Neutral vs. zwitterionic form of arginine—an ab initio study

Abstract

The problem of the intramolecular proton transfer isomerism in arginine, leading to conventional neutral and zwitterionic forms of this compound, is addressed by high level theoretical models. It is shown that arginine has two neutral and two zwitterionic isomers implying that there exist two additional unconventional isomers, which have not been identified so far. It appears also that the most stable neutral isomer is energetically more favourable than both zwitterions, which implies that the former should be preferred in the gas phase. Examination of atomic charges obtained by the electron density partitioning techniques reveals that the charge distributions of neutral and zwitterionic isomers are not as widely different as expected. This finding is counterintuitive, since it contradicts the classical notion of chemical bonding and a customary picture of zwitterions involving two local complementary fragments possessing unit charges of opposite sign. The true distribution of the electron density is more uniform and quite similar to that of the neutral form. The proton affinity of arginine is estimated to be 249 kcal mol–1. Hence, it follows that arginine is a very basic compound although it belongs to a family of 20 fundamental α-amino acids. A very high proton affinity is interpreted in terms of the resonance effect spurred by protonation in the guanidine moiety and by a strong hydrogen bonding taking place in the protonated form.