Tuning of hydrogen bond strength using substituents on phenol and aniline: A possible ligand design strategy

Tuning of hydrogen bond strength using substituents on phenol and aniline: A possible ligand design strategy Using Density Functional Theory, the hydrogen bonding energy is calculated for the interaction of phenol and aniline with four model compounds representing the protein backbone and various amino acid side chain residues. The models are methanol, protonated methylamine, formaldehyde and acetate anion. The H- bond energies for the uncharged species are similar to2.5 kcal mol(-1), whereas the charged model compounds bind with much higher energies of similar to20 kcal mol(-1). The effect of para-substitution on the hydrogen bond energies is determined. Substitution has little effect on the H-bond energy of the neutral complexes (