The global emergence of COVID-19, caused by SARS-CoV-2, has underscored the critical need for effective antivirals against coronaviruses. The 3-chymotrypsin-like protease (3CLpro) of coronavirus has been a primary target for drug development due to its critical role across various coronaviruses. Following our initial report, this study focuses on the structure-based optimization of 3CLpro covalent inhibitors. With the guidance of molecular docking and covalent binding parameters measured from an innovative isothermal titration calorimetry-kinetic competition (ITC-KC) assay, we optimized and synthesized series of potent covalent inhibitors with antiviral activity in cell-based assays.
{"title":"Structure-Based Optimization and Biological Evaluation of SARS-CoV-2 3CLpro Covalent Inhibitors","authors":"Nicolas, Moitessier, Guanyu, Wang, Julia, Stille, Richard, Boulon, Christopher, Hennecker, Xiaocong, Zhang, Nicole, Blaine, Steven, Laplante, Anthony, Mittermaier","doi":"10.26434/chemrxiv-2024-091mt","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-091mt","url":null,"abstract":"The global emergence of COVID-19, caused by SARS-CoV-2, has underscored the critical need for effective antivirals against coronaviruses. The 3-chymotrypsin-like protease (3CLpro) of coronavirus has been a primary target for drug development due to its critical role across various coronaviruses. Following our initial report, this study focuses on the structure-based optimization of 3CLpro covalent inhibitors. With the guidance of molecular docking and covalent binding parameters measured from an innovative isothermal titration calorimetry-kinetic competition (ITC-KC) assay, we optimized and synthesized series of potent covalent inhibitors with antiviral activity in cell-based assays.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruton's tyrosine kinase (BTK) and Interleukin-2-inducible T-cell kinase (ITK) are two important members of the Tec family with crucial roles in immune system function. Deregulation in ITK and BTK activity is linked to several hematological malignancies, making them key targets for cancer immunotherapy. In this study, we synthesized new azaspirooxindolinone derivatives and evaluated their cytotoxic activity against ITK/BTK-negative and -positive cancer cell lines. Compounds 3d and 3j exhibited high cytotoxicity in both ITK-positive Jurkat (IC50 = 3.58 µM and 4.16 µM, respectively) and BTK-positive Ramos (IC50 = 3.06 µM and 1.38 µM, respectively) cell lines, indicating their potential dual activity against ITK and BTK. 3a and 3e showed high cytotoxicity specifically in ITK-positive Jurkat cells with IC50 values of 9.36 µM and 10.85 µM, respectively. Compounds 3f and 3g were highly cytotoxic specifically in Ramos cells with IC50 values of 1.82 µM and 1.42 µM, respectively. None of the active compounds exhibited cytotoxic effects against non-cancer cell lines (IC50 > 50 µM). These findings suggest that the synthesized azaspirooxindolinone derivatives, particularly compounds 3d and 3j, hold promise as dual inhibitors for ITK and BTK-positive cancers, while compounds 3a, 3e, 3f, and 3g demonstrate potential as specific inhibitors, warranting further investigation.
