A high-field solid-state 35/37Cl NMR and quantum chemical investigation of the chlorine quadrupolar and chemical shift tensors in amino acid hydrochlorides

Abstract

A series of six L-amino acid hydrochloride salts has been studied by 35/37Cl solid-state NMR spectroscopy (at 11.75 and 21.1 T) and complementary quantum chemical calculations. Analyses of NMR spectra acquired under static and magic-angle-spinning conditions for the six hydrochloride salts, those of aspartic acid, alanine, cysteine, histidine, methionine and threonine, allowed the extraction of information regarding the chlorine electric field gradient (EFG) and chemical shift tensors, including their relative orientation. Both tensors are found to be highly dependent on the local environment, with chlorine-35 quadrupolar coupling constants (CQ) ranging from -7.1 to 4.41 MHz and chemical shift tensor spans ranging from 60 to 100 ppm; the value of CQ for aspartic acid hydrochloride is the largest in magnitude observed to date for an organic hydrochloride salt. Quantum chemical calculations performed on cluster models of the chloride ion environment demonstrated agreement between experiment and theory, reproducing CQ to within 18%. In addition, the accuracy of the calculated values of the NMR parameters as a function of the quality of the input structure was explored. Selected X-ray structures were determined (L-Asp HCl; L-Thr HCl) or re-determined (L-Cys HCl.H2O) to demonstrate the benefits of having accurate crystal structures for calculations. The self-consistent charge field perturbation model was also employed and was found to improve the accuracy of calculated quadrupolar coupling constants, demonstrating the impact of the neighbouring ions on the EFG tensor of the central chloride ion. Taken together, the present work contributes to an improved understanding of the factors influencing 35/37Cl NMR interaction tensors in organic hydrochlorides.

Exploring Systematic Discrepancies in DFT Calculations of Chlorine Nuclear Quadrupole Couplings

“…This system is the only example where the C Q value calculated using the PBE functional under CASTEP was lower (2.72 MHz) than the experimental one (4.59 MHz). 21 The sample for NMR experiments potentially contained impurities, which may have affected the spectral fitting, 40 but the presence of the impurities probably cannot explain large deviations from the calculated C Q value. Recent measurements of the C Q ( 35 Cl) value in histidine hydrochloride monohydrate using one-dimensional 35 Cl NMR and two-dimensional proton-detected 35 Cl-1 H correlation NMR experiments gave chlorine a C Q of 1.8-2 MHz, 26 which fits well the correlation between experimental and calculated C Q .…”

DFT studies of NH–Cl hydrogen bond of amino acid hydrochloride salts in ion channels

“…All DFT calculations were performed using the GAMESS electronic structure package. 38 Alanine hydrochloride atomic coordinates and unit cell parameters were derived from X-ray or neutron diffraction studies of Di Blasio et al, 39 while threonine hydrochloride atomic coordinates from the X-ray structures of L. Bryce et al 25 were used. The geometry optimizations were performed using M06-2X method with 6-31++G(d,p) basis set to find the position of hydrogen atoms in the stable state of the system from monomer to pentamer in threonine hydrochloride ( Figure 1) and alanine hydrochloride ( Figure 2).…”

“…According to available experimental data for chlorine nucleus, 25,43 we can compare four methods used for calculating NQR parameters in these two amino acids. By comparing the experimental and calculated values shown in Tables 1 and 3, the M06L/6-311++G(d,p) method is more accurate and has the lowest computational error for calculating C Q in these molecules.…”

“…19 In general, the study of biological molecules, such as proteins, use the NMR spectroscopy technique that is beneficial for determining structure in both the solution 20,21 and solid states. 22,23 Solid-state NMR has been considered a lot over the past several decades, 24,25 including studies on proteins, 26 polymers, inorganic materials, 27 as well as clays and minerals. 28 More accurate information can be obtained by using NQR data in addition to NMR data.…”

24 T High-Resolution and -Sensitivity Solid-State NMR Measurements of Low-Gamma Half-Integer Quadrupolar Nuclei 35Cl and 37Cl

“…This should be attributed to the different crystalline form of L-histidine·HCl·H2O used here (purchased from Kanto Kagaku, Japan, and used without further purification) with respect to that reported earlier. 19,32 This observation is a good example for showing how quadrupolar/ chemical shift interactions are sensitive to the local environment. It should be interesting to point out the nuclear spin precession can also be observed in the presence of quadrupolar interactions even without the magnetic field.…”