For obvious reasons, anti-viral molecules are very much in the news at the moment. Thus Derek Lowe highlights Molnupiravir which is shown as a hydroxylamine, the representation originating from the Wikipedia page on the molecule. I like stereocentres more clearly identified using eg R / S notation and so I went to another source of information, SciFinder, which represents the molecule in a different way.

I have occasionally covered the topic of colours here, such as those of flowers and minerals, since it is at least possible to illustrate these using photographs or colour charts to illustrate the theme.

The last post addressed the concept of “steric clashes” in a pericyclic reaction transition state as an extension of the time honoured practice of building molecular models to analyse reaction outcomes. A modern computer generated model might express this in terms of a NCI (non-covalent-interaction) surface.

Another foray into one of the more famous anecdotal chemistry “models”, the analysis of which led directly to the formulation of the WoodWard-Hoffmann (stereochemical) rules for pericyclic reactions.

In a recent post, I told the story of how in the early 1960s, Robert Woodward had encountered an unexpected stereochemical outcome to the reaction of a hexatriene, part of his grand synthesis of vitamin B12. He had constructed a model of the reaction he wanted to undertake, perhaps with the help of a physical model, concluding that the most favourable of the two he had built was not matched by the actual outcome of the reaction.

Last May, I wrote an update to the story sparked by the report of the chemical synthesis of C ₂ .[cite]10.1038/s41467-020-16025-x[/cite] This species has a long history of spectroscopic observation in the gas phase, resulting from its generation at high temperatures.[cite]10.1021/acs.accounts.0c00703[/cite] The chemical synthesis however was done in solution at ambient or low temperatures, a game-changer as they say.

The quote of the post title comes from R. B. Woodward explaining the genesis of the discovery of what are now known as the Woodward-Hoffmann rules for pericyclic reactions.[cite]10.1021/ja01080a054[/cite] I first wrote about this in 2012, noting that “*for (that) blog, I do not want to investigate the transition states”.* Here I take a closer look at this aspect. I will start by explaining my then reluctance to discuss transition states.

In the previous post, I showed the geometries of three large cyclic porphyrins, as part of an article[cite]10.1038/s41557-019-0398-3[/cite] on exploring the aromaticity of large 4n+2 cyclic rings. One of them had been induced into a “figure-eight” or lemniscular conformation, as shown below.

Here is another of the “large” molecules in the c&e news shortlist for molecule-of-the-year, 2020. This one is testing the Hückel 4n+2 rule out to a value never before seen (n = 40, or 162 π-electrons).[cite]10.1038/s41557-019-0398-3[/cite] The take-home message is that this rule seems to behave well in predicting global aromaticity even at this sort of scale!

The title derives from an article[cite]10.1038/s41586-020-2614-0[/cite] which was shortlisted for the annual c&en molecule of the year 2020 awards (and which I occasionally cover here). In fact this year’s overall theme is certainly large molecules, the one exception being a smaller molecule with a quadruple bond to boron, a theme I have already covered here.