Accurate prediction of proton chemical shifts. I. Substituted aromatic hydrocarbons

by Wang, B.; Fleischer, U.; Hinton, J. F.; Pulay, P.

Forty-five proton chemical shifts in 14 aromatic molecules have been calculated at several levels of theory: Hartree-Fock and density functional theory with several different basis sets, and also second-order Moller-Plesset (MP2) theory. To obtain consistent experimental data, the NMR spectra were remeasured on a 500 MHz spectrometer in CDCl3 solution. A set of 10 molecules without strong electron correlation effects was selected as the parametrization set. The calculated chemical shifts (relative to benzene) of 29 different protons in this set correlate very well with the experiment, and even better after linear regression. For this set, all methods perform roughly equally. The best agreement without linear regression is given by the B3LYP/TZVP method (rms deviation 0.060 ppm), although the best linear fit of the calculated shifts to experimental values is obtained for B3LYP/6-311++G**, with an rms deviation of only 0.037 ppm. Somewhat larger deviations were obtained for the second test set of 4 more difficult molecules: nitrobenzene, azulene, salicylaldehyde, and o-nitroaniline, characterized by strong electron correlation or resonance-assisted intramolecular hydrogen bonding. The results show that it is possible, at a reasonable cost, to calculate relative proton shieldings in a similar chemical environment to high accuracy. Our ultimate goal is to use calculated proton shifts to obtain constraints for local con-formations in proteins; this requires a predictive accuracy of 0.1-0.2 ppm.

Journal of Computational Chemistry
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1096-987X; 0192-8651