A scalemic molecule is the term used by Eliel to describe any non-racemic chiral compound. Synthetic chemists imply it when they describe a synthetic product with an observable enantiomeric excess or ee (which can range from close to 0% to almost 100%). There are two cheminformatics questions of interest to me: (more…)
Posts Tagged ‘chiroptical’
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. Linus Pauling took most of the credit (and a Nobel prize) when in a famous paper in 1951 he suggested a mechanism that involved (inter alia) the formation of what he termed α-helices. Jack Dunitz in 2001 wrote a must-read article on the topic of “Pauling’s Left-handed α-helix” (it is now known to be right handed). I thought I would revisit this famous example with a calculation of my own and here I have used the ωB97XD/6-311G(d,p) DFT procedure to calculate some of the energy components of a small helix comprising (ala)6 in both left and right handed form.
One of my chemical heroes is William Perkin, who in 1856 famously (and accidentally) made the dye mauveine as an 18 year old whilst a student of August von Hofmann, the founder of the Royal College of Chemistry (at what is now Imperial College London). Perkin went on to found the British synthetic dyestuffs and perfumeries industries. The photo below shows Charles Rees, who was for many years the Hofmann professor of organic chemistry at the very same institute as Perkin and Hofmann himself, wearing his mauveine tie. A colleague, who is about to give a talk on mauveine, asked if I knew why it was, well so very mauve. It is a tad bright for today’s tastes!
Science is about making connections. Plenty are on show in Watson and Crick’s famous 1953 article on the structure of DNA (DOI: 10.1038/171737a0), but often with the tersest of explanations. Take for example their statement “Both chains follow right-handed helices“. Where did that come from? This post will explore the subtle implications of that remark (and how in one aspect they did not quite get it right!).
Our understanding of science mostly advances in small incremental and nuanced steps (which can nevertheless be controversial) but sometimes the steps can be much larger jumps into the unknown, and hence potentially more controversial as well. More accurately, it might be e.g. relatively unexplored territory for say a chemist, but more familiar stomping ground for say a physicist. Take the area of asymmetric synthesis, which synthetic chemists would like to feel they understand. But combine this with gravity, which is outside of their normal comfort zone, albeit one we presume is understood by physicists. Around 1980, chemists took such a large jump by combining the two, in an article spectacularly entitled Asymmetric synthesis in a confined vortex; Gravitational fields and asymmetric synthesis (DOI: 10.1021/ja00521a068). Their experiment was actually quite simple. They treated isophorone (a molecule with a plane of symmetry and hence achiral) with hydrogen peroxide and then measured the optical rotation.
Lactide is a small molecule made from lactic acid, which is itself available in large quantities by harvesting plants rather than drilling for oil. Lactide can be turned into polymers with remarkable properties, which in turn degrade down easily back to lactic acid. A perfect bio-renewable material!
Stereo-induction is, lets face it, a subtle phenomenon. The ratio of two stereoisomers formed in a reaction can be detected very accurately by experiment, and when converted to a free energy difference using ΔG = -RT Ln K, this can amount to quite a small value (between 0.5 – 1.5 kcal/mol). Can modelling reproduce effects originating from such small energy differences? Well one system that has been argued about now for several decades is shown below as 1.
In the first part of the post on this topic, I described how an asymmetric sulfoxide could be prepared as a pure enantiomer using a chiral oxygen transfer reagent. In the second part, we now need to deliver a different group, cyano, to a specific face of the previously prepared sulfoxide-imine. The sulfoxide is now acting as a chiral auxilliary, and helps direct the delivery of the cyanide group to specifically one face of the imine rather than the other. After removal of the aluminum carrier for the cyano group and hydrolysis of the cyano group to a carboxylic acid group, we end up with an enantiomerically pure amino acid.