{"title":"Design, synthesis, and biological evaluation of novel azaspirooxindolinone derivatives as potent inhibitors of ITK and BTK-positive cancers","authors":"Viswanath, Das, Gopal , Muddasani, Naveen Kumar , Rampeesa, Sreenivasareddy , Anugu, Pullareddy , Muddasani, Soňa, Gurská, Petr , Džubák, Marián , Hajdúch, Rambabu, Gundla","doi":"10.26434/chemrxiv-2024-hrfmw-v2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-hrfmw-v2","url":null,"abstract":"Bruton's tyrosine kinase (BTK) and Interleukin-2-inducible T-cell kinase (ITK) are two important members of the Tec family with crucial roles in immune system function. Deregulation in ITK and BTK activity is linked to several hematological malignancies, making them key targets for cancer immunotherapy. In this study, we synthesized new azaspirooxindolinone derivatives and evaluated their cytotoxic activity against ITK/BTK-negative and -positive cancer cell lines. Compounds 3d and 3j exhibited high cytotoxicity in both ITK-positive Jurkat (IC50 = 3.58 µM and 4.16 µM, respectively) and BTK-positive Ramos (IC50 = 3.06 µM and 1.38 µM, respectively) cell lines, indicating their potential dual activity against ITK and BTK. 3a and 3e showed high cytotoxicity specifically in ITK-positive Jurkat cells with IC50 values of 9.36 µM and 10.85 µM, respectively. Compounds 3f and 3g were highly cytotoxic specifically in Ramos cells with IC50 values of 1.82 µM and 1.42 µM, respectively. None of the active compounds exhibited cytotoxic effects against non-cancer cell lines (IC50 > 50 µM). These findings suggest that the synthesized azaspirooxindolinone derivatives, particularly compounds 3d and 3j, hold promise as dual inhibitors for ITK and BTK-positive cancers, while compounds 3a, 3e, 3f, and 3g demonstrate potential as specific inhibitors, warranting further investigation.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipids are major constituents of food but are also highly relevant substructures of drugs and are increasingly applied for the development of lipid-based drug delivery systems. Lipids are prone to oxidative degradation, thus affecting the quality of food or medicines. Therefore, analytical methods or tools that enable to assess the degree of lipid oxidation are of utmost importance to guarantee food and drug safety. Herein, we report the design, synthesis, and application of the first-in-class fluorogenic triacylglycerols that enable a dynamic monitoring of lipid oxidation via straightforward fluorescence readout. Our fluorogenic triacylglycerols can be used both in an aqueous and lipid-based environment. Further, we showed that the sensitivity of our fluorescent tracers towards oxidation can be tuned by incorporating either saturated or unsaturated acyl chains in their triacylglycerol core structure. With this, we provide a first proof-of-principle for the applicability of fluorescently labelled triacylglycerols as tracers to monitor the dynamics of lipid oxidation, thus paving the way for novel discoveries in the area of lipid analytics.
{"title":"New fluorogenic triacylglycerols as sensors for dynamic measurement of lipid oxidation","authors":"Matthias, Schiedel, Simon, Hammann, Maria, Handke, Frank, Beierlein, Petra, Imhof","doi":"10.26434/chemrxiv-2024-shsjs-v2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-shsjs-v2","url":null,"abstract":"Lipids are major constituents of food but are also highly relevant substructures of drugs and are increasingly applied for the development of lipid-based drug delivery systems. Lipids are prone to oxidative degradation, thus affecting the quality of food or medicines. Therefore, analytical methods or tools that enable to assess the degree of lipid oxidation are of utmost importance to guarantee food and drug safety. Herein, we report the design, synthesis, and application of the first-in-class fluorogenic triacylglycerols that enable a dynamic monitoring of lipid oxidation via straightforward fluorescence readout. Our fluorogenic triacylglycerols can be used both in an aqueous and lipid-based environment. Further, we showed that the sensitivity of our fluorescent tracers towards oxidation can be tuned by incorporating either saturated or unsaturated acyl chains in their triacylglycerol core structure. With this, we provide a first proof-of-principle for the applicability of fluorescently labelled triacylglycerols as tracers to monitor the dynamics of lipid oxidation, thus paving the way for novel discoveries in the area of lipid analytics.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Methods that accelerate the evaluation of molecular properties are essential for chemical discovery. While some degree of ligand additivity has been established for transition metal complexes, it is underutilized in asymmetric complexes, such as the square pyramidal coordination geometries highly relevant to catalysis. To develop predictive methods beyond simple additivity, we apply a many-body expansion to octahedral and square pyramidal complexes and introduce a correction based on adjacent ligands (i.e., the cis interaction model, or cis model). We first test the cis model on adiabatic spin-splitting energies of octahedral Fe(II) complexes, predicting DFT-calculated values of unseen binary complexes to within an average of 1.4 kcal/mol. We next show that the cis model infers both DFT- and CCSD(T)-calculated model catalytic reaction energies to within 1 kcal/mol on average. The cis model predicts low-symmetry complexes with reaction energies outside the range of binary complex reaction energies. We observe that trans interactions are unnecessary for most monodentate systems but can be important for some combinations of ligands, such as complexes containing a mixture of bidentate and monodentate ligands. Finally, we demonstrate that the cis model may be combined with -learning to predict CCSD(T) reaction energies from exhaustively calculated DFT reaction energies and the same fraction of CCSD(T) reaction energies needed for the cis model, achieving around 30% of the error from using the CCSD(T) reaction energies in the cis model alone.
