Posts Tagged ‘Tutorial material’

Updating a worked problem in conformational analysis. Part 2: an answer.

Tuesday, May 17th, 2011

The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post.

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Updating a worked problem in conformational analysis. Part 1: the question.

Friday, May 13th, 2011

Conformational analysis comes from the classical renaissance of physical organic chemistry in the 1950s and 60s. The following problem is taken from E. D. Hughes and J. Wilby J. Chem. Soc., 1960, 4094-4101, DOI: 10.1039/JR9600004094, the essence of which is that Hofmann elimination of a neomenthyl derivative (C below) was observed as anomalously faster than its menthyl analogue. Of course, what is anomalous in one decade is a standard student problem (and one Nobel prize) five decades later.

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The Sn1…Sn2 mechanistic continuum. The special case of neopentyl bromide

Monday, May 9th, 2011

Introductory organic chemistry invariably features the mechanism of haloalkane solvolysis, and introduces both the Sn1 two-step mechanism, and the Sn2 one step mechanism to students. They are taught to balance electronic effects (the stabilization of carbocations) against steric effects in order to predict which mechanism prevails. It was whilst preparing a tutorial on this topic that I came across what was described as the special case of neopentyl bromide, the bimolecular solvolysis of which has been identified (DOI: 10.1021/ja01182a117) as being as much as 3 million times slower than methyl bromide. This is attributed to a very strong steric effect on the reaction, greater even than that which might be experienced by t-butyl bromide! Time I thought, to take a look at what might make neopentyl bromide so special, and what those supposed electronic and steric effects were really up to.

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What is the future of books?

Friday, April 29th, 2011

At a recent conference, I talked about what books might look like in the near future, with the focus on mobile devices such as the iPad. I ended by asserting that it is a very exciting time to be an aspiring book author, with one’s hands on (what matters), the content. Ways of expressing that content are currently undergoing an explosion of new metaphors, and we might even expect some of them to succeed! But content is king, as they say.

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Ferrocene

Sunday, April 17th, 2011

The structure of ferrocene was famously analysed by Woodward and Wilkinson in 1952[1],[2], symmetrically straddled in history by Pauling (1951) and Watson and Crick (1953). Quite a trio of Nobel-prize winning molecular structural analyses, all based on a large dose of intuition. The structures of both proteins and DNA succumbed to models built from simple Lewis-type molecules with covalent (and hydrogen) bonds; ferrocene is intriguingly similar and yet different. Similar because e.g. carbon via four electron pair bonds. He did not (in 1916) realise that 8 = 2(1 + 3), and that the next in sequence would be 18 = 2(1 + 3 + 5). That would have to wait for quantum mechanics, and of course inorganic chemists now call it the 18-electron rule (for an example of the 32-electron rule, or 2+6+10+14, as first suggested by Langmuir in 1921[3] (see also here[4]).

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References

  1. G. Wilkinson, M. Rosenblum, M.C. Whiting, and R.B. Woodward, "THE STRUCTURE OF IRON BIS-CYCLOPENTADIENYL", Journal of the American Chemical Society, vol. 74, pp. 2125-2126, 1952. https://doi.org/10.1021/ja01128a527
  2. G. Wilkinson, "The iron sandwich. A recollection of the first four months", Journal of Organometallic Chemistry, vol. 100, pp. 273-278, 1975. https://doi.org/10.1016/s0022-328x(00)88947-0
  3. I. Langmuir, "Types of Valence", Science, vol. 54, pp. 59-67, 1921. https://doi.org/10.1126/science.54.1386.59
  4. J. Dognon, C. Clavaguéra, and P. Pyykkö, "Towards a 32‐Electron Principle: Pu@Pb<sub>12</sub> and Related Systems", Angewandte Chemie International Edition, vol. 46, pp. 1427-1430, 2007. https://doi.org/10.1002/anie.200604198

Why are α-helices in proteins mostly right handed?

