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A tourist trip around London Overground with a chemical theme.

Saturday, August 29th, 2015

Most visitors to London use the famous underground trains (the “tube”) or a double-decker bus to see the city (one can also use rivers and canals). So I thought, during the tourism month of August, I would show you an alternative overground circumnavigation of the city using the metaphor of benzene.

Benzene you see is a ring, comprising three “HCCH” segments. The so-called Kekule vibration in benzene  (the b2u mode for anyone interested) induces three pairs of carbon atoms to repeatedly travel towards each other and then reverse and travel away from each other. One can also travel in this manner using the London Overground train system. The three segments connect Clapham Junction (yes, more or less the same Clapham of Kekule’s omnibus) to Willesden Junction.  A second segment goes from there to  Highbury and Islington, and a third from there on to Clapham again to complete the cycle in the clockwise direction. Since trains travel in both directions on each of the three segments, one can (like a carbon atom) oscillate to and fro in any segment, or (like an electron) circulate all the way round (no doubt either diatropic or paratropically with respect to the earth’s magnetic field). Yes, the metaphors are rather contrived; sorry but it is August after all. 

Here are some photos. The first is along the Clapham/Willesden Junctions section, showing the new chemistry building at Imperial College in the early stages of construction. This will be part of the new White City campus about 5km west of the  original South Kensington one. The completed buildings on the right are residences, and the whole site used to be where BBC Enterprises first marketed its productions worldwide and not far from where the BBC television studios broadcast from until recently.

Scheme

This is at Clapham junction itself, platform 1 of 18.

Scheme

This is also along this segment (Imperial’s very own station :-). Way out indeed!

Scheme

And the Thames finally, looking east. On the left is the very exclusive Chelsea harbour apartment complex, some of the most expensive in London. Residents commute by boat rather than train. In the distance somewhere are London and  Tower bridges.

Scheme

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Single Figure (nano)publications, reddit AMAs and other new approaches to research reporting

Wednesday, August 5th, 2015

I recently received two emails each with a subject line new approaches to research reporting. The traditional 350 year-old model of the (scientific) journal is undergoing upheavals at the moment with the introduction of APCs (article processing charges), a refereeing crisis and much more. Some argue that brand new thinking is now required. Here are two such innovations (and I leave you to judge whether that last word should have an appended ?).

To set the scene for the first, I will quote the abstract: “The single figure publication is a novel, efficient format by which to communicate scholarly advances. It will serve as a forerunner of the nano-publication, a modular unit of information critical for machine-driven data aggregation and knowledge integration[1] The kernel of this suggestion is (again I quote) “We offer the idea of the micro-publication unit, the single figure publication (SFP), to provide scholars with a real-world, manageable method to inform research.” I was struck by the overlap between this suggestion and the one you may find on many of the posts on this blog, where what I refer to as FAIR Data is assigned a digital object identifier (DOI) and included in the citation lists at the end of the post. The key phrase in the above abstract is machine-driven data aggregation and knowledge, although the article does not really go into any mechanisms for easily achieving this. It is my argument that the act of assigning a DOI carries with it the association that there is machine searchable metadata which can be retrieved and used for the aggregation and knowledge mining. The authors of this article, Do and Mobley, advocate adoption of nanopublications defined by inclusion of just a single figure (notably, not a table of results!) and some accompanying context which they claim would reduce the unit of publication to a more tractable size. This does raise the question of whether science needs more publications (in chemistry alone there are said to be more than a million published each year) or whether we should instead be concentrating our efforts on improving the data side of things by increasing its semantic content and formalising its structures, its preservation and curation. I certainly argue that far too little effort has been poured into these latter activities. You only have to look at the typical SI (supporting information) associated with many chemistry articles to realise that in many cases they are still hardly fit for purpose. There is one concept introduced by Do and Mobley that also deserves mention. Their nanopublications are structured to be read by machines, not people. They will therefore not be refereed by people (my inference). They do not really discuss how else the quality will be assessed, but of course if you treat their nanopublication as essentially FAIR data, then it does become possible to develop methods of machine refereeing.

