Posts Tagged ‘Stereochemistry’

« Older Entries

Impossible molecules.

Monday, April 1st, 2019

Members of the chemical FAIR data community have just met in Orlando (with help from the NSF, the American National Science Foundation) to discuss how such data is progressing in chemistry. There are a lot of themes converging at the moment. Thus this article[1] extolls the virtues of having raw NMR data available in natural product research, to which we added that such raw data should also be made FAIR (Findable, Accessible, Interoperable and Reusable) by virtue of adding rich metadata and then properly registering it so that it can be searched. These themes are combined in another article which made a recent appearance.[2]

One of the speakers made a very persuasive case based in part on e.g. the following three molecules which are discussed in the first article[1] (the compound numbers are taken from there). The question was posed at our meeting: why did the referees not query these structures? And the answer in part is to provide referees with access to the full/primary/raw NMR data (which almost invariably they currently do not have) to help them check on the peaks, the purity and indeed the assignments. I am sure tools that do this automatically from such supplied data by machines on a routine basis do exist in industry (and which is something FAIR is designed to enable). Perhaps there are open source versions available?

17 18 19

 
328[3] 348 713

Here I suggest a particularly simple and rapid “reality check” which I occasionally use myself. This is to compute the steric energy of the molecule using molecular mechanics. The mechanics method is basically a summation of simple terms such as the bond length, bond angle, torsion angle, a term which models non bonded repulsions, dispersion attractions and electrostatic contributions. The first three are close to zero for an unstrained molecule (by definition). The last three terms can be negative or positive, but unless the molecule is protein sized, they also do not depart far from zero. A suitable free tool that packages all this up is Avogadro.

The procedure is as follows

  1. Start from the Chemdraw representation of the molecule. If the publishing authors have been FAIR, you might be able to acquire that from their deposited data. Otherwise, redraw it yourself and save as e.g. a molfile or Chemdraw .cdxml file.
  2. Drop into Avogadro, which will build a 3D model for you using stereochemical information present in the Chemdraw or Molfile.
  3. In the  E tool (at the top on the left of the Avogadro menu) select e.g. the MMFF94 force field. This is a good one to use for “organic” molecules for which the total steric energy for “normal” molecules is likely to be < 200 kJ. Calculate that for your system; this normally takes less than one minute to complete. The values obtained for the three above are shown in the table. All three are well over 200 kJ/mol, which should set alarm bells ringing.
  4. A “more reasonable” structure for 17 is shown below. This has a steric energy of 152 kJ/mol, some 176 kJ/mol lower than the original structure. This does not of itself “prove” this alternative, but it is a starting point for showing it might be correct.Of course mis-assigned but otherwise reasonable structures are unlikely to be revealed by the steric energy test. But impossible ones will probably always be flagged as such using this procedure. 

Postscript: Hot on the heels of writing this, the molecule Populusone came to my attention.[4] On first sight, it seems to have some of the attributes of an “impossible molecule” (click on diagram below for 3D coordinates).

However, it has been fully characterised by x-ray analysis! The steric energy using the method above comes out at 384 kJ/mol, which in the region of impossibility! This can be decomposed into the following components: bond stretch 30, bend 51, torsion 32, van der Waals (including repulsions) 177, electrostatics 87 (+ some minor cross terms). These are fairly evenly distributed, with internal steric repulsions clearly the largest contributor. The C=C double bond is hardly distorted however, which is in its favour. Clearly a natural product can indeed load up the unfavourable interactions, and this one must be close to the record of the most intrinsically unstable natural product known!

