High throughput experiments using a molecular recognition probe reveal a simple relationship between solvent functional group concentration and selective solvation. The 1 : 1 association constant for the H-bonding interaction between tri-n-butylphosphine oxide and 4-phenylazophenol was measured in 1088 different alkane–ether mixtures using a UV-Vis plate reader. Although the stability of the complex decreased with increasing concentration of the more polar ether cosolvent as expected, the results show that it is the functional group composition rather than the constitution of the solvent molecules or the properties of the bulk liquid that determines the solvation thermodynamics. Thus the solvent properties of a simple ether can be reproduced by an appropriate mixture of a polyether and an alkane that has the same net concentration of ether oxygen functional groups. The results suggest that solvation may be understood at the molecular level simply by considering the polarities and the concentrations of the functional groups present in the solvent, because these are the parameters that affect local solvation interactions with the solutes.