The second email alerted me to an article[2] in the Winnower, a forum that offers a bridge between “traditional scholarly publishing tools to traditional and non-traditional scholarly outputs—because scholarly communication doesn’t just happen in scholarly journals“. Here, the concept of scholarly communication is extended to the New Reddit Journal of Science and introduces the concept pioneered by reddit of the AMA, or “ask me anything” environment. I occasionally publish some of the posts on this blog to the Winnower, receiving in return the increasingly ubiquitous DOI. I have also occasionally quoted these DOIs in articles submitted to conventional chemistry journals. What we see now is the propagation of a Winnower DOI on to e.g. https://www.reddit.com/r/science/ where anyone† can post a question related to the original research reporting. I must state that I do have some reservations about this. Whilst it is likely that the majority of traditional scholarly reporting is likely to receive no AMAs (just as a very high proportion of research articles attract few if any citations in other articles over a period of decades), it is also likely that the quality of posted AMAs may turn out to be very low. At which point the original researcher has to make a judgement as to whether to devote any of their increasingly precious and fragmented time to answering them. And if few if any answers are posted in response to an AMA, the system seems unlikely to flourish.

But what we see here are two serious attempts to develop new approaches to research reporting, and not doubt others will emerge. To quote Yogi Berra, the future is not what it used to be.

†Anyone can also post to this blog to ask similar questions. But note that associating an ORCID with such comments is highly recommended. I do not think that reddit currently supports ORCID, but  I would argue if the intent is serious, it certainly should.

References

  1. L. Do, and W. Mobley, "Single Figure Publications: Towards a novel alternative format for scholarly communication", F1000Research, vol. 4, pp. 268, 2015. https://doi.org/10.12688/f1000research.6742.1
  2. . RobustTempComparison, and . r/Science, "Science AMA Series: Climate models are more accurate than previous evaluations suggest. We are a bunch of scientists and graduate students who recently published a paper demonstrating this, Ask Us Anything!", The Winnower, . https://doi.org/10.15200/winn.143871.12809

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How many water molecules does it take to ionise HCN/HNC? An NCI exploration.

Monday, March 2nd, 2015

HCN is a weak acid (pKa +9.2, weaker than e.g. HF), although it does have an isomer, isocyanic acid or HNC (pka < +9.2 ?) which is simultaneously stronger and less stable. I conclude my halide acid series by investigating how many water molecules (in gas phase clusters) are required for ionisation of this “pseudo-halogen” acid.

First some observations about the structures of these complexes. The negative charge that develops on the cyanide is no longer atom-centered but is delocalised across two atoms, and furthermore the C≡N triple bond is also quite basic. So the stabilising hydrogen bonds have more choices than with the halide anions. To characterise these weak interactions, I show the structures here with the NCI (non-covalent-interaction) function included.[1] The colour coding is blue=strong attraction, green=weaker attraction, yellow=weak repulsions.

  1. The 2H2O complexes have insufficient length to bridge across from the H to the developing charge on the cyanide. Hence instead you see weaker π-facial interactions. Contrast also the dark blue of the NCI interaction to NH but the lighter cyan to CH.
    HNC+2H2O
    HCN+2H2O
  2. The 3H2O complexes abandon the weaker π-facial interactions to form a more normal H-bond to the terminal atom of the cyanide. The angle is far from optimal, and the colour coding reflects this weakening (cyan rather than deep blue). Note the small green zone in the middle of the ring, a residual π-facial mode.
    HNC+3H2OHCN+3H2O
  3. Here we see conventional H-bonds, but note now the deep blue NCI for the CH…O interaction, and the cyan for the OH…N for the first example.
    HNC+4H2O

