The pKa Slide Rule as a Tool for Predicting Hydrogen-Bond Strengths

D-H...:A H-bonded interactions (D and :A = H-bond donor and acceptor) display a wide interval of binding energies, EHB, ranging from less than one to more than 30 kcal/mol (45 kcal/mol if [F...H...F]- bonds are considered) because of two independent factors: (i) H-bonds are the stronger the more electronegative the donor (D) and acceptor (:A) atoms are [1,2]; (ii) for a same D-A couple [or H-bond electronegativity class, EC(D,A)] H-bonds are the stronger the more similar the proton affinities of D and A are, a fact easily expressible in terms of the PA/pKa equalization principle [3-5] for which really strong H-bonds can be observed only when the differences ΔPA = PA(D-) - PA(:A) or ΔpKa = pKa(D-H) - pKa(A-H+) tend to zero (PA being the gas-phase proton affinity and pKa the co-logarithm of the corresponding acid-base dissociation constant in water). These properties are at variance with all other types of chemical bond and derive from the dual nature of the H-bond, which is not really ‘a bond’ but rather ‘two bonds’ formed by a same central proton with the two lone pairs located on the so-called donor and acceptor atoms. These considerations emphasize the role played by PA/pKa equalization in strengthening the H-bond, a hypothesis often invoked but never fully verified in the past which is now reconsidered in this communication by a new instrument, the pKa slide rule. This is a bar-chart reporting, in separate scales, the pKa’s of the D-H proton donors and :A proton acceptors most frequently involved in D-H...:A bond formation (103 entries over the -14<pKa<53 range). Allowing the two scales to shift so to bring into coincidence the donor and acceptor molecules, the ruler permits graphical evaluation of ΔpKa and then empirical appreciation of D-H...:A bond strengths according to the pKa equalization principle.