiments.pdf |
649bf5039ea64cc1671b1ea3 | 10.26434/chemrxiv-2023-gr155-v2 | Which boronic acids are used most frequently for synthesis of bioactive molecules ? | Boronic acids are essential building blocks used for the synthesis of bioactive molecules, the generation of chemical libraries and the exploration of structure-activity relationships. As a result, more than ten thousand boronic acids are commercially available. Medicinal chemists are therefore facing a challenge; which of them should they select to maximize information obtained by the synthesis of new target molecules. The present article aims to help them to make the right choices. The boronic acids used frequently in the synthesis of bioactive molecules were identified by mining several large molecular and reaction databases and their properties were analyzed. Based on the results a diverse set of boronic acids covering well the bioactive chemical space was selected and is suggested as a basis for library design for the efficient exploration of structure-activity relationships. A Boronic Acid Navigator web tool which helps chemists to make their own selection is also made available at https://bit.ly/boronics.
| Peter Ertl; Eva Altmann; Sophie Racine; Odile Decoret | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-06-28 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/649bf5039ea64cc1671b1ea3/original/which-boronic-acids-are-used-most-frequently-for-synthesis-of-bioactive-molecules.pdf |
60c74d55469df46d13f44278 | 10.26434/chemrxiv.12612026.v1 | Dynamic Chiral Cyclohexanohemicucurbit[12]uril | <div>This research with title "Dynamic chiral cyclohexanohemicucurbit[12]uril" is<i> dedicated to the memory of late Professor Hans J. Reich.</i></div><br /><div><i>Abstract:</i></div>NMR and DFT studies of chiral
cyclohexanohemicucurbit[12]uril indicate that the macrocycle adopts a concave
octagon shape with three distinct ranges of conformational flexibility in
solution. Methylene bridge flipping occurs at temperatures above 265 K, while
urea monomers rotate at
temperatures above 308 K resulting in the loss
of confined space within the macrocycle. | Kamini A. Mishra; Jasper Adamson; Mario Öeren; Sandra Kaabel; Maria Fomitšenko; Riina Aav | Physical Organic Chemistry; Supramolecular Chemistry (Org.); Spectroscopy (Physical Chem.); Structure; Thermodynamics (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-06 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d55469df46d13f44278/original/dynamic-chiral-cyclohexanohemicucurbit-12-uril.pdf |
6584409fe9ebbb4db96d838b | 10.26434/chemrxiv-2023-m908q | Scalable Quasi-divided Cell Operation using Spinning Cylinder Electrode Technology: Multigram Electrochemical Synthesis of an Axinitib Intermediate | Electrochemical synthesis of a key thiol intermediate in the preparation of axitinib has been achieved on a multi-10 gram scale using a modified spinning cylinder electrode reactor adapted for “quasi-divided” cell operation. This concept enables the target cathodic reduction to take place without the need for sacrificial electrodes or divided cells equipped with ion exchange membranes. The new reactor design, based on a scalable platform, features an inner spinning cathode made of leaded bronze and reactor vessel to which a variable number of counter electrode rods can be attached. This setup permits a high flexibility in the cathode/anode surface area ratio required for “quasi-divided” cell operation. The setup has been shown to provide excellent yields for the target thiol intermediate in batch and flow recirculation modes. Continuous operation using a cascade of three reactors has also been demonstrated. | Bhanwar K. Malviya; Eric C. Hansen; Caleb J. Kong; Joseph Imbrogno; Jenson Verghese; Steven M. Guinness; Chase A. Salazar; Jean-Nicolas Desrosiers; C. Oliver Kappe; David Cantillo | Organic Chemistry; Organic Synthesis and Reactions; Process Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-12-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6584409fe9ebbb4db96d838b/original/scalable-quasi-divided-cell-operation-using-spinning-cylinder-electrode-technology-multigram-electrochemical-synthesis-of-an-axinitib-intermediate.pdf |
64a729fb6e1c4c986beec64b | 10.26434/chemrxiv-2022-sq34x-v3 | Designing solvent systems in chemical processes using self-evolving solubility databases and graph neural networks | Designing solvent systems is key to achieving the facile synthesis and separation of desired products from chemical processes, so many machine learning models have been developed to predict solubilities. However, breakthroughs are needed to address deficiencies in the model’s predictive accuracy and generalizability; this can be addressed by expanding and integrating experimental and computational solubility databases. To maximize predictive accuracy, these two databases should not be trained separately, and they should not be simply combined without reconciling the discrepancies from different magnitudes of errors and uncertainties. Here, we introduce self-evolving solubility databases and graph neural networks developed through semi-supervised self-training approaches. Solubilities from quantum-mechanical calculations are referred to during semi-supervised learning, but they are not directly added to the experimental database. Dataset augmentation is performed from 11,637 experimental solubilities to >900,000 data points in the integrated database, while correcting for the discrepancies between experiment and computation. Our model was successfully applied to study solvent selection in organic reactions and separation processes. The accuracy (mean absolute error around 0.2 kcal/mol for the test set) is quantitatively useful in exploring Linear Free Energy Relationships between reaction rates and solvation free energies for 11 organic reactions. Our model also accurately predicted the partition coefficients of lignin-derived monomers and drug-like molecules. We anticipate this approach will be attractive to other areas of predictive chemistry where experimental, computational, and any other heterogeneous data sources should be combined. | Yeonjoon Kim; Hojin Jung; Sabari Kumar; Robert S. Paton; Seonah Kim | Theoretical and Computational Chemistry; Physical Chemistry; Organic Chemistry; Computational Chemistry and Modeling; Machine Learning; Chemoinformatics - Computational Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64a729fb6e1c4c986beec64b/original/designing-solvent-systems-in-chemical-processes-using-self-evolving-solubility-databases-and-graph-neural-networks.pdf |
67d88f95fa469535b98f33d7 | 10.26434/chemrxiv-2025-419nt | Fourier transform data analysis for mass spectra of small polymers and pyrolysates with accurate-mass data and mass defect preprocessing. | Early applications of Fourier transform (FT) data analysis of polymer mass spectra made use of nominal-mass spectra to determine the monomer mass. More recently, FT data analysis has been applied to the interpretation of the unresolved envelope in complex electrospray ionization mass spectra of ionic polymers and macromolecules. Here, FT data analysis is applied to determine the monomer composition for isotopically resolved accurate-mass MALDI, pyrolysis DART, and PaperSpray mass spectra of synthetic homopolymers, copolymers, and polymer mixtures. Monomer compositions are determined from the transformed data by accurate mass search and elemental composition calculations. Data analysis is facilitated for complex mass spectra containing multiple polymers, multiple charge states, and nonperiodic fragments by graphically selecting individual series from mass defect plots. | Robert Cody | Analytical Chemistry; Polymer Science; Organic Polymers; Analytical Chemistry - General; Mass Spectrometry; Materials Chemistry | CC BY NC 4.0 | CHEMRXIV | 2025-03-19 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67d88f95fa469535b98f33d7/original/fourier-transform-data-analysis-for-mass-spectra-of-small-polymers-and-pyrolysates-with-accurate-mass-data-and-mass-defect-preprocessing.pdf |
645004b06ee8e6b5ed6b505a | 10.26434/chemrxiv-2021-xhhbv-v7 | Actual Molecule of Benzene and its Resonance Structures: An Explanation Using the Analogy of a Macro Entity and Its Sketches | Confusion about basic concepts is common among many students in the early stages of education in all areas, which later diminished as they gained more advance knowledge of their subject. This study focuses on the most important fundamental concept in chemistry i.e., namely “Molecular Resonance Phenomena” to explain the benzene molecular structure and its canonical forms. Enormous literature available on the subject; However, chemistry students still find it difficult to understand the difference between a real molecular entity and its proposed sketch or model early in their learning. To solve this problem macro entities and their sketch analogies were used in front of students and found to be more effective. A tough or difficult topic in the lecture can be simplified by a suitable analogy with minimal resources. | Faiz Ahmed; Sohail Shahzad | Organic Chemistry; Chemical Education; Organic Compounds and Functional Groups; Chemical Education - General | CC BY NC ND 4.0 | CHEMRXIV | 2023-05-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/645004b06ee8e6b5ed6b505a/original/actual-molecule-of-benzene-and-its-resonance-structures-an-explanation-using-the-analogy-of-a-macro-entity-and-its-sketches.pdf |