    HCN+4H2O

  4. An interesting new feature appears with five water molecules. Lots of blue-coloured NCI, but one is missing (red arrow). This is because NCI is filtered to remove electron densities above a specified threshold, since these are no longer deemed “non-covalent” but start to fall into the covalent regions. The hydrogen bond specified by the red arrow is such.
    HNC+5H2O
    If that density threshold is raised (0.07 au), the deep blue feature can now be seen. So we have the concept here that a hydrogen bond can indeed be too strong to be “non-covalent” and it passes the (rather arbitrary) threshold into being covalent. A new way of classifying hydrogen bonds!
    HNC+5H2Oa
    The surprises are not quite over yet. Below is an isomer in which the water arrangement is different. This is much more ionic, as shown by three regions of covalent hydrogen bonds (red arrows) and a fully ionised cyanide supporting two hydrogen bonds to it, not one as before. The free energy of this alternative however is 5.1 kcal mol-1 higher than the previous non-ionic form.
    HNC-iso+5H2O
    With the HCN isomer, the normal thresholds again apply.
    HCN+5H2O
  5. With six waters and HNC, ionisation now occurs and the NCI feature appears in the N…H region rather than the H…O. The ionic nature also manifests with four other H…O regions (red arrows) where the non-covalent NCI threshold is passed or almost passed, and the covalent one starts.
    HNC+6H2O
    Note how much green dispersion attraction is starting to appear in this caged structure and how strong (NCI = deep blue) the C-H…O hydrogen bond has become (CH hydrogen bonds in ionic systems are indeed much stronger than they are given credit for).
    HCN+6H2O

The transition to ionicity can also be seen with the trend bond lengths, and the sudden discontinuity with six water molecules.

HCN HNC
n C-H H-O N-H H-O
1 1.077 2.021[2] 1.015 1.806[3]
2 1.078 2.064[4] 1.027 1.736[5]
3 1.086 1.913[6] 1.037 1.667[7]
4 1.089 1.864[8] 1.042 1.637[9]
5 1.103 1.795[10] 1.074
1.609		 1.522[11]
1.021[12]
6 1.106 1.767[13] 1.525 1.041[14]

To summarise, HNC is a relatively strong acid, and six water molecules are required to ionise it. In contrast, HCN is much weaker and so it is not ionised even by six waters, much like HF.

References

  1. A. Armstrong, R.A. Boto, P. Dingwall, J. Contreras-García, M.J. Harvey, N.J. Mason, and H.S. Rzepa, "The Houk–List transition states for organocatalytic mechanisms revisited", Chem. Sci., vol. 5, pp. 2057-2071, 2014. https://doi.org/10.1039/c3sc53416b
  2. H.S. Rzepa, "C 1 H 3 N 1 O 1", 2015. https://doi.org/10.14469/ch/190936
  3. H.S. Rzepa, "C 1 H 3 N 1 O 1", 2015. https://doi.org/10.14469/ch/190935
  4. H.S. Rzepa, "C 1 H 5 N 1 O 2", 2015. https://doi.org/10.14469/ch/190940
  5. H.S. Rzepa, "C 1 H 5 N 1 O 2", 2015. https://doi.org/10.14469/ch/190937
  6. H.S. Rzepa, "C 1 H 7 N 1 O 3", 2015. https://doi.org/10.14469/ch/190938
  7. H.S. Rzepa, "C 1 H 7 N 1 O 3", 2015. https://doi.org/10.14469/ch/190939
  8. H.S. Rzepa, "C 1 H 9 N 1 O 4", 2015. https://doi.org/10.14469/ch/190951
  9. H.S. Rzepa, "C 1 H 9 N 1 O 4", 2015. https://doi.org/10.14469/ch/190954
  10. H.S. Rzepa, "C 1 H 11 N 1 O 5", 2015. https://doi.org/10.14469/ch/190964
  11. H.S. Rzepa, "C 1 H 11 N 1 O 5", 2015. https://doi.org/10.14469/ch/190957
  12. H.S. Rzepa, "C 1 H 11 N 1 O 5", 2015. https://doi.org/10.14469/ch/190968
  13. H.S. Rzepa, "C 1 H 13 N 1 O 6", 2015. https://doi.org/10.14469/ch/190971
  14. H.S. Rzepa, "C 1 H 13 N 1 O 6", 2015. https://doi.org/10.14469/ch/190965

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How many water molecules does it take to ionise HI?

Saturday, February 28th, 2015

Why is this post orphaned from the previous? In order to have the opportunity of noting that treating iodine computationally can be a little different from the procedures used for F, Cl and Br.