{"title":"Ligand Many-Body Expansion as a General Approach for Accelerating Transition Metal Complex Discovery","authors":"Heather, Kulik, Daniel, Chu, David, Gonzalez-Narvaez, Ralf, Meyer, Aditya, Nandy","doi":"10.26434/chemrxiv-2024-m39d9","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-m39d9","url":null,"abstract":"Methods that accelerate the evaluation of molecular properties are essential for chemical discovery. While some degree of ligand additivity has been established for transition metal complexes, it is underutilized in asymmetric complexes, such as the square pyramidal coordination geometries highly relevant to catalysis. To develop predictive methods beyond simple additivity, we apply a many-body expansion to octahedral and square pyramidal complexes and introduce a correction based on adjacent ligands (i.e., the cis interaction model, or cis model). We first test the cis model on adiabatic spin-splitting energies of octahedral Fe(II) complexes, predicting DFT-calculated values of unseen binary complexes to within an average of 1.4 kcal/mol. We next show that the cis model infers both DFT- and CCSD(T)-calculated model catalytic reaction energies to within 1 kcal/mol on average. The cis model predicts low-symmetry complexes with reaction energies outside the range of binary complex reaction energies. We observe that trans interactions are unnecessary for most monodentate systems but can be important for some combinations of ligands, such as complexes containing a mixture of bidentate and monodentate ligands. Finally, we demonstrate that the cis model may be combined with -learning to predict CCSD(T) reaction energies from exhaustively calculated DFT reaction energies and the same fraction of CCSD(T) reaction energies needed for the cis model, achieving around 30% of the error from using the CCSD(T) reaction energies in the cis model alone.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"130 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.26434/chemrxiv-2024-t9r77
Harendra, Kumar, Akihiro, Yoshida
The issue of fossil-based plastics presents a paradox, with conflicting solutions proposed. While an idealistic vision promotes biodegradable plastics as the ultimate solution, the reality is that fossil-based plastics dominate production, constituting approximately 99%. Despite the conceptual appeal of biodegradable plastics, their practical implementation remains limited with minimal production. Consequently, the current plastic waste management system faces challenges, with only 25% of total plastic waste being recycled. A significant portion, around 31.2%, is incinerated, and 43.8% ends up in landfills or is improperly disposed of, reflecting a non-sustainable approach. Projections suggest a potential increase in recycling rates to nearly 44% by 2050, but incineration remains alarmingly high at close to 50%. To achieve sustainable growth and create a carbon and toxic-free environment, there is a need for a renewed commitment to accelerate the reuse and recycling of plastic waste. Failure to do so risks perpetuating the condemnation of fossil-based plastics, despite their significant historical contributions to society and the environment.
