GIAO NMR Calculations of Some Novel 8-Thio-Substituted 1,3,7-Trimethylxanthines: Comparison of Theoretical and Experimental 1H Chemical Shifts

Abstract

ABSTRACTA direct molecular structure implementation of the gauge-including atomic orbital (GIAO) method for calculation of nuclear magnetic shielding tensors at density functional (B3LYP) level of theory with 6–31G(d, p) and 6–311+G(2d, p) basis sets is presented. The influence of the choice of the basis set on the 'H chemical shift for six 8-substituted 1,3,7-trimethylxanthines with brain antihypoxic activity was investigated. The theoretical values were compared with the experimental data. The performed least squares regression analysis resulted in r2 values greater than 0.84 for the total data set and 0.77 when sorted by compound. The obtained linear regression equations δcalc = a + bδexp yield rms errors of (0.61 ± 0.08) ppm for the first basis set and (0.70 ± 0.08) ppm for the second one, when calculated for the separate compounds. Since the computed b values differ from zero with statistical significance, the applied linear model is adequate and describes correctly the dependence between the experimental and the calculated values of the corresponding chemical shifts. Thus for NMR spectral calculation of xanthine derivatives both basis sets may be used, whereas the 6–31G (d, p) gives a little better correlation.