References

  1. J.B. McAlpine, S. Chen, A. Kutateladze, J.B. MacMillan, G. Appendino, A. Barison, M.A. Beniddir, M.W. Biavatti, S. Bluml, A. Boufridi, M.S. Butler, R.J. Capon, Y.H. Choi, D. Coppage, P. Crews, M.T. Crimmins, M. Csete, P. Dewapriya, J.M. Egan, M.J. Garson, G. Genta-Jouve, W.H. Gerwick, H. Gross, M.K. Harper, P. Hermanto, J.M. Hook, L. Hunter, D. Jeannerat, N. Ji, T.A. Johnson, D.G.I. Kingston, H. Koshino, H. Lee, G. Lewin, J. Li, R.G. Linington, M. Liu, K.L. McPhail, T.F. Molinski, B.S. Moore, J. Nam, R.P. Neupane, M. Niemitz, J. Nuzillard, N.H. Oberlies, F.M.M. Ocampos, G. Pan, R.J. Quinn, D.S. Reddy, J. Renault, J. Rivera-Chávez, W. Robien, C.M. Saunders, T.J. Schmidt, C. Seger, B. Shen, C. Steinbeck, H. Stuppner, S. Sturm, O. Taglialatela-Scafati, D.J. Tantillo, R. Verpoorte, B. Wang, C.M. Williams, P.G. Williams, J. Wist, J. Yue, C. Zhang, Z. Xu, C. Simmler, D.C. Lankin, J. Bisson, and G.F. Pauli, "The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research", Natural Product Reports, vol. 36, pp. 35-107, 2019. https://doi.org/10.1039/c7np00064b
  2. A. Barba, S. Dominguez, C. Cobas, D.P. Martinsen, C. Romain, H.S. Rzepa, and F. Seoane, "Workflows Allowing Creation of Journal Article Supporting Information and Findable, Accessible, Interoperable, and Reusable (FAIR)-Enabled Publication of Spectroscopic Data", ACS Omega, vol. 4, pp. 3280-3286, 2019. https://doi.org/10.1021/acsomega.8b03005
  3. A.I. Savchenko, and C.M. Williams, "The Anti‐Bredt Red Flag! Reassignment of Neoveratrenone", European Journal of Organic Chemistry, vol. 2013, pp. 7263-7265, 2013. https://doi.org/10.1002/ejoc.201301308
  4. K. Liu, Y. Zhu, Y. Yan, Y. Zeng, Y. Jiao, F. Qin, J. Liu, Y. Zhang, and Y. Cheng, "Discovery of Populusone, a Skeletal Stimulator of Umbilical Cord Mesenchymal Stem Cells from <i>Populus euphratica</i> Exudates", Organic Letters, vol. 21, pp. 1837-1840, 2019. https://doi.org/10.1021/acs.orglett.9b00423

Tags:, , , , , , , , , , , , , , , , , , , , , , , ,
Posted in Chemical IT | No Comments »

Organocatalytic cyclopropanation of an enal: (computational) assignment of absolute configurations.

Saturday, September 1st, 2018

I am exploring the fascinating diverse facets of a recently published laboratory experiment for undergraduate students.[1] Previously I looked at a possible mechanistic route for the reaction between an enal (a conjugated aldehyde-alkene) and benzyl chloride catalysed by base and a chiral amine, followed by the use of NMR coupling constants to assign relative stereochemistries. Here I take a look at some chiroptical techniques which can be used to assign absolute stereochemistries (configurations).

I will focus on the compound 4a, the major stereochemical product of this student laboratory reaction, with the stereochemistry as represented in e.g. the abstract of the main article[1] and shown below with added CIP (Cahn-Ingold-Prelog) notation as (1S,2R,3R);‡

Its enantiomer (not shown in the article) is of course;

In the article supporting information[1]), the major diasteromer of 4a deriving from use of the S stereoisomer of the prolinol catalyst is reported as having an optical rotation (ORP) [α]D25 of -62.4°, p6 or -58.1°, p5), but the stereo-labels are not added there. On  p1 (“based on a student report”) 4a was however labelled as (1R,2S,3S) and the chirality (S) of the catalyst used was also noted in the adjacent experimental procedure. One might then reasonably match (1R,2S,3S)-4a to the S-catalyst and hence (1S,2R,3R)-4a to the R-catalyst.  However, in a laboratory environment where both S and R catalysts are in circulation, it is always useful to have procedures available for independent checks.†

There are two methods of assigning absolute chirality, crystallography and chiroptical spectroscopy. The former does require crystalline samples; the latter can use solutions. To cut to the chase, the former method was used for a related compound where the n-heptyl group above is replaced by a p-chlorophenyl substituent (perhaps because the latter imparts suitable crystallinity). On p S123 of the SI of an earlier article[2] the assignment for the p-chlorophenyl derivative was as (1R,2S,3S)-4a for S-catalyst (see DOI: 10.5517/ccdc.csd.cc1mcqg5 OZAXEU). But this procedure is not entirely foolproof; the stereochemistry is decided by interactions between often bulky substituents at the transition state and it might be that here the p-chlorophenyl derivative has different properties from n-heptyl. Moreover bulk solutions may be different in their composition from single crystals. So it is useful to obtain independent proof.

