In proteins as well as host molecules, metal ions generally bind to a shell of polar hydrophilic residues surrounded by a shell of nonpolar hydrophobic groups. The hydrophilic protein residues tend to bind directly to the metal (inner-sphere mode), instead of indirectly via a metal-bound water molecule (inner-sphere mode). However, it is not fully understood why metal ions tend to bind in an inner-sphere fashion and at centers of high hydrophobic contrast. Ab initio and continuum dielectric calculations have been employed to compute the free energy (Delta G(ex)) of the exchange reaction between a metal-bound water molecule and ligands of biological interest in metal complexes for various dielectric media. The results show that Delta G(ex) is sensitive to the dielectric constant of the environment and that a low dielectric medium favors the inner-sphere binding of protein ligands, especially negatively charged amino acid residues, to the metal.