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

Abstract

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 Møller-Plesset (MP2) theory. To obtain consistent experimental data, the NMR spectra were remeasured on a 500 MHz spectrometer in CDCl 3 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 conformations in proteins; this requires a predictive accuracy of 0.1-0.2 ppm.

Global versus Local Aromaticity in Porphyrinoid Macrocycles: Experimental and Theoretical Study of “Imidacene”, an Imidazole‐Containing Analogue of Porphycene

“…Data for the calculated 1 H and 13 C chemical shifts were obtained from the NICS calculations. Previous work suggests that the methods we applied can be expected to yield accurate proton chemical shifts, [26] and we assume a similar level of accuracy holds for the carbon shifts. In general, large negative NICS values (ca < À 9) reflect aromatic rings, while less negative or positive values reflect non-aromatic or antiaromatic systems.…”

Aromaticity of Giant Polycyclic Aromatic Hydrocarbons with Hollow Sites: Super Ring Currents in Super‐Rings

“…[86] Another study on a smaller range of organic compounds, namely on 10 small PAHs (substituted and unsubstituted), shows that the RMS and largest deviations between experimental and B3LYP/6-31G**//B3LYP/6-31G*-calculated chemical shifts are equal to 0.065 and 0.171 ppm, respectively. [87] Our 1 H NMR shifts, being obtained at a slightly lower level of theory (B3LYP/6-31G) and without any parametric corrections, are certainly a little less accurate. Except for kekulene (31) and [18] [88] which is in very reasonable agreement with our B3LYP/6-31G results (7.9, 8.2, and 10.0 ppm, respectively, that is,~0.5 ppm accuracy).…”

Probing multiple effects on 15N, 13Cα, 13Cβ, and 13C′ chemical shifts in peptides using density functional theory

“…This is a fairly small basis set, and it is known to have deficiencies when used to compute chemical shifts for nuclei in very different chemical environments. 14,27,28 Less is known about its performance in studies of conformational-dependent shifts, where the structural variation only involves rotations about carbon-carbon single bonds. To study this, we used a larger basis set to recompute the shifts of amide nitrogen in the central residue of the GAAAG peptide in 51 conformations that span the allowed backbone conformations in helical and sheet regions.…”