Posts Tagged ‘Imperial College’

A short history of molecular modelling: 1860-1890.

Saturday, February 5th, 2011

In 1953, the model of the DNA molecule led to what has become regarded as the most famous scientific diagram of the 20th century. It had all started 93 years earlier in 1860, at a time when the tetravalency of carbon was only just established (by William Odling) and the concept of atoms as real entities was to remain controversial for another 45 years (for example Faraday, perhaps the most famous scientist alive in 1860 did not believe atoms were real). So the idea of constructing a molecular model from atoms as the basis for understanding chemical behaviour was perhaps bolder than we might think. It is shown below, part of a set built for August Wilhelm von Hofmann as part of the lectures he delivered at the Royal College of Chemistry in London (now Imperial College).

The original August Wilhelm von Hofmann molecular model

This grand-daddy of all molecular models does have some interesting features. The most obvious is that the carbon atom at the centre is square planar (tetrahedral carbon was still 14 years in the future). What HAS survived to the present day is the colour scheme used (black=carbon, white=hydrogen, and not shown here, red=oxygen, blue=nitrogen, green=chlorine).  But another noteworthy aspect is the relative size of the white hydrogen, which is larger than the black carbon. This deficiency was however very soon rectified in 1861 by Josef Loschmidt, who published  a famous pamphlet in which he set out his ideas for the structures of more than  270 molecules (many of which by the way were cyclic, and this some four years before Kekule’s dream!). An example (#239) is shown below, which gets the relative sizes of the atoms more or less correct (OK, chlorine is shown with rather an odd shape). To get an idea of how good Loschmidt’s model actually was, click on the diagram to load a modern model, and compare the two! Even more impressive, these diagrams pre-date van der Waals work on the finite sizes of atoms, first presented in 1873.

Loschmidt’s molecular models. Click for 3D

To conclude, I cannot resist showing one more model. Hermann Sachse believed cyclohexane could not be planar. To try to convince people, in 1890 he included a  “flat-packed” model in the pages of a journal article,  evidently believing that people would cut it out, and assemble it into a 3D shape.

Flat-packed molecular model of cyclohexane

You might have noticed a theme in the present blog of presenting 3D models for many of the molecules I discuss (include the Loschmidt one above). For the historians amongst you, I note our 1995 article in which we updated[1] Sachse’s origami with an article featuring how to incorporate interactive models into journals (still sadly only too rare). Perhaps a history of the molecular model, and how it has been presented over 150 years might be an interesting one to trace!

References

  1. O. Casher, G.K. Chandramohan, M.J. Hargreaves, C. Leach, P. Murray-Rust, H.S. Rzepa, R. Sayle, and B.J. Whitaker, "Hyperactive molecules and the World-Wide-Web information system", Journal of the Chemical Society, Perkin Transactions 2, pp. 7, 1995. https://doi.org/10.1039/p29950000007

A historical detective story: 120 year old crystals

Wednesday, November 17th, 2010

In 1890, chemists had to work hard to find out what the structures of their molecules were, given they had no access to the plethora of modern techniques we are used to in 2010. For example, how could they be sure what the structure of naphthalene was? Well, two such chemists, William Henry Armstrong (1847-1937) and his student William Palmer Wynne (1861-1950; I might note that despite working with toxic chemicals for years, both made it to the ripe old age of ~90!) set out on an epic 11-year journey to synthesize all possible mono, di, tri and tetra-substituted naphthalenes. Tabulating how many isomers they could make (we will call them AW here) would establish beyond doubt the basic connectivity of the naphthalene ring system. This was in fact very important, since many industrial dyes were based on this ring system, and patents depended on getting it correct! Amazingly, their collection of naphthalenes survives to this day. With the passage of 120 years, we can go back and check their assignments. The catalogued collection (located at Imperial College) comprises 263 specimens. Here the focus is on just one, specimen number number 22, which bears an original label of trichloronaphthalene [2:3:1] and for which was claimed a melting point of 109.5°C. What caught our attention is that a search for this compound in modern databases (Reaxys if you are interested, what used to be called Beilstein) reveals the compound to have a melting point of ~84°C. So, are alarm bells ringing? Did AW make a big error? Were many of the patented dyes not what they seemed?