Saturday, April 9th, 2011

Understanding why and how proteins fold continues to be a grand challenge in science. I have described how Wrinch in 1936 made a bold proposal for the mechanism, which however flew in the face of much of then known chemistry. Linus Pauling took most of the credit (and a Nobel prize) when in a famous paper[1] in 1951 he suggested a mechanism that involved (inter alia) the formation of what he termed α-helices. Jack Dunitz in 2001[2] wrote a must-read article[3] on the topic of “Pauling’s Left-handed α-helix” (it is now known to be right handed). I thought I would revisit this famous example with a calculation of my own and here I have used the ωB97XD/6-311G(d,p) DFT procedure[4] to calculate some of the energy components of a small helix comprising (ala)6 in both left and right handed form.

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References

  1. L. Pauling, R.B. Corey, and H.R. Branson, "The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain", Proceedings of the National Academy of Sciences, vol. 37, pp. 205-211, 1951. https://doi.org/10.1073/pnas.37.4.205
  2. J.D. Dunitz, "Pauling's Left-Handed α-Helix", Angewandte Chemie International Edition, vol. 40, pp. 4167-4173, 2001. https://doi.org/10.1002/1521-3773(20011119)40:22<4167::aid-anie4167>3.0.co;2-q
  3. https://doi.org/
  4. K.S. Thanthiriwatte, E.G. Hohenstein, L.A. Burns, and C.D. Sherrill, "Assessment of the Performance of DFT and DFT-D Methods for Describing Distance Dependence of Hydrogen-Bonded Interactions", Journal of Chemical Theory and Computation, vol. 7, pp. 88-96, 2010. https://doi.org/10.1021/ct100469b

The Cyclol Hypothesis for protein structure: castles in the air.

Monday, April 4th, 2011

Most scientific theories emerge slowly, over decades, but others emerge fully formed virtually overnight as it were (think Einstein in 1905). A third category is the supernova type, burning brightly for a short while, but then vanishing (almost) without trace shortly thereafter. The structure of DNA (of which I have blogged elsewhere) belongs to the second class, whilst one of the brightest (and now entirely forgotten) examples of the supernova type concerns the structure of proteins. In 1936, it must have seemed a sure bet that the first person to come up with a successful theory of the origins of the (non-random) relatively rigid structure of proteins would inevitably win a Nobel prize. Of course this did happen for that other biologically important system, DNA, some 17 years later. Compelling structures for larger molecules providing reliable atom-atom distances based on crystallography were still in the future in 1936, and so structural theories contained a fair element of speculation and hopefully inspired guesswork (much as cosmological theories appear to have nowadays!).

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The thermodynamic energies of left and right handed DNA.

Saturday, March 5th, 2011

In this earlier post, I noted some aspects of the calculated structures of both Z- and B-DNA duplexes. These calculations involved optimising the positions of around 250-254 atoms, for d(CGCG)2 and d(ATAT)2, an undertaking which has taken about two months of computer time! The geometries are finally optimised to the point where 2nd derivatives can be calculated, and which reveal up to 756 all-positive force constants and 6 translations and rotations which are close to zero! This now lets one compute the thermodynamic relative energies using ωB97XD/6-31G(d) (for 2nd derivatives) and 6-31G(d,p) (for dispersion terms). All geometries are optimized using a continuum solvent field (water), and are calculated, without a counterion, as hexa-anions. (more…)

The formation of cyanohydrins: re-writing the text books. ! or ?

Friday, March 4th, 2011

Nucleophilic addition of cyanide to a ketone or aldehyde is a standard reaction for introductory organic chemistry. But is all as it seems? The reaction is often represented as below, and this seems simple enough.

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Valentine chemistry

Sunday, February 13th, 2011

The Möbius band is an experimental delight. In its original forms, it came flat-packed as below. The one shown on the left is related to the international symbol for recycling (if we denote the number of half twists imparted as m, this one has m=3). The middle one (m=4) shows a 4-twisted variant, and the one on the right has a 5-twist (m=5). These all come from Möbius’ original sketches, found amongst his belongings when he died. In this post they will form the basis for some experiments in molecular chirality.

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