DFT-SCRF Calculations of Nitrogen Isotopic Reduced Partition Function Ratios for Amino Acids in Aqueous Solution at pH 7.4

• Published in: The journal of physical chemistry. A, Molecules, spectroscopy, kinetics, environment, & general theory Molecules, spectroscopy, kinetics, environment, & general theory, 2024-12, Vol.128 (48), p.10345-10357
• Main Authors: Yanase, Satoshi, Oi, Takao, Kikawada, Yoshikazu
• Format: Article
• Language: English
• Subjects: A: Structure, Spectroscopy, and Reactivity of Molecules and Clusters; Amino Acids - chemistry; Density Functional Theory; Hydrogen Bonding; Hydrogen-Ion Concentration; Nitrogen - chemistry; Nitrogen Isotopes; Solutions; Water - chemistry
• ISSN: 1089-5639; 1520-5215; 1520-5215
• DOI: 10.1021/acs.jpca.4c04487

Using the self-consistent reaction field (SCRF) method, the nitrogen isotopic reduction partition function ratio (RPFR), a fundamental physical quantity for theoretical consideration of equilibrium isotope effects, was evaluated by density functional theory (DFT) for 20 proteinogenic and two related amino acids under physiological conditions at pH 7.4. At this pH value, all amino acids were of the zwitterion-type form with α-NH3 + and α-COO– groups, regardless of the net charge of −1 (monoanion), 0 (zwitterion), or +1 (monocation). The largest RPFR value by far was for proline (Pro). This is due to the fact that the nitrogen atom of Pro has two C–N bonds and two N–H bonds, whereas the α-nitrogen atoms of other amino acids form one C–N bond and three N–H bonds. There was a clear correlation between the RPFR value of α-nitrogen and the distance of the N–H covalent bond of the hydrogen atom involved in the formation of the intramolecular hydrogen bond (HB); the stronger the intramolecular HB, the lower the RPFR value of α-nitrogen. It was suggested that equilibrium isotope effects were partially responsible for the nitrogen isotope fractionation in the enzymatic glutamic acid/aspartic acid transamination and in ammonia assimilation during the formation of glutamine from glutamic acid.