Archive for January, 2024

3D Molecular model visualisation: 3 Million atoms +

Saturday, January 27th, 2024

In the late 1980s, as I recollected here[1] the equipment needed for real time molecular visualisation as it became known as was still expensive, requiring custom systems such as Evans and Sutherland PS390 workstations. One major breakthrough in making such techniques generally available on less specialised equipment was achieved by Roger Sayle[2], then working at Imperial College around 1990 and using a Silicon Graphics workstation. He greatly optimised up the rendering algorithms by creating a program called RasMol (after his initials), which meant such visualisations could very rapidly also be achieved even on a personal computer. Moving from vector display technology (the PS390) to Raster/bitmap graphics had allowed spacefilling representations of molecules containing 100s if not 1000s of atoms – and in turn enabled the new World-Wide Web to exploit the technique.[3]

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References

  1. H. Rzepa, "Computers 1967-2011: a personal perspective. Part 2. 1985-1989.", 2011. http://dx.doi.org/10.59350/g4j62-4xk50
  2. R. Sayle, "RASMOL: biomolecular graphics for all", Trends in Biochemical Sciences, vol. 20, pp. 374-376, 1995. http://dx.doi.org/10.1016/s0968-0004(00)89080-5
  3. H.S. Rzepa, B.J. Whitaker, and M.J. Winter, "Chemical applications of the World-Wide-Web system", Journal of the Chemical Society, Chemical Communications, pp. 1907, 1994. http://dx.doi.org/10.1039/C39940001907

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The Macintosh computer at 40.

Thursday, January 25th, 2024

On 24th January 1984, the Macintosh computer was released, as all the media are informing us. Apparently, some are still working. I thought I would give my own personal recollections of that period.

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A mechanistic exploration of the Wilkinson hydrogenation catalyst. Part 1: Model templates

Sunday, January 21st, 2024

Geoffrey Wilkinson first reported his famous work on the hydrogenation catalyst that now bears his name in 1965[1] and I met him at Imperial College around 1969 and again when I returned there in 1977. He was still working on these catalysts then and I was privileged to collaborate with him on unravelling the NMR spectra of some of these compounds.[2],[3],[4]. During that period, computational modelling of the mechanisms of molecules containing transition elements was still in its infancy and I never extended my collaboration into this area at that time. Now, even if belatedly, I decided to explore this aspect and started to do this about two weeks ago. Here I thought that I would use this opportunity to show how I am going about it.

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References

  1. J.F. Young, J.A. Osborn, F.H. Jardine, and G. Wilkinson, "Hydride intermediates in homogeneous hydrogenation reactions of olefins and acetylenes using rhodium catalysts", Chemical Communications (London), pp. 131, 1965. http://dx.doi.org/10.1039/C19650000131
  2. K.W. Chiu, H.S. Rzepa, R.N. Sheppard, G. Wilkinson, and W. Wong, "Two-dimensional δ/J-resolved31P n.m.r. spectroscopy of [bis(diphenylphosphino)methane](trimethylphosphine)chlororhodium(I)", J. Chem. Soc., Chem. Commun., pp. 482-484, 1982. http://dx.doi.org/10.1039/C39820000482
  3. C. Kwok W., C.G. Howard, H.S. Rzepa, R.N. Sheppard, G. Wilkinson, A.M. Galas, and M.B. Hursthouse, "Trimethyl and diethylphenylphosphine complexes of rhenium(I, III, IV, V) and their reactions. X-ray crystal structures of a bis(η5-cyclopentadienyl)-ethane-bridged dirhenium(I) complex obtained from phenylacetylene, tetrakis-(diethylphenylphosphine) (dinitrogen) hydridorhenium (I), tetrakis(trimethyl-phosphine) (η2-dimethylphosphinomethyl) rhenium(I) and tetrakis(trimethylphosphine) (iodo)methyl rhenium(III) iodide-tetramethylphosphonium iodide", Polyhedron, vol. 1, pp. 441-451, 1982. http://dx.doi.org/10.1016/S0277-5387(00)86558-4
  4. K.W. Chiu, H.S. Rzepa, R.N. Sheppard, G. Wilkinson, and W. Wong, "Bis(diphenylphosphino)methane trimethylphosphine alkyl and η5-cyclopentadienyl compounds of rhodium(I); 31P{1H} two dimensional δ/J resolved and Overhauser effect nuclear magnetic resonance spectroscopy", Polyhedron, vol. 1, pp. 809-817, 1982. http://dx.doi.org/10.1016/0277-5387(82)80008-9

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Scholarly journals vs Scholarly Blogs.

