The kinetic shift that exists between two competing unimolecular fragmentation processes has been used to establish whether or not gas-phase Mn 2ϩ exhibits preferential solvation when forming mixed clusters with water and methanol. Supported by molecular orbital calculations, these first results for a metal dication demonstrate that Mn 2ϩ prefers to be solvated by methanol in the primary solvation shell. (J Am Soc Mass Spectrom 2008, 19, 520 -530 [4 -9], but equally important is behavior in many-component solvents, where competing interactions may be dominated by differences in molecular properties [10 -12]. In general, a condensed phase solution containing solvents with very similar pure-state properties might be expected to behave in a manner that reflects the composition of the solvent mixture [13]. There have been several attempts to simulate the behavior of metal dications in mixed solvent systems, [14 -18], and of particular significance to the work discussed here are the molecular dynamics studies of Day and Patey [14,15]. From simulations of an ion in the presence of water and methanol they concluded that a positively charged solute exhibits a pronounced preference for water. If there are large differences in the solvating abilities of the components, selective or preferential solvation may occur [11,12]; however, the degree of averaging present in a typical condensed phase system means that subtle effects due to small differences in free energy are unlikely to make their presence felt [13]. In contrast, the consequences of small, individual differences in molecular properties can be amplified in the gas phase because of the influence they may have on establishing equilibria or determining fragmentation pathways [10, 19 -21]. Presented here are the results of a study designed to see if an established technique for generating multiply charged metal/solvent complexes in the gas phase can yield useful information on behavior in mixed solvent systems. From this first study, the experimental results demonstrate that for water and methanol as solvents, gas-phase Mn 2ϩ does exhibit preferential solvation. This conclusion is supported by detailed molecular orbital calculations on a wide range of mixed [Mn(MeOH) 2ϩ complexes, which show that small differences in the binding energies of methanol and water are sufficient to account for the experimental results. ExperimentalThe experimental apparatus used for the generation and detection of gas-phase multiply charged metalligand complexes has been described extensively in previous publications [22]. Briefly, mixed neutral argon/ligand clusters are produced by the adiabatic expansion of solvent vapor mixed with argon through a pulsed supersonic nozzle. Previous work on the preferential solvation of hydrogen ions in clusters composed of methanol and water showed that the composition of ionized clusters depended quite significantly on the composition of the coexpansion mixture [19]. In this study, several mixtures were evaluated, but it was found that a ratio of 5:1,...