A theoretical study of the methyl ligation in tetraaza macrocycle nickel complexes which model the acetyl-CoA synthase active site

Abstract

Recently, great attention has been devoted to the study of structural and functional features of the Cluster A of CO dehydrogenase/acetyl-CoA synthase as well as of several synthetic complexes which may serve as model systems (S.W. Ragsdale and C.G. Riordan, J. Biol. Chem., 1 (1996) 489). It has been shown experimentally that all these systems are capable of performing alkyl transfer reactions, but a general consensus concerning the reaction mechanism has not yet been reached. The aim of this study was the theoretical investigation, by means of the Hartree-Fock (HF) method, of the methyl ligation reaction to tetraaza macrocycle nickel complexes. To this end, the Hartree-Fock computational approach was first tested by comparing its results with those obtained experimentally and using other theoretical approaches. Once demonstrated that, for this class of compounds. Hartree—Fock calculations produce structural and energetic data fairly accurately, the study was extended to the investigation of possible methyl ligation paths to the RRRR and RRSS configurational isomers of [Ni(cyclam)] complexes. These reactions are discussed considering the geometries of the nickel complexes which correspond to optimum ab initio structures as well as the associated reaction energies and electron and spin distribution. Our theoretical results indicate that (i) the methyl transfer reaction is highly unfavoured for Ni(II) complexes, (ii) the most probable mechanism of methyl ligation involves methyl radical transfer, in agreement with some proposals based on experimental observations, and (iii) the RRRR [Ni(cyclam)] isomer undergoes a more exothermic methyl ligation reaction with respect to the RRSS isomer. Furthermore, this difference in reactivity can be rationalized on the basis of steric and electronic effects, revising a previously proposed hypothesis.