The use of computed NMR coupling constants is starting to grow. In a previous post I discussed a general study by Rablen and Bally on methods for computing JHH coupling constants. Now Williamson reports methods to experimentally obtain 1 JCC and 3JCC coupling constants.1 These were obtained for strychnine. He then computed the coupling constants in two steps. Using the B3LYP/6-31G(d) optimized geometry, first the Fermi contact contribution was computed at B3LYP/6-31+G(d,p) by uncontracting the basis set and adding an additional tighter set of polarization functions. Second, the remaining terms (spin-dipolar, paramagnetic spin-orbit and diamagnetic spin-orbit coupling) were computed with the 6-31+Gd,p) set without modifications. The two computed terms were added to give the final estimate.
A plot of the experimental vs. the DFT computed 1 JCC and 3JCC coupling constants shows
an excellent linear relation, with correlation coefficient of 0.9986 and a slope of 0.98. The mean absolute deviation for the computed and experimental 1 JCC and 3JCC coupling constants is 1.0
Hz and 0.4 Hz, respectively, both well within the experimental error.
I expect that computed NMR spectra will continue to be a growth area, especially for structural identification.
References
(1) Williamson, R. T.; Buevich, A. V.; Martin, G. E. "Experimental and Theoretical Investigation of 1JCC and nJCC Coupling Constants in Strychnine," Org. Letters 2012, 14, 5098-5101, DOI: 10.1021/ol302366s
InChIs
strychnine:
InChI=1S/C21H22N2O2/c24-18-10-16-19-13-9-17-21(6-7-22(17)11-12(13)5-8-25-16)14-3-1-2-4-15(14)23(18)20(19)21/h1-5,13,16-17,19-20H,6-11H2/t13-,16-,17-,19-,20-,21+/m0/s1
InChIKey=QMGVPVSNSZLJIA-FVWCLLPLSA-N
Henry Rzepa responded on 24 Nov 2012 at 2:41 am #
I am not entirely sure what is novel about this approach? For example, the trick of getting the Fermi contact contributions accurately by uncontracting the basis set is a feature that has been present in the Gaussian program for a little while (see here ). Thus we have been using the nmr(spinspin,mixed) keyword in our taught undergraduate course for a year or more, and can certainly verify that the 3-bond couplings tend to come our very well indeed using this procedure.
I note in 10.1021/ol302366 that the calculations were carried out for the gas phase. Since a solvation correction (for CDCl3) adds little to the computational cost, it seems it (rather than the gas phase) should routinely be the default. It would be worth while finding if this improves the fit at all. I suspect it might improve the conformational angles of less constrained parts of the molecule, and hence the couplings, if nothing else.
Computational spectroscopy (NMR shieldings and couplings, vibrational and electronic, including ECD and VCD) is certainly now an absolutely essential tool of the synthetic chemist, and yet it is rarely practised by most.
Steven Bachrach responded on 24 Nov 2012 at 7:47 am #
I agree that there is nothing novel about the computations performed in this paper. I also agree that solvent effects should have been incorporated. However, your last line explains why I chose to write this post ‘it is rarely practiced‘. I am trying to promote this technique which should become standard practice, even by synthetic chemists.
Henry Rzepa responded on 24 Nov 2012 at 8:34 am #
We both agree Steve that synthetic chemists should do more (quantum) simulation to reinforce their spectroscopic inferences. Perhaps one reason why they not do this is that it is much easier to ask the crystallographer to provide the connectivity and stereochemistry of their molecules, than it is for them to poor over extracting coupling constants from a complex, and probably second order, NMR spectrum. The art of solving the Bloch equations given chemical shifts and couplings and then comparing the result with experiment is also largely lost nowadays (who now remembers LAOCOON and its successors?). I have also encountered synthetic chemists who believe that the (cheap) simulation provided by chemical structure drawing programs is entirely reliable.
Whatever the practicalities, it is rather distressing to know that around 80% of structures solved by X-ray are never published (and probably a far higher proportion of recorded NMR spectra), very probably because they were obtained merely to establish connectivity, and not because there might be intrinsic value in adding to the database of structures.