biostudies-literatureZhou SShenzhen Municipal Science and Technology Innovation CommissionNational Institutes of HealthNational Institute of General Medical SciencesNIGMS NIH HHS137-141https://www.ebi.ac.uk/biostudies/studies/S-EPMC8058934biostudies-literatureUnknown143(1)In aqueous solution, biological decarboxylation reactions proceed irreversibly to completion, whereas the reverse carboxylation processes are typically powered by the hydrolysis of ATP. The exchange of the carboxylate of ring-substituted arylacetates with isotope-labeled CO₂ in polar aprotic solvents reported recently suggests a dramatic change in the partition of reaction pathways. Yet, there is little experimental data pertinent to the kinetic barriers for protonation and thermodynamic data on CO₂ capture by the carbanions of decarboxylation reactions. Employing a combined quantum mechanical and molecular mechanical simulation approach, we investigated the decarboxylation reactions of a series of organic carboxylate compounds in aqueous and in dimethylformamide soluJournal of the American Chemical SocietyOrigin of Free Energy Barriers of Decarboxylation and the Reverse Process of CO₂ Capture in Dimethylformamide and in Water.PMC8058934R35 GM134881GM134881GM046736R01 GM046736KQTD2017-0330155106581Richard JPNguyen BTZhou SKluger RGao JfalseOrigin of Free Energy Barriers of Decarboxylation and the Reverse Process of CO₂ Capture in Dimethylformamide and in Water.In aqueous solution, biological decarboxylation reactions proceed irreversibly to completion, whereas the reverse carboxylation processes are typically powered by the hydrolysis of ATP. The exchange of the carboxylate of ring-substituted arylacetates with isotope-labeled CO₂ in polar aprotic solvents reported recently suggests a dramatic change in the partition of reaction pathways. Yet, there is little experimental data pertinent to the kinetic barriers for protonation and thermodynamic data on CO₂ capture by the carbanions of decarboxylation reactions. Employing a combined quantum mechanical and molecular mechanical simulation approach, we investigated the decarboxylation reactions of a series of organic carboxylate compounds in aqueous and in dimethylformamide solu2021-01-01T00:00:00Z2021 Jan2026-06-06T20:34:24.894Z2022-02-11T15:11:08.44ZS-EPMC80589343337579210.1021/jacs.0c12414