The concept of acid-base interactions between metallic cations and putative ligands, widely used in cation coordination and complexation chemistry, is discussed from the analysis of M 3ϩ lanthanide cation binding to phosphoryl ligands in the gas phase. We report quantum mechanical calculations on the effect of alkyl vs. O-alkyl substitution in phosphoryl-containing ligands L interacting with M 3ϩ (La 3ϩ , Eu 3ϩ , Yb 3ϩ ; L = Me 3 PO, Me 2 (MeO)PO, Me(MeO) 2 PO and (MeO) 3 PO). In the charged 1 : 1 LM 3ϩ complexes, O-alkyl substituted ligands yield lower interaction energies than the alkyl substituted ones, in agreement with the calculated gas phase basicities. However, the effect is surprisingly small (about 10 times smaller than the alkyl vs. aryl substituent effect). The comparison of LM 3ϩ with neutral LMCl 3 and L 2 MCl 3 complexes reveals an amplification of O-alkyl vs. alkyl weakening effect, though, due to repulsions between L, the counterions, and the other ligand, and to the softer character of the metal-ligand bond. Thus, in condensed phases where the first coordination shell of the cation is saturated and generally contains neutralizing counterions, the better binding of (alkyl) n PO ligands, compared to (alkyl-O) n PO ones results mostly from "steric" interactions in the first coordination sphere, rather than from the changes in oxygen "basicity". The conclusions are validated by a number of comparisons using polarization functions on the ligand and accounting for correlation effects (MP2 or DFT-B3LYP calculations). They are important in the context of designing efficient ionophores for lanthanide and actinide cations.