Ever since the concept of a shared two-electron bond was conjured by Gilbert N. Lewis in 1916,[cite]10.1021/ja02261a002[/cite] chemists have been fascinated by the related concept of a bond order (the number of such bonds that two atoms can participate in, however a bond is defined) and pushing it ever higher for pairs of like-atoms. Lewis first showed in 1916[cite]10.1021/ja02261a002[/cite] how two carbon atoms could share two, four or six electrons to achieve a bond order of up to three. It took quite a few decades for this to be extended to four for carbon (and nitrogen) and that only with some measure of controversy and dispute (for one recent brief summary, see[cite]10.1039/D1CP02056K[/cite]).
Chasing ever higher bond orders; the strange case of beryllium.
February 7th, 2022Data base or Data repository? – A brief and very selective history of data management in chemistry.
January 26th, 2022Way back in the late 1980s or so, research groups in chemistry started to replace the filing of their paper-based research data by storing it in an easily retrievable digital form. This required a computer database and initially these were accessible only on specific dedicated computers in the laboratory. These gradually changed from the 1990s onwards into being accessible online, so that more than one person could use them in different locations. At least where I worked, the infrastructures‡ to set up such databases were mostly not then available as part of the standard research provisions and so had to be installed and maintained by the group itself. The database software took many different forms and it was not uncommon for each group in a department to come up with a different solution that suited its needs best. The result was a proliferation of largely non-interoperable solutions which did not communicate with each other. Each database had to be searched locally and there could be ten or more such resources in a department. The knowledge of how the system operated also often resided in just one person, which tended to evaporate when this guru left the group.
Quantum chemistry interoperability (library): another step towards FAIR data.
January 1st, 2022To be FAIR, data has to be not only Findable and Accessible, but straightforwardly Interoperable. One of the best examples of interoperability in chemistry comes from the domain of quantum chemistry. This strives to describe a molecule by its electron density distribution, from which many interesting properties can then be computed. The process is split into two parts:
Molecule of the year 2021: Infinitene.
December 16th, 2021The 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 »
Protein-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.