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) studies were performed for alcohol and water complexes of 1H-pyrrolo[3,2-h]quinoline (PQ), 2-(2'pyridyl)indole (PyIn-2), and 7-azaindole (7AI). The experiment shows that these molecules form different types of intermolecular complexes 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 correctly reproduce these observations and allow predictions for water solvates that have not been yet studied experimentally. MD simulations show that for PQ, the population of cyclic 1:1 species is dominant even in bulk methanol. 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 noncyclic 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 PyIn-2, which still form mainly cyclic 1:1 complexes solvated by another alcohol molecule, and 7AI, which preferentially forms a triply hydrogen-bonded, quasi-eight-membered ring structure. These differences are retained in bulk methanol. DFT results predict that the stability of the cyclic 1:1 complexes with methanol increases in the order 7AI < PyIn-2 < PQ. An opposite trend is obtained for 1:2 solvates that form a closed network of three hydrogen bonds.