PREDICTING C-13 NUCLEAR-MAGNETIC-RESONANCE CHEMICAL SHIELDING TENSORSIN ZWITTERIONIC L-THREONINE AND L-TYROSINE VIA QUANTUM-CHEMISTRY

We report the ab initio evaluation of the carbon-13 nuclear magnetic r esonance shielding tensors for each carbon atom in crystalline, zwitte rionic, L-threonine and L-tyrosine, using a gauge-including atomic orb ital (GIAO) quantum chemical approach, with and without charge-field p erturbation (CFP). For isolated molecules, there is a correlation coef ficient, R(2), of 0.975 between experimental shift and computed shield ing, with a slope of -1.03 and an rmsd of 12.3 ppm. This error is due primarily to large deviations in the C degrees sigma(11) (in the CO sp (2) plane and perpendicular to C-alpha-C degrees) and sigma(22) (perpe ndicular to the sp(2) plane). Incorporation of a point-charge lattice to represent the local charge field results in a decrease in rmsd to 6 .4 ppm, due primarily to changes in sigma(11) and sigma(22) In the ico sahedral representation and with charge field perturbation, we find an overall rmsd of 4.4 ppm over a 200 ppm chemical shift range (slope = -0.992, R(2) = 0.997), while for the isotropic shifts alone the rmsd r educes to 3.8 ppm. Thus, combined use of charge-field perturbation and a gauge-including atomic orbital approach permits excellent predictio n of carbon-13 isotropic chemical shifts and principal shift tenser el ements in two zwitterionic polar amino acids. The charge-field approac h is particularly useful since it allows for inclusion of environmenta l effects on shielding without adding to the number of contracted func tions. Moreover, the polarization effects are primarily limited to C d egrees, supporting the idea that for C-13,long-range electrostatic fie ld contributions to shielding will be small, especially for sp(3) carb ons. The ability to successfully predict C-13 Shielding tenser element s in highly polar (zwitterionic, hydroxyl-containing) amino acids prov ides strong additional support for the adequacy of GIAO/CFP-GIAO metho ds in predicting C-13 chemical shifts in proteins, and other macromole cules as well.