Molecular dynamics and DFT studies of intermolecular hydrogen bonds between bifunctional heteroazaaromatic molecules and hydroxylic solvents

Molecular dynamics (MD) and ab initio/density functional theory (DFT) studi es were performed for alcohol and water complexes of 1H-pyrrolo[3,2-h]quino line (PQ), 2-(2'pyridyl)indole (PyIn-2), and 7-azaindole (7AI). The experim ent shows that these molecules form different types of intermolecular compl exes with hydroxylic solvents in the ground electronic state. The solvates of PQ consist mostly of cyclic, doubly hydrogen-bonded species; in PyIn-2, both cyclic and noncyclic forms are detected, while in 7AI the ground state population of cyclic species seems to be negligible. Our calculations corr ectly reproduce these observations and allow predictions for water solvates that have not been yet studied experimentally. MD simulations show that fo r PQ, the population of cyclic 1:1 species is dominant even in bulk methano l. On the contrary, no such species are predicted in bulk methanol for 7AI. Three forms are obtained for PyIn-2 in bulk methanol: one cyclic and two n oncyclic ones, with comparable populations. Simulations of dilute mixtures with methanol in n-hexane reveal that a I:1 cyclic structure is preferable in all compounds. At 1:2 stoichiometry, differences arise between PQ and Py In-2, which still form mainly cyclic 1:1 complexes solvated by another alco hol molecule, and 7AI, which preferentially forms a triply hydrogen-bonded, quasi-eight-membered ring structure. These differences are retained in bul k methanol. DFT results predict that the stability of the cyclic 1:1 comple xes with methanol increases in the order 7AI < PyIn-2 < PQ. An opposite tre nd is obtained for 1:2 solvates that form a closed network of three hydroge n bonds.