Effect of solvent on proton location and dynamic behavior in short intramolecular hydrogen bonds studied by molecular dynamics simulations and NMR experiments

Abstract

Hydrogen phthalate anion has a short strong O–H–O hydrogen bond (H-bond). According to previous experimental studies, the H-bond is asymmetric and two tautomers are interconverted in aqueous solutions. In the present study, the effects of polar solvents on the H-bond in a zwitterionic hydrogen phthalate derivative 1 were investigated by quantum mechanics/molecular mechanics molecular dynamics (MD) simulations. The analyses of the trajectories for the methanol solution showed that the H-bonding proton tends to be located closer to the carboxylate group that forms fewer intermolecular H-bonds, than to the other carboxylate group and that the intramolecular proton transfer in 1 is triggered by the breakage and/or formation of an intermolecular H-bond. The enol form of dibenzoylmethane (2) also has a short H-bond, and the OH bond is reported to be rather long (>1.1Å) in the crystal. In the present study, the effects of the solvent on the H-bond in 2 were investigated by molecular orbital (MO) calculations, MD simulations and nuclear magnetic resonance (NMR) spectroscopy. Density functional theory (DFT) calculations for 2 in vacuum indicated that the barrier height for the intramolecular proton transfer is almost the same as the zero-point energy of the vibrational ground state, resulting in broad distribution of the proton density along the H-bond, owing to the nuclear quantum effect. The OH distances were determined in CCl4, acetonitrile, and dimethylsulfoxide solutions from the magnetic dipolar interactions between the 17O and 1H nuclei monitoring the nuclear magnetic relaxation times of 1H. The experimental results indicated that the H-bond geometry of 2 is influenced by the interactions with dimethylsulfoxide, suggesting the formation of a bifurcated H-bond, which was supported by the DFT calculations. The MD simulations for the methanol solution of 2 showed that the asymmetry of the OH distance is correlated with the asymmetry in the electrostatic field of the solvent, although the correlation is weaker than that for the methanol solution of 1. The lower sensitivity of 2 to the solvent is attributed to the smaller number of oxygen atoms and the less negative electrostatic potential at the proton-accepting sites. The present study indicates that the specific interactions with protic solvents or strong H-bond-accepting solvents affect the geometry and dynamic behavior of short intramolecular H-bonds.