An absolute assignment procedure based on chiroptical methods was first famously used by Kirkwood in 1951 (the Fischer convention is confirmed as a structurally correct representation of absolute configuration).[3] Such calculations need to take into account e.g. rotational conformers about the two bonds labelled in red above. In the previous post, I had noted variation of up to 2Hz in the calculated 3JHH coupling constants as a result of this mobility. This variation is probably too small to really influence any relative stereochemical interpretations, but is the same true for chiroptical assignments?

In Table 1 we can see whether this is still true for the predicted optical rotation of compound 4a, using two different functionals for the calculation (B3LYP and M062X respectively). The results rather surprised me; a simple bond rotation of an aryl or carbonyl group can invert the sign of the rotation. Clearly the observed optical rotation of -62.4° arises from a suitable combination of different Boltzmann populations of the individual bond rotamers, but to combine these accurately you would need to know the solution populations themselves very accurately and that is quite a challenge. So at this stage, we do not really have totally convincing independent evidence of whether the observed negative optical rotation corresponds to (1S,2R,3R)-4a or to its enantiomer (1R,2S,3S).

Table 1. Calculated Optical rotations for (1S,2R,3R)-4a. 

FAIR Data DOI: 10.14469/hpc/4678
Conformer

ORP [α]D, B3LYP+GD3BJ/Def2-TZVPP/SCRF=chloroform

ORP [α]D, M062X/Def2-TZVPP/SCRF=chloroform
4 +376 +238
3 -335 -301
2 -247 -223
1 +710 +522

Next, another chiroptical technique, electronic circular dichroism, or ECD. Here, the sign of the difference in absorption of polarized light (Δε), and known at the Cotton effect, characterises the specific enantiomer. The experimental Cotton effect for compound 4a obtained from S-catalyst (known as 3d in the SI, p S142[2]) can be simply summarised as +ve@315nm and -ve@275nm. Comparison with calculated spectra (Figure S17, p S146-7[2])♣  was performed using a Boltzmann-averaging (albeit based on enthalpies rather than the formally correct free energies), for three significant populations and this procedure matched to (1R,2S,3S).  Since the reported calculations were apparently for gas phase (and replacing n-heptyl with methyl) here I have repeated them in the actual solvent used (acetonitrile) and with the heptyl present. Although the ECD responses can still be severely dependent on the conformation, three of the spectra qualitatively agree that the responses at ~300nm♦ and 260 nm are respectively -ve and +ve. This confirms that (1S,2R,3R)-4a is the wrong enantiomer for S-catalyst and that the correct assignment is therefore (1R,2S,3S), as was indeed reported.[2]

Table 2. Calculated electronic circular dichroism for

 (1S,2R,3R)-4a. FAIR Data DOI: 10.14469/hpc/4678
Conformer

ECD calculation, ωB97XD/Def2-TZVPP
4
3
2
1

It is still true that the overall the fit between chiroptical experiment and theory can be sensitive to the Boltzmann population, as obtained from e.g. ΔΔG = -RT ln [1]/[2]), where 1 and 2 are two different conformers. ΔΔG is a difficult energy difference to compute accurately. Here is a suggested exercise in the statistics of error propagation. How does an error in ΔΔG propagate to the ratio of concentrations of two conformers [1]/[2]? Or, how accurately must ΔΔG be calculated in order to predict conformer populations to say better than 5%.

One more go at chiroptics, this time Vibrational Circular Dichroism, or VCD. The nature of the chromophore is different, but the principle is the same as ECD. I have deliberately truncated the spectrum to cut off all vibrations below 1000 cm-1 (these being the modes associated with group rotations) but to no avail, the four conformations all still look too different to avoid doing a Boltzmann averaging.

Table 3. Calculated VCD spectra for (1S,2R,3R)-4a. 
Conformer Spectrum
4
3
2
1

A modern VCD instrument does have one trick up its sleeve for coping with the conformer problem. The sample (as a thin-film) can be annealed down to very low temperatures before the spectrum is recorded. This effectively removes all higher energy forms, leaving just the most stable conformation as the only species present. However, that is an expensive experiment (and instrument!) to use.

