The annual “molecule of the year” results for 2021 are now available … and the winner is Infinitene.[cite]10.33774/chemrxiv-2021-pcwcc[/cite],[cite]10.1021/jacs.1c10807[/cite] This is a benzocirculene in the form of a figure eight loop (the infinity symbol), a shape which is also called a lemniscate [cite]10.1021/jo801022b[/cite] after the mathematical (2D) function due to Bernoulli. The most common class of molecule which exhibits this (well known) motif are hexaphyrins (hexaporphyrins; porphyrin is a tetraphyrin)[cite]10.1039/b502327k[/cite],[cite]10.1021/ol0521937[/cite],[cite]10.1002/chem.200600158[/cite], many of which exhibit lemniscular topology as determined from a crystal structure. Straightforward annulenes have also been noted to display this[cite]10.1107/S1600536811048604[/cite] (as first suggested here for a [14]annulene[cite]10.1021/ol0518333[/cite]) and other molecules show higher-order Möbius forms such as trefoil knots.[cite]10.1038/NCHEM.1955[/cite],[cite]10.1039/D0CC04190D[/cite] This new example uses twelve benzo groups instead of six porphyrin units to construct the lemniscate. So the motif is not new, but this is the first time it has been constructed purely from benzene rings. Read the rest of this entry »
Molecule of the year 2021: Infinitene.
December 16th, 2021Protein-Biotin complexes. Crystal structure mining.
December 12th, 2021In the previous post, I showed some of the diverse “non-classical”interactions between Biotin and a protein where it binds very strongly. Here I take a look at two of these interactions to discover how common they are in small molecule structures.
Biotin’s biggest lesson is the importance of nonclassical H-bonds in protein−ligand complexes.
November 27th, 2021The title comes from the abstract of an article[cite]10.1021/acs.jmedchem.1c00975[/cite] analysing why Biotin (vitamin B7) is such a strong and effective binder to proteins, with a free energy of (non-covalent) binding approaching 21 kcal/mol. The author argues that an accumulation of both CH-π and CH-O together with more classical hydrogen bonds and augmented by a sulfur centered hydrogen bond, oxyanion holes and water solvation, accounts for this large binding energy. 
First came Molnupiravir – now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand.
November 13th, 2021Earlier this year, Molnupiravir hit the headlines as a promising antiviral drug. This is now followed by Paxlovid, which is the first small molecule to be aimed by design at the SAR-CoV-2 protein and which is reported as reducing greatly the risk of hospitalization or death when given within three days of symptoms appearing in high risk patients.
More examples of crystal structures containing embedded linear chains of iodines.
October 17th, 2021The previous post described the fascinating 170-year history of a crystalline compound known as Herapathite and its connection to the mechanism of the Finkelstein reaction via the complex of Na+I2– (or Na22+I42-). Both compounds exhibit (approximately) linear chains of iodine atoms in their crystal structures, a connection which was discovered serendipitously. Here I pursue a rather more systematic way of tracking down similar compounds.
Herapathite: an example of (double?) serendipity.
October 14th, 2021On October 13, 2021, the historical group of the Royal Society of Chemistry organised a symposium celebrating ~150 years of the history of (molecular) chirality. We met for the first time in person for more than 18 months and were treated to a splendid and diverse program about the subject. The first speaker was Professor John Steeds from Bristol, talking about the early history of light and the discovery of its polarisation. When a slide was shown about herapathite[cite]10.1126/science.1173605[/cite] my “antennae” started vibrating. This is a crystalline substance made by combining elemental iodine with quinine in acidic conditions and was first discovered by William Herapath as long ago as 1852[cite]10.1080/14786445208646983[/cite] in unusual circumstances. Now to the serendipity!
A comparison of searches based on metadata records from three (update: five) research repositories.
September 28th, 2021In the previous blog post, I looked at the metadata records registered with DataCite for some chemical computational modelling files as published in three different repositories. Here I take it one stage further, by looking at how searches of the DataCite metadata store for three particular values of the metadata associated with this dataset compare.
A comparison of descriptive metadata across different data repositories.
September 28th, 2021The number of repositories which accept research data across a wide spectrum of disciplines is on the up. Here I report the results of conducting an experiment in which chemical modelling data was deposited in six such repositories and comparing the richness of the metadata describing the essential properties of the six depositions.
HPC Access and Metadata Portal (CHAMP).
September 13th, 2021You might have noticed if you have read any of my posts here is that many of them have been accompanied since 2006 by supporting calculations, normally based on density functional theory (DFT) and these calculations are accompanied by a persistent identifier pointer‡ to a data repository publication. I have hitherto not gone into the detail here of the infrastructures required to do this sort of thing, but recently one of the two components has been updated to V2, after being at V1 for some fourteen years[cite]10.1021/ci500302p[/cite] and this provides a timely opportunity to describe the system a little more.
More record breakers for the anomeric effect involving C-N bonds.
September 4th, 2021An earlier post investigated large anomeric effects involving two oxygen atoms attached to a common carbon atom.