As the nuclear charge increases proceeding down the periodic table, the inner electron shells start becoming relativistic. Iodine is the first halogen where this might really start to matter.* There are two ways in which one can compute molecules with I; the first adopts the same procedure as for the earlier halogens, whereby all the electrons are described by basis functions (called an all-electron basis). This effect does not really include the effects of relativistic contractions on the inner (1s) shell unless special relativistic Hamiltonians are also used. The second replaces these inner cores with a pseudopotential, and this does incorporate some of the relativistic effects. To find out how much this might matter, I have included both types:

I
n I-H H-O
1 1.637†/1.623‡ 2.032/2.060[1]
2 1.657/1.641 1.863/1.889[2]
3 1.696/1.675 1.641/1.670[3]
4  2.316/2.304 1.014/1.015[4]

†Non-relativistic calculation with an all-electron 6-311G(d,p) basis on I, 6-311++G(2d,2p) on O and H. ‡Def2-TZVPPD basis, with pseudopotential just on I.

As with bromine, iodine shows a precipitous ionisation when the 4th water molecule is added. In the previous post, I compared this with pKa values, and a comment posted there reminded us that a pKa is measured for macroscopic bulk water and that all sorts of new effects due to free energy/entropy, continuum solvation and much else will take hold. But qualitatively at least, the ionisation of HI in a gas-phase cluster of water molecules seems to match the bulk properties. Relativistic effects do not appear to play a major role here.

*Whilst such effects can be prominent for I, arguably they actually start at Cl via an effect called spin-orbit (SO) coupling. This manifests in the calculation of chemical magnetic shieldings. If one uses standard GIAO NMR theories, one can calculate shieldings for e.g. C pretty accurately. But with Cl, the shieldings may be SO-perturbed by about 3ppm, with Br it’s about 12 ppm and with I it reaches 50 ppm![5]

References

  1. H.S. Rzepa, "H 3 I 1 O 1", 2015. https://doi.org/10.14469/ch/190924
  2. H.S. Rzepa, "H 5 I 1 O 2", 2015. https://doi.org/10.14469/ch/190921
  3. H.S. Rzepa, "H 7 I 1 O 3", 2015. https://doi.org/10.14469/ch/190925
  4. H.S. Rzepa, "H 9 I 1 O 4", 2015. https://doi.org/10.14469/ch/190927
  5. D.C. Braddock, and H.S. Rzepa, "Structural Reassignment of Obtusallenes V, VI, and VII by GIAO-Based Density Functional Prediction", Journal of Natural Products, vol. 71, pp. 728-730, 2008. https://doi.org/10.1021/np0705918

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How many water molecules does it take to ionise HF and HBr?

Friday, February 27th, 2015

No doubt answers to the question posed in the previous post are already being obtained by experiment. Just in case that does not emerge in the next day or so, I offer a prediction here.

The methodology is the same as before, and I have not tried to look for new isomeric forms compared with the structures found with HCl. The method as before is DFT-based: ωB97XD/6-311++G(2d,2p). In the table below, I am recording the halogen-H distance and the distance from the same H to oxygen. You might also observe a more general principle here; first calibrate the method you intend to use with a system where there is an experimental answer. If the two match, use the same method to predict (extrapolate) to systems as yet unmeasured.

F Cl Br
n F-H, Å H-O Cl-H H-O Br-H H-O
1 0.937 1.702[1] 1.300 1.857 1.438 1.912[2]
2 0.951 1.631[3] 1.322 1.728 1.463 1.754[4]
3 0.967 1.532[5] 1.351 1.579 1.506 1.554[6]
4 0.972 1.504[7] 1.387 1.470 2.032 1.028[8]
5 1.043 1.329[9] 1.841 1.034 2.039 1.021[10]
6 1.067 1.283[11] 1.880 1.023 2.073 1.013[12]

From the bond distances, one notices that “ionisation” is an abrupt discontinuous event, happening for four molecules with HBr, five molecules with HCl and more than six molecules with HF. This nicely parallels the pka values: HBr (pKa = -9.0) < HCl (pKa = -6.0) << HF (pKa = +3.1).

It is good to see that such a process modelled on the nanoscale using just a few discrete molecules can map onto the macroscopic scale of solutions.