Friday, January 12th, 2024

First, a very brief history of scholarly publishing, starting in 1665[1] when scientific journals started to be published by learned societies. This model continued until the 1950s, when commercial publishers such as Pergamon Press started with their USP (unique selling point) of rapid time to publication of ~3 months,[2] compared to typical times for many learned society publishers of 2 years or longer. Fast forward another 50 years or so, and the commercial publishers were now dominating the scene, but the business model was still based on institutional subscriptions, whereby the institution rather than authors paid the costs of publication. As the number of journals expanded, even well-off institutions had to make difficult decisions on which subscriptions to keep and which to cancel. By the late 1990s the delivery model was changing from print to online, but the overall issue was that many scientists around the world no longer had access to many journals.

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References

  1. "Epistle dedicatory", Philosophical Transactions of the Royal Society of London, vol. 1, 1665. http://dx.doi.org/10.1098/rstl.1665.0001
  2. D. Ginsburg, and W.J. Rosenfelder, "Alicyclic studies—X", Tetrahedron, vol. 1, pp. 3-8, 1957. http://dx.doi.org/10.1016/0040-4020(57)85003-0

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Macrocyclic peptide antibiotics – now Zosurabalpin – then antibacterial agents based on cyclic D,L-α-peptide architectures.

Monday, January 8th, 2024

Zosurabalbin[1],[2], is receiving a great deal of attention as a new class of antibiotic which can target infections for which current treatment options are inadequate. It is a cyclic peptide and seeing this triggered memory of an earlier such species reported way back in 1995[3],[4]. This octa-peptide (YIJDIE, DOI: 10.5517/cc58gxs) was presumed to function in a novel manner, having linear water channels wide enough to form a molecular nanoscale pipe for a stream of water molecules to flow along. When inserted into the bacterial cell membrane via its lipophilic sidechains, it drained the bacterium of its cell water within seconds, thus killing it. A 3D model shows the effect very clearly.

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References

  1. C. Zampaloni, P. Mattei, K. Bleicher, L. Winther, C. Thäte, C. Bucher, J. Adam, A. Alanine, K.E. Amrein, V. Baidin, C. Bieniossek, C. Bissantz, F. Boess, C. Cantrill, T. Clairfeuille, F. Dey, P. Di Giorgio, P. du Castel, D. Dylus, P. Dzygiel, A. Felici, F. García-Alcalde, A. Haldimann, M. Leipner, S. Leyn, S. Louvel, P. Misson, A. Osterman, K. Pahil, S. Rigo, A. Schäublin, S. Scharf, P. Schmitz, T. Stoll, A. Trauner, S. Zoffmann, D. Kahne, J.A.T. Young, M.A. Lobritz, and K.A. Bradley, "A novel antibiotic class targeting the lipopolysaccharide transporter", Nature, vol. 625, pp. 566-571, 2024. http://dx.doi.org/10.1038/s41586-023-06873-0
  2. S. Hawser, N. Kothari, T. Valmont, S. Louvel, and C. Zampaloni, "2131. Activity of the Novel Antibiotic Zosurabalpin (RG6006) against Clinical Acinetobacter Isolates from China", Open Forum Infectious Diseases, vol. 10, 2023. http://dx.doi.org/10.1093/ofid/ofad500.1754
  3. M.R. Ghadiri, K. Kobayashi, J.R. Granja, R.K. Chadha, and D.E. McRee, "The Structural and Thermodynamic Basis for the Formation of Self‐Assembled Peptide Nanotubes", Angewandte Chemie International Edition in English, vol. 34, pp. 93-95, 1995. http://dx.doi.org/10.1002/anie.199500931
  4. S. Fernandez-Lopez, H. Kim, E.C. Choi, M. Delgado, J.R. Granja, A. Khasanov, K. Kraehenbuehl, G. Long, D.A. Weinberger, K.M. Wilcoxen, and M.R. Ghadiri, "Antibacterial agents based on the cyclic d,l-α-peptide architecture", Nature, vol. 412, pp. 452-455, 2001. http://dx.doi.org/10.1038/35086601

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