Chlorine-35/37 NMR Spectroscopy of Solid Amino Acid Hydrochlorides:  Refinement of Hydrogen-Bonded Proton Positions Using Experiment and Theory

Abstract

Trends in the chlorine chemical shift (CS) tensors of amino acid hydrochlorides are investigated in the context of new data obtained at 21.1 T and extensive quantum chemical calculations. The analysis of chlorine-35/37 NMR spectra of solid L-tryptophan hydrochloride obtained at two magnetic field strengths yields the chlorine electric field gradient (EFG) and CS tensors, and their relative orientations. The chlorine CS tensor is also determined for the first time for DL-arginine hydrochloride monohydrate. The drastic influence of 1 H decoupling at 21.1 T on the spectral features of salts with particularly small 35 Cl quadrupolar coupling constants (C Q ) is demonstrated. The chlorine CS tensor spans (Ω) of hydrochloride salts of hydrophobic amino acids are found to be larger than those for salts of hydrophilic amino acids. A new combined experimental-theoretical procedure is described in which quantum chemical geometry optimizations of hydrogen-bonded proton positions around the chloride ions in a series of amino acid hydrochlorides are cross-validated against the experimental chlorine EFG and CS tensor data. The conclusion is reached that the relatively computationally inexpensive B3LYP/ 3-21G* method provides proton positions which are suitable for subsequent higher-level calculations of the chlorine EFG tensors. The computed value of Ω is less sensitive to the proton positions. Following this cross-validation procedure, |C Q ( 35 Cl)| is generally predicted within 15% of the experimental value for a range of HCl salts. The results suggest the applicability of chlorine NMR interaction tensors in the refinement of proton positions in structurally similar compounds, e.g., chloride ion channels, for which neutron diffraction data are unavailable. IntroductionThe availability of high-field solid-state nuclear magnetic resonance (NMR) spectrometers, e.g., those with 1 H resonance frequencies of 800 MHz, 900 MHz, and above, has created new opportunities for the study of quadrupolar nuclei (I > 1/ 2) with low resonance frequencies or large quadrupole moments, and for nuclei with both of these properties. For example, Stebbins et al. have described applications of 18.8 and 21.1 T solid-state 27 Al, 17 O, 39 K, and 35 Cl NMR spectroscopy to study oxide materials. 1-3 Gan et al. used magnetic fields as high as 40 T to achieve chemical shift resolution between four different aluminum environments in aluminoborate. 4 Ellis and colleagues have applied high-field 67 Zn NMR at low temperature to study zinc binding environments of biological relevance. 5,6,7,8 Magicangle-spinning (MAS) NMR in a magnetic field of 19.6 T has been applied by Wu and co-workers to detect potassium cations in guanine-quadruplex structures 9 as well as to explore cation-π interactions in alkali metal tetraphenylborates. 10 Cross and coworkers have demonstrated the utility of 17 O solid-state NMR at 21.1 T for characterizing the ion channel gramicidin. 11,12 The major reason that higher fields are so beneficial for the study of quadrupolar nuclei in ...

Alkaline Earth Chloride Hydrates: Chlorine Quadrupolar and Chemical Shift Tensors by Solid‐State NMR Spectroscopy and Plane Wave Pseudopotential Calculations

“…The span of the CS tensor, 72 AE 15 ppm, is the largest measured amongst the alkaline earth chloride hydrates (Table 2). This value is intermediate with respect to the range of all experimentally known chlorine CS tensor spans, [8,25,26] and significantly larger than previously reported spans for inorganic chlorides. [50] Calcium chloride dihydrate proved to be an excellent sample for 35 Cl QCPMG NMR experiments as shown in Figures 6b and 7a.…”

“…The magnitudes of the chlorine EFG and CS tensors are, on the whole, comparable to those observed previously for a series of amino acid hydrochlorides. [25,26,53,66] Plane wave pseudopotential calculations were found to reproduce the experimental trend in chlorine quadrupolar coupling constants particularly well; however, their absolute values were consistently overestimated relative to experiment. With respect to the chemical shift tensor, all three principal components were also overestimated relative to experiment, while the span of the CS tensor was predicted with somewhat more accuracy.…”

“…This chlorine CS tensor span is comparable to those obtained for a variety of amino acid hydrochlorides. [25,26] Due to the C 3 symmetry axis passing through chlorine, the skew 22 Àd iso )/W) of the CS tensor must be AE 1.0 and the Euler angles (a, b, g) describing the relative orientations of the EFG and CS tensors are restricted to possibilities which place one of the principal axes of the CS tensor coincident with V 33 . The known crystal symmetry therefore helps greatly in narrowing down the parameter space to be searched during spectral simulation.…”

“…Our recent chlorine-35/37 NMR investigations of solid amino acid hydrochlorides reveal that the chlorine chemical shift tensor spans (W) in these compounds are generally less than 100 ppm, with the value for l-phenylalanine hydrochloride being the largest reported to date, 129 AE 20 ppm. [25,26] For this reason, we anticipate that particularly high magnetic field strengths will be required to extract the CS tensor information for the alkaline earth chloride hydrates. Data at 11.75 and 21.1 T were therefore acquired in the present work.…”

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

“…Since chloride is a quite important nucleus in pharmaceutical, organic, and inorganic chemistry, both 35 Cl and 37 Cl have been extensively studied. [19][20][21][22][23][24][25][26][27] To demonstrate the advantage of the high magnetic field, we propose a simple theoretical model a) to predict the sensitivity enhancement at higher magnetic fields, and b) to estimate the isotope effect. In the present study, this model is experimentally verified utilizing 35 Cl and 37 Cl solid-state NMR at two different magnetic fields.…”