To verify that this behavior is not specific to water, we used methanol as an alternative HB donor; this is an important test, as methanol is a model for the amino acid sidechains of serine or threonine, and the largest experimentally observed ∆𝜈̅ 𝐻𝐵 occurred for a threoninenitrile interaction. We found that the VSE model's ability to recapitulate the DFT results for TDMs is just as robust as in the case where water is the HB donor (R 2 = 0.96, Fig. ), and highly similar VSE parameters were obtained to those derived for water H-bonding scenarios (Table ). Yet, the correlation of VSE (eq. 1a) and DFT 𝜈̅ values for nitriles with methanol HBs is just as poor as the case for water HBs (R 2 = -4.2, Fig. ).