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

Forty-five proton chemical shifts in 14 aromatic molecules have been calcul ated at several levels of theory: Hartree-Fock and density functional theor y with several different basis sets, and also second-order Moller-Plesset ( MP2) theory. To obtain consistent experimental data, the NMR spectra were r emeasured on a 500 MHz spectrometer in CDCl3 solution. A set of 10 molecule s without strong electron correlation effects was selected as the parametri zation set. The calculated chemical shifts (relative to benzene) of 29 diff erent 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 o btained for the second test set of 4 more difficult molecules: nitrobenzene , azulene, salicylaldehyde, and o-nitroaniline, characterized by strong ele ctron correlation or resonance-assisted intramolecular hydrogen bonding. Th e results show that it is possible, at a reasonable cost, to calculate rela tive 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 o f 0.1-0.2 ppm. (C) 2001 John Wiley & Sons, Inc.