Posts Tagged ‘HTML’

Revisiting (and maintaining) a twenty year old web page. Mauveine: The First Industrial Organic Fine-Chemical.

Thursday, February 2nd, 2017
No Gravatar

Almost exactly 20 years ago, I started what can be regarded as the precursor to this blog. As part of a celebration of this anniversary,[1] I revisited the page to see whether any of it had withstood the test of time. Here I recount what I discovered.

(more…)

References

  1. P.W. May, S.A. Cotton, K. Harrison, and H.S. Rzepa, "The ‘Molecule of the Month’ Website—An Extraordinary Chemistry Educational Resource Online for over 20 Years", Molecules, vol. 22, pp. 549, 2017. http://dx.doi.org/10.3390/molecules22040549

500 chemical twists: a (chalk and cheese) comparison of the impacts of blog posts and journal articles.

Friday, June 3rd, 2016
No Gravatar

The title might give it away; this is my 500th blog post, the first having come some eight years ago. Very little online activity nowadays is excluded from measurement and so it is no surprise that this blog and another of my "other" scholarly endeavours, viz publishing in traditional journals, attract such "metrics" or statistics. The h-index is a well-known but somewhat controversial measure of the impact of journal articles; here I thought I might instead take a look at three less familiar ones – one relating to blogging, one specific to journal publishing and one to research data.

(more…)

How to stop (some) acetals hydrolysing.

Thursday, November 12th, 2015
No Gravatar

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? acetal This reminded me of some work we did a few years ago on herbicides containing such an acetal substructure, where one diastereoisomer was very unstable to hydrolysis (and hence did not have the lifetime required of a herbicide) whereas the other diastereomer was far less labile and hence more suitable.[2],[3] Crystal structures (below) revealed that the two C-O bond lengths of the labile form were very unequal in length (Δ0.043Å), whereas the stable form had two equal C-O lengths (1.408Å, Δ=0.0Å).

Click for 3D

2, but there is one example[cite]10.5517/CC71HVL[/cite],[cite]10.1107/S1600536803006287[/cite] of an orthoformate in which the group equivalent to X is protonated as Me2NH+. For this example, all three C-O lengths are shorter than even the hydrolytically stable herbicide above (1.405, 1.402, 1.396Å). The distribution for 6-ring acetals in general shows hot-spots at ~1.415Å and 1.43Å (but sadly it is not possible to e.g. use this database to correlate these lengths with the aqueous stability of the entries). OCO Is this tentative further evidence that a group X = NH2 positioned as above in an acetal can inhibit its hydrolysis? [caption id="attachment_14757" align="aligncenter" width="400"]HUZKEZ, click for 3D HUZKEZ, click for 3D

Time for calculations. A model (X=R=H) for the hydrolysis was constructed as above in which proton transfer from an acid (ethanoic) is achieved via a cyclic 8-ring transition state and which includes a continuum solvent field as ωB97XD/6-311G(d,p)/SCRF=water and one explicit water in the proton relay. The IRC looks thus: acetalH This shows that the first event is protonation of an oxygen, closely followed by cleavage of the associated C-O bond, and ending with deprotonation of the erstwhile water molecule. acetalha The value of ΔG298 is 38.2 kcal/mol (38.4 in relative total energy). Although rather high for a facile thermal reaction (perhaps the 8-ring TS is a bit too strained; possibly adding a second active water molecule to form a 10-ring might lead to a lower barrier?), we are more interested in the effect upon this barrier of group X (Table below).

(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-pKaPolar Moiety", ACS Medicinal Chemistry Letters, vol. 6, pp. 1241-1246, 2015. http://dx.doi.org/10.1021/acsmedchemlett.5b00398
  2. P. Camilleri, D. Munro, K. Weaver, D.J. Williams, H.S. Rzepa, and A.M.Z. Slawin, "Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives", J. Chem. Soc., Perkin Trans. 2, pp. 1265-1269, 1989. http://dx.doi.org/10.1039/P29890001265
  3. P. Camilleri, D. Munro, K. Weaver, D.J. Williams, H.S. Rzepa, and A.M.Z. Slawin, "Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives", J. Chem. Soc., Perkin Trans. 2, pp. 1929-1933, 1989. http://dx.doi.org/10.1039/P29890001929

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

Sunday, September 6th, 2015
No Gravatar

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

Blasts from the past. A personal Web presence: 1993-1996.

Saturday, November 1st, 2014
No Gravatar

Egon Willighagen recently gave a presentation at the RSC entitled “The Web – what is the issue” where he laments how little uptake of web technologies as a “channel for communication of scientific knowledge and data” there is in chemistry after twenty years or more. It caused me to ponder what we were doing with the web twenty years ago. Our HTTP server started in August 1993, and to my knowledge very little content there has been deleted (it’s mostly now just hidden). So here are some ancient pages which whilst certainly not examples of how it should be done nowadays, give an interesting historical perspective. In truth, there is not much stuff that is older out there!

(more…)

Publishing a procedure with a doi.

Wednesday, October 2nd, 2013
No Gravatar

In the two-publisher model I proposed a post or so back, I showed an example of how data can be incorporated (transcluded) into the story narrative of a scientific article, with both that story and the data each having their own independently citable reference (using a doi for the citation). Here I take it a step further, by publishing a functional procedure in a digital repository[1] and assigned its own doi:10.6084/m9.figshare.811862.

(more…)

References

  1. Henry S. Rzepa., "Script for creating an NCI surface as a JVXL compressed file from a (Gaussian) cube of total electron density", 2013. http://dx.doi.org/10.6084/m9.figshare.811862

Science publishers (and authors) please take note.

Monday, October 24th, 2011
No Gravatar

I have for perhaps the last 25 years been urging publishers to recognise how science publishing could and should change. My latest thoughts are published in an article entitled “The past, present and future of Scientific discourse” (DOI: 10.1186/1758-2946-3-46). Here I take two articles, one published 58 years ago and one published last year, and attempt to reinvent some aspects. You can see the result for yourself (since this journal is laudably open access, and you will not need a subscription). The article is part of a special issue, arising from a one day symposium held in January 2011 entitled “Visions of a Semantic Molecular Future” in celebration of Peter Murray-Rust’s contributions over that period (go read all 15 articles on that theme in fact!).

(more…)

Computers 1967-2011: a personal perspective. Part 3. 1990-1994.

Tuesday, July 12th, 2011
No Gravatar

In 1986 or so, molecular modelling came of age. Richard Counts, who ran an organisation called QCPE (here I had already submitted several of the program codes I had worked on) had a few years before contacted me to ask for my help with his Roadshow. He had started these in the USA as a means of promoting QCPE, which was the then main repository of chemistry codes, and as a means of showing people how to use the codes. My task was to organise a speakers list, the venue being in Oxford in a delightful house owned by the university computing services. Access to VAX computers was provided, via VT100 terminals. Amazingly, these terminals could do very primitive molecular graphics (using delightfully named escape codes, which I learnt to manipulate).

(more…)

Monastral: the colour of blue

Tuesday, March 8th, 2011
No Gravatar

The story of Monastral is not about a character in the Magic flute, but is a classic of chemical serendipity, collaboration between industry and university, theoretical influence, and of much else. Fortunately, much of that story is actually recorded on film (itself a unique archive dating from 1933 and being one of the  very first colour films in existence!). Patrick Linstead, a young chemist then (he eventually rose to become rector of Imperial College) tells the story himself here. It is well worth watching, if only for its innocent social commentary on the English class system (and an attitude to laboratory safety that should not be copied nowadays). Here I will comment only on its colour and its aromaticity.

Copper phthalocyanine

(more…)