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

We report the ab initio evaluation of the carbon-13 nuclear magnetic resonance shielding tensors for each carbon atom in crystalline, zwitterionic, L-threonine and L-tyrosine, using a gauge-including atomic orbital (GIAO) quantum chemical approach, with and without charge-field perturbation (CFP). For isolated molecules, there is a correlation coefficient, R(2), of 0.975 between experimental shift and computed shielding, 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) (perpendicular 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 icosahedral 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 reduces to 3.8 ppm. Thus, combined use of charge-field perturbation and a gauge-including atomic orbital approach permits excellent prediction of carbon-13 isotropic chemical shifts and principal shift tenser elements in two zwitterionic polar amino acids. The charge-field approach is particularly useful since it allows for inclusion of environmental effects on shielding without adding to the number of contracted functions. Moreover, the polarization effects are primarily limited to C degrees, supporting the idea that for C-13,long-range electrostatic field contributions to shielding will be small, especially for sp(3) carbons. The ability to successfully predict C-13 Shielding tenser elements in highly polar (zwitterionic, hydroxyl-containing) amino acids provides strong additional support for the adequacy of GIAO/CFP-GIAO methods in predicting C-13 chemical shifts in proteins, and other macromolecules as well.