Silver(i) affinities of amides: a combined ab initio and experimental study

Abstract

The interaction of Ag⁺ with amides was studied through prototypical systems mimicking the binding of Ag⁺ to the peptide bond. The Ag⁺ binding affinities (energies) of formamide, N-methylformamide, N,N-dimethylformamide, acetamide, N-methylacetamide and N,N-dimethylacetamide were determined by the mass spectrometric kinetic method to be 162, 179, 193, 181, 198 and 208 kJ mol⁻¹, respectively, with an estimated uncertainty of ±11 kJ mol⁻¹. The relative stability of different possible Ag⁺ binding modes was investigated effectively at the ab initio CCSD(T)/[HW(f),6-31+G(d)] level of theory. The absolute theoretical affinities are in good general agreement with the experimental values, even though calculated values tend to be too high by an average of 10 kJ mol⁻¹. The theoretical results show that Ag⁺ binds preferentially to the amide carbonyl oxygen, whereas monodentate binding to the amino nitrogen, or bidentate binding to both oxygen and nitrogen, are about 40 to 60 kJ mol⁻¹ less stable. Methyl substitution at the amide carbon and amino nitrogen enhances the Ag⁺ affinity by increasing the molecular polarizability of the amide. The effects of C-methyl and N-methyl substitution on Ag⁺ binding at the amide carbon and amino nitrogen are found to be significantly different and this difference is discussed.