{"title":"Sustainable Development Growth in the Plastic Industries is Promising or Just a Hoax: Past, Present, and Future aspects on Global Perspective","authors":"Harendra, Kumar, Akihiro, Yoshida","doi":"10.26434/chemrxiv-2024-t9r77","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-t9r77","url":null,"abstract":"The issue of fossil-based plastics presents a paradox, with conflicting solutions proposed. While an idealistic vision promotes biodegradable plastics as the ultimate solution, the reality is that fossil-based plastics dominate production, constituting approximately 99%. Despite the conceptual appeal of biodegradable plastics, their practical implementation remains limited with minimal production. Consequently, the current plastic waste management system faces challenges, with only 25% of total plastic waste being recycled. A significant portion, around 31.2%, is incinerated, and 43.8% ends up in landfills or is improperly disposed of, reflecting a non-sustainable approach. Projections suggest a potential increase in recycling rates to nearly 44% by 2050, but incineration remains alarmingly high at close to 50%. To achieve sustainable growth and create a carbon and toxic-free environment, there is a need for a renewed commitment to accelerate the reuse and recycling of plastic waste. Failure to do so risks perpetuating the condemnation of fossil-based plastics, despite their significant historical contributions to society and the environment.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catalyst surfaces in contact with liquid media are subject to spontaneous charge transfer reactions that electrically polarize the solid-liquid interface. Consequently, the electrochemical potential, Ecat, of the surface is a critical parameter that defines the free-energy landscape of catalysis. Ecat can be readily measured for a catalyst supported on a conductive material and wired to an external circuit but is difficult to quantify for the vast majority of thermochemical catalysts that are supported on electrical insulators. This measurement gap has impeded a unifying understanding of the role of electrochemical polarization in thermochemical catalysis. Herein, we develop a methodology for quantifying Ecat of metal catalysts supported on insulators by introducing a small concentration of a redox-active molecule to establish a wireless electrical connection between the dispersed catalyst and an inert sensing electrode. We validate this approach by quantifying Ecat during catalytic reactions involving H2 or O2 in water and acetonitrile solvent. Using this methodology, we expose distinct rate-potential scalings for aerobic formic acid oxidation catalysis on SiO2- and Al2O3- versus TiO2-supported Pt catalysts. The methodology we develop herein enables the broad-based investigation of the role of electrochemical polarization in thermochemical catalysis.
{"title":"Wireless potentiometry of thermochemical heterogeneous catalysis","authors":"Neil, Razdan, Karl, Westendorff, Yogesh, Surendranath","doi":"10.26434/chemrxiv-2024-vm26z-v2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-vm26z-v2","url":null,"abstract":"Catalyst surfaces in contact with liquid media are subject to spontaneous charge transfer reactions that electrically polarize the solid-liquid interface. Consequently, the electrochemical potential, Ecat, of the surface is a critical parameter that defines the free-energy landscape of catalysis. Ecat can be readily measured for a catalyst supported on a conductive material and wired to an external circuit but is difficult to quantify for the vast majority of thermochemical catalysts that are supported on electrical insulators. This measurement gap has impeded a unifying understanding of the role of electrochemical polarization in thermochemical catalysis. Herein, we develop a methodology for quantifying Ecat of metal catalysts supported on insulators by introducing a small concentration of a redox-active molecule to establish a wireless electrical connection between the dispersed catalyst and an inert sensing electrode. We validate this approach by quantifying Ecat during catalytic reactions involving H2 or O2 in water and acetonitrile solvent. Using this methodology, we expose distinct rate-potential scalings for aerobic formic acid oxidation catalysis on SiO2- and Al2O3- versus TiO2-supported Pt catalysts. The methodology we develop herein enables the broad-based investigation of the role of electrochemical polarization in thermochemical catalysis.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.26434/chemrxiv-2024-q6dkh-v2
Quentin, Stern, Guillaume, Verhaeghe, Théo, El Daraï, Damien, Montarnal, Nghia, Huu Le, Laurent, Veyre, Chloé, Thieuleux, Charlotte, Bocquelet, Olivier, Cala, Sami, Jannin
The low sensitivity of liquid-state nuclear magnetic resonance (NMR) can be overcome by hyperpolarizing nuclear spins by dissolution dynamic nuclear polarization (dDNP). It consists of transferring the near-unity polarization of unpaired electron spins of stable radicals to the nuclear spins of interest at liquid helium temperatures, below 2 K, before melting the sample in view of hyperpolarized liquid-state magnetic resonance experiments. Reaching such a temperature is challenging and requires complex instrumentation, which impedes the deployment of dDNP. Here, we propose organic conductive polymers such as polyaniline (PANI) as a new class of polarizing matrices and report 1H polarizations of up to 5%. We also show that 13C spins of a host solution impregnated in porous conductive polymers can be hyperpolarized by relayed DNP. Such conductive polymers can be synthesized as chiral and display current induced spin selectivity leading to electron spin hyperpolarization close to unity without the need for low temperatures nor high magnetic fields. Our results show the feasibility of solid-state DNP in conductive polymers that are known to exhibit chirality-induced spin selectivity.
