High-Field Chlorine NMR Spectroscopy of Solid Organic Hydrochloride Salts:  A Sensitive Probe of Hydrogen Bonding Environment

Abstract

A series of organic hydrochloride salts has been investigated using solid-state 35 Cl and 37 Cl NMR spectroscopy at applied magnetic field strengths of 9.4 and 18.8 T. Magic-angle spinning, static Hahn-echo, and quadrupolar Carr-Purcell Meiboom-Gill (QCPMG) echo experiments have been applied to investigate the chlorine electric field gradient (EFG) and chemical shift (CS) tensors for L-tyrosine hydrochloride, L-cysteine methyl ester hydrochloride, L-cysteine ethyl ester hydrochloride, quinuclidine hydrochloride, and tris sarcosine calcium chloride. Chlorine-35 nuclear quadrupolar coupling constants for these compounds range from 2.23 to 5.25 MHz, and isotropic chemical shifts range from approximately 9 to 53 ppm relative to the chloride ion in aqueous solution. The results demonstrate the feasibility and benefits of high-field 35/37 Cl NMR studies of organic chloride salts. A discussion of the data in the context of the known X-ray or neutron diffraction structures for these compounds suggests that the chlorine EFG tensor is a valuable probe of hydrogen bonding to the chloride ion. Because the anisotropies of the CS tensors are rather small, precise determination of the chlorine CS tensors proved to be challenging and was only feasible for L-cysteine ethyl ester hydrochloride, where the span, Ω, was found to be 47 ( 4 ppm. This represents the first determination of Ω(Cl) from a powder sample. Results of ab initio calculations of the chlorine EFG and CS tensors in L-tyrosine hydrochloride are presented and compared with the experimental data.

Solid-state NMR spectroscopy of the quadrupolar halogens: chlorine-35/37, bromine-79/81, and iodine-127

“…The value reported for NaCl is in good agreement with the value of 45.4 ppm obtained with respect to an infinitely dilute NaCl solution in H 2 O. 55 In the case of bromine, solid KBr is a suitable standard (and is convenient since it may be used to set the magic angle as well), although other alkali metal bromides have also been used. Solid KI and NaI are useful standards for 127 I SSNMR.…”

“…116 Gervais et al have recently carried out a thorough experimental and computational study of the NMR parameters of various amino acids and amino acid hydrochloride salts. 32 In addition to confirming the previously reported results 55 for L-tyrosine hydrochloride, new isotropic chemical shifts, quadrupolar coupling constants, and asymmetry parameters were determined for glycine HCl, L-valine HCl, and L-glutamic acid HCl using static and MAS methods applied to powdered samples at 14.1 T. Furthermore, first-principles calculations provided small CS tensor spans ranging between 78 and 157 ppm. Calculations of the chlorine quadrupolar coupling constants were found to be in fair agreement with experiment; however, a systematic overestimation of experimental values was noted and attributed to the effect of the hydrogen bonding environment around chloride.…”

“…55 The results were in good qualitative agreement and indicate the potential of quantum chemical methods in the prediction and interpretation of halogen NMR interaction tensors. Further improvements between experiment and theory are likely to be obtained by including more of the crystal lattice in the structural model used in the calculations.…”

“…3). 55 CT second-order quadrupolar lineshapes were observed under MAS at 18.8 T, and simulations yielded values of C Q ranging from 2.23 MHz for L-tyrosine hydrochloride to 5.25 MHz for quinuclidine hydrochloride. Marked variations in Á Q were also observed.…”

“…infinitely dilute NaCl(aq)). 55 These spectra also allowed an upper limit of 150 ppm to be placed on the span of the chlorine CS tensor. Alkylammonium chlorides are another class of compounds that have received attention.…”