Postscript: If you check on the structures of these systems (click on the pictures in the previous post) you will see that the discontinuous ionisation event occurs in a bicyclic system, with the water forming two separate rings. Evidence that this really is the structure of microsolvated species has recently been put forward[13].

hf5h2o

References

  1. H.S. Rzepa, "H 3 F 1 O 1", 2015. https://doi.org/10.14469/ch/190911
  2. H.S. Rzepa, "H 3 Br 1 O 1", 2015. https://doi.org/10.14469/ch/190907
  3. H.S. Rzepa, "H 5 F 1 O 2", 2015. https://doi.org/10.14469/ch/190910
  4. H.S. Rzepa, "H 5 Br 1 O 2", 2015. https://doi.org/10.14469/ch/190909
  5. H.S. Rzepa, "H 7 F 1 O 3", 2015. https://doi.org/10.14469/ch/190912
  6. H.S. Rzepa, "H 7 Br 1 O 3", 2015. https://doi.org/10.14469/ch/190913
  7. H.S. Rzepa, "H 9 F 1 O 4", 2015. https://doi.org/10.14469/ch/190915
  8. H.S. Rzepa, "H 9 Br 1 O 4", 2015. https://doi.org/10.14469/ch/190916
  9. H.S. Rzepa, "H 11 F 1 O 5", 2015. https://doi.org/10.14469/ch/190918
  10. H.S. Rzepa, "H 11 Br 1 O 5", 2015. https://doi.org/10.14469/ch/190919
  11. H.S. Rzepa, "H 13 F 1 O 6", 2015. https://doi.org/10.14469/ch/190928
  12. H.S. Rzepa, "H 13 Br 1 O 6", 2015. https://doi.org/10.14469/ch/190917
  13. C. Pérez, J.L. Neill, M.T. Muckle, D.P. Zaleski, I. Peña, J.C. Lopez, J.L. Alonso, and B.H. Pate, "Water–Water and Water–Solute Interactions in Microsolvated Organic Complexes", Angewandte Chemie International Edition, vol. 54, pp. 979-982, 2014. https://doi.org/10.1002/anie.201409057

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How-open-is-it?

Thursday, February 12th, 2015

The title of this post refers to the site http://howopenisit.org/  which is in effect a license scraper for journal articles. In the past 2-3 years in the UK, we have been able to make use of grants to our university to pay publishers to convert our publications into Open Access (also called GOLD). I thought I might check out a few of my recent publications to see what http://howopenisit.org/ makes of them.

This was catalysed by an article which revealed that UK universities spent £9M in 2014 on the purchase of such openness. One of the “challenges” identified is the difficulty in converting such payment into an article that actually is open. Apparently, publishers make not a few mistakes in their quality controls in ensuring it is so, relying on irate authors informing them of such mistakes. This can be quite tedious to do, and so a tool that largely automates this checking is most useful. So here we go.

  1. doi: 10.1039/C3SC53416B[1] This is a good start. The output looks like thus. Green is GOLD so to speak. Well done the Royal Society of Chemistry.
    10.1039:C3SC53416B
  2. doi: 10.1021/ci500302p[2] from the ACS this time. Pink, but at least free to read. Quite what that means is less certain. There is an adage, “the right to read means the right to mine” presumably means this article is OK to mine, but then why does it not say so?10.1021:ci500302p
  3. doi: 10.1002/anie.201405238[3]. Pink again, but the colour now simply means no information about the license could be obtained from the publisher (Wiley). 10.1002:anie.201405238

I ran a few more and sadly the third of the above, “no information” was the most common response. And the legal response is invariably that if no information can be obtained, the answer is NO, it is not free to read. In other words, not providing a license is just as bad as saying it’s not free to read.

Article aggregators such as Symplectic do not yet perform the service above (which to be fair is still in beta), and so I cannot yet check how many GOLD articles there are to my name. I think it should be about 8, and I might add that the time I have to spend in arranging for this to happen is not negligible. Hell, I could probably have found a few more reactions mechanism in the time I have spent on achieving GOLD. This is one of those topics which would be interesting to revisit say in five years time to see how the world has changed. So I leave this little time capsule and will update it then!

