Density functional theory study of nitrogen‐14 nuclear quadrupole coupling parameters of L‐histidine: hydrogen‐bonded system

Abstract

The calculations of nitrogen‐14 nuclear quadrupole parameters, nuclear quadrupole coupling constant, χ, and asymmetry parameter, η, of L‐His were done in two distinct environments: one as a free fully optimized molecule, an isolated molecule with the geometrical parameters taken from X‐ray, and the other in the orthorhombic and monoclinic solid states. The most probable interacting molecules with the central molecule in the crystalline phase were considered in the hexameric clusters to include hydrogen‐bonding effects in the calculations. The computations were performed with PW91P86/6‐31++G** and B3LYP6‐31++G** methods using the Gaussian 98 program. The good agreement between the nitrogen‐14 quadrupole parameters of the free His and imidazole molecules with their microwave available data demonstrates that the applied level of theory and the 6‐31++G** basis set are suitable to obtain reliable electric field gradient values. In the solid state, the shifts of quadrupole coupling parameters from the monomer to the solid phase are reasonably well reproduced for the amino and imino sites of imidazole ring in a hexameric cluster. That implies the fact that the hexameric cluster worked effectively to generate the results which are compatible with the experiment. The quadrupole coupling constant values of –N+H3 group are in fair agreement with the experiment. This discrepancy is due to the absences of vibrational effects and the rotation of –N+H3 group around N–C(α) bond. Copyright © 2012 John Wiley & Sons, Ltd.

Natural abundance 14N and 15N solid-state NMR of pharmaceuticals and their polymorphs

“…Both nuclides yield NMR responses that are exceptionally sensitive to their local environments, and yet are among the most challenging isotopes for spectroscopic investigation by NMR (vide infra). Numerous studies employing 14 N and 15 N SSNMR, as well as quantum chemical computations, have recently been attempted for a variety of different compounds, including organic and biological samples, [45][46][47][48][49][50][51][52][53][54] amino acids, [55][56][57][58][59][60][61][62] and pharmaceuticals. 27,63-69 14 N nuclear quadrupole resonance (NQR) spectroscopy has also recently been applied, with some success, to a variety of APIs for purposes of quantification and polymorph differentiation.…”