Computing the optical rotation of simple organic molecules can be a real challenge. One of the classic problems is methyloxirane. DFT typically gets the wrong sign, let alone the wrong value. Cappelli and Barone1 have developed a QM/MM procedure where methyloxirane is treated with DFT (B3LYP/aug-cc-pVDZ or CAM-B3LYP/aubg-cc-pVDZ). Then 2000 arrangements of water about methyloxirane were obtained from an MD simulation. For each of these configurations, a supermolecule containing methyloxirane and all water molecules with 16 Å was identified. The waters of the supermolecule were treated as a polarized force field. This supermolecule is embedded into bulk water employing a conductor-polarizable continuum model (C-PCM). Lastly, inclusion of vibrational effects, and averaging over the 2000 configurations, gives a predicted optical rotation at 589 nm that is of the correct sign (which is not accomplished with a gas phase or simple PCM computation) and is within 10% of the correct value. The full experimental ORD spectrum is also quite nicely matched using this theoretical approach.
References
(1) Lipparini, F.; Egidi, F.; Cappelli, C.; Barone, V. "The Optical Rotation of Methyloxirane in Aqueous Solution: A Never Ending Story?," J. Chem. Theor. Comput. 2013, 9, 1880-1884, DOI: 10.1021/ct400061z.
InChIs
(R)-Methyloxirane:
InChI=1S/C3H6O/c1-3-2-4-3/h3H,2H2,1H3/t3-/m1/s1
InChIKey=GOOHAUXETOMSMM-GSVOUGTGSA-N
Henry Rzepa responded on 16 May 2013 at 11:25 am #
The chemical shift of the nuclei of a single water molecule entrained in C60 is similarly difficult to simulate. I recollect that an MD simulation resulted in a number of configurations which were considered as having a significant Boltzmann population, and each was subjected to GIAO-NMR shielding calculation. Whilst the individual errors were large, this averaged method did the trick.
But as a practical tool for eg assigning the absolute configuration of a small to medium sized molecule resulting from eg an asymmetric synthesis, MD simulations on such supermolecules seem unlikely to be widely adopted.
I have noted the recent publication of the determination of the absolute/relative stereochemistry of the natural produce Miyakosyne A in microgram quantities using the cavity of a MOF (metal organic framework). If this method proves robust, it certainly seems to have the potential to reduce the need for the recently reinvigorated application of chiroptical measurement/simulation as an assignment method. If the rumours are to be believed, in about six months you may see a deluge of articles reporting whether the MOF method is indeed so robust (and if generally confirmed, who knows, the Nobel prize to follow thereafter!).
What can chemistry learn from photos? « Henry Rzepa responded on 02 Jun 2013 at 1:17 am #
[…] is deployed here in this blog. It certainly is on Steve Bachrach’s site (see for example this recent post where you will find InChI keys for every molecule displayed; […]