There are perhaps some 2 million scalemic molecules (substances where one chiral form is in excess over the mirror image) for which chiroptical properties have been reported, but probably <50,000 crystal structures where absolute configurations have been assigned. Thus the vast majority of absolute configuration assignments have been done either chiroptically or by synthetic correlations (chemical transformations from molecules of known absolute configuration, with the assumption that you know how each transformation affects the chiral centres present). Given some of the difficulties and challenges noted above, it is tempting to conclude that a significant proportion of those 2 million molecules may have been mis-assigned (I once estimated up to 20%). However, we may conclude that the molecules discussed here are safely assigned correctly! 

‡No CIP-stereolabels appear in the article itself.[1] Perhaps this assignment is omitted in order to provide a student exercise? †There are many errors in stereochemical assignments in the literature. A good many of them may be the result of simple sample mis-labelling.[4] ♣The caption to Figure S17 states All the simulations are for the 1R,2R,3S absolute configuration. This is probably an error and should read 1R,2S,3S. ♦A correction of ~+15nm is sometimes applied to these values, but not done here.

 

References

  1. M. Meazza, A. Kowalczuk, S. Watkins, S. Holland, T.A. Logothetis, and R. Rios, "Organocatalytic Cyclopropanation of (<i>E</i>)-Dec-2-enal: Synthesis, Spectral Analysis and Mechanistic Understanding", Journal of Chemical Education, vol. 95, pp. 1832-1839, 2018. https://doi.org/10.1021/acs.jchemed.7b00566
  2. M. Meazza, M. Ashe, H.Y. Shin, H.S. Yang, A. Mazzanti, J.W. Yang, and R. Rios, "Enantioselective Organocatalytic Cyclopropanation of Enals Using Benzyl Chlorides", The Journal of Organic Chemistry, vol. 81, pp. 3488-3500, 2016. https://doi.org/10.1021/acs.joc.5b02801
  3. W.W. Wood, W. Fickett, and J.G. Kirkwood, "The Absolute Configuration of Optically Active Molecules", The Journal of Chemical Physics, vol. 20, pp. 561-568, 1952. https://doi.org/10.1063/1.1700491
  4. H.S. Rzepa, "The Chiro-optical Properties of a Lemniscular Octaphyrin", Organic Letters, vol. 11, 2009. https://doi.org/10.1021/ol901172g

Tags:, , , , , , , , , , , , , , , , , ,
Posted in Interesting chemistry | No Comments »

Tetrahedral carbon and cyclohexane.

Wednesday, August 22nd, 2018

Following the general recognition of carbon as being tetrahedrally tetravalent in 1869 (Paterno) and 1874 (Van’t Hoff and Le Bell), an early seminal exploitation of this to the conformation of cyclohexane was by Hermann Sachse in 1890.[1] This was verified when the Braggs in 1913[2], followed by an oft-cited article by Mohr in 1918,[3] established the crystal structure of diamond as comprising repeating rings in the chair conformation.† So by 1926, you might imagine that the shape (or conformation as we would now call it) of cyclohexane would be well-known. No quite so for everyone!

When The Journal of the Imperial College Chemical Society (Volume 6) was brought to my attention, I found an article by R. F Hunter;

He proceeds to argue as follows:

  1. The natural angle subtended at a tetrahedral carbon is 109.47°.
  2. “The internal angle between the carbon to carbon valencies of a six-membered ring cyclohexane will, if the ring is uniplanar, be … 120°.
  3. “When the cyclohexane ring is prepared … we must therefore have the pushing apart of two of the valencies”.
  4. The object of the experiments commenced in this College in 1914 was “to find what effect the pushing apart of the valencies …must have on the angle between the remaining pair of valencies“.
  5. You do wonder then why the assumption highlighted in red above was never really questioned during the twelve-year period of investigating angles around tetrahedral carbon.

The article itself is quite long, reporting the synthesis of many compounds in search of the postulated effect. Of course around twenty years later, Derek Barton used the by then generally accepted conformation of cyclohexane to explain reactivity in what become known as the theory of conformational analysis.

