Thermodynamics of homolytic C–H bond cleavage in proteinogenic α-amino acids: Zwitterions in aqueous solution

Abstract

This work provides the systematic M06-2X theoretical study of C–H bond dissociation enthalpies (BDE) in aqueous solution for 21 proteinogenic α-amino acids present in eukaryotes. The results reveal that the formation of zwitterions in an aqueous solution significantly affects the thermodynamics of the homolytic C–H bond cleavage for alpha, beta, and gamma carbon atoms. We have found that zwitterions show significantly greater stability against a free radical attack due to considerably higher enthalpies of the hydrogen atom abstraction from the C_α atom. This kind of stabilization can be beneficial during the synthesis of proteins in cells. Compared to the canonical forms, the average increase in BDE is ca. 60 kJ mol⁻¹. For all amino acids, the BDE of the most labile C–H bond was calculated using the ab initio G4 and G4(MP2) composite methods, as well.