References

  1. A. Armstrong, R.A. Boto, P. Dingwall, J. Contreras-García, M.J. Harvey, N.J. Mason, and H.S. Rzepa, "The Houk–List transition states for organocatalytic mechanisms revisited", Chem. Sci., vol. 5, pp. 2057-2071, 2014. https://doi.org/10.1039/c3sc53416b
  2. M.J. Harvey, N.J. Mason, and H.S. Rzepa, "Digital Data Repositories in Chemistry and Their Integration with Journals and Electronic Notebooks", Journal of Chemical Information and Modeling, vol. 54, pp. 2627-2635, 2014. https://doi.org/10.1021/ci500302p
  3. A. Jana, I. Omlor, V. Huch, H.S. Rzepa, and D. Scheschkewitz, "N‐Heterocyclic Carbene Coordinated Neutral and Cationic Heavier Cyclopropylidenes", Angewandte Chemie International Edition, vol. 53, pp. 9953-9956, 2014. https://doi.org/10.1002/anie.201405238

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A convincing example of the need for data repositories. FAIR Data.

Thursday, January 15th, 2015

Derek Lowe in his In the Pipeline blog is famed for spotting unusual claims in the literature and subjecting them to analysis. This one is entitled Odd Structures, Subjected to Powerful Computations. He looks at this image below, and finds the structures represented there might be a mistake, based on his considerable experience of these kinds of molecules. I expect he had a gut feeling within seconds of seeing the diagram.

Indeed, so, you will now find that the authors have apparently acknowledged a mistake[1]. My interest piqued, I went to the article, and immediately tracked down the supplementary information. Surely, if these molecules had been subjected to powerful computation, this supporting information should contain coordinates of some kind that would allow a correlation with the 2D structural representation shown above. I have just returned from FORCE2015, a three-day event in Oxford. From the detailed agenda, you can see that a lot of the conference centered around what is called FAIR Data. FAIR stands for:

  1. Findable
  2. Accessible
  3. Interoperable
  4. Re-usable

So I then set out to find if the supplementary information WAS FAIR. Well, check for yourself (unlike the narrative article, the data should be accessible outside of the paywall, i.e. you should not need a subscription to access it). It is certainly big, running out to 45 pages, in the form of a paginated PDF file (the norm). The table of contents does not refer to data as such, but it does quote 25 figures, from which you might just be able to extract some data. But no molecules as such! So:

  1. No data is findable, although the  PDF which might contain it is reasonably so.
  2. The data is not easily accessible,
  3. let alone interoperable (thus many of the charts were probably created using spreadsheet software, but the source files for these are not available),
  4. and not-reusable (certainly not without loss and possible error in any attempt at capture).

I think it fair to say that the data for these powerful computations are not FAIR. Had we had at least some coordinates (the computations involved molecular mechanics based dynamics simulations, which certainly involve manipulating atom coordinates in some form) then the structures shown in the figure above could be checked, and perhaps even the apparent error would have been quickly spotted.

Derek does not make the point about FAIR data (to be fair, he was not at FORCE2015) and so I will make the case. If you are reporting a computational model or simulation, there is no excuse for not supplying FAIR data to accompany it. If the data is FAIR it will be inter-operable and re-usable. And this will instantly allow anyone to check e.g. the structures above. You would not need to have Derek’s vast experience and instinct (although having it is also helps). And of course we might presume that there were 2-3 referees that also looked at the article, and presumably none of them requested FAIR data.

Oh, if you are interested in my take on FAIR data, I gave a talk about that at FORCE2015, which you are welcome to view; I hope it constitutes a FAIR talk!

References

  1. K.J. Kohlhoff, D. Shukla, M. Lawrenz, G.R. Bowman, D.E. Konerding, D. Belov, R.B. Altman, and V.S. Pande, "Cloud-based simulations on Google Exacycle reveal ligand modulation of GPCR activation pathways", Nature Chemistry, vol. 6, pp. 15-21, 2013. https://doi.org/10.1038/nchem.1821

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The demographics of a blog readership – updated

Thursday, January 8th, 2015

About two years ago, I posted on the distribution of readership of this blog. The passage of time has increased this from 144 to 176 countries. There are apparently between 189-196 such, so not quite yet complete coverage! 2015
Of course, it is the nature of the beast that whilst we can track countries, very little else is known about such readerships. Is the readership young or old, student or professor, chemist or not (although I fancy the latter is less likely). Another way of keeping tabs on some of the activity are aggregators such as Chemical Blogspace, which has been rather quiet recently. Perhaps we have become too obsessed by metrics, and with the Internet-of-things apparently the “next-big-thing”, the metrics are only likely to increase. This will only encourage “game playing“, and I urge you to see a prime example of this in the UK REF (research excellence framework), the measure which attempts to rank UK universities in terms of their “excellence”.