These two articles dating from 1926, and probably thought lost to science, show how some ideas can take decades to have any influence, whilst others can take root very much more quickly.

†The chair cyclohexane structure is easily discerned from Figure 7 in the Braggs’ paper![2]

References

  1. H. Sachse, "Ueber die geometrischen Isomerien der Hexamethylenderivate", Berichte der deutschen chemischen Gesellschaft, vol. 23, pp. 1363-1370, 1890. https://doi.org/10.1002/cber.189002301216
  2. W.H. Bragg, and W.L. Bragg, "The structure of the diamond", Proceedings of the Royal Society of London. Series A, Containing Papers of a Mathematical and Physical Character, vol. 89, pp. 277-291, 1913. https://doi.org/10.1098/rspa.1913.0084
  3. E. Mohr, "Die Baeyersche Spannungstheorie und die Struktur des Diamanten", Journal für Praktische Chemie, vol. 98, pp. 315-353, 1918. https://doi.org/10.1002/prac.19180980123

Tags:, , , , , , , , , , , , , , ,
Posted in Interesting chemistry | 1 Comment »

Multispectral Chiral Imaging with a Metalens.

Saturday, January 6th, 2018

The title here is from an article on metalenses[1] which caught my eye.

Metalenses are planar and optically thin layers which can be manufactured using a single-step lithographic process. This contrasts with traditional lenses that are not flat and where the optical properties result from very accurately engineered curvatures, which in turn are expensive to manufacture. Metalenses can have built into them many interesting optical properties, including light polarisation and dispersion. Nanoengineering has now resulted[1] in a metalens which can simultaneously present two images of opposite helicity of an object within the same field of view.

What is the relevance to chemistry? Well, a well-known chiroptical technique is known as electronic circular dichroism (ECD). At its simplest, it probes the difference in absorption by a chiral molecule of UV and visible light with opposite circular polarisation. This difference plotted as a function of the wavelength of the light is known as the ECD response. Importantly, this response can also be calculated for either enantiomer of the chiral molecule and hence the absolute configuration can be assigned on the basis of which calculated response matches the observed spectrum. Because the difference in response to the two polarisations of the light (Δε) is actually very small, the ECD technique is intrinsically less sensitive than e.g. normal UV/Visible spectra and this requires the use of expensive instruments to record that small difference. Chiral metalenses offer an interesting future opportunity to create new forms of ECD instrument, perhaps ones that are far more sensitive. In turn, this could lower the costs of acquiring ECD functionality in the standard laboratory (see [2] for an application in teaching laboratories). Very possibly, the most expensive component would in fact then be the computational simulations required to match up with the experimental spectrum!

When metalenses were first introduced, they were only able to lens a limited range of wavelengths. In another article by the same group[3] they now announce a new generation of metalens that covers the region 470 to 670 nm. This excludes the UV regions (<300nm) or the IR regions (>1200nm). The latter covers another important chiroptical instrumental technique known as vibrational circular dichroism, or VCD. As with ECD, the VCD response of a chiral molecule can be pretty well calculated using quantum chemistry and indeed often the VCD method is the only one that can successfully be used to assign absolute molecular configurations.[4] Unfortunately, VCD instruments are even more expensive than ECD ones, again largely due to the intrinsic insensitivity and the need to accumulate data using Fourier Transform methods over many hours. Few chemistry departments have such an instrument. So I will keep an eye out for when an effective chiral metalens operating in infra-red regions is announced! The prospect of routine VCD analyses is tantalising! 

 

