From what I understand, if you have a NMR spectra, you can determine the structure of a macromolecule but it is very difficult to determine what the NMR spectra of an expected structure would look like? Why is this the case?

  • $\begingroup$ I think you can sort of determine the qualitative NMR spectrum, but getting the heights right is harder. But I'm not sure. $\endgroup$ – ManishEarth Jun 1 '12 at 3:39

Macromolecular NMR spectra are difficult to compute because macromolecular electronic structures are computationally expensive to solve with accuracy. Obtaining precise chemical shifts and splitting requires accurate treatment of electron density and geometry, especially for simulation of NOESY, which I understand is important in macromolecular structural elucidation. This requires good methodology and large basis sets.

An interesting case study by Saielli and Bagno demonstrates the use of DFT (with cc-PVTZ basis) in predicting NMR spectra for two candidate structures and the correlating them with experimental data, however the mean error in chemical shifts is nontrivial1 (0.2 ppm in the best match). The same people do $^{1}\ce{H}$ and $\ce{^{13}C}$ NMR predictions of a number of complex molecules2 (with intriguing discrepancies in shifts) however this is a far cry from predicting, say, a large protein $^{1}\ce{H}$ NMR spectrum.

I have seen EPR spectra of transition metal clusters simulated as abstract spin systems (for instance by EasySpin) however I presume that this is very qualitative.

(1) Saielli, G.; Bagno, A.; Can two molecules have the same NMR spectrum? Hexacyclinol revisited.; Org. Lett.; (2009) 11, pp. 1409-1412

(2) Bagno, A.; Rastrelli, F.; Saielli, G.; Toward the complete prediction of the $\ce{^1H}$ and $\ce{^{13}C}$ NMR spectra of complex organic molecules by DFT methods. Application to natural substances.; Chem. Eur. J.; (2006) 12, pp. 5514-5525

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  • $\begingroup$ In summary: There are a freaking huge number of atoms present, the complexity goes up more then linearly, as you have more relaxation types to consider, tumbling speed becomes an issue, and other things. Net result: Bigger molecules = harder, macromolecules are freaking huge. ^^ $\endgroup$ – Canageek Jun 1 '12 at 19:34
  • $\begingroup$ What order of magnitude of mass can NMR achieve nowadays? I vaguely recall 10 kDa being some sort of reasonable limit but I don't know how old that figure is. $\endgroup$ – Nick T Jun 2 '12 at 5:40

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