Intermolecular atom-atom bonds in crystals? The O…O case.

July 25th, 2015
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I recently followed this bloggers trail; link1link2 to arrive at this delightful short commentary on atom-atom bonds in crystals[1] by Jack Dunitz. Here he discusses that age-old question (to chemists), what is a bond? Even almost 100 years after Gilbert Lewis’ famous analysis,[2] we continue to ponder this question. Indeed, quite a debate on this topic broke out in a recent post here. My eye was caught by one example in Jack’s article: “The close stacking of planar anions, as occurs in salts of croconic acid …far from producing a lowering of the crystal energy, this stacking interaction in itself leads to an increase by several thousand kJ mol−1 arising from Coulombic repulsion between the doubly negatively charged anions” I thought I might explore this point a bit further in this post.

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References

  1. J.D. Dunitz, "Intermolecular atom–atom bonds in crystals?", Int Union Crystallogr J, vol. 2, pp. 157-158, 2015. http://dx.doi.org/10.1107/S2052252515002006
  2. G.N. Lewis, "THE ATOM AND THE MOLECULE.", J. Am. Chem. Soc., vol. 38, pp. 762-785, 1916. http://dx.doi.org/10.1021/ja02261a002

The structure of naphthalene: 1890-1925, and a modern twist.

July 18th, 2015
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This is a little historical essay into the electronic structure of naphthalene, presented as key dates (and also collects comments made which were appended to other posts).

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Reproducibility in science: calculated kinetic isotope effects for cyclopropyl carbinyl radical.

July 11th, 2015
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Previously on the kinetic isotope effects for the Baeyer-Villiger reaction, I was discussing whether a realistic computed model could be constructed for the mechanism. The measured KIE or kinetic isotope effects (along with the approximate rate of the reaction) were to be our reality check. I had used ΔΔG energy differences and then HRR (harmonic rate ratios) to compute[1] the KIE, and Dan Singleton asked if I had included heavy atom tunnelling corrections in the calculation, which I had not. His group has shown these are not negligible for low-barrier reactions such as ring opening of cyclopropyl carbinyl radical.[2] As a prelude to configuring his suggested programs for computing tunnelling (GAUSSRATE and POLYRATE), it was important I learnt how to reproduce his KIE values.[2] Hence the title of this post. Now, read on.

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References

  1. Rzepa, Henry S.., "KINISOT. A basic program to calculate kinetic isotope effects using normal coordinate analysis of transition state and reactants.", 2015. http://dx.doi.org/10.5281/zenodo.19272
  2. O.M. Gonzalez-James, X. Zhang, A. Datta, D.A. Hrovat, W.T. Borden, and D.A. Singleton, " Experimental Evidence for Heavy-Atom Tunneling in the Ring-Opening of Cyclopropylcarbinyl Radical from Intramolecular 12 C/ 13 C Kinetic Isotope Effects ", J. Am. Chem. Soc., vol. 132, pp. 12548-12549, 2010. http://dx.doi.org/10.1021/ja1055593

Electrides (aka solvated electrons).

July 8th, 2015
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Peter Edwards has just given the 2015 Hofmann lecture here at Imperial on the topic of solvated electrons. An organic chemist knows this species as “e” and it occurs in ionic compounds known as electrides; chloride = the negative anion of a chlorine atom, hence electride = the negative anion of an electron. It struck me how very odd these molecules are and so I thought I might share here some properties I computed after the lecture for a specific electride known as GAVKIS.[1] If you really want to learn (almost) everything about these strange species, go read the wonderful review by Zurek, Edwards and Hoffmann,[2] including a lesson in the history of chemistry stretching back almost 200 years.

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References

  1. D.L. Ward, R.H. Huang, and J.L. Dye, "Structures of alkalides and electrides. I. Structure of potassium cryptand[2.2.2] electride", Acta Crystallographica Section C Crystal Structure Communications, vol. 44, pp. 1374-1376, 1988. http://dx.doi.org/10.1107/S0108270188002847
  2. E. Zurek, P.P. Edwards, and R. Hoffmann, "A Molecular Perspective on Lithium-Ammonia Solutions", Angewandte Chemie International Edition, vol. 48, pp. 8198-8232, 2009. http://dx.doi.org/10.1002/anie.200900373

Reproducibility in science: calculated kinetic isotope effects for the Baeyer-Villiger reaction.

July 1st, 2015
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Recollect this earlier post on the topic of the Baeyer-Villiger reaction. In 1999 natural abundance kinetic isotope effects were reported[1] and I set out to calculate the values predicted for a particular model constructed using Quantum mechanics. This comparison of measurement and calculation is nowadays a standard verification of both experiment and theory. When the two disagree either the computational model is wrong or incomplete, or the remoter possibility that there is something not understood about the experiment.