References

  1. M. Khorasaninejad, W.T. Chen, A.Y. Zhu, J. Oh, R.C. Devlin, D. Rousso, and F. Capasso, "Multispectral Chiral Imaging with a Metalens", Nano Letters, vol. 16, pp. 4595-4600, 2016. https://doi.org/10.1021/acs.nanolett.6b01897
  2. K.K.(. Hii, H.S. Rzepa, and E.H. Smith, "Asymmetric Epoxidation: A Twinned Laboratory and Molecular Modeling Experiment for Upper-Level Organic Chemistry Students", Journal of Chemical Education, vol. 92, pp. 1385-1389, 2015. https://doi.org/10.1021/ed500398e
  3. W.T. Chen, A.Y. Zhu, V. Sanjeev, M. Khorasaninejad, Z. Shi, E. Lee, and F. Capasso, "A broadband achromatic metalens for focusing and imaging in the visible", Nature Nanotechnology, vol. 13, pp. 220-226, 2018. https://doi.org/10.1038/s41565-017-0034-6
  4. J.I. Murray, N.J. Flodén, A. Bauer, N.D. Fessner, D.L. Dunklemann, O. Bob‐Egbe, H.S. Rzepa, T. Bürgi, J. Richardson, and A.C. Spivey, "Kinetic Resolution of 2‐Substituted Indolines by <i>N</i>‐Sulfonylation using an Atropisomeric 4‐DMAP‐<i>N</i>‐oxide Organocatalyst", Angewandte Chemie International Edition, vol. 56, pp. 5760-5764, 2017. https://doi.org/10.1002/anie.201700977

Tags:, , , , , , , , , , ,
Posted in Interesting chemistry | No Comments »

VSEPR Theory: Octet-busting or not with trimethyl chlorine, ClMe3.

Sunday, November 12th, 2017

A few years back, I took a look at the valence-shell electron pair repulsion approach to the geometry of chlorine trifluoride, ClF3 using so-called ELF basins to locate centroids for both the covalent F-Cl bond electrons and the chlorine lone-pair electrons. Whereas the original VSEPR theory talks about five “electron pairs” totalling an octet-busting ten electrons surrounding chlorine, the electron density-based ELF approach located only ~6.8e surrounding the central chlorine and no “octet-busting”. The remaining electrons occupied fluorine lone pairs rather than the shared Cl-F regions. Here I take a look at ClMe3, as induced by the analysis of SeMe6.

The difference between ClF3 and ClMe3 is that octet-excess electrons (two in this case) in the former can relocate into fluorine lone pairs by occupying in effect anti-bonding orbitals and hence end up not contributing to the central atom valence shell.‡ With ClMe3 the methyl groups cannot apparently sustain such lone pairs, at least not distinct from the Cl-C bond region. So might we get an octet-busting example with this molecule? A ClMe3 calculation (ωb97xd/6-311++g(d,p)) reveals a molecule with all real vibrational modes (i.e. a minimum, FAIR data DOI: 10.14469/hpc/3241) and ELF (FAIR data DOI 10.14469/hpc/3242)† basins as shown below:

Density-derived approach: Two of the C-Cl bonds each exhibit two ELF basins; one disynaptic basin (0.94e) and one monosynaptic basin (0.20e) closer to the chlorine. The former pair integrate to 1.88e, density which largely arises from carbon (natural charge -0.84) and which contribute to a total integration for these carbons of 7.17e. The latter pair contributes to a total chlorine integration of 7.19e. The angle subtended at chlorine for the two 2.68e “lone pair” basins is 141°. Thus an inner, octet-compliant, valence-shell for chlorine is revealed, plus an expanded-octet outer one into which the two additional electrons go. The latter contribute to forming an octet-compliant carbon valence shell, but may be considered as not contributing to the valence shell of the other atom of the pair, the chlorine. An endo lone-pair rather than the more usual exo lone-pair if you will. These results reveal that the molecular feature we know as a (single) “bond” may in fact have more complex inner structures or zones, something we do not normally consider bonds as having. In this model, these zones are not invariably considered as shared between both the atoms comprising the bond.

Orbital-derived approach: NBO analysis (FAIR data DOI: 10.14469/hpc/3241) reveals the chlorine electronic configuration as [core]3S(1.83)3p(4.67)4S(0.01)3d(0.03)5p(0.02,) showing very little population of the Rydberg shells (4s, 3d, 5p) occurs (0.13e in total). This method of partitioning the electrons allocates a chlorine Wiberg bond index of 2.00 and the methyl carbon bond index of  3.83. If the regular valence of Cl is taken as 1, then the central chlorine can be regarded as non-Rydberg hypervalent (the electrons in the 0.94e basins are taken as contributing to the chlorine bond index).

