Thermal and Solvent Effects On NMR Indirect Spin–Spin Coupling Constants of a Prototypical Chagas Disease Drug

Abstract

NMR J-couplings across hydrogen bonds reflect the static and dynamic character of hydrogen bonding. They are affected by thermal and solvent effects and can therefore be used to probe such effects. We have applied density functional theory (DFT) to compute the NMR (n)J(N,H) scalar couplings of a prototypical Chagas disease drug (metronidazole). The calculations were done for the molecule in vacuo, in microsolvated cluster models with one or few water molecules, in snapshots obtained from molecular dynamics simulations with explicit water solvent, and in a polarizable dielectric continuum. Hyperconjugative and electrostatic effects on spin-spin coupling constants were assessed through DFT calculations using natural bond orbital (NBO) analysis and atoms in molecules (AIM) theory. In the calculations with explicit solvent molecules, special attention was given to the nature of the hydrogen bonds formed with the solvent molecules. The results highlight the importance of properly incorporating thermal and solvent effects into NMR calculations in the condensed phase.

99Tc NMR as a promising technique for structural investigation of biomolecules: theoretical studies on the solvent and thermal effects of phenylbenzothiazole complex

“…This can be explained by the indirect effect of solvent in the system, causing the geometry to depart from the average conformation in solution, thus justifying a deviation in the values of chemical shifts when compared with the experimental results. However, when the implicit solvent effects were introduced in the NMR calculation, a better agreement between experiment and theoretical results was observed {compare δ e [//BP86/PCM(H 2 O)] and δ e [PCM(H 2 O)//BP86/PCM(H 2 O)] entries in Table }, which it is in agreement with recent studies in the literature involving NMR spectroscopy in solution …”

“…To describe the solvent effect in the spectroscopic property of 1a and 1b compounds (Fig. ), in this paper, we used some theoretical methodologies that were validated in previous studies, such as continuum models, explicit solvation model, and molecular dynamics (ADMP) . As a continuum approach, we used the well‐known PCM.…”

“…ADMP employs an extended Lagrangian similar to the well‐known Car–Parrinello MD. It can treat all electrons quantum‐mechanically and can control the deviations from the Born‐Oppenheimer surface precisely . In this work, we have used a temperature of 310 K (physiologic temperature) throughout the simulation.…”

1H NMR spectra of alcohols in hydrogen bonding solvents: DFT/GIAO calculations of chemical shifts

“…More elaborate approaches, based on the inclusion of explicit solvent molecules and/or clusters and molecular dynamics (MD) simulations, have therefore been developed in order to handle short‐range effects, notably hydrogen bonding, which are not reproduced by a continuum . Because it is relatively easy to handle a large number of small molecules, many MD studies have been devoted to water as a solvent, gas or liquid . Other approaches include hybrid QM/molecular mechanics and QM/Monte Carlo calculations, the incorporation of the hydrogen nuclear quantum effect by a multicomponent scheme, and the optimization of functionals and basis set parameters by multivariate techniques .…”

Exploring EPR Parameters of 99Tc Complexes for Designing New MRI Probes: Coordination Environment, Solvent, and Thermal Effects on the Spectroscopic Properties

“…It can treat all electrons quantum-mechanically and can control the deviations from the Born-Oppenheimer surface precisely [25,29]. In this work, a temperature of 310 K (physiologic temperature) was used throughout the simulation.…”