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References

  1. D.A. Singleton, and M.J. Szymanski, " Simultaneous Determination of Intermolecular and Intramolecular 13 C and 2 H Kinetic Isotope Effects at Natural Abundance ", J. Am. Chem. Soc., vol. 121, pp. 9455-9456, 1999. http://dx.doi.org/10.1021/ja992016z

The 2015 Bradley-Mason prize for open chemistry.

June 26th, 2015
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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.

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The formation of tetrahedral intermediates.

June 12th, 2015
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In the preceding post, I discussed the reaction between mCPBA (meta-chloroperbenzoic acid) and cyclohexanone, resulting in Baeyer-Villiger oxidation via a tetrahedral intermediate (TI). Dan Singleton, in whose group the original KIE (kinetic isotope measurements) were made, has kindly pointed out on this blog that his was a mixed-phase reaction, and that mechanistic comparison with homogenous solutions may not be justified. An intriguing aspect of the (solution) mechanism would be whether the TI forms quickly and/or reversibly and what the position of any equilibrium between it and the starting ketone is. This reminded me of work we did some years ago,[1] and here I discuss that.

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References

  1. A.M. Lobo, M.M. Marques, S. Prabhakar, and H.S. Rzepa, "Tetrahedral intermediates formed by nitrogen and oxygen attack of aromatic hydroxylamines on acetyl cyanide", J. Org. Chem., vol. 52, pp. 2925-2927, 1987. http://dx.doi.org/10.1021/jo00389a050

Natural abundance kinetic isotope effects: mechanism of the Baeyer-Villiger reaction.

June 10th, 2015
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I have blogged before about the mechanism of this classical oxidation reaction. Here I further explore computed models, and whether they match the observed kinetic isotope effects (KIE) obtained using the natural-abundance method described in the previous post.

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Natural abundance kinetic isotope effects: expt. vs theory.

June 3rd, 2015
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My PhD thesis involved determining kinetic isotope effects (KIE) for aromatic electrophilic substitution reactions in an effort to learn more about the nature of the transition states involved.[1] I learnt relatively little, mostly because a transition state geometry is defined by 3N-6 variables (N = number of atoms) and its force constants by even more and you get only one or two measured KIE per reaction; a rather under-defined problem in terms of data! So I decided to spend a PostDoc learning how to invert the problem by computing the anticipated isotope effects using quantum mechanics and then comparing the predictions with measured KIE.[2] Although such computation allows access to ALL possible isotope effects, the problem is still under-defined because of the lack of measured KIE to compare the predictions with. In 1995 Dan Singleton and Allen Thomas reported an elegant strategy to this very problem by proposing a remarkably simple method for obtaining KIE using natural isotopic abundances.[3] It allows isotope effects to be measured for all the positions in one of the reactant molecules by running the reaction close to completion and then recovering unreacted reactant and measuring the changes in its isotope abundances using NMR. The method has since been widely applied[4],[5] and improved.[6] Here I explore how measured and calculated KIE can be reconciled.

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References

  1. B.C. Challis, and H.S. Rzepa, "The mechanism of diazo-coupling to indoles and the effect of steric hindrance on the rate-limiting step", J. Chem. Soc., Perkin Trans. 2, pp. 1209, 1975. http://dx.doi.org/10.1039/p29750001209
  2. M.J.S. Dewar, S. Olivella, and H.S. Rzepa, "Ground states of molecules. 49. MINDO/3 study of the retro-Diels-Alder reaction of cyclohexene", J. Am. Chem. Soc., vol. 100, pp. 5650-5659, 1978. http://dx.doi.org/10.1021/ja00486a013
  3. D.A. Singleton, and A.A. Thomas, "High-Precision Simultaneous Determination of Multiple Small Kinetic Isotope Effects at Natural Abundance", J. Am. Chem. Soc., vol. 117, pp. 9357-9358, 1995. http://dx.doi.org/10.1021/ja00141a030
  4. Y. Wu, R.P. Singh, and L. Deng, "Asymmetric Olefin Isomerization of Butenolides via Proton Transfer Catalysis by an Organic Molecule", J. Am. Chem. Soc., vol. 133, pp. 12458-12461, 2011. http://dx.doi.org/10.1021/ja205674x
  5. J. Chan, A.R. Lewis, M. Gilbert, M. Karwaski, and A.J. Bennet, "A direct NMR method for the measurement of competitive kinetic isotope effects", Nature Chemical Biology, vol. 6, pp. 405-407, 2010. http://dx.doi.org/10.1038/nchembio.352