The carbon-halogen bond internal structures simplify for Br (DOI: 10.14469/hpc/3248, 10.14469/hpc/3250) and I (DOI: 10.14469/hpc/3249, 10.14469/hpc/3247); for each only a single ELF basin is located and the NBO Br and I bond indices are respectively 2.10 and 2.1. This is not due to incursion of  Rydberg hypervalence (Br: [core]4S(1.83)4p(4.46)5S(0.02)4d(0.03)6p( 0.01); I: [core]5S(1.82)5p(4.29)6S(0.02)5d(0.02)6p(0.01) ) but of a merging of the carbon and halogen valence basin such that the ELF contributions to each cannot be deconvoluted. In each case the NBO bond indices of ~2 suggest hypervalency for the halogen.

What have we learnt?  That the shared electron (covalent) bond can have complex internal features, such as two discrete basins for the apparently shared electrons. How one partitions these electrons can influence the value one obtains for the total shared electron count and hence whether the octet is retained or expanded for main group elements such as the halogens. And finally, that hypervalence and hyper-coordination are related in the orbital model at least. Thus along the series MenI (n= coordination number 1,3,5,7), the values of the Wiberg bond index at the halogen progress as 1.0, 2.1, 3.1 (DOI: 10.14469/hpc/3236) and 4.01 (DOI: 10.14469/hpc/3238), or one extra atom bond index per electron pair.  Given this, it seems useful to retain the distinction between the terms hypervalence and hyper-coordination, but also recognize that we still may have much to learn about the former.

‡See the previous post on SeMe6 for a more detailed discussion.

† The FAIR Data accompanying this blog post is organised in a new way here. All the calculations are collected together with an over-arching DOI: 10.14469/hpc/3252 associated with this post, with individual entries accessible directly using the DOIs given above. The post itself has a  DOI: 10.14469/hpc/3255 and the two identifiers are associated with each-other via their respective metadata.  A set of standards (https://jats.nlm.nih.gov) with implementation guidelines for e.g. repositories, authors and publishers-editors  are expected in the future to establish infra-structures for cross-linking narratives/stories with the data on which they are based.

Tags:, , , , , , , , , ,
Posted in Chemical IT, Hypervalency | 5 Comments »

The di-anion of dilithium (not the Star Trek variety): Another “Hyper-bond”?

Saturday, September 16th, 2017

Early in 2011, I wrote about how the diatomic molecule Be2 might be persuaded to improve upon its normal unbound state (bond order ~zero) by a double electronic excitation to a strongly bound species. I yesterday updated this post with further suggestions and one of these inspired this follow-up.

The standard molecular orbital diagram for Be2 below shows two electrons in both the 2s Σg and Σu levels, the first being considered bonding and the second antibonding. By exciting the two electrons from the Σu into the Πu MO to form a triplet, one converts one antibonding occupancy into two bonding occupancies, in the process changing the total formal bond order from zero to two.

 

The triplet excited state of diberyllium

You can see the results of my playing with these ideas both in my appended comments to the original post and the table below. This shows that the calculated bond order for the excited triplet state of Be2 is actually closer to 1.50 rather than to two, but definitely not zero!

System Wiberg bond order Bond length FAIR Data
Be2 singlet 0.15 2.805 10.14469/hpc/3082
Be2 excited triplet 1.50 1.785 10.14469/hpc/3075
Be22+ 1.00 2.135 10.14469/hpc/3076
Be22- triplet 0.89 2.242 10.14469/hpc/3074
Be22- excited singlet 3.00 1.817 10.14469/hpc/3083

The games above represent isoelectronic substitutions and here I try one more, namely that Li22- is isoelectronic with Be2. Unlike the latter, there is no need to force an electronic excitation (ωB97XD/Def2-QZVPPD/SCRF=water) to achieve the required occupancies with Li22-.

System Wiberg bond order Bond length FAIR Data
Li22- triplet 1.501 2.381 10.14469/hpc/3087

I also checked what crystal structures could tell us about Li-Li bonds and it seems 2.38Å is about as short as they get.

At this point, the NBO analysis of the Li22- localised orbitals alerted me to another feature, which is that the Rydberg occupancy amounted to 2.18e. This in turn reminded me of the previous post which dealt with such occupancy in another small molecule, CH3F2-, but here the Rydberg occupancy involved the 3s/3p AOs of the carbon and the fluorine. With Li22- triplet, it is of the lithium 2p AO (2.18e) and only a tiny occupancy of 3d (0.03). By definition, for alkali metals such as Li the normal valence shell is just 2s, whereas 2p occupancy is considered a Rydberg state; a hypervalent state if you will. So Li22- triplet has a Li-Li hyper-bond!‡ Of course, by this definition most Li compounds are then hypervalent, since many have populated 2p shells.

