Low barrier hydrogen bonds within salicylate mono-anions

Progressive incorporation of electron-withdrawing substituents into the aromatic ring of salicylic acid selectively acidifies the ArOH group, until the intrinsic pKa values of the ArOH and ArCO2H groups become matched, as in the case of 3-chloro-5-nitrosalicylic acid. The corresponding salicylate mono-anion at −50°C in aqueous deuterioacetone solution exhibits a low barrier hydrogen bond intramolecularly linking the adjacent anionic oxygens, according to NMR evidence (δ 18.1 ppm for bridging proton, H–D fractionation factor φ 0.4, versus δ 14 and φ 0.7 for a more typical asymmetric salicylate H-bond). Induction of this unique linkage correlates with a 1.4 pK-unit increase in acidity for pKa1 of a substituted salicylic acid, while not perturbing pKa2. For the postulated occurrence of such anomalous H-bonds in the course of enzymic catalysis, the implications are that only ∼2 kcal/mol of special transition-state stabilization energy might be available from this source, and that it should become manifested chiefly in a facilitation of general acid–base proton transfers.