675fee0ffa469535b9cd0d41 | 10.26434/chemrxiv-2024-0z7g6 | Overcoming DMTA Cycle Challenges: A Unified AI-Driven System for Efficient Drug Design | The integration of artificial intelligence (AI) and machine learning (ML) in drug design has the potential to transform small molecule drug discovery in the pharmaceutical industry, enhancing the efficiency and productivity of the drug design and discovery process. However, the manual and segmented nature of the Design, Make, Test, Analyze (DMTA) cycle is a major obstacle to any significant progress being made. The design of synthetically tractable molecules that meet project specific criteria requires a comprehensive system capable of accounting simultaneously for all synthetic constraints as well as bioactivity and physicochemical properties in order to reach an optimal outcome. The development of such an AI system is complex, requiring the integration of diverse technologies and expertise synergistically. This article outlines our vision and efforts towards the development of a unified system in which AI, ML, computational chemistry, organic chemistry, biology and human expertise converge to drive innovation in drug discovery. | Matthew Medcalf; Varsha Jain; Stefani Gamboa; Brian Atwood; Maoussi Lhuillier-Akakpo; Victoire Cachoux; Quentin Perron | Theoretical and Computational Chemistry; Biological and Medicinal Chemistry; Drug Discovery and Drug Delivery Systems; Computational Chemistry and Modeling; Artificial Intelligence | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/675fee0ffa469535b9cd0d41/original/overcoming-dmta-cycle-challenges-a-unified-ai-driven-system-for-efficient-drug-design.pdf |
60c759be4c8919ff44ad4e32 | 10.26434/chemrxiv.14729445.v1 | SCONES: Self-Consistent Neural Network for Protein Stability Prediction Upon Mutation | <div>Engineering proteins to have desired properties by mutating amino acids at specific sites is commonplace. Such engineered proteins must be stable to function. Experimental methods used to determine stability at throughputs required to scan the protein sequence space thoroughly are laborious. To this end, many machine learning based methods have been developed to predict thermodynamic stability changes upon mutation. These methods have been evaluated for symmetric consistency by testing with hypothetical reverse mutations. In this work, we propose transitive data augmentation, evaluating transitive consistency, and a new machine learning based method, first of its kind, that incorporates both symmetric and transitive properties into the architecture. Our method, called SCONES, is an interpretable neural network that estimates a residue's contributions towards protein stability dG in its local structural environment. The difference between independently predicted contributions of the reference and mutant residues in a missense mutation is reported as dG. We show that this self-consistent machine learning architecture is immune to many common biases in datasets, relies less on data than existing methods, and is robust to overfitting.</div><div><br /></div> | Yashas Samaga B L; Shampa Raghunathan; U. Deva Priyakumar | Biochemistry; Bioengineering and Biotechnology; Bioinformatics and Computational Biology; Computational Chemistry and Modeling; Machine Learning; Artificial Intelligence | CC BY NC ND 4.0 | CHEMRXIV | 2021-06-04 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c759be4c8919ff44ad4e32/original/scones-self-consistent-neural-network-for-protein-stability-prediction-upon-mutation.pdf |
662c2744418a5379b0d2d9af | 10.26434/chemrxiv-2024-79678 | A new synthesis of the amine fragment: an important intermediate to the anti-HIV drug lenacapavir | Herein, we describe a new five-step approach to prepare 1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethan-1-amine, an important intermediate in the synthesis of lenacapavir. The key step in the sequence is the Weinreb amide-based ketone synthesis, which provides an alternative entry point to the core structural component. Starting from the inexpensive 2-(3,5-difluorophenyl)acetic acid, the Weinreb amide synthesis and the followed nucleophilic substitution afford the ketone in 47% yield. The subsequent functional group manipulation delivers the racemic amine which can be resolved with known mandelic acid resolution. This synthetic route has been demonstrated on decagram scale and affords the racemic amine in an overall isolated yield of 25%. | Anand Shinde; Ramakrishna Sayini; Piyal Singh; Justina Burns; Saeed Ahmad; George Laidlaw; Frank Gupton; Douglas Klumpp; limei jin | Organic Chemistry; Organic Compounds and Functional Groups; Organic Synthesis and Reactions; Process Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-05-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/662c2744418a5379b0d2d9af/original/a-new-synthesis-of-the-amine-fragment-an-important-intermediate-to-the-anti-hiv-drug-lenacapavir.pdf |
6707f8b2cec5d6c142ca5846 | 10.26434/chemrxiv-2024-5hc8g-v2 | A Hybrid Meta On-Top Functional for Multiconfiguration Pair-Density Functional Theory | Multiconfiguration pair-density functional theory (MC-PDFT) was proposed a decade ago, but it
is still in the early stage of density functional development. MC-PDFT uses functionals that are
called on-top functionals; they depend on the density and the on-top pair density. Most MCPDFT
calculations to date have been unoptimized translations of generalized gradient
approximations (GGAs) of Kohn–Sham density functional theory (KS-DFT). A hybrid MCPDFT
has also been developed, in which one includes a fraction of the CASSCF wave function
energy in the total energy. Meta-GGA functionals, which use kinetic-energy densities in addition
to GGA ingredients, have shown higher accuracy than GGAs in KS-DFT, yet the translation of
meta-GGA has not been previously proposed for MC-PDFT. In this paper, we propose a way to
include kinetic energy density in a hybrid on-top functional for MC-PDFT, and we optimize the
parameters of the resulting functional by training with a new database containing a wide variety
of systems with diverse characters. The resulting hybrid meta functional is called the MC23
functional. We find that MC23 has equally improved performance as compared to KS-DFT
functionals for both strongly and weakly correlated systems. We recommend MC23 for future
MC-PDFT calculations. | Jie J. Bao; Dayou Zhang; Shaoting Zhang; Laura Gagliardi; Donald Truhlar | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2024-10-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6707f8b2cec5d6c142ca5846/original/a-hybrid-meta-on-top-functional-for-multiconfiguration-pair-density-functional-theory.pdf |
60ddcc6af7373f002443f07b | 10.26434/chemrxiv-2021-qcw2s | Understanding and Overcoming Proximity Effects in Multi-Spot Two-Photon Direct Laser Writing | Although additive manufacturing using multi-photon direct laser writing is nowadays considered as a major tool in the fabrication of future nano/micro-objects and optical components, it is currently limited by the low throughput of the writing process. To circumvent this issue, massive parallelization of the write process is a very promising avenue. However, simultaneous writing of structures in close spatial proximity generates fabrication artefacts, collectively referred to as “proximity effects”, which strongly limit the accessible structure resolution. In this work, we systematically investigate the experimental parameters that influence these effects using specifically designed N×N spot diffractive optical elements. Through computer simulations, we show that these effects can be modeled remarkably successfully simply by taking Point Spread Function overlap and diffusion processes into account. We illustrate the usefulness of the concept by designing a parallel write approach giving access to periodic structures with short inter-object distances while very largely overcoming proximity effects. | Caroline Arnoux; Luis-Adrian Perez-Covarrubias; Alexandre Khaldi; Quentin Carlier; Patrice Baldeck; Kevin Heggarty; Akos Banyasz; Cyrille Monnereau | Polymer Science; Nanoscience; Organic Polymers; Nanofabrication; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2021-07-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60ddcc6af7373f002443f07b/original/understanding-and-overcoming-proximity-effects-in-multi-spot-two-photon-direct-laser-writing.pdf |
66a6e6e201103d79c517aaa6 | 10.26434/chemrxiv-2024-86jl2 | Highly Tolerant Living/Controlled Anionic Polymerization of Dialkyl Acrylamides Enabled by Zinc Triflate/Phosphine Lewis Pair | Living polymerizations of polar vinyl monomers have been successful for decades. However, they still suffer the following challenges: fast propagation, air/moisture tolerance, and negligible side reactions even at elevated temperatures. Here, we developed an unprecedented polymerization that overcomes these limitations using a Lewis pair catalyst. The anionic polymerization of dialkyl acrylamides proceeded in a living/controlled matter using Zn(OTf)2/PPh3 within a wide temperature range of 25–100 °C for short times (1–10 min) even under open-air conditions. The recovery and reuse of Zn(OTf)2 without loss of polymerization activity were observed to be possible. The polymerization was retarded by excess Zn(OTf)2, additive methanol, and water, indicating equilibriums of the propagating species with them. The putative propagating zinc triflate-ate complex was tolerant to the protic additives and significantly selective for the propagation. | Riki Akita; Shin-ichi Matsuoka | Organic Chemistry; Catalysis; Polymer Science; Polymerization catalysts | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66a6e6e201103d79c517aaa6/original/highly-tolerant-living-controlled-anionic-polymerization-of-dialkyl-acrylamides-enabled-by-zinc-triflate-phosphine-lewis-pair.pdf |