1,2,3-trichloronaphthalene

The story starts to get murky when Reaxys reports the earliest literature for this compound as being 1941 (DOI: 10.1039/JR9410000243), the authority being Wynne himself (now a sprightly 80). The collection of 263 specimens was thought to go back to the 1890s, so how could it contain a compound only made about 50 years later? Time to do an X-ray determination. Remarkably, the 120 year old crystals of specimen 22 were still in good shape, but the determined structure held an initial surprise. The compound was in fact 1,6,7-trichloronaphthalene, quite a different species from the label.

1,6,7-trichloronaphthalene

So, did AW get things badly wrong, and were all those patents based on these structures potentially invalid? A little more detective work using Reaxys reveals that the 1,6,7 isomer melts at 109.5°C, the same as reported by AW in 1890 (Chem. News J. Ind. Sci., 1890 , 61, p. 273). So how did the 1,6,7-compound come to be mistaken for a 1,2,3,-isomer? The culprit turns out to be one prime (‘).

1,6,7 = 2:3:1' Click for 3D

Updated (see comment) Click for 3D

The numbering system in 1890 was different from what it is now. Then, primes were used to distinguish the numbering on each ring. When the collection was catalogued (in the 1990s), the 1′ was mistaken for 1 (you can see the prime on the original label). AW were correct all along, and the patent owners for all those naphthalene dyes can rest easy.

Sample 22 from AW collection

What this teaches us is that crystallography on 120 year old organic compounds is perfectly viable. Indeed, can anyone else claim to have solved the structure of such an old compound? And that those old chemists knew what they were doing, despite not having any instrumentation to help them. Oh, and a final comment. Precious few collections of molecules made by the original scientists exist nowadays. Many a collection has literally been skipped because of health and safety concerns. The AW collection itself was rescued from oblivion by the narrowest of margins. And we have permanently lost the opportunity for any detective work of the type described above. You can see that I am very upset by this. Heritage conservation should not just be old buildings, paintings etc, but the chemical heritage collections as well.

Thanks to Andrew White for the crystal structures (of this and three other samples, but their stories are for another day).

Conformational analysis of biphenyls: an upside-down view

Friday, April 2nd, 2010

One of the (not a few) pleasures of working in a university is the occasional opportunity that arises to give a new lecture course to students. New is not quite the correct word, since the topic I have acquired is Conformational analysis. The original course at Imperial College was delivered by Derek Barton himself about 50 years ago (for articles written by him on the topic, see DOI 10.1126/science.169.3945.539 or the original 10.1039/QR9561000044), and so I have had an opportunity to see how the topic has evolved since then, and perhaps apply some quantitative quantum mechanical interpretations unavailable to Barton himself.

The example I have chosen to focus on here is biphenyl (a derivative of which also happens to be the first structure shown by Barton in his 1970 Science article noted above), but modified with iso-electronic B/N substitution for carbon for a particular reason.

biphenylFour hydrogen atoms are highlighted in the above drawings by virtue of how close they might approach each-other, and what impact this will have on the conformation of each species. Such close approaches are normally defined with reference to the so-called van der Waals radius of the element concerned. For hydrogen, this radius is either 1.2Å (if the contact is to another hydrogen) or 1.1Å (if its to any other element, see DOI: 10.1021/jp8111556). An interpretation of this value is that the van der Waals attraction due to to dispersion or long range correlation effects reaches a maximum for two non-bonded hydrogen atoms at ~2.4Å. Significantly, a slightly closer approach than this value might still be mildly attractive, but it would be generally agreed that any distance less than ~2.1Å now represents a genuine repulsion between the hydrogens (see also this post). This represents a somewhat more quantitative judgement on what used to be called steric interactions.

With the scene set, let me introduce the results of a calculation (wB97XD/6-31G(d,p), a DFT method selected because it treats the long range correlation effects with a specific correction)

Conformational analysis of biphenyl 1

One can see here minima at ~45, 135, 225 and 315° for 1 (see DOI 10042/to-4853). Due to symmetry, the first and last are identical as are 2nd and 3rd, and the 1st and 2nd minima are in fact enantiomers of each other (the symmetry is D2, which is chiral). Two different transition states connect these minima, one with angles of 0/180 and the other slightly lower energy at 90/270°.