{"title":"Dynamic Nuclear Polarization with Conductive Polymers","authors":"Quentin, Stern, Guillaume, Verhaeghe, Théo, El Daraï, Damien, Montarnal, Nghia, Huu Le, Laurent, Veyre, Chloé, Thieuleux, Charlotte, Bocquelet, Olivier, Cala, Sami, Jannin","doi":"10.26434/chemrxiv-2024-q6dkh-v2","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-q6dkh-v2","url":null,"abstract":"The low sensitivity of liquid-state nuclear magnetic resonance (NMR) can be overcome by hyperpolarizing nuclear spins by dissolution dynamic nuclear polarization (dDNP). It consists of transferring the near-unity polarization of unpaired electron spins of stable radicals to the nuclear spins of interest at liquid helium temperatures, below 2 K, before melting the sample in view of hyperpolarized liquid-state magnetic resonance experiments. Reaching such a temperature is challenging and requires complex instrumentation, which impedes the deployment of dDNP. Here, we propose organic conductive polymers such as polyaniline (PANI) as a new class of polarizing matrices and report 1H polarizations of up to 5%. We also show that 13C spins of a host solution impregnated in porous conductive polymers can be hyperpolarized by relayed DNP. Such conductive polymers can be synthesized as chiral and display current induced spin selectivity leading to electron spin hyperpolarization close to unity without the need for low temperatures nor high magnetic fields. Our results show the feasibility of solid-state DNP in conductive polymers that are known to exhibit chirality-induced spin selectivity.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142226940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Proton-coupled electron transfer (PCET) reactions play a crucial role in the interconversion of metal-aqua and metal-hydroxo species present in transition metal complexes and oxide surfaces (M(III)-OH + e− + H+ M(II)-OH2). For ruthenium-based water oxidation catalysts, PCET reactions involved in the mechanism of oxygen evolution have demonstrated a strong dependence on the identity and concentration of the proton donor and acceptor with significant rate enhancements observed for electrocatalysis performed in acetate, phosphate, and borate buffered electrolytes. However, the systematic study of this phenomenon has been hampered by the inability to independently measure discrete rates for electron transfer (ET) and proton transfer (PT) under electrochemical applied potentials. Herein, the PCET kinetics and mechanism of metal aqua bond formation in a ruthenium water oxidation catalyst [Ru(tpy)(bpy′)H2O]2+, Ru(II)−OH2 where tpy is 2,2′:6′,2″-terpyridine and bpy′ is 4,4′-diaminopropylsilatrane-2,2′-bypyridine were investigated at a conductive metal oxide interface as a function of buffer identity and concentration. The reaction of interest was triggered by visible light excitation of the catalyst and the kinetics of the independent ET and PT steps of the PCET mechanism were determined through nanosecond transient absorption spectroscopy. Kinetic measurements performed in aqueous acetate, phosphate, or borate buffer solutions revealed two distinct regimes of PT kinetics solely dependent on the buffer concentration. At the greatest buffer concentrations investigated (2 M acetate) spectral signals corresponding to the discreet ET and PT steps were absent indicative in a change in underlying PCET mechanism. Likewise, kinetic modeling indicated that PT from protonated acetate or phosphate occurred with rate constants that were 2-4 orders of magnitude greater than those for bulk water. In all, these results suggest that the presence of buffer-bases can significantly enhance PCET rates and, in this reaction, may alter the underlying mechanism.