67641b276dde43c9089e963e | 10.26434/chemrxiv-2024-4cb43-v2 | A guide to reverse metabolomics – a framework for big data discovery strategy. | Untargeted metabolomics is evolving into a field of big data science. There is a growing interest within the metabolomics community in mining MS/MS-based data from public repositories. The theme of this protocol, reverse metabolomics, is a data science strategy that differs from the traditional LC-MS/MS-based untargeted metabolomics approach. In traditional untargeted metabolomics, we first collect the samples to address a predefined question and then collect LC-MS/MS data. We then identify metabolites associated with a phenotype (e.g., disease vs. healthy), and elucidate or validate their structural details (e.g., molecular formula, structural classification, substructure, or complete structural annotation or identification). Reverse metabolomics, however, does not necessarily involve collecting new data or requiring the structural characterization of molecules. Instead, we start with MS/MS spectra for known or unknown molecules and discover phenotype-relevant information such as organ/biofluid distribution, disease condition, intervention status (e.g., pre- and post-intervention), organisms (e.g., mammals vs. others), geography, and any other biologically relevant associations available in public repositories. This protocol guides the reader through the step-by-step process of utilizing available MS/MS data and discovering repository-scale associations of the associated MS/MS spectra. As example, we utilize MS/MS spectra from three small molecules: phenylalanine-cholic acid (a microbially conjugated bile acid), phenylalanine-C4:0, and histidine-C4:0 (two N-acyl amides). We leverage the GNPS-based framework to explore the microbial producers of these molecules and their associations with health conditions and organ distributions in humans and rodents. | Vincent Charron-Lamoureux; Helena Mannochio-Russo; Santosh Lamichhane; Shipei Xing; Abubaker Patan; Paulo Wender Portal Gomes; Prajit Rajkumar; Victoria Deleray; Andrés Mauricio Caraballo-Rodriguez; Kee Voon Chua; Lye Siang Lee; Zhao Liu; Jianhong Ching; Mingxun Wang; Pieter C. Dorrestein | Analytical Chemistry; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67641b276dde43c9089e963e/original/a-guide-to-reverse-metabolomics-a-framework-for-big-data-discovery-strategy.pdf |
66754df3c9c6a5c07a057ef5 | 10.26434/chemrxiv-2024-r3nsd | Regio- and Enantioselective N-Heterocyclic Carbene-Catalyzed Annulation of Aminoindoles Initiated by Friedel-Crafts Alkylation | Chiral annulated indoles are unique molecules with numerous examples of this structural motif in natural and medicinally relevant compounds. However, accessing these enantioenriched molecules, particularly indoles annulated on the benzene ring, has been limited and often overlooked. This study presents a highly efficient organocatalytic protocol for synthesizing chiral annulated indoles. The efficiency of the developed methodology is demonstrated by its broad substrate scope, excellent functional group tolerance, and the use of only 1 mol% of a chiral conjugated acid of catalyst. Additionally, the study of the observed regioselectivity, gram-scale reaction, and various follow-up transformations underscore the potential of this method. | Vojtěch Dočekal; Yaroslava Niderer; Adam Kurčina; Ivana Císařová; Jan Veselý | Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Stereochemistry; Organocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2024-06-21 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66754df3c9c6a5c07a057ef5/original/regio-and-enantioselective-n-heterocyclic-carbene-catalyzed-annulation-of-aminoindoles-initiated-by-friedel-crafts-alkylation.pdf |
628654dd59f0d6448895ffff | 10.26434/chemrxiv-2022-x8s7x-v2 | Thiocyanate Ions Form Antiparallel Populations at the Concentrated Electrolyte / Charged Surfactant Interface | Anions play significant roles in the separation of lanthanides and actinides. The molecular-scale details of how these anions behave at aqueous interfaces are not well understood, especially at high ionic strengths. Here, we describe the interfacial structure of thiocyanate anions at a soft charged interface up to 5 M bulk concentration with combined classical and phase-sensitive vibrational sum frequency generation (PS-VSFG) spectroscopy, and molecular dynamics (MD) simulations. At low concentrations thiocyanate ions are mostly oriented with their sulfur end pointing towards the charged surfactants. VSFG signal reaches a plateau around 100 mM bulk concentration, followed by significant changes above 1 M. At high concentrations a new thiocyanate population emerges with their sulfur end pointing towards the bulk liquid. The -CN stretch frequency is different for up and down oriented SCN- ions, indicating different coordination environments. These results provide key molecular-level insights for the interfacial behavior of complex anions in highly concentrated solutions. | Raju R. Kumal; Pubudu N. Wimalasiri; Michael Servis; Ahmet Uysal | Theoretical and Computational Chemistry; Physical Chemistry; Theory - Computational; Interfaces; Spectroscopy (Physical Chem.) | CC BY NC ND 4.0 | CHEMRXIV | 2022-05-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/628654dd59f0d6448895ffff/original/thiocyanate-ions-form-antiparallel-populations-at-the-concentrated-electrolyte-charged-surfactant-interface.pdf |
64b4640eb053dad33a5f00ca | 10.26434/chemrxiv-2023-4l9cz | Molecular-Orbital Framework of Two-Electron Processes: Application to Auger and Intermolecular Coulomb Decay. | States with core vacancies, which are commonly created by absorption of X-ray photons, can decay by a two-electron process in which one electron fills the core hole and the second one is ejected. These processes accompany many X-ray spectroscopies. Depending on the nature of the initial core-hole state and the decay valence-hole states, these processes are called Auger decay, intermolecular Coulomb decay, or electron-transfer-mediated decay. To connect many-body wavefunctions of the initial and final states with molecular orbital picture of the decay, we introduce a concept of natural Auger orbitals (NAOs). NAOs are obtained by two-step singular value decomposition of the two-body Dyson orbitals, reduced quantities that enter the expression of the decay rate in the Feshbach--Fano treatment. NAOs afford chemical insight and interpretation of the high-level ab intio calculations of Auger decay and related two-electron relaxation processes. | Nayanthara Karippara Jayadev; Wojciech Skomorowski; Anna. I. Krylov | Theoretical and Computational Chemistry; Theory - Computational | CC BY NC ND 4.0 | CHEMRXIV | 2023-07-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64b4640eb053dad33a5f00ca/original/molecular-orbital-framework-of-two-electron-processes-application-to-auger-and-intermolecular-coulomb-decay.pdf |
6769a40a6dde43c9081bac97 | 10.26434/chemrxiv-2024-sd1wl-v4 | Non-Uniform Chiralization of Metal-Organic Frameworks Using Imine Chemistry | Homochiral metal-organic frameworks (MOFs) are exceptional media for heterogenous enantiodifferentation processes. Modifying available achiral structure-bearing MOF scaffolds is a preferred method to extend this class of materials. Reported postsynthetic covalent chiralizations generally lead to uniform, site-specific modifications. The use of chemically versatile modifying agents, like aldehydes, may instead result in the statistical formation of chemically non-uniform anchored products. In addition, use of such modifying agents gives rise to spatial non-uniformities in the radial direction, due to prohibited diffusion through the MOF bulk. The advantageous grain structure formation plus molecular non-uniformity greatly increase the complexity of such systems. The use of such modifying agents, therefore, necessitates a broader, holistic characterization. The present work explores the adaptation of imine chemistry for post-synthetic chiralization. A chiral aldehyde and a chiral ketone are probed on two amine-functionalized MOF substrates - MIL-125 NH2, and UiO-66 NH2. The UiO-66 NH2 modified with the natural product-derived (R)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde ((R)-1 aldehyde) is found to have the best performance in terms of reactivity and MOF stability. A comprehensive toolbox of methods was demonstrated to robustly characterize the obtained material. This includes high-resolution accurate mass electrospray ionization mass spectrometry (HRAM-ESI-MS) to reveal the competing reactions that yield a statistical set of oligomer-rich structures. In silico modeling correctly predicts the localization of the modification. The modification is found to be covalent, chiral, and mainly proceeding through imine formation, resulting in a surface enantioselector display formation. Restricted diffusion lengths in the solid phase infer good retention of resolving power in ascending van Deemter régimes in chromatography. Meeting this criterion makes the yielding material a promising potential stationary phase candidate for performant chromatographic enantioseparations. | Balázs Álmos Novotny; Sauradeep Majumdar; Andres Ortega-Guerrero; Kevin Maik Jablonka; Elias Moubarak; Natalia Gasilova; Nency P. Domingues; Raluca-Ana Kessler; Emad Oveisi; Fatmah Mish Ebrahim; Berend Smit | Theoretical and Computational Chemistry; Analytical Chemistry; Chemoinformatics; Mass Spectrometry; Separation Science; Materials Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-12-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6769a40a6dde43c9081bac97/original/non-uniform-chiralization-of-metal-organic-frameworks-using-imine-chemistry.pdf |
