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A functional group interaction profile maps the free-energy contribution of a solute donor–acceptor contact after accounting for competing solvent contacts. Solvent polarity and preferential solvation determine favourable and unfavourable regions.

The functional group interaction profile compares donor strength $\alpha$ and acceptor strength $\beta$. In water, strong–strong contacts compensate for desolvation, giving the upper-right black region. Strong–weak contacts lose favourable solvent interactions without adequate replacement, giving the two grey regions. Weak–weak association gives the lower-left black region through the hydrophobic effect.

Ethanol's ethyl groups preferentially solvate weakly polar sites, removing this incentive for their association: the lower-left region becomes approximately neutral. Its hydroxyl group retains competition for hydrogen bonds elsewhere in the profile.^[ref]