{"title":"Direct Evidence for Buffer-Enhanced Proton-Coupled Electron Transfer in Metal Aquo Bond Formation","authors":"Matthew, Kessinger, Gerald, Meyer, Thomas, Whittemore, Silvia, Grandi, Evgeny, Danilov, Stefano, Caramori, Felix, Castellano","doi":"10.26434/chemrxiv-2024-l776x","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-l776x","url":null,"abstract":"Proton-coupled electron transfer (PCET) reactions play a crucial role in the interconversion of metal-aqua and metal-hydroxo species present in transition metal complexes and oxide surfaces (M(III)-OH + e− + H+ M(II)-OH2). For ruthenium-based water oxidation catalysts, PCET reactions involved in the mechanism of oxygen evolution have demonstrated a strong dependence on the identity and concentration of the proton donor and acceptor with significant rate enhancements observed for electrocatalysis performed in acetate, phosphate, and borate buffered electrolytes. However, the systematic study of this phenomenon has been hampered by the inability to independently measure discrete rates for electron transfer (ET) and proton transfer (PT) under electrochemical applied potentials. Herein, the PCET kinetics and mechanism of metal aqua bond formation in a ruthenium water oxidation catalyst [Ru(tpy)(bpy′)H2O]2+, Ru(II)−OH2 where tpy is 2,2′:6′,2″-terpyridine and bpy′ is 4,4′-diaminopropylsilatrane-2,2′-bypyridine were investigated at a conductive metal oxide interface as a function of buffer identity and concentration. The reaction of interest was triggered by visible light excitation of the catalyst and the kinetics of the independent ET and PT steps of the PCET mechanism were determined through nanosecond transient absorption spectroscopy. Kinetic measurements performed in aqueous acetate, phosphate, or borate buffer solutions revealed two distinct regimes of PT kinetics solely dependent on the buffer concentration. At the greatest buffer concentrations investigated (2 M acetate) spectral signals corresponding to the discreet ET and PT steps were absent indicative in a change in underlying PCET mechanism. Likewise, kinetic modeling indicated that PT from protonated acetate or phosphate occurred with rate constants that were 2-4 orders of magnitude greater than those for bulk water. In all, these results suggest that the presence of buffer-bases can significantly enhance PCET rates and, in this reaction, may alter the underlying mechanism.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
First prepared in the late 70s, the pro-ligand 1,3-bis(3,5-dioxo-1-hexyl)benzene (H2bdhb) contains two acetoacetyl terminations linked to a central 1,3-phenylene unit through dimethylene bridges. Since each termination can be either in diketonic or keto-enolic form, in organic solution it exists as a mixture of three spectroscopically resolvable tautomers. In the presence of pyridine, Co2+ and the bdhb2- dianion form a crystalline dimeric compound with formula [Co2(bdhb)2(py)4] (2) and a Co•••Co separation of >11 Å. Complex 2 contains two pseudo-octahedrally coordinated and non-interacting high-spin cobalt(II) ions (S = 3/2) displaying a large easy-plane anisotropy (D ~ 70 cm-1), as consistently indicated by magnetic measurements, X-band EPR spectra, and complete active space self-consistent field/N-electron valence state perturbation theory (CASSCF/NEVPT2) calculations. At cryogenic temperatures and in an applied static magnetic field, the compound shows detectably slow magnetic relaxation, which occurs through direct and Raman mechanisms. Combined mass spectrometry, UV-Vis, and 1H/2H NMR data, including a determination of molecular weight by diffusion ordered spectroscopy (DOSY), show that 2 loses its dimeric structure in dichloromethane solution and rearranges to monomeric high-spin [Co(bdhb)(py)x] species (x = 0, 1, or 2) with concomitant partial dissociation of the py ligands. The X-band EPR spectra in a frozen CH2Cl2/toluene matrix concurrently suggest a significant alteration of the coordination environment upon dissolution. These observations are fairly well reproduced by density functional theory (DFT) and CASSCF/NEVPT2 calculations on the low-lying conformers of each species, as provided by an extensive conformational search based on meta-dynamics simulations and semiempirical tight-binding methods. After the vanadyl analogue, compound 2 provides the second example of polymerization isomerism in the 1:1 adducts of bdhb2- with divalent metal ions.