60c74d25567dfeecd7ec52d6 | 10.26434/chemrxiv.12592346.v1 | Semi-Supervised Machine Learning Enables the Robust Detection of Multireference Character at Low Cost | Multireference (MR) diagnostics are common tools for identifying strongly correlated electronic structure that makes single reference (SR) methods (e.g., density functional theory or DFT) insufficient for accurate property prediction. However, MR diagnostics typically require computationally demanding correlated wavefunction theory (WFT) calculations, and diagnostics often disagree or fail to predict MR effects on properties. To overcome these challenges, we introduce a semi-supervised machine learning (ML) approach with virtual adversarial training (VAT) of an MR classifier using 15 WFT and DFT MR diagnostics as inputs. In semi-supervised learning, only the most extreme SR or MR points are labeled, and the remaining point labels are learned. The resulting VAT model outperforms the alternatives, as quantified by the distinct property distributions of SR- and MR-classified molecules. To reduce the cost of generating inputs to the VAT model, we leverage the VAT model’s robustness to noisy inputs by replacing WFT MR diagnostics with regression predictions in a MR decision engine workflow that preserves excellent performance. We demonstrate the transferability of our approach to larger molecules and those with distinct chemical composition from the training set. This MR decision engine demonstrates promise as a low-cost, high-accuracy approach to the automatic detection of strong correlation for predictive high-throughput screening. | Chenru Duan; Fang Liu; Aditya Nandy; Heather Kulik | Computational Chemistry and Modeling; Theory - Computational; Machine Learning | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74d25567dfeecd7ec52d6/original/semi-supervised-machine-learning-enables-the-robust-detection-of-multireference-character-at-low-cost.pdf |
6400185332cd591f12b4e0f4 | 10.26434/chemrxiv-2023-pn7db | Bright, photostable, and long-circulating NIR-II nanoparticles for wholeprocess monitoring and evaluation of renal transplantation | Kidney transplantation is the gold standard for the treatment of end-stage renal disease (ESRD). However, the scarcity of kidneys has caused more and more ESRD patients being stuck on the waiting-list for surgery. Improving the survival rate of kidney grafts as much as possible is not only responsible for patients, but also an alternative solution to kidney shortage. Thus, rapid
diagnosis and timely management of surgical complications are of vital importance to the success
of renal transplantation but lack efficient methods and technologies. Herein, a fluorescence technology based on bright, photostable, and long-circulating aggregation-induced emission (AIE) active NIR-II nano contrast agent for the whole-process monitoring and evaluation of renal
transplantation has been reported. The outstanding optical property and long-circulating characteristic of the AIE NPs help to achieve renal angiography in the kidney retrieval surgery, donor kidney quality evaluation before transplantation, diagnosing vascular complications, and
assessment of renal graft reperfusion after revascularization, which considerably outperforms the
clinically approved indocyanine green (ICG). | Rongyuan Zhang; Ping Shen; Yu Xiong; Tianjing Wu; Gang Wang; Yucheng Wang; Liping Zhang; Han Yang; Wei He; Jian Du; Xuedong Wei; Siwei Zhang; Zijie Qiu; Weijie Zhang; Zheng Zhao; Ben Zhong Tang | Organic Chemistry; Nanoscience; Organic Synthesis and Reactions; Nanofabrication; Materials Chemistry | CC BY 4.0 | CHEMRXIV | 2023-03-02 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6400185332cd591f12b4e0f4/original/bright-photostable-and-long-circulating-nir-ii-nanoparticles-for-whole-process-monitoring-and-evaluation-of-renal-transplantation.pdf |
63725bae2079814ffe2631b0 | 10.26434/chemrxiv-2022-hxq55 | Thermodynamic, kinetic and dynamic aspects of biogas upgrading using nano-engineered grazynes | Different nano-engineered grazynes have been studied as possible membranes to separate methane (CH4) from carbon dioxide (CO2) by computational simulations based on density functional theory (DFT) and molecular dynamics (MD). The study focuses on the thermodynamics, kinetics, and dynamical aspects associated to the diffusion rates and selectivities in the context of biogas upgrading. Small adsorption energy values have been obtained for three semi-permeable grazynes, with low diffusion energy barriers below 1 eV and getting lower values as the grazyne pore increases. Selectivity estimates are found to decrease with temperature with [1],[1,2]{0,1}-grazyne obtaining the highest CO2 selectivity over CH4 at room temperature, of ca. 17, while, for the rest of grazynes studied, the selectivity falls below 5. MD simulations reveal that selectivities can be larger, up to 39 at high pressures on [1],[2]{2}-grazyne, closely to the value obtained for [1],[2]{(00),2}-grazyne, suiting grazynes membranes for biogas upgrading. | Francesc Viñes Solana; Adrià Calzada Escrig; Pablo Gamallo Belmonte | Theoretical and Computational Chemistry; Physical Chemistry; Materials Science; Carbon-based Materials; Computational Chemistry and Modeling; Surface | CC BY NC 4.0 | CHEMRXIV | 2022-11-15 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/63725bae2079814ffe2631b0/original/thermodynamic-kinetic-and-dynamic-aspects-of-biogas-upgrading-using-nano-engineered-grazynes.pdf |
669fa58a5101a2ffa8b833c4 | 10.26434/chemrxiv-2024-q1k6s | From Hydrocarbons to Highly Functionalized Molecules in a Single Measurement: Comprehensive Analysis of Complex Gas Mixtures by Multi-Pressure Chemical Ionization Mass Spectrometry | Chemical Ionization Mass Spectrometry (CIMS) is a well-established analytical method in atmospheric research, process monitoring, forensics, breathomics and food science. Despite significant advancements in procedural techniques, several instrument configurations, especially operating at different ionization pressures, are typically needed to analyze the full range of compounds from non-functionalized parent compounds to their functionalized reaction products. For polar, functionalized compounds, very sensitive detection schemes are provided by high-pressure adduct-forming chemical ionization techniques, whereas for non-functionalized, non-polar compounds, low-pressure chemical ionization techniques have consistently demonstrated superior performance. Here, using a MION2 chemical ionization inlet and an Orbitrap Exploris TM 120 mass spectrometer, we present multi-pressure chemical ionization mass spectrometry (MPCIMS), the combination of high and low pressure ionization schemes in a single instrument enabling quantification of the full distribution of precursor molecules and their oxidation reaction products from the same stream of gas without alterations. We demonstrate the performance of the new methodology in a laboratory experiment employing a-pinene, a monoterpene relevant to atmospheric particle formation, where MPCIMS allows to measure the spectrum of compounds ranging from the volatile precursor hydrocarbon to highly functionalized condensable reaction products. MPCIMS carries the potential as an all-in-one method for the analysis of complex gas mixtures, reducing technical complexities and the need for multiple instruments without compromise of sensitivity. | Aleksei Shcherbinin; Henning Finkenzeller; Jyri Mikkilä; Jussi Kontro; Netta Vinkvist; Juha Kangasluoma; Matti Rissanen | Analytical Chemistry; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2024-07-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/669fa58a5101a2ffa8b833c4/original/from-hydrocarbons-to-highly-functionalized-molecules-in-a-single-measurement-comprehensive-analysis-of-complex-gas-mixtures-by-multi-pressure-chemical-ionization-mass-spectrometry.pdf |
60c74dfa337d6c15d5e27ee7 | 10.26434/chemrxiv.12685886.v1 | Automated Fast-Flow Synthesis of Antisense Phosphorodiamidate Morpholino Oligomers | <p>The
antisense phosphorodiamidate morpholino oligomer (PMO) drugs Eteplirsen and Golodirsen
are improving the lives of some Duchenne muscular dystrophy (DMD) patients, but
treating all DMD subtypes would require the development of over 50 novel
antisense therapies. To rapidly prototype personalized PMO for diseases such as
DMD, we designed a fully automated flow-based oligonucleotide synthesizer. Our
optimized high temperature synthesis platform reduces coupling times by up to
22-fold compared to previously reported batch methods. We demonstrate the power
of our new automated technology with the synthesis of milligram quantities of
an 18-mer reporter PMO sequence in 3.5 hours, three new potential therapeutic
PMO sequences targeted to exon 46 of the dystrophin gene in a single day, and a
candidate antiviral PMO sequence targeted to the SARS-CoV-2 genomic mRNA in 3.5
hours. This flexible flow synthesis platform can be used for on-demand
production of a broad range of personalized therapeutic polymers.</p> | Chengxi Li; Alexander J. Callahan; Mark D. Simon; Kyle A. Totaro; Alexander J. Mijalis; Nina Hartrampf; Carly K. Schissel; Ming Zhou; Hong Zong; Gunnar J. Hanson; Andrei Loas; Nicola L. B. Pohl; Bradley L. Pentelute | Organic Synthesis and Reactions; Process Chemistry; Biopolymers; Pharmaceutical Industry | CC BY NC ND 4.0 | CHEMRXIV | 2020-07-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74dfa337d6c15d5e27ee7/original/automated-fast-flow-synthesis-of-antisense-phosphorodiamidate-morpholino-oligomers.pdf |
60c74818337d6c5088e274a2 | 10.26434/chemrxiv.11857857.v1 | Ligand-Enabled γ-C(sp3)–H Olefination of Free Carboxylic Acids | We report the ligand enabled C(sp3)–H activation/olefination of free carboxylic acids in the γ-position. Through an intramolecular Michael-addition, δ-lactones are obtained as products. Two distinct ligand classes are identified that enable the challenging palladium-catalyzed activation of free carboxylic acids in the γ-position. The developed protocol features a wide range of acid substrates and olefin reaction partners and is shown to be applicable on a preparatively useful scale. Insights into the underlying reaction mechanism obtained through kinetic studies are reported.<br /> | Kiron Kumar Ghosh; Alexander Uttry; Francesca Ghiringhelli; Arup Mondal; Manuel van Gemmeren | Organic Synthesis and Reactions; Homogeneous Catalysis; Catalysis; Ligand Design | CC BY NC ND 4.0 | CHEMRXIV | 2020-02-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74818337d6c5088e274a2/original/ligand-enabled-c-sp3-h-olefination-of-free-carboxylic-acids.pdf |
