Solid-state 35/37CI NMR spectroscopy of hydrochloride salts of amino acids implicated in chloride ion transport channel selectivity:: Opportunities at 900 MHz

The results of a detailed systematic chlorine solid-state NMR study of several hydrochloride salts of amino acids implicated in chloride ion transport channel selectivity are reported. Cl-35 and Cl-37 NMR spectra have been obtained for stationary and/or magic-angle spinning powdered samples of the following compounds on 500 and/or 900 MHz spectrometers: DL-arginine HCl monohydrate, L-lysine HCl, L-serine HCl, L-glutamic acid HCl, L-proline HCl, L-isoleucine HCl, L-valine HCl, L-phenylalanine HCl, and glycine HCl. Spectral analyses provide information on the anisotropic properties and relative orientations of the chlorine electric field gradient and chemical shift (CS) tensors, which are intimately related to the local molecular and electronic structure. Data obtained at 900 MHz provide unique examples of the effects of CS anisotropy on the NMR spectrum of a quadrupolar nucleus. The range of chlorine quadrupolar coupling constants (C-Q) measured, -6.42 to 2.03 MHz, demonstrates the sensitivity of this parameter to the chloride ion environment and suggests the applicability of chlorine solid-state NMR as a novel experimental tool for defining chloride binding environments in larger ion channel systems. Salts of hydrophobic amino acids are observed to tend to exhibit larger values of C-Q than salts of hydrophilic amino acids. A simple model for rationalizing the observed trend in C-Q is proposed. For salts for which neutron diffraction structures are available, we identify a quantum chemical method which reproduces experimental values of C-Q with a root-mean-square deviation of 0.1 MHz and a correlation coefficient of 0.9998. On the basis of this, chlorine NMR tensors are predicted for the Cl- binding site in CIC channels.