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Abstract

The biologically relevant S-alkylation reactions of thiolate ligands bound to a transition metal ion were investigated with particular attention paid to the role of the metal identity: Zn^II versus Ni^II. The reactivity of two mononuclear diamine dithiolate Zn and Ni complexes with CH₃I was studied. With the [ZnL] complex (1) (LH₂ = 2,2′-(2,2′-bipyridine-6,6′-diyl)bis(1,1-diphenylethanethiolate)), a double S-methylation occurs leading to [ZnL^Me₂I₂] (1^Me₂), while with [NiL] (2), only the mono-S-methylated product [NiL^Me]I (2^Me) is formed. Complexes 1 and 1^Me₂ have been characterized by X-ray crystallography, while the structures of 2 and 2^Me have been previously described. The kinetics of the first S-methylation reaction, investigated by ¹H NMR, is found to follow a second-order rate law, and the activation parameters, ΔH^⧧ and ΔS^⧧, are similar for both 1 and 2. S K-edge X-ray absorption spectroscopy measurements have been carried out on 1, 2, and 2^Me, and a TD-DFT approach was employed to interpret the data. The electronic structures of 1 and 2 calculated by DFT reveal that the thiolate–metal bond is predominantly ionic in 1 and covalent in 2. However, evaluation of the molecular electrostatic potential minima around the lone pairs of the thiolate sulfur atoms gives similar values for 1 and 2, suggesting a comparable nucleophilicity. The DFT-optimized structures of the mono-S-methylation products have been calculated for the Zn and Ni complexes. Molecular electrostatic potential analysis of these products shows that (i) the nucleophilicity of the remaining thiolate sulfur atom is partly quenched for the Ni complex while it is conserved in the Zn complex and, more importantly, (ii) that the accessibility for the methyl transfer agent to the remaining thiolate is favored for the mono-S-methylated Zn complex compared to the Ni one. This explains the absence of a double S-methylation process in the case of the Ni complex at room temperature.