672bc93e7be152b1d0397d06 | 10.26434/chemrxiv-2024-hz3r3-v2 | Techno-Economic Analysis of an Integrated Process for Cyanobacteria-Based Nutrient Recovery from Livestock Waste | The dairy industry largely operates as a linear economy in which large amounts of non-renewable energy and mining resources are used for the production of synthetic chemical fertilizers (e.g., phosphate rock and ammonia). Moreover, significant greenhouse gas emissions (carbon dioxide, methane, nitrous oxide, ammonia) and nutrient emissions (phosphorus and nitrogen species) result from the improper management of manure waste, leading to the simultaneous degradation of valuable air, soil, and water resources. In this work, we present a techno-economic analysis (TEA) framework to investigate the viability of an integrated process that aims to recover nutrients from dairy manure. A central tenet of the proposed process (which we call ReNuAl) is that it uses cyanobacteria (CB) as a key integrative component that simultaneously: (i) harnesses renewable energy (solar energy via photosynthesis) to capture waste nutrients and (ii) captures carbon dioxide that results the anaerobic digestion of waste. Moreover, because biogas can be obtained via anaerobic digestion and CB biomass can be used as a concentrated biofertilizer, ReNuAl provides a pathway to a more circular fertilizer economy that helps manage air and water pollution. Our TEA framework is used to evaluate the phosphorus recovery costs and capital/operating expenses under varying levels of process integration. This analysis highlights key aspects of the process that have the most impact on economic/environmental performance and to provide performance targets for new CB strain variants. | Leonardo D. González; Brenda Cansino-Loeza; Theodore A. Chavkin; Justin D. Gay; Rebecca A. Larson; Brian F. Pfleger; Victor M. Zavala | Earth, Space, and Environmental Chemistry; Chemical Engineering and Industrial Chemistry; Environmental Science; Wastes; Natural Resource Recovery | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-07 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/672bc93e7be152b1d0397d06/original/techno-economic-analysis-of-an-integrated-process-for-cyanobacteria-based-nutrient-recovery-from-livestock-waste.pdf |
6398288792f084601e338799 | 10.26434/chemrxiv-2022-sfrb3 | CRISPR-based nucleic acid diagnostics for pathogens | Pathogenic infections remain the primary threat for human health, especially the global COVID-19 pandemic. It is important to develop rapid, sensitive and multiplexed tools for detecting pathogens and their mutations, particularly the tailor-made strategies for point-of-care diagnosis allowing for use in resource-constrained settings. The rapidly evolving CRISPR/Cas systems have provided a powerful toolbox for pathogenic diagnostics via nucleic acid tests. In this review, we first describe the resultant promising class 2 (single, multidomain effector) and recently explored class 1 (multisubunit effector complexes) CRISPR tools. We present the diverse engineering nucleic acid diagnostics based on CRISPR/Cas systems for pathogenic viruses, bacteria and fungi, and highlight the application for detecting viral variants and drug-resistant bacteria enabled by CRISPR-based mutation profiling. Finally, we discuss the challenges such as the development of preamplification-free diagnostic assays and present the emerging CRISPR systems and CRISPR cascade that potentially enable multiplexed and preamplification-free pathogenic diagnostics. | Hao Yang; Yong Zhang; Xucong Teng; Hongwei Hou; Ruijie Deng; Jinghong Li | Analytical Chemistry; Analytical Chemistry - General | CC BY NC ND 4.0 | CHEMRXIV | 2022-12-13 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6398288792f084601e338799/original/crispr-based-nucleic-acid-diagnostics-for-pathogens.pdf |
60c74be94c89192922ad3523 | 10.26434/chemrxiv.12387452.v1 | Nicotinamide: Seven New Polymorphic Structures Revealed by Melt Crystallization and Crystal Structure Prediction | <p>Here, we reported nicotinamide (NIC), a long-known vitamin, was revealed in fact to be a highly polymorphic compound with nine solved single-crystal structures by performing melt crystallization. A CSP calculation successfully identified all six Z’ = 1 and 2 experimental structures. Melt crystallization has turned out to be an efficient tool for exploring polymorphic landscape, especially in regions inaccessbile by solution crystallization.</p> | Xizhen Li; Xiao Ou; Bingquan Wang; Haowei Rong; Bing Wang; Chao Chang; Baimei Shi; Lian Yu; Ming Lu | Crystallography; Crystallography – Organic | CC BY NC ND 4.0 | CHEMRXIV | 2020-06-01 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74be94c89192922ad3523/original/nicotinamide-seven-new-polymorphic-structures-revealed-by-melt-crystallization-and-crystal-structure-prediction.pdf |
619799e878db4e4f7814e542 | 10.26434/chemrxiv-2021-kq8f0 | Ion-mediated charge-charge interactions drive aggregation of surface-functionalized gold nanoparticles | Monolayer-protected metal nanoparticles (NPs) are not only promising materials with a wide range of potential industrial and biological applications, but they are also a powerful tool to investigate the behavior of matter at nanoscopic scales, including the stability of dispersions and colloidal systems. This stability is dependent on a delicate balance between electrostatic and steric interactions that occur in the solution, and it is described in quantitative terms by the classic Derjaguin-Landau-Vewey-Overbeek (DLVO) theory, that posits that aggregation between NPs is driven by hydrophobic interactions and opposed by electrostatic interactions. To investigate the limits of this theory at the nanoscale, where the continuum assumptions required by the DLVO theory break down, here we investigate NP dimerization by computing the Potential of Mean Force (PMF) of this process using fully atomistic MD simulations. Serendipitously, we find that electrostatic interactions can lead to the formation of metastable NP dimers. These dimers are stabilized by complexes formed by negatively charged ligands belonging to distinct NPs that are bridged by positively charged ions present in solution. We validate our findings by collecting tomographic EM images of NPs in solution and by quantifying their radial distribution function, that shows a marked peak at interparticle distance comparable with that of MD simulations. Taken together, our results suggest that not only hydrophobic interactions, but also electrostatic interactions, contribute to attraction between nano-sized charged objects at very short length scales. | Emanuele Petretto; Quy K. Ong; Francesca Olgiati; Mao Ting; Pablo Campomanes; Francesco Stellacci; Stefano Vanni | Materials Science; Nanoscience; Core-Shell Materials; Nanostructured Materials - Materials; Surfactants | CC BY NC ND 4.0 | CHEMRXIV | 2021-11-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/619799e878db4e4f7814e542/original/ion-mediated-charge-charge-interactions-drive-aggregation-of-surface-functionalized-gold-nanoparticles.pdf |
659d9e9a66c13817291608f3 | 10.26434/chemrxiv-2024-5znpw | Hemispherical light capture with a plane-faced, polymer film: the Omnidirectional Waveguide Encoded Lattice (OWEL) | The first of its kind, a polymer film (≈ 2 mm) embedded with a population of waveguides arranged in a frustrum geometry has demonstrated an omnidirectional field of view (FOV) of 104° to 108°. Avoiding the use of complex multi-component and multi-step fabrication processes, the omnidirectional waveguide encoded lattice (OWEL) is fabricated through a single-step, room temperature process by which diverging waveguides are self-inscribed in a photopolymerizable medium, using a broadband incoherent light source. Due to the overlapping angular acceptance ranges of the embedded waveguides, the near hemispherical FOV demonstrated by the OWEL film is seamless and continuous. As a result of this enhanced omnidirectional FOV, when integrated with a CMOS camera chip the OWEL can capture 3-dimensional objects resulting in an increase of image capture. The OWEL film is highly customizable, resulting in the potential for a variety of uniquely tailored planar films. Its omnidirectional FOV, enhanced image capture and slim size lend it for applications as coatings on solar cells to enhance their light collection, and integration with smartphones cameras to expand their imaging capabilities. | Kathryn Benincasa; Kalaichelvi Saravanamuttu | Physical Chemistry; Materials Science; Optics | CC BY NC ND 4.0 | CHEMRXIV | 2024-01-12 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/659d9e9a66c13817291608f3/original/hemispherical-light-capture-with-a-plane-faced-polymer-film-the-omnidirectional-waveguide-encoded-lattice-owel.pdf |
677fb9a0fa469535b9508daf | 10.26434/chemrxiv-2025-2lb14 | A Machine Learning Workflow to Enhance Microfluidic Development of Nanomedicines | Artificial intelligence (AI) is being implemented in almost every facet of modern-day life, and machine learning, a subfield of AI, has the potential to greatly streamline the process of developing various nanomedicines using microfluidic fabrication techniques. The availability of open-source machine learning frameworks makes these powerful tools accessible to scientists, facilitating the integration of wet-bench activities with computational analysis. Here, we present a machine learning workflow aimed at optimizing the microfluidic formulation development of nanomedicines. A database of almost 200 unique nanomedicine formulations with over 550 total measurements was curated by producing liposomes, lipid nanoparticles, and PLGA nanoparticles using a benchtop microfluidic system. Microfluidic and materials input features, including the total flow rate, aqueous:organic flow rate ratio, and reagent concentrations, were systematically varied, and the resulting particles were characterized for their hydrodynamic diameter (dH), polydispersity index (PdI), and encapsulation efficiency (EE) for a model therapeutic agent, curcumin (CURC). These data were used to train, test, and validate 13 different machine learning models with the task of returning the most accurate prediction of the nanomedicine attributes – dH, PdI, EE. The most accurate machine learning models, based on random forest regression, were implemented to provide the optimal formulation to yield particles with user-specified attributes. Finally, this system, dubbed MicrofluidicML, was compared against generative large language models as represented by the Open AI ChatGPT and Google’s Gemini platforms. The application of machine learning in the field of nanomedicine is inevitable, and MicrofluidicML represents a step towards implementing a machine learning framework towards accelerating formulation development. | Thomas Lee Moore; Cristiano Pesce; Antonietta Greco; Claudia Pisante; Paolo Decuzzi | Materials Science; Nanoscience; Controlled-Release Systems | CC BY NC 4.0 | CHEMRXIV | 2025-01-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/677fb9a0fa469535b9508daf/original/a-machine-learning-workflow-to-enhance-microfluidic-development-of-nanomedicines.pdf |