Ah well, I had better leave this blog and go off and check on my h-index just in case it has notched up another integer.

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Why is mercury a liquid at room temperatures?

Saturday, July 12th, 2014

Computational quantum chemistry has made fantastic strides in the last 30 years. Often deep insight into all sorts of questions regarding reactions and structures of molecules has become possible. But sometimes the simplest of questions can prove incredibly difficult to answer. One such is how accurately can the boiling point of water be predicted from first principles? Or its melting point? Another classic case is why mercury is a liquid at room temperatures? The answer to that question (along with another, why is gold the colour it is?) is often anecdotally attributed to Einstein. More accurately, to his special theory of relativity.[1] But finally in 2013 a computational proof of this was demonstrated for mercury.[2] The proof was built up in three stages.

  1. Potential energy surfaces for the Hg2 dimer showed that inclusion of a relativistic Hamiltonian contracts the Hg-Hg distance by 0.2Å. This can be traced back to the value of the 1S0(6s2)→3P0(6s16p11/2) electronic excitation in the atom being 4.67eV, compared to a non-relativistic value of 3.40eV. This in turn is the result of the strong relativistic 6s shell contraction and hence stabilisation. But it has previously been shown that bulk mercury cannot be described by such a simple two-body interaction.
  2. Next many-body clusters of various sizes were built. This is a complex task, since for each size, various types of packing might be possible. The largest was  a “two-layer Mackay icosahedron”, with 55 Hg atoms. These clusters however did not show any monotonic convergence to a clear melting point.
  3. Finally, using Monte Carlo (MC) simulations within a quantum diatomics-in-molecules (DIM) model and with periodic boundary conditions to simulate the bulk metal,  it was possible to show that without a relativistic Hamiltonian, the predicted melting point was predicted as 355K (82°C) but when the relativistic effects were switched on, this decreased to 250K (-23°C). This lowering of 105K is dominated by scalar relativistic effects through many-body contributions.
  4. The experimental melting point is 234K. The density is well predicted as well (the non-relativistic model predicts mercury to be denser than it actually is).

What I did not get from this article is why mercury is such a very special case (i.e. why neither gold, m.p. 1337K nor thallium, m.p. 577K, are liquids at room temperature). No doubt someone will explain. In the past, gold and mercury were said to be the only two visual manifestations of Einstein’s special theory in every-day objects. I say the past, because mercury is now rarely seen in any every-day objects (digital thermometers have taken over, and the mercury barometer has long since gone). If anyone knows of other examples, do let us know.

References

  1. A. Einstein, "Ist die Trägheit eines Körpers von seinem Energieinhalt abhängig?", Annalen der Physik, vol. 323, pp. 639-641, 1905. https://doi.org/10.1002/andp.19053231314
  2. F. Calvo, E. Pahl, M. Wormit, and P. Schwerdtfeger, "Evidence for Low‐Temperature Melting of Mercury owing to Relativity", Angewandte Chemie International Edition, vol. 52, pp. 7583-7585, 2013. https://doi.org/10.1002/anie.201302742

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The 5σ-confidence level: how much chemistry achieves this?

