Low barrier hydrogen bonds within salicylate mono-anions

Progressive incorporation of electron-withdrawing substituents into the aromatic ring of salicylic acid selectively acidities the ArOH group, until the intrinsic pK(a) 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 degreesC in aqueous deuterioacetone solution exhibits a low barrier hydrogen bond intramolecularly linking the adjacent anionic oxygens, according to NMR evidence (delta 18.1 ppm for bridging proton, H-D fractionation factor phi 0.4, versus delta 14 and phi 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 pK(a1) of a substituted salicylic acid, while not perturbing pK(a2). For the postulated occurrence of such anomalous Ii-bonds in the course of enzymic catalysis, the implications are that only similar to2 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. (C) 2001 Elsevier Science Ltd. All rights reserved.