64bbc839b053dad33ab1d46a | 10.26434/chemrxiv-2023-tvkp2 | Catalysis Driven by an Amyloid-Substrate Complex | Amyloid catalysis is an emerging area of research. Here, we report a new catalysis system, i.e., catalysis driven by amyloid-substrate complex (CASL), by exploiting amyloid binding with the ligands. The ammonium ion attached to the amyloid-binding motif was activated by its proximity to the amyloid catalyst, formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH2 (NL6) derived from islet amyloid polypeptide (IAPP), thereby promoting amine modifications in the acidic buffer. Consistent with the mode of action of CASL, the affinity of the substrates with amyloid catalysts correlated with the reaction yields. In addition, the direction of the amine extension from the amyloid-binding site markedly influenced the reaction progress. Crystallographic analysis and amide-to-ester substitution of the amyloid catalysts indicated that the carbonyl oxygen of the Phe–Gly amide bond of NL6 played a key role in activating the substrate amine via forming a hydrogen bond. With CASL, we succeeded in the selective conversion of substrates possessing equivalently reactive amine functionalities and introduced a new reaction scope (various amine modifications) to catalytic reactions using amyloids. The substrate-selective conversion ability of CASL significantly expands the applicability of catalytic amyloids in diverse research fields, including chemical biology and materials science. | Taka Sawazaki; Daisuke Sasaki; Youhei Sohma | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis | CC BY 4.0 | CHEMRXIV | 2023-07-24 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64bbc839b053dad33ab1d46a/original/catalysis-driven-by-an-amyloid-substrate-complex.pdf |
6430ab000784a63aeeb976bf | 10.26434/chemrxiv-2023-sq85v | Non-Native Site-Selective Enzyme Catalysis | The ability to a site-selectively modify equivalent functional groups in a molecule has the potential to streamline syntheses and increase product yields by lowering step counts. Enzymes catalyze site-selective transformations throughout primary and secondary metabolism, but leveraging this capability for non-native substrates and reactions requires a detailed understanding of the potential and limitations of enzyme catalysis and how these bounds can be extended by protein engineering. In this review, we discuss representative examples of site-selective enzyme catalysis involving functional group manipulation and C-H bond functionalization. We include illustrative examples of native catalysis, but our focus is on cases involving non-native substrates and reactions often using engineered enzymes. We then discuss the use of these enzymes for chemoenzymatic transformations and target-oriented synthesis and conclude with a survey of tools and techniques that could expand the scope of non-native site-selective enzyme catalysis. | Dibyendu Mondal; Harrison M. Snodgrass; Christian A. Gomez; Jared C. Lewis | Biological and Medicinal Chemistry; Organic Chemistry; Catalysis; Organic Synthesis and Reactions; Bioengineering and Biotechnology; Biocatalysis | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-10 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6430ab000784a63aeeb976bf/original/non-native-site-selective-enzyme-catalysis.pdf |
60c7470d0f50db7618396543 | 10.26434/chemrxiv.11494389.v1 | Ligand-Free Iron-Catalyzed Regiodivergent Hydroboration of Unactivated Terminal Alkenes | The
control of regioselectivities has been recognized as the elementary issue for
alkene hydroboration. Despite considerable progress, the specificity of alkene
substrates or the adjustment of ligands were necessary for specific
regioselectivities, which restrict the universality and practicability. Herein,
we report a ligand-free iron-catalyzed regiodivergent hydroboration of
unactivated terminal alkenes that obtains both Markovnikov and anti-Markovnikov
hydroboration products in excellent regioselectivities. Notably, solvents and
bases were shown to be crucial factors influencing the regioselectivities and
further studies suggested the iron-boron alkoxide ate complex is the key
intermediate that determines the unusual Markovnikov regioselectivity. Terminal
alkenes with diverse structures (mono-substituted and 1,1-disubstituted,
open-chain and exocyclic) underwent the transformation smoothly. The reaction
does not require the addition of auxiliary ligands and it can be performed on a
gram scale, thus providing an efficient and sustainable method for the
synthesis of primary, secondary, and tertiary alkyl borates. | Wei Su; Ruixiao Qiao; Xiaoli Zheng; Xia Tian; Jianrong Han; Shiming Fan; Qiushi Cheng; Shouxin Liu | Organic Synthesis and Reactions; Homogeneous Catalysis; Catalysis; Reaction (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2020-01-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c7470d0f50db7618396543/original/ligand-free-iron-catalyzed-regiodivergent-hydroboration-of-unactivated-terminal-alkenes.pdf |
6744d5ad7be152b1d0ce50e6 | 10.26434/chemrxiv-2024-4m1f0 | Linker-Mediated Domain Separation Enhances Cold Adaptation in Cellulases | Cold-adapted cellulases are crucial for reducing energy demands in industrial processes by enabling efficient cellulose saccharification at lower temperatures. However, the structural basis of cold adaptation in bidomain cellulases remains poorly understood. Our prior studies on bidomain amylases suggest the hypothesis that a greater degree of domain separation is linked to improved cold adaptation. Here, we investigated the hypothesis in the bidomain cellulase Cel5G and its linker-modified variants through molecular dynamics simulations. Domain separation, quantified by domain separation index (DSI), positively correlates with catalytic efficiency at 10°C, meaning that Cel5G variants with a greater DSI demonstrates a higher activity. Structural analyses show that disulfide-bonded loops are pivotal to maintain a high population of extended conformations that involve a greater DSI and reduced interdomain hydrogen bonding (H-bonding). Besides serving as a spacer, linkers in bidomain enzymes can also modulate the active site through dynamic allostery, fine-tuning the frequency of H-bond interactions to influence catalytic residues’ capability of binding or reacting to the substrate. Overall, this study enhances our structural and dynamics-based understanding of cold adaptation of bidomain enzymes and provide a new strategy for cold-adapted enzyme engineering. | Robbie Ge; Ning Ding; Yaoyukun Jiang; Zhongyue J. Yang | Theoretical and Computational Chemistry; Catalysis; Chemical Engineering and Industrial Chemistry | CC BY NC ND 4.0 | CHEMRXIV | 2024-11-27 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6744d5ad7be152b1d0ce50e6/original/linker-mediated-domain-separation-enhances-cold-adaptation-in-cellulases.pdf |
60c75549702a9b34e918c68d | 10.26434/chemrxiv.14065025.v1 | Limited Hydrolysis of Polysialic Acid by Human Neuraminidase Enzymes | Regulation
of sialic acids by human neuraminidase (hNEU) enzymes is important to many biological
processes. Defining hNEU substrate tolerance can help to elucidate the roles of
these enzymes in regulating sialosides in human health and disease. Polysialic
acid (polySia) is a polyanion of α(2→8) linked sialic acids with roles in nervous,
reproductive, and immune systems and is dysregulated in some malignancies and
mental disorders. The unique chemical properties of this polymer, which include
an enhanced susceptibility to acid-catalyzed hydrolysis, have hampered its
study. Herein we describe the first<i> </i>systematic study of hNEU isoenzyme
activity towards polysialic acid <i>in vitro.</i> The experimental design allowed
us to study the impact of several factors that may influence polysialic acid
degradation including pH, polymer size, and the relative ionic strength of the
surrounding media. We report that short chains of polysialic acid (degree of
polymerization, DP 3-8) were substrates of NEU3 and NEU4 at acidic pH, but not
at neutral pH. No hNEU-catalyzed hydrolysis of longer polymers (DP 10-20) was
detected. These findings suggest a neuraminidase-independent mechanism for
polysialic acid turnover such as internalization and degradation in endosomes
and lysosomes. | Carmanah
D. Hunter; Christopher Cairo | Chemical Biology | CC BY NC ND 4.0 | CHEMRXIV | 2021-02-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c75549702a9b34e918c68d/original/limited-hydrolysis-of-polysialic-acid-by-human-neuraminidase-enzymes.pdf |
