Reactions of [M(H2O)(n)](+), M = Cr, Mn, Fe, Co, Ni, Cu, and Zn, n < 50, with CH3CN are studied in the gas phase by Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Sequential uptake of 4-6 acetonitrile molecules is observed for all metals. Rate constants show a weak dependence on both the metal and the number of acetonitrile molecules already in the cluster. Nanocalorimetry yields the enthalpy of the first reaction step. For most metals, this is consistent with a ligand exchange of water against acetonitrile. For M = Cr, however, the strong exothermicity of Delta E-nc = -195 +/- 26 kJ mol(-1) suggests an electron transfer from Cr+ to CH3CN. Exclusively for M = Zn, a relatively slow oxidation of the metal center to Zn2+, with formation of ZnOH+ and release of CH3CNH or CH3CHN is observed. Density functional theory molecular dynamics simulations and geometry optimizations show that charge transfer from Zn+ to CH3CN as well as the subsequent proton transfer are associated with a barrier.