Computational study of the thermodynamic stabilities of hydrogen-bonded complexes in solution

Understanding of the multiple H-bonding arrays of heterocyclic compounds is essential to design effective building blocks of supramolecular polymers. We have carried out a comprehensive computational study on the thermodynamic stabilities of thirty-six H-bonded complexes with all possible H-bonding arrays in the gas phase and chloroform solvent by using M06-2X, SMD calculations and cc-pVDZ basis set. The multiple H-bonding arrays include donor acceptor–acceptor donor (DA–AD), DD–AA for the doubly H-bonded pairs, and DAD–ADA, DDA–AAD and DDD–AAA for the triply H-bonded pairs. The computational results have provided insights into the geometrical, energetic and solvation effects on the stabilities of these H-bonded complexes. The calculated free energies of association for the DD–AA (8–9) and the DDD–AAA (33–35, 36–35) H-bonded complexes are found to be inconsistent with the experimental measurements and observations that these complexes are the most strongly doubly and triply H-bonded pairs in solution, respectively, while the calculated binding free energies for all other H-bonding arrays are in good agreement with experimental values. The computational protocol can be used by practical chemists and undergraduate researchers as an efficient and state-of-the-art tool to study H-bonding interactions in supramolecular chemistry.