The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers A-D , each in two conformations ( 1/2 ) were calculated at the ωB97D/6-311G(d,p)/SCRF=ethanol level, and are shown here relative to A1 (kcal/mol) as free energies.
Conformational analysis comes from the classical renaissance of physical organic chemistry in the 1950s and 60s. The following problem is taken from E. D. Hughes and J. Wilby J. Chem. Soc. , 1960, 4094-4101, DOI: 10.1039/JR9600004094, the essence of which is that Hofmann elimination of a neomenthyl derivative (C below) was observed as anomalously faster than its menthyl analogue.
Understanding why and how proteins fold continues to be a grand challenge in science. I have described how Wrinch in 1936 made a bold proposal for the mechanism, which however flew in the face of much of then known chemistry.
When Watson and Crick (WC) constructed their famous 3D model for DNA, they had to decide whether to make the double helix left or right handed.
Here I offer another spin-off from writing a lecture course on conformational analysis. This is the famous example of why 1,2-difluoroethane adopts a gauche rather than antiperiplanar conformation.
One of the (not a few) pleasures of working in a university is the occasional opportunity that arises to give a new lecture course to students.
In an earlier post, I re-visited the conformational analysis of cyclohexane by looking at the vibrations of the entirely planar form (of D 6h symmetry). The method also gave interesting results for the larger cyclo-octane ring. How about a larger leap into the unknown? Let us proceed as follows. One fun game to play in chemistry is to invoke i so-electronic substitutions.
In the previous post, I suggested that inspecting the imaginary modes of planar cyclohexane might be a fruitful and systematic way in which at least parts of the conformational surface of this ring might be probed.
Chemistry can be very focussed nowadays. This especially applies to target-driven synthesis, where the objective is to make a specified molecule, in perhaps as an original manner as possible. A welcome, but not always essential aspect of such syntheses is the discovery of new chemistry.
The diagram below summarizes an interesting result recently reported by Hanson and co-workers (DOI: 10.1021/jo800706y. At ~neutral pH, compound 13 hydrolyses with a half life of 21 minutes, whereas 14 takes 840 minutes. Understanding this difference in reactivity may allow us to understand why some enzymes can catalyze the hydrolysis of peptides with an acceleration of up to twelve orders of magnitude.
