Mechanistic Aspects of Nucleophilic Substitution at Half-Sandwich Metal Complexes

The hydrolysis reactions of organometallic ruthenium(II) piano-stool complexes of the type [Ru II (η 6 -cymene)(L)Cl] 0/+ ( 1 − 5, where L = κ 1 - or κ 2 -1,1-bis(diphenylphosphino)methane, 1,1-bis(diphenylphosphino)methane oxide, κ 1 -mercaptobenzothiazole) have been studied using density functional theory at the B3LYP level. In addition to considering a syn attack in an associative fashion, where the nucleophile approaches from the same side as the leaving group, we have explored alternative paths such as an anti attack in an associative manner, where the nucleophile attacks from the opposite side of the leaving group. During the anti attack, an intermediate is formed and there is a coordination mode change of the arene ring from η 6 to η 2 along with its rotation. When the intermediate goes to the product, the arene ring slips back from η 2 to η 6 coordination. This coordinated movement of the arene ring makes the associative anti attack an accessible pathway for the substitution process. Our calculations predict very similar activation barriers for both syn and anti attacks. In the dissociative path, the rate-determining step is the generation of a coordinatively unsaturated 16-electron ruthenium species. This turns out to be viable once solvent effects are included. The large size of the ancillary ligands on Ru makes the dissociative process as favorable as the associative process. Activation energy calculations reveal that although the dissociative path is favorable for κ 1 complexes, both dissociative and associative processes can have significant contribution to the hydrolysis reaction in κ 2 complexes. Once activated by hydrolysis, these complexes react with guanine and adenine bases of DNA. The thermodynamic stabilities of complexes formed with the nucleobases are also presented.