The non-bonded H…H distance are as follows: 1.95Å@0°, 2.39Å@45° and 3.54Å@90°. We may conclude that the first of these is repulsive, the second attractive and the third non interacting. Counterbalancing this effect is of course resonance due to π-π-overlaps across the central bond, which decreases to zero as the angle moves to 90°. The conformational minimum @45° is such because of the maximal H…H dispersion attraction and the still significant π-π-overlap. This brief analysis suggests however that these two effects are finely balanced, and so the next question is whether one might be able to perturb the system to distort the balance. The perturbation chosen is to replace one or two pairs of carbon atoms with the iso-electronic combination B+N.

The first perturbation is to replace the central rotating bond by a B-N combination 2 (DOI: 10042/to-4854).

Rotation about the B-N bond in 2

For this species, the H…H distances are 2.02Å@0°, 2.36Å@45° and 3.61Å@90°, the only significant difference with 1 emerging as the 0° conformation being around 1 kcal/mol lower relative to the other two. It is tempting to attribute this to the longer H…H separation for this rotamer in 2 due to the B-N bond being longer (1.562Å) than the C-C bond it replaced (1.496Å)

The next perturbation is to relocate the N/B pair as in 3 (DOI: 10042/to-4855). If one imagines that this will be a minor perturbation, take a look at the profile below.

Rotation about central C-C bond in 3.

The world has been turned upside down. What were transition states @0° and @180° are now minima and the reason is easy to find. The central C-C bond is now only 1.400Å long, having acquired substantial double bond character, and being accordingly very much more difficult to twist (the barrier being ~30 kcal/mol). The π-π-overlap has won out completely, and in the process has forced the H…H distance down to a presumably repulsive 1.918Å. The penalty for this is that the overall energy of 3 is some 22.8 kcal/mol higher than 2.

Added in proof (as the expression goes): If the above profile is conducted with full geometry optimization in a solvent field (water), which helps stabilise charge separations, the profile changes to the below. The solvation reduces the barrier to rotation considerably, the energy maxima now reveal a proper stationary point (rather than the cusp), the minima are very slightly non-planar, but the basic inversion of the potential energy surface compared to 1 or 2 is still observed.

Rotation about the C-C bond for 3, with solvation correction

The final perturbation is 4 (DOI: 10042/to-4856) with the following rotational profile. Another surprise:

Rotation about the central C-C bond in 4.

The H…H distances are 1.930Å@0°, 1.789/2.275Å@180°. The difference from 1 is that the hydrogens now have opposite polarity for the N-H (which is positive) and the B-H (which is negative). At the rotation angle of 0°, two H(+)…(-)H style dihydrogen bonds (see also this post) are established (these are presumed to be very attractive); at an angle of 180°, the H(+)…(+)H and H(-)…(-)H interactions are presumed to be very repulsive. The difference between the two is ~18 kcal/mol.

We have learnt that conformational analysis for molecules such as these is a fight between π-π-overlaps, which themselves can have unexpected outcomes, weak van der Waals dispersion interactions between “neutral” non-bonded hydrogen atoms, and strong electrostatic attractions and repulsions between “ionic” hydrogens. Now perhaps the reason for the choice of the wB97XD DFT method can be seen; it is capable (at least in theory) of balancing these forces properly.

So the world of conformational analysis can be turned upside down, and analysing what happens from this topsy-turvy viewpoint can teach a lot!

A lab in a backpack

Friday, April 3rd, 2009

We recently developed a new computational chemistry practical laboratory here at Imperial College. I gave a talk about it at the recent ACS meeting in Salt Lake City. If you want to see the details of the lab, do go here. The talk itself contains further links and examples. Perhaps here I can quote only the final remark, namely that computational chemistry can now provide chemical accuracy for many problems, including spectroscopy and mechanism, and that the basic tools for doing it can easily be carried around in a backpack! Or, perhaps in the not to distant future, an iPhone!