60c73d914c891934dcad1c0d | 10.26434/chemrxiv.5885203.v1 | Catalytic, Enantioselective Synthesis of Allenyl Boronates | A method to achieve enantioselective 1,4-hydroboration of terminal enynes to access allenyl boronates under CuH catalysis is described. The reaction typically proceeds in a highly stereoselective manner and tolerates an array of synthetically useful functional groups. The utility of the enantioenriched allenyl boronate products is demonstrated through several representative downstream derivatizations. | De-Wei Gao; Yiyang Xiao; Mingyu Liu; Zhen Liu; Malkanthi K. Karunananda; Jason S. Chen; Keary Engle | Stereochemistry; Acid Catalysis; Base Catalysis; Homogeneous Catalysis; Catalysis; Ligands (Organomet.) | CC BY NC ND 4.0 | CHEMRXIV | 2018-02-14 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c73d914c891934dcad1c0d/original/catalytic-enantioselective-synthesis-of-allenyl-boronates.pdf |
66734173c9c6a5c07ae019a6 | 10.26434/chemrxiv-2024-g1pb0 | Simultaneous Overcoming Approach for Poor Wettability and Low Stability in Stomach by Simple Methods; Formulation Design and Development of Monoacylglycerol Acyltransferase 2 Inhibitor, S-309309 | N-[(4R)-5,7-difluoro-2'-(5-methylpyridin-2-yl)-4'-oxo-2,2',3,4',5',7'-hexahydrospiro[1-benzopyran-4,6'-pyrazolo[4,3-c]pyridin]-3'-yl]-2-(methanesulfonyl)acetamide (S-309309) is an anti-obesity drug developed by Shionogi & Co., Ltd. that has a monoacylglycerol acyltransferase 2 inhibitory effect. S-309309 has poor wettability, and the amount of the degradation product (4R)-3'-amino-5,7-difluoro-2'-(5-methylpyridin-2-yl)-2,2',3,7'-tetrahydrospiro[[1]benzopyran-4,6'-pyrazolo[4,3-c]pyridin]-4'(5'H)-one (compound 8) increases over time under acidic conditions. In this study, we have tried to improve S-309309 wettability and suppress the amount of degradation product increased under acidic conditions. As a result of the study, we found that by mixing with a water-soluble polymer, the wettability of S-309309 and its dissolved concentration in fluid were increased, suggesting that its dissolution behavior should be enhanced. In addition, by encapsulating S-309309, the increase of degradation product amount was suppressed under acidic conditions, suggesting that the suppression of degradation product formation would be expected in the stomach after oral dosing. Overall, these results suggest that the drug property issues of S-309309 can be overcome by mixing S-309309 with a water-soluble polymer and encapsulation. | Shojiro Shimokawa; Masato Gomi; Yuta Nakagawa; Atsushi Inoue; Takeshi Funaki | Chemical Engineering and Industrial Chemistry; Industrial Manufacturing; Pharmaceutical Industry | CC BY 4.0 | CHEMRXIV | 2024-06-20 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66734173c9c6a5c07ae019a6/original/simultaneous-overcoming-approach-for-poor-wettability-and-low-stability-in-stomach-by-simple-methods-formulation-design-and-development-of-monoacylglycerol-acyltransferase-2-inhibitor-s-309309.pdf |
61de3e92db4d9f7ec495b2a1 | 10.26434/chemrxiv-2022-90b49-v2 | On the Separation of Enantiomers by Drift Tube Ion Mobility Spectrometry | Racemic mixtures of twelve common α-amino acids and three chiral drugs were tested for the separation of their enantiomers by drift tube ion mobility spectrometry (IMS)-quadrupole mass spectrometry (QMS) by introducing chiral selectors into the buffer gas of the IMS instrument. (R)-α-(trifluoromethyl) benzyl alcohol, (L)-ethyl lactate, methyl (S)-2-chloropropionate, and the R and S enantiomers of 2-butanol and 1-phenyl ethanol were evaluated as chiral selectors. Experimental conditions were varied during the tests, including buffer gas temperature, concentration and type of chiral selectors, analyte concentration, electrospray (ESI) voltage, ESI solvent pH, and buffer gas flow rate. The individual enantiomers yielded the same drift times and the racemic mixtures could not be separated as opposed to a previous report (Dwivedi et al. Anal. Chem. 2006, 78, 8200). Energy calculations of the chiral selector –ion interactions showed that these separations are unlikely using 2-butanol as a chiral selector but they might be theoretically feasible depending on the chiral selector nature and the type of enantiomers. Several plausible explanations for not succeeding were analyzed. A critical review of previously claimed enantiomer separations by drift-tube IMS-MS is presented and recommendations for potential enantiomer separations by IMS are proposed. | Roberto Fernandez-Maestre; Markus Doerr | Analytical Chemistry; Analytical Chemistry - General; Mass Spectrometry | CC BY NC ND 4.0 | CHEMRXIV | 2022-01-25 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/61de3e92db4d9f7ec495b2a1/original/on-the-separation-of-enantiomers-by-drift-tube-ion-mobility-spectrometry.pdf |
60c74b91ee301c1f96c79eae | 10.26434/chemrxiv.12355406.v1 | Building a Shp: A New Rare-Earth Metal-Organic Framework and Its Application in a Catalytic Photo-Oxidation Reaction | The design and synthesis of new metal–organic frameworks (MOFs) is important from both a fundamental and application standpoint. In this work, a novel, highly‐connected rare‐earth (RE) MOF with shp topology is reported, named RE‐CU‐10 (RE = rare‐earth, CU = Concordia University), comprised of nonanuclear RE(III)‐cluster nodes and tetratopic pyrene‐based linkers. This represents the first time that the 1,3,6,8‐tetrakis(p‐benzoic acid)pyrene (H4TBAPy) linker is integrated in the shp topology. Y‐CU‐10 was explored as a heterogeneous photocatalyst for the selective oxidation and detoxification of a sulfur mustard simulant, 2‐chloroethyl ethyl sulfide (2‐CEES), showing a halflife for conversion to the less toxic 2‐chloroethyl ethyl sulfoxide (2‐CEESO) of 6.0 min.<br /> | Victor Quezada-Novoa; Hatem M. Titi; Amy Sarjeant; Ashlee J Howarth | Hybrid Organic-Inorganic Materials; Coordination Chemistry (Inorg.); Crystallography – Inorganic | CC BY NC ND 4.0 | CHEMRXIV | 2020-05-22 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/60c74b91ee301c1f96c79eae/original/building-a-shp-a-new-rare-earth-metal-organic-framework-and-its-application-in-a-catalytic-photo-oxidation-reaction.pdf |
658a7fc466c1381729109408 | 10.26434/chemrxiv-2023-vdhcd | Sequence and structural analysis of main protease Mpro mutants of SARS CoV-2 from variant of concern (VoCs) | In light of the emergence of new and potentially more virulent SARS-CoV-2 variants, an in-depth analysis of the main protease (Mpro) or 3CLpro, a critical target for COVID-19 therapy due to its essential role in viral replication, was conducted. This study focused on the alpha, beta, gamma, delta, and omicron variants, comparing them to the reference sequence (Wuhan-Hu-1). The comprehensive analysis of the mutational landscape of SARS-CoV-2 Mpro across Variants of Concern (VOCs) provides valuable insights into the evolving nature of the virus. The study utilized a substantial dataset of 222,980 sequences (quality data) and created a library of a total of 51,733 mutations for the Mpro protein. The distribution of mutations varied among the variants, with distinct patterns observed. Certain regions crucial for drug binding and protease function showed relatively fewer mutation rates, unlike the interdomain site, which exhibited higher mutation rates compared to catalytic and dimeric interface sites. Notably, the Omicron variant displayed the prevalent P132H mutation, while the Beta variant featured the prevalent K90R mutation. Furthermore, proline positions in Mpro were investigated, with mutations identified in ten out of thirteen positions, underscoring the potential impact on protein stability. Additionally, the catalytic site S1 sub-pocket was found to be less mutated, whereas the S3 sub-pocket was highly mutated. These findings suggest a critical role in maintaining the structural and functional integrity of Mpro, offering valuable insights for future research and therapeutic development. | MOHD KHAN | Biological and Medicinal Chemistry | CC BY NC 4.0 | CHEMRXIV | 2024-02-08 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/658a7fc466c1381729109408/original/sequence-and-structural-analysis-of-main-protease-mpro-mutants-of-sars-co-v-2-from-variant-of-concern-vo-cs.pdf |
6439826c1d262d40ea73d8d6 | 10.26434/chemrxiv-2023-ft6wd | Accurate calculation of many-body energies in water clusters using a classical geometry-dependent induction model | We incorporate geometry-dependent distributed multipole and polarizability surfaces into an induction model that is used to describe the 3- and 4-body terms of the
interaction between water molecules. The expansion is carried out up to hexadecapole with the multipoles distributed on the atom sites. Dipole-dipole, dipole-quadrupole, and quadrupole-quadrupole distributed polarizabilities are used to represent the response of the multipoles to an electric field. We compare the model against two large databases consisting of 43,844 3-body terms and 3,603 4-body terms obtained from
high level ab initio calculations previously used to fit the MB-pol and q-AQUA interaction potentials. The classical induction model with no adjustable parameters
reproduces the ab-initio 3- and 4-body terms contained in these two Databases with a Root-Mean-Square-Error (RMSE) of 0.104/0.058 and a Mean-Absolute-Error (MAE)
of 0.054/0.026 kcal/mol, respectively, results that are on a par with those obtained by fitting the same data using tens of thousands of Permutationally Invariant Polynomials (PIPs). This demonstrates the accuracy of this physically motivated model in describing the 3- and 4-body terms in the interactions between water molecules with no
adjustable parameters. The triple-dipole-dispersion energy was included in the 3-body energy and was found to be small but not quite negligible. The model represents a
practical, efficient and transferable approach for obtaining accurate non-additive interactions for multi-component systems without the need of performing tens of thousands
of high level electronic structure calculations and fitting them with tens of thousands of PIPs. | Kristina M. Herman; Anthony J. Stone; Sotiris S. Xantheas | Theoretical and Computational Chemistry; Computational Chemistry and Modeling | CC BY NC ND 4.0 | CHEMRXIV | 2023-04-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6439826c1d262d40ea73d8d6/original/accurate-calculation-of-many-body-energies-in-water-clusters-using-a-classical-geometry-dependent-induction-model.pdf |