{"title":"Phase-dependent polymerization isomerism in the coordination complexes of a flexible bis(β-diketonato) ligand","authors":"Andrea, Cornia, Manuel, Imperato, Alessio, Nicolini, Matteo, Boniburini, Silvia, Gómez-Coca, Eliseo, Ruiz, Fabio, Santanni, Lorenzo, Sorace","doi":"10.26434/chemrxiv-2024-hghfg","DOIUrl":"https://doi.org/10.26434/chemrxiv-2024-hghfg","url":null,"abstract":"First prepared in the late 70s, the pro-ligand 1,3-bis(3,5-dioxo-1-hexyl)benzene (H2bdhb) contains two acetoacetyl terminations linked to a central 1,3-phenylene unit through dimethylene bridges. Since each termination can be either in diketonic or keto-enolic form, in organic solution it exists as a mixture of three spectroscopically resolvable tautomers. In the presence of pyridine, Co2+ and the bdhb2- dianion form a crystalline dimeric compound with formula [Co2(bdhb)2(py)4] (2) and a Co•••Co separation of >11 Å. Complex 2 contains two pseudo-octahedrally coordinated and non-interacting high-spin cobalt(II) ions (S = 3/2) displaying a large easy-plane anisotropy (D ~ 70 cm-1), as consistently indicated by magnetic measurements, X-band EPR spectra, and complete active space self-consistent field/N-electron valence state perturbation theory (CASSCF/NEVPT2) calculations. At cryogenic temperatures and in an applied static magnetic field, the compound shows detectably slow magnetic relaxation, which occurs through direct and Raman mechanisms. Combined mass spectrometry, UV-Vis, and 1H/2H NMR data, including a determination of molecular weight by diffusion ordered spectroscopy (DOSY), show that 2 loses its dimeric structure in dichloromethane solution and rearranges to monomeric high-spin [Co(bdhb)(py)x] species (x = 0, 1, or 2) with concomitant partial dissociation of the py ligands. The X-band EPR spectra in a frozen CH2Cl2/toluene matrix concurrently suggest a significant alteration of the coordination environment upon dissolution. These observations are fairly well reproduced by density functional theory (DFT) and CASSCF/NEVPT2 calculations on the low-lying conformers of each species, as provided by an extensive conformational search based on meta-dynamics simulations and semiempirical tight-binding methods. After the vanadyl analogue, compound 2 provides the second example of polymerization isomerism in the 1:1 adducts of bdhb2- with divalent metal ions.","PeriodicalId":9813,"journal":{"name":"ChemRxiv","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142214941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.26434/chemrxiv-2024-ld2k6
Michael, Webb, Shengli, Jiang
The architectural, compositional, and chemical complexities of polymers are fundamentally important to their properties; however, these same factors obfuscate effective predictions. Machine learning offers a promising approach for predicting polymer properties, but model transferability remains a major challenge, particularly when data is insufficient due to high acquisition costs and practical limitations. We explore the integration of polymer physics theory with machine learning architectures to enhance the predictive capabilities of polymer properties. Using a dataset of 18,450 polymers with diverse architectures, molecular weights, compositions, and chemical patterns, we focus on transferability tasks for predicting moments of the distribution of squared radius of gyration. Our tandem model, GC-GNN, which combines a graph neural network with a fittable model based on ideal Gaussian chain theory, surpasses both standalone polymer-physics and graph neural network models in predictive accuracy and transferability. We also demonstrate that predictive transferability varies with polymer architecture due to deviations from the ideal Gaussian chain assumption. This study highlights the potential of combining polymer physics with data-driven models to improve predictive transferability across diverse conditions and also pathways for improvement.
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