Optimizations at the BLYP and B3LYP levels are reported for mixed uranyl-water/acetonitrile complexes [UO2(H2O)(5-n)(MeCN)(n)](2+) (n = 0-5), in both the gas phase and a polarizable continuum modeling acetonitrile. Car-Parrinello molecular dynamics (CPMD) simulations have been performed for these complexes in the gas phase, and for selected species (n = 0, 1, 3, 5) in a periodic box of liquid acetonitrile. According to structural and energetic data, uranyl has a higher affinity for acetonitrile than for water in the gas phase, in keeping with the higher dipole moment and polarizability of acetonitrile. In acetonitrile solution, however, water is the better ligand because of specific solvation effects. Analysis of the dipole moment of the coordinated water molecule in [UO2(H2O)(MeCN)(4)](2+) reveals that the interaction with the second-shell solvent molecules (through fairly strong and persistent O-H center dot center dot center dot N hydrogen bonds) causes a significant increase of this dipole moment (by more than 1 D). This cooperative polarization of water reinforces the uranyl-water bond as well as the water solvation via strengthened (UO2)OH2 center dot center dot center dot NCMe hydrogen bonds. Such cooperativity is essentially absent in the acetonitrile ligands that make much weaker (UO2)NCMe center dot center dot center dot NCMe hydrogen bonds. Beyond the uranyl case, this study points to the importance of cooperative polarization effects to enhance the Mn+ ion affinity for water in condensed phases involving Mn+-OH2 center dot center dot center dot A fragments, where A is a H-bond proton acceptor and Mn+ is a hard cation.