Quantum chemistry interoperability (library): another step towards FAIR data.

January 1st, 2022

To 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:

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Molecule of the year 2021: Infinitene.

December 16th, 2021

The annual “molecule of the year” results for 2021 are now available … and the winner is Infinitene.[1] This is a benzocirculene in the form of a figure eight loop (the infinity symbol), a shape which is also called a lemniscate [2] 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)[3],[4],[5], many of which exhibit lemniscular topology as determined from a crystal structure. Straightforward annulenes have also been noted to display this[6] (as first suggested here for a [14]annulene[7]) and other molecules show higher-order Möbius forms such as trefoil knots.[8],[9] 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 »

References

  1. K. Itami, M. Krzeszewski, and H. Ito, "Infinitene: A Helically Twisted Figure-Eight [12]Circulene Topoisomer", 2021. http://dx.doi.org/10.33774/chemrxiv-2021-pcwcc
  2. C.S.M. Allan, and H.S. Rzepa, "Chiral Aromaticities. AIM and ELF Critical Point and NICS Magnetic Analyses of Möbius-Type Aromaticity and Homoaromaticity in Lemniscular Annulenes and Hexaphyrins", The Journal of Organic Chemistry, vol. 73, pp. 6615-6622, 2008. http://dx.doi.org/10.1021/jo801022b
  3. H. Rath, J. Sankar, V. PrabhuRaja, T.K. ChandrashekarPresent address: The D, B.S. Joshi, and R. Roy, "Figure-eight aromatic core-modified octaphyrins with six meso links: syntheses and structural characterization", Chemical Communications, pp. 3343, 2005. http://dx.doi.org/10.1039/b502327k
  4. H. Rath, J. Sankar, V. PrabhuRaja, T.K. Chandrashekar, and B.S. Joshi, "Aromatic Core-Modified Twisted Heptaphyrins[1.1.1.1.1.1.0]:  Syntheses and Structural Characterization", Organic Letters, vol. 7, pp. 5445-5448, 2005. http://dx.doi.org/10.1021/ol0521937
  5. S. Shimizu, N. Aratani, and A. Osuka, "meso-Trifluoromethyl-Substituted Expanded Porphyrins", Chemistry - A European Journal, vol. 12, pp. 4909-4918, 2006. http://dx.doi.org/10.1002/chem.200600158
  6. T. Perera, F.R. Fronczek, and S.F. Watkins, "2,9,16,23-Tetrakis(1-methylethyl)-5,6,11,12,13,14,19,20,25,26,27,28-dodecadehydrotetrabenzo[a,e,k,o]cycloeicosene", Acta Crystallographica Section E Structure Reports Online, vol. 67, pp. o3493-o3493, 2011. http://dx.doi.org/10.1107/S1600536811048604
  7. H.S. Rzepa, "A Double-Twist Möbius-Aromatic Conformation of [14]Annulene", Organic Letters, vol. 7, pp. 4637-4639, 2005. http://dx.doi.org/10.1021/ol0518333
  8. G.R. Schaller, F. Topić, K. Rissanen, Y. Okamoto, J. Shen, and R. Herges, "Design and synthesis of the first triply twisted Möbius annulene", Nature Chemistry, vol. 6, pp. 608-613, 2014. http://dx.doi.org/10.1038/NCHEM.1955
  9. S.M. Bachrach, and H.S. Rzepa, "Cycloparaphenylene Möbius trefoils", Chemical Communications, vol. 56, pp. 13567-13570, 2020. http://dx.doi.org/10.1039/D0CC04190D

Protein-Biotin complexes. Crystal structure mining.

December 12th, 2021

In 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.

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Biotin’s biggest lesson is the importance of nonclassical H-bonds in protein−ligand complexes.

November 27th, 2021

The title comes from the abstract of an article[1] 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.

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References

  1. D.B. McConnell, "Biotin’s Lessons in Drug Design", Journal of Medicinal Chemistry, vol. 64, pp. 16319-16327, 2021. http://dx.doi.org/10.1021/acs.jmedchem.1c00975

First came Molnupiravir – now there is Paxlovid as a SARS-CoV-2 protease inhibitor. An NCI analysis of the ligand.

November 13th, 2021

Earlier 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.

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More examples of crystal structures containing embedded linear chains of iodines.

October 17th, 2021

The 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.

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Herapathite: an example of (double?) serendipity.

October 14th, 2021

On 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[1] 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[2] in unusual circumstances. Now to the serendipity!

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References

  1. B. Kahr, J. Freudenthal, S. Phillips, and W. Kaminsky, "Herapathite", Science, vol. 324, pp. 1407-1407, 2009. http://dx.doi.org/10.1126/science.1173605
  2. W.B. Herapath, "XXVI. On the optical properties of a newly-discovered salt of quinine, which crystalline substance possesses the power of polarizing a ray of light, like tourmaline, and at certain angles of rotation of depolarizing it, like selenite", The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science, vol. 3, pp. 161-173, 1852. http://dx.doi.org/10.1080/14786445208646983

A comparison of searches based on metadata records from three (update: five) research repositories.

September 28th, 2021

In 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.

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A comparison of descriptive metadata across different data repositories.

September 28th, 2021

The 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 three such repositories and comparing the richness of the metadata describing the essential properties of the three depositions.

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HPC Access and Metadata Portal (CHAMP).

September 13th, 2021

You 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[1]  and this provides a timely opportunity to describe the system a little more. 

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References

  1. M.J. Harvey, N.J. Mason, and H.S. Rzepa, "Digital Data Repositories in Chemistry and Their Integration with Journals and Electronic Notebooks", Journal of Chemical Information and Modeling, vol. 54, pp. 2627-2635, 2014. http://dx.doi.org/10.1021/ci500302p