Posts Tagged ‘Cambridge’

Imaging vibrational normal modes of a single molecule.

Thursday, April 18th, 2019

The topic of this post originates from a recent article which is attracting much attention.[1] The technique uses confined light to both increase the spatial resolution by around three orders of magnitude and also to amplify the signal from individual molecules to the point it can be recorded. To me, Figure 3 in this article summarises it nicely (caption: visualization of vibrational normal modes). Here I intend to show selected modes as animated and rotatable 3D models with the help of their calculation using density functional theory (a mode of presentation that the confinement of Figure 3 to the pages of a conventional journal article does not enable).

(more…)

References

  1. J. Lee, K.T. Crampton, N. Tallarida, and V.A. Apkarian, "Visualizing vibrational normal modes of a single molecule with atomically confined light", Nature, vol. 568, pp. 78-82, 2019. http://dx.doi.org/10.1038/s41586-019-1059-9

How to stop (some) acetals hydrolysing.

Thursday, November 12th, 2015

Derek Lowe has a recent post entitled "Another Funny-Looking Structure Comes Through". He cites a recent medchem article[1] in which the following acetal sub-structure appears in a promising drug candidate (blue component below). His point is that orally taken drugs have to survive acid (green below) encountered in the stomach, and acetals are famously sensitive to hydrolysis (red below). But if X=NH2, compound "G-5555" is apparently stable to acids.[1] So I pose the question here; why?

(more…)

References

  1. C.O. Ndubaku, J.J. Crawford, J. Drobnick, I. Aliagas, D. Campbell, P. Dong, L.M. Dornan, S. Duron, J. Epler, L. Gazzard, C.E. Heise, K.P. Hoeflich, D. Jakubiak, H. La, W. Lee, B. Lin, J.P. Lyssikatos, J. Maksimoska, R. Marmorstein, L.J. Murray, T. O’Brien, A. Oh, S. Ramaswamy, W. Wang, X. Zhao, Y. Zhong, E. Blackwood, and J. Rudolph, "Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pKa Polar Moiety", ACS Medicinal Chemistry Letters, vol. 6, pp. 1241-1246, 2015. http://dx.doi.org/10.1021/acsmedchemlett.5b00398

Yes, no, yes. Computational mechanistic exploration of (nickel-catalysed) cyclopropanation using tetramethylammonium triflate.

Thursday, October 1st, 2015

A fascinating re-examination has appeared[1] of a reaction first published[2] in 1960 by Wittig and then[3] repudiated by him in 1964 since it could not be replicated by a later student. According to the new work, the secret to a successful replication seems to be the presence of traces of a nickel catalyst (originally coming from e.g. a nickel spatula?). In this recent article[1] a mechanism for the catalytic cycle is proposed. Here I thought I might explore this mechanism using calculations to see if any further insights might emerge.

(more…)

References

  1. S.A. Künzi, J.M. Sarria Toro, T. den Hartog, and P. Chen, "Nickel-Catalyzed Cyclopropanation with NMe4 OTf and n BuLi", Angewandte Chemie International Edition, vol. 54, pp. 10670-10674, 2015. http://dx.doi.org/10.1002/anie.201505482
  2. V. Franzen, and G. Wittig, "Trimethylammonium-methylid als Methylen-Donator", Angewandte Chemie, vol. 72, pp. 417-417, 1960. http://dx.doi.org/10.1002/ange.19600721210
  3. G. Wittig, and D. Krauss, "Cyclopropanierungen bei Einwirkung vonN-Yliden auf Olefine", Justus Liebigs Annalen der Chemie, vol. 679, pp. 34-41, 1964. http://dx.doi.org/10.1002/jlac.19646790106

Deviations from tetrahedral four-coordinate carbon: a statistical exploration.

Sunday, September 6th, 2015

An article entitled "Four Decades of the Chemistry of Planar Hypercoordinate Compounds"[1] was recently reviewed by Steve Bacharach on his blog, where you can also see comments. Given the recent crystallographic themes here, I thought I might try a search of the CSD (Cambridge structure database) to see whether anything interesting might emerge for tetracoordinate carbon.

(more…)

References

  1. L. Yang, E. Ganz, Z. Chen, Z. Wang, and P.V.R. Schleyer, "Four Decades of the Chemistry of Planar Hypercoordinate Compounds", Angewandte Chemie International Edition, vol. 54, pp. 9468-9501, 2015. http://dx.doi.org/10.1002/anie.201410407

A visualisation of the effects of conjugation; dienes and biaryls.

Tuesday, August 25th, 2015

Here is another exploration of simple chemical concepts using crystal structures. Consider a simple diene: how does the central C-C bond length respond to the torsion angle between the two C=C bonds?

(more…)

The 2015 Bradley-Mason prize for open chemistry.

Friday, June 26th, 2015

Open principles in the sciences in general and chemistry in particular are increasingly nowadays preached from funding councils down, but it can be more of a challenge to find innovative practitioners. Part of the problem perhaps is that many of the current reward systems for scientists do not always help promote openness. Jean-Claude Bradley was a young scientist who was passionately committed to practising open chemistry, even though when he started he could not have anticipated any honours for doing so. A year ago a one day meeting at Cambridge was held to celebrate his achievements, followed up with a special issue of the Journal of Cheminformatics. Peter Murray-Rust and I both contributed and following the meeting we decided to help promote Open Chemistry via an annual award to be called the Bradley-Mason prize. This would celebrate both “JC” himself and Nick Mason, who also made outstanding contributions to the cause whilst studying at Imperial College. The prize was initially to be given to an undergraduate student at Imperial, but was also extended to postgraduate students who have promoted and showcased open chemistry in their PhD researches.

(more…)

Artemisinin: are stereo-electronics at the core of its (re)activity?

Sunday, April 13th, 2014

Around 100 tons of the potent antimalarial artemisinin is produced annually; a remarkable quantity given its very unusual and fragile looking molecular structure (below). When I looked at this, I was immediately struck by a thought: surely this is a classic molecule for analyzing stereoelectronic effects (anomeric and gauche). Here this aspect is explored.

(more…)

The butterfly effect in chemistry: Bimodal M~S bonds?

Sunday, July 14th, 2013

I noted previously that some 8-ring cyclic compounds could exist in either a planar-aromatic or a non-planar-non-aromatic mode, the mode being determined by apparently quite small changes in a ring substituent. Hunting for other examples of such chemistry on the edge, I did a search of the Cambridge crystal database for metal sulfides. 

(more…)

Computers 1967-2013: a personal perspective. Part 5. Network bandwidth.

Wednesday, June 5th, 2013

In a time of change, we often do not notice that Δ = ∫δ. Here I am thinking of network bandwidth, and my personal experience of it over a 46 year period.

(more…)

The mysterious (aromatic) structure of n-Butyl lithium.

Sunday, March 17th, 2013

n-Butyl lithium is hexameric in the solid state and in cyclohexane solutions. Why? Here I try to find out some of its secrets.

(more…)