Saturday, July 5th, 2014

I was lucky enough to attend the announcement made in 2012 of the discovery of the Higgs Boson. It consisted of a hour-long talk mostly about statistics, and how the particle physics community can only claim a discovery when their data has achieved a 5σ confidence level. This represents a 1 in 3.5 million probability of the result occurring by chance. I started thinking: how much chemistry is asserted at that level of confidence? Today, I read Steve Bachrach’s post on the structure of Citrinalin B and how “use of Goodman’s DP4 method indicates a 100% probability that the structure of citrinalin B is (the structure below)”. Wow, that is even higher than the physicists. Of course, 100% has been obtained by rounding 99.7 (3σ is 99.73%) or whatever (this is one number that should never be so rounded!). pc But there was one aspect of this that I did want to have a confidence level for; the absolute configuration of citrinalin B. Reading the article Steve quotes[1], one sees this aspect is attributed to ref 5[2], dating from 2005. There the configuration was assigned on the basis of “comparison of the electronic circular dichroism (ECD) spectra for 1 and 2 with those of known spirooxiindole alkaloids“. However, this method can fail[3]. Also, one finds “comparison of the vibrational circular dichroism (VCD) spectra of 1 with those of model compounds“[2]. Nowadays, one would say that there is no need for model compounds, why not measure and compute the VCD of the actual compound? Even a determination using the Flack crystallographic method can occasionally be wrong![4]. Which leads to asking what typical confidence levels might be for these three techniques, and indeed whether improving instrumentation means that the confidence level gets higher with time. OK, I am going to guess these.

  1. I think the confidence level for assigning absolute configurations on the basis of ECD analogy with other compounds is the lowest of all the methods. Around 1σ or 68.3% (and this mostly from additional information such as the chemical transforms performed from starting materials of known absolute configuration).
  2. VCD is higher. If performed on the actual compound, I think it can be as high as 2-3σ or 95.5-99.7%. It is difficult to know how much of this certainty is lost by using only model compounds.
  3. Flack analysis (of anomalous X-ray)[5] is probably also at 2-3σ; I suggest however that a fair bit of uncertainly not included in the 2-3σ probably arises from analysing a tiny crystal (1 µg) arising from a solution perhaps 10,000 times larger in weight of sample.
  4. And of course combining the uncertainties from multiple experiments reduces it overall.

I am not casting any doubts on an assigned absolute configuration on which that of citrinalin B is based, as done in 2005. I have no grounds to think it is wrongly assigned. I am merely suggesting that in 2014, one should be able to achieve an even greater confidence level. And do what the physicists do, try to estimate the confidence level attained. I wonder how much chemistry would match the physicists 5σ-confidence level (99.99994%)?

References

  1. E.V. Mercado-Marin, P. Garcia-Reynaga, S. Romminger, E.F. Pimenta, D.K. Romney, M.W. Lodewyk, D.E. Williams, R.J. Andersen, S.J. Miller, D.J. Tantillo, R.G.S. Berlinck, and R. Sarpong, "Total synthesis and isolation of citrinalin and cyclopiamine congeners", Nature, vol. 509, pp. 318-324, 2014. https://doi.org/10.1038/nature13273
  2. T. Mugishima, M. Tsuda, Y. Kasai, H. Ishiyama, E. Fukushi, J. Kawabata, M. Watanabe, K. Akao, and J. Kobayashi, "Absolute Stereochemistry of Citrinadins A and B from Marine-Derived Fungus", The Journal of Organic Chemistry, vol. 70, pp. 9430-9435, 2005. https://doi.org/10.1021/jo051499o
  3. F. Cherblanc, Y. Lo, E. De Gussem, L. Alcazar‐Fuoli, E. Bignell, Y. He, N. Chapman‐Rothe, P. Bultinck, W.A. Herrebout, R. Brown, H.S. Rzepa, and M.J. Fuchter, "On the Determination of the Stereochemistry of Semisynthetic Natural Product Analogues using Chiroptical Spectroscopy: Desulfurization of Epidithiodioxopiperazine Fungal Metabolites", Chemistry – A European Journal, vol. 17, pp. 11868-11875, 2011. https://doi.org/10.1002/chem.201101129
  4. F.L. Cherblanc, Y. Lo, W.A. Herrebout, P. Bultinck, H.S. Rzepa, and M.J. Fuchter, "Mechanistic and Chiroptical Studies on the Desulfurization of Epidithiodioxopiperazines Reveal Universal Retention of Configuration at the Bridgehead Carbon Atoms", The Journal of Organic Chemistry, vol. 78, pp. 11646-11655, 2013. https://doi.org/10.1021/jo401316a
  5. H.D. Flack, and G. Bernardinelli, "The use of X‐ray crystallography to determine absolute configuration", Chirality, vol. 20, pp. 681-690, 2007. https://doi.org/10.1002/chir.20473

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