Outline of a transition-state hydrogen-bond theory

Though the H-bond is well characterized as a D–H⋯:A three-center-four-electron interaction, the formulation of a general H-bond theory has turned out to be a rather formidable problem because of the extreme variability of the bonds formed (for instance, O–H⋯O energies range from 0.1 to 31 kcal mol−1). This paper surveys our previous contributions to the problem, including: (a) the H-bond chemical leitmotifs (CLs), showing that there are only four classes of strong H-bonds and one of moderately strong ones; (b) the PA/pKa equalization principle, showing that the four CLs forming strong H-bonds are actually molecular devices apt to equalize the acid–base properties (PA or pKa) of the H-bond donor and acceptor groups; (c) the driving variable of the H-bond strength, which remains so identified as the difference ΔpKa=pKAH(D–H)−pKBH(A–H+) or, alternatively, ΔPA=PA(D−)−PA(A); and, in particular, (d) the transition-state H-bond theory (TSHBT), which interprets the H-bond as a stationary point along the complete proton transfer pathway going from D–H⋯A to D⋯H–A via the D⋯H⋯A transition state. TSHBT is verified in connection with a series of seven 1-(X-phenylazo)-2-naphthols, a class of compounds forming a strong intramolecular resonance-assisted H-bond (RAHB), which is switched from N–H⋯O to N⋯H–O by the decreasing electron-withdrawing properties of the substituent X. The system is studied in terms of: (i) variable-temperature X-ray crystallography; (ii) DFT emulation of stationary points and full PT pathways; (iii) Marcus rate-equilibrium analysis correlated with substituent LFER Hammett parameters.