Exploring Intra- and Intermolecular Interactions in Selected N-Oxides-The Role of Hydrogen Bonds

Abstract

Intra- and intermolecular interactions have been explored in selected N-oxide derivatives: 2-(N,N-dimethylamino-N-oxymethyl)-4,6-dimethylphenyl (1) and 5,5'-dibromo-3-diethylaminomethyl-2,2'-biphenol N-oxide (2). Both compounds possess intramolecular hydrogen bonding, which is classified as moderate in 1 and strong in 2, and resonance-assisted in both cases. Density Functional Theory (DFT) in its classical formulation as well as Time-Dependent extension (TD-DFT) were employed to study proton transfer phenomena. The simulations were performed in the gas phase and with implicit and explicit solvation models. The obtained structures of the studied N-oxides were compared with experimental data available. The proton reaction path was investigated using scan with an optimization method, and water molecule reorientation in the monohydrate of 1 was found upon the proton scan progress. It was found that spontaneous proton transfer phenomenon cannot occur in the electronic ground state of the compound 1. An opposite situation was noticed for the compound 2. The changes of nucleophilicity and electrophilicity upon the bridged proton migration were analyzed on the basis of Fukui functions in the case of 1. The interaction energy decomposition of dimers and microsolvation models was investigated using Symmetry-Adapted Perturbation Theory (SAPT). The simulations were performed in both phases to introduce polar environment influence on the interaction energies. The SAPT study showed rather minor role of induction in the formation of homodimers. However, it is worth noticing that the same induction term is responsible for the preference of water molecules' interaction with N-oxide hydrogen bond acceptor atoms in the microsolvation study. The Natural Bond Orbital (NBO) analysis was performed for the complexes with water to investigate the charge flow upon the polar environment introduction. Finally, the TD-DFT was applied for isolated molecules as well as for microsolvation models showing that the presence of solvent affects excited states, especially when the N-oxide acceptor atom is microsolvated.

Keywords: DFT; Fukui functions; IEF-PCM; N-oxides; NBO; SAPT; TD-DFT; microsolvation.

Figure 1

Molecular forms of studied N-oxides: 2-(N,N-dimethylamino-N-oxymethyl)-4,6-dimethylphenol (1) and 5,5’-dibromo-3-diethylaminomethyl-2,2’-biphenol N-oxide (2). The intramolecular hydrogen bridges are denoted O1-HBP…O2 in the case of 1 and O1-HBP1-O2 and O3-HBP2-O2 in the case of 2. Atoms coloring and numbering scheme: nitrogen atom—blue, oxygen atoms—red, hydrogen atoms—white, carbon atoms—grey and bromine atoms—brown. BP—bridged proton. The presence of quasi-rings is denoted using I and II Roman numerals.

Figure 2

Conformers of the compound 1 (monohydrate form) computed at the B3LYP/6-311++G(d,p) level of theory. (a) closed form; (b) open form.

Figure 3

Conformers of the compound 2 computed at the B3LYP/6-311++G(d,p) level of theory. (a) closed form; (b) with one hydrogen bond; (c) open form.

Figure 4

Dimers investigated in the SAPT study. (a) dimer 1 of the compound 1 with water molecule; (b) dimer 2 of the compound 1 with water molecule; (c) dimer 1 of the compound 2.

Figure 5

Microsolvation models of the compound 1. (a) two water molecules on the acceptor side, 1-A2; (b) one water molecule on the acceptor side and one on the donor side, 1-AD; (c) four water molecules, two on the acceptor and two on the donor sides, respectively, 1-A2D2.

Figure 6

Microsolvation models of the compound 2. (a) two water molecules on the O1 (acceptor atom) side, 2-A2; (b) two water molecules on the O1 acceptor side and one water molecule on the O2 donor side, 2-A2D${}_{\mathrm{A}}$; (c) two water molecules on the O1 acceptor side and one water molecules on the O3 donor side, 2-A2D${}_{\mathrm{B}}$.

Figure 7

Proton potential profiles for the hydrogen bonds in the investigated systems—results of DFT relaxed scans. (a) compound 1 without water molecule; (b) compound 1 as monohydrate; (c) compound 2—bridge O1…O2; (d) compound 2—bridge O2…O3.

Figure 8

Calculated Fukui functions describing changes of nucleophilicity of O1 (top left, (a)) and O2 (bottom left; (c)) oxygen atoms and electrophilicity of O1 (top right, (b)) and O2 (bottom right, (d)) oxygen atoms along the proton HBP shift pathway. HBP—bridged proton, GP—gas phase, PCM—simulations with Polarizable Continuum Model and water as a solvent.