66ad2ad3c9c6a5c07adc1d43 | 10.26434/chemrxiv-2024-szzsf-v2 | Theoretical Study of the Isotope Effect in Optical Rotation | In this work, the isotope effect in optical rotation (OR) is examined by exploring structure- property relationships for H → D substitutions in chiral molecules. While electronic effects serve as the dominant source of optical activity, there is a non-negligible contribution from nuclear vibrations, which changes with isotopic substitution. We employ a test set of 50 small organic molecules: three-membered rings with varying heteroatoms (PCl, PH, S, NCl, NH, O, NBr) and functional groups (Me, F), and simulations were run at the B3LYP/aug- cc-pVDZ level of theory. The objectives of this work are to determine locations of isotopic substitution that result in significant changes in the vibrational correction to the OR and to evaluate which vibrational modes and electronic response are the major contributors to the isotope effect. Molecules with more polarizable heteroatoms in the ring (e.g., S and P) have the largest change in the vibrational correction compared to the unsubstituted parent molecules. In many cases, isotopic substitution made to the hydrogens on the opposite side of the ring from the functional group provides the largest change in the OR. H/D wagging modes and C vibrations (for D–C centers) are the largest contributors to the isotope effect. This is explained with a molecular orbital decomposition analysis of the OR. The relevant vibrational modes affect the orbital transitions that are already significant at the equilibrium geometry. However, this effect is only large when polarizable heteroatoms are involved, because the electron density surrounding them is diffuse enough to feel the subtle effect of change in mass due to isotopic substitution on the relevant vibrational modes. | Brian Faintich; Taylor Parsons; Ty Balduf; Marco Caricato | Theoretical and Computational Chemistry; Physical Chemistry; Computational Chemistry and Modeling; Theory - Computational; Spectroscopy (Physical Chem.) | CC BY NC 4.0 | CHEMRXIV | 2024-08-05 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/66ad2ad3c9c6a5c07adc1d43/original/theoretical-study-of-the-isotope-effect-in-optical-rotation.pdf |
64def1de694bf1540c8b1e3c | 10.26434/chemrxiv-2023-64h1m | When is a bond broken? The polarizability perspective. | The question of when a chemical bond can be said to be broken is of fundamental chemical interest but has not been widely studied. Herein we propose that the maxima of static polarizability along bond dissociation coordinates naturally define cutoff points for bond rupture, as they represent the onset of localization of shared electron density into constituent fragments. Examples of computed polarizability maxima over the course of bond cleavage in main-group and transition metal compounds are provided, across covalent, dative and charge-shift bonds. The behavior along reaction paths is also considered. Overall, the static polarizability is found to be a sensitive reporter of electronic structure reorganization associated with bond stretching, and thus can serve as a metric for describing bond cleavage (or diagnose the absence of a chemical bond). | Diptarka Hait; Martin Head-Gordon | Theoretical and Computational Chemistry; Physical Chemistry; Inorganic Chemistry; Bonding; Theory - Computational; Quantum Mechanics | CC BY NC ND 4.0 | CHEMRXIV | 2023-08-18 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/64def1de694bf1540c8b1e3c/original/when-is-a-bond-broken-the-polarizability-perspective.pdf |
6475c5cc4f8b1884b7896739 | 10.26434/chemrxiv-2023-br1h5 | Estimating Free Energy Barriers for Heterogeneous Catalytic Reactions with Machine Learning Potentials and Umbrella Integration | Predicting the rate constants of elementary reaction steps is key for the computational modelling of catalytic processes. Within transition state theory (TST), this requires an accurate estimation of the corresponding free energy barriers. While sophisticated methods for estimating free energy differences exist, these typically require extensive (biased) molecular dynamics simulations that are computationally prohibitive with the first-principles electronic structure methods that are typically used in catalysis research. In this contribution, we show that machine-learning (ML) interatomic potentials can be trained in an automated iterative workflow to perform such free energy calculations at a much reduced computational cost as compared to a direct density-functional theory (DFT) based evaluation. For the decomposition of CHO on Rh(111), we find that thermal effects are substantial and lead to a decrease in the free energy barrier, which can be vanishingly small depending on the DFT functional used. This is in stark contrast to previously reported estimates based on a harmonic TST approximation, which predicted an increase of the barrier at elevated temperatures. Since CHO is the educt of the putative rate limiting reaction step in syngas conversion on Rh(111) and essential for the selectivity towards $\mathrm{C}_\mathrm{2+}$ oxygenates, our results call into question the reported mechanism established by microkinetic models. | Sina Stocker; Hyunwook Jung; Gábor Csányi; C. Franklin Goldsmith; Karsten Reuter; Johannes T. Margraf | Theoretical and Computational Chemistry; Computational Chemistry and Modeling; Machine Learning | CC BY NC 4.0 | CHEMRXIV | 2023-05-30 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/6475c5cc4f8b1884b7896739/original/estimating-free-energy-barriers-for-heterogeneous-catalytic-reactions-with-machine-learning-potentials-and-umbrella-integration.pdf |
67694db56dde43c908142885 | 10.26434/chemrxiv-2024-d34rk | A Water Soluble, Long Fluorescent Lifetime DNA Probe for Real-Time Dynamic Visualization of Mitosis in Live Cells and Applicability for FLIM/Time-gated Imaging | Long-lived and photostable fluorescent probes for real-time monitoring of cell division, particularly for dynamic visualization of mitosis and interphase, are rare. We have developed a water soluble diazaoxatriangulenium cation based fluorescent probe, Nuc-DAOTA+, that meets these criteria. Nuc-DAOTA+ has a long fluorescence lifetime (~20 ns) and exclusively targets the nucleus for specific DNA binding in live cells, essential for real-time dynamic imaging of cell-division, including mitosis and interphase. Addition of dsDNA (0 – 50 μg/mL) to Nuc-DAOTA+, results in a red-shift (~10 nm) of the absorption and a blue shift (~5 nm) of the fluorescence maxima, along with an intensity increase in both. A very good linear correlation (R2 = 0.999) from plot between fluorescence intensity versus concentration of dsDNA (up to 30 μg/mL) resulted in a detection limit of 0.7 μg/mL. The Benesi – Hildebrand plot was used to calculate the binding constant between the Nuc-DAOTA+ and DNA, which was found to be 1.6 x 104 M-1 and mechanism of binding interactions was investigated using CD spectroscopy. The long fluorescence lifetime and excellent biocompatibility of Nuc-DAOTA+ enabled its use for real-time dynamic imaging of mitotic phases and interphase in live CHO (Chinese hamster ovary) cells by using confocal microscopy. In addition, the Nuc-DAOTA+ exhibited high photostability during photo-bleaching experiments and was successfully applied for fluorescence lifetime imaging microscopy (FLIM) and time gated imaging of mouse embryonic fibroblast 3T3 cell line. | Kapil Kumar; Thomas Hartig Braunstein; Pablo Hernández Varas; Mikkel Baldtzer Liisberg; Bo Wegge Laursen | Biological and Medicinal Chemistry; Organic Chemistry; Nanoscience; Bioorganic Chemistry; Cell and Molecular Biology; Chemical Biology | CC BY 4.0 | CHEMRXIV | 2024-12-26 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67694db56dde43c908142885/original/a-water-soluble-long-fluorescent-lifetime-dna-probe-for-real-time-dynamic-visualization-of-mitosis-in-live-cells-and-applicability-for-flim-time-gated-imaging.pdf |
67988b24fa469535b92582fe | 10.26434/chemrxiv-2024-k6jnq-v2 | Site-Selective and Late-Stage Deuteration of (Hetero)arenes with Supported Iridium Nanoparticles | Deuterated compounds have emerged as critical tools across diverse research areas, including pharmaceuticals, where deuterium incorporation can modulate the absorption, distribution, metabolism, and excretion (ADME) properties of drugs. In this study, we report the development of a new hydrogen/deuterium (H/D) exchange catalyst based on support-ed iridium nanoparticles, which enables selective deuteration of arenes and heteroarenes under mild conditions. Using C6D6 as the deuterium source, our catalytic system achieves high chemo- and regioselectivity, avoiding the common side reactions such as hydrogenation and dehalogenation observed with traditional heterogeneous catalysts. Notably, the deuteration occurs selectively at the para- and meta-C(sp2)–H bonds, leaving ortho C(sp2)–H and C(sp3)–H bonds intact, and exhibits broad functional group tolerance, including with ketones, amides, alkenes, aryl ethers, and acidic protons. The heterogeneous nature of the catalyst was confirmed via filtration and mercury drop tests. This work presents a new cata-lytic system for regioselective deuteration of complex molecules, offering complementary site selectivity to existing homogeneous and heterogeneous methods and the possibility to be used in the late-stage deuteration of pharmaceuticals. | Chengbo Yao; Christophe Copéret | Organic Chemistry; Catalysis; Organometallic Chemistry | CC BY NC 4.0 | CHEMRXIV | 2025-01-29 | https://chemrxiv.org/engage/api-gateway/chemrxiv/assets/orp/resource/item/67988b24fa469535b92582fe/original/site-selective-and-late-stage-deuteration-of-hetero-arenes-with-supported-iridium-nanoparticles.pdf |
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