Exploring the Dynamical Nature of Intermolecular Hydrogen Bonds in Benzamide, Quinoline and Benzoic Acid Derivatives

Abstract

The hydrogen bonds properties of 2,6-difluorobenzamide, 5-hydroxyquinoline and 4-hydroxybenzoic acid were investigated by Car-Parrinello and path integral molecular dynamics (CPMD and PIMD), respectively. The computations were carried out in vacuo and in the crystalline phase. The studied complexes possess diverse networks of intermolecular hydrogen bonds (N-H…O, O-H…N and O-H…O). The time evolution of hydrogen bridges gave a deeper insight into bonds dynamics, showing that bridged protons are mostly localized on the donor side; however, the proton transfer phenomenon was registered as well. The vibrational features associated with O-H and N-H stretching were analyzed on the basis of the Fourier transform of the atomic velocity autocorrelation function. The spectroscopic effects of hydrogen bond formation were studied. The PIMD revealed quantum effects influencing the hydrogen bridges providing more accurate free energy sampling. It was found that the N…O or O…O interatomic distances decreased (reducing the length of the hydrogen bridge), while the O-H or N-H covalent bond was elongated, which led to the increase in the proton sharing. Furthermore, Quantum Theory of Atoms in Molecules (QTAIM) was used to give insight into electronic structure parameters. Finally, Symmetry-Adapted Perturbation Theory (SAPT) was employed to estimate the energy contributions to the interaction energy of the selected dimers.

Keywords: CPMD; PIMD; QTAIM; SAPT; hydrogen bond; non-covalent interactions; spectroscopic signatures.

Figure 1

Crystalline (first row) and gaseous phases (second row) of (A) 2,6-difluorobenzamide, (B) 5-hydroxyquinoline, and (C) co-crystal of 4-hydroxybenzoic acid and quinoxaline. For clarity, the oxygen donor atoms for (C) are denoted as OD1, OD2 and OD3—this adopted nomenclature is used throughout the study. Dotted line indicates the intermolecular hydrogen bond. Color coding: white—hydrogen, grey—carbon, red—oxygen, blue—nitrogen, green—fluorine.

Figure 2

Dimers taken from the crystalline phase of (D) 2,6-difluorobenzamide and (E) 4-hydroxybenzoic acid to study intermolecular hydrogen bonds. Dotted line indicates the intermolecular hydrogen bond.

Figure 3

Atomic velocity power spectra obtained from the CPMD simulations. Left panel: the whole atomic spectra in the gas phase. Middle panel: the whole atomic spectra in the crystalline phase. Right panel: the contribution of the bridged protons in the crystalline and in the gaseous phases. (A) 2,6-difluorobenzamide, (B) 5-hydroxyquinoline and (C) 4-hydroxybenzoic acid.

Figure 4

Histograms presenting the relationship between the length of the corresponding donor–proton covalent bonds as well as the distance between the proton and its acceptor. CPMD vs. PIMD in the crystalline phase. (A) 2,6-difluorobenzamide, (B) 5-hydroxyquinoline and (C) 4-hydroxybenzoic acid. ND, OD and CD indicate proton donors. Probability density isocontours drawn at the 1 Å${}^{-2}$ value.

Figure 5

Time evolution of the metric parameters between the atoms involved in the hydrogen bond formation in the studied dimers. (D) 2,6-difluorobenzamide, (E) 4-hydroxybenzoic acid.

Figure 6

Potential of mean force (PMF) for the proton motion in the hydrogen bond of examined dimers with respect to the distance between the proton and its acceptor. (D) 2,6-difluorobenzamide and (E) 4-hydroxybenzoic acid.

Figure 7

QTAIM molecular graphs of the studied dimers. Ball and stick model was used for visualization. Bond paths, BCPs and RCPs are presented as green lines and small green and yellow spheres, respectively. Color coding: white—hydrogen, grey—carbon, red—oxygen, blue—nitrogen, yellow—fluorine. (D1,E1) are the experimental structures, whereas (D2,E2) are the structures after the relaxation at the $\omega$B97XD/def2-TZVP level of theory.