2. From the Gas Phase to a Lipid Membrane Environment: DFT and MD Simulations of Structure and Dynamics of Hydrogen-Bonded Solvates of Bifunctional Heteroazaaromatic Compounds

We present a review of our recent developments in computational modeling of hydrogen-bonding-induced phenomena in a series of biologically relevant bifunctional proton donor–acceptor heteroazaaromatic compounds. Different types of hydrogen-bonded solvates, in which water or alcohol molecules form a bridge connecting the proton donor (pyrrole NH group) and the acceptor (pyridine or quinoline nitrogen) atoms of bifunctional solutes, are explored by combining density functional theory (DFT) and molecular dynamics (MD) simulation approaches. Structure and dynamics of multiple hydrogen-bonded solute-solvent complexes are studied starting from isolated complexes in the gas phase, elucidating their solvation dynamics in solutions and, finally, in a heterogeneous environment of a lipid bilayer. Our results indicate that the structure, stoichiometry and hydrogen bond strength in such solvates are tuned by local topologies of the hydrogen-bonding sites of a bifunctional proton donor–acceptor molecule. A role of such solvates in hydrogen-bond-dependent photophysics and in controlling excited-state behavior of heteroazaaromatic compounds is discussed.