Even if use of the term hyper-bond to describe Li22- triplet is rather artificial, this example does reveal the games one can play with the first row elements Li-B (see table above). Given that most introductory text books on bonding normally only explain the diatomics formed from N-Ne (occasionally including C), I might suggest that these earlier elements are equally instructive and fun to play with.

‡ This species is 36.0 kcal/mol higher in free energy than two separated Li– anions.

Tags:, , , , , , , , , , , , , , ,
Posted in Interesting chemistry | 3 Comments »

The di-anion of dilithium (not the Star Trek variety): Another "Hyper-bond"?

Saturday, September 16th, 2017

Early in 2011, I wrote about how the diatomic molecule Be2 might be persuaded to improve upon its normal unbound state (bond order ~zero) by a double electronic excitation to a strongly bound species. I yesterday updated this post with further suggestions and one of these inspired this follow-up.

The standard molecular orbital diagram for Be2 below shows two electrons in both the 2s Σg and Σu levels, the first being considered bonding and the second antibonding. By exciting the two electrons from the Σu into the Πu MO to form a triplet, one converts one antibonding occupancy into two bonding occupancies, in the process changing the total formal bond order from zero to two.

 

The triplet excited state of diberyllium

You can see the results of my playing with these ideas both in my appended comments to the original post and the table below. This shows that the calculated bond order for the excited triplet state of Be2 is actually closer to 1.50 rather than to two, but definitely not zero!

System Wiberg bond order Bond length FAIR Data
Be2 singlet 0.15 2.805 10.14469/hpc/3082
Be2 excited triplet 1.50 1.785 10.14469/hpc/3075
Be22+ 1.00 2.135 10.14469/hpc/3076
Be22- triplet 0.89 2.242 10.14469/hpc/3074
Be22- excited singlet 3.00 1.817 10.14469/hpc/3083

The games above represent isoelectronic substitutions and here I try one more, namely that Li22- is isoelectronic with Be2. Unlike the latter, there is no need to force an electronic excitation (ωB97XD/Def2-QZVPPD/SCRF=water) to achieve the required occupancies with Li22-.

System Wiberg bond order Bond length FAIR Data
Li22- triplet 1.501 2.381 10.14469/hpc/3087

I also checked what crystal structures could tell us about Li-Li bonds and it seems 2.38Å is about as short as they get.

At this point, the NBO analysis of the Li22- localised orbitals alerted me to another feature, which is that the Rydberg occupancy amounted to 2.18e. This in turn reminded me of the previous post which dealt with such occupancy in another small molecule, CH3F2-, but here the Rydberg occupancy involved the 3s/3p AOs of the carbon and the fluorine. With Li22- triplet, it is of the lithium 2p AO (2.18e) and only a tiny occupancy of 3d (0.03). By definition, for alkali metals such as Li the normal valence shell is just 2s, whereas 2p occupancy is considered a Rydberg state; a hypervalent state if you will. So Li22- triplet has a Li-Li hyper-bond!‡ Of course, by this definition most Li compounds are then hypervalent, since many have populated 2p shells.

Even if use of the term hyper-bond to describe Li22- triplet is rather artificial, this example does reveal the games one can play with the first row elements Li-B (see table above). Given that most introductory text books on bonding normally only explain the diatomics formed from N-Ne (occasionally including C), I might suggest that these earlier elements are equally instructive and fun to play with.

‡ This species is 36.0 kcal/mol higher in free energy than two separated Li– anions.

Tags:, , , , , , , , , , , , , , ,
Posted in Interesting chemistry | 3 Comments »

The conformation of enols: revealed and explained.

Thursday, April 6th, 2017

Enols are simple compounds with an OH group as a substituent on a C=C double bond and with a very distinct conformational preference for the OH group. Here I take a look at this preference as revealed by crystal structures, with the theoretical explanation.

First, a search of the Cambridge structure database (CDS), using the search query shown below (DOI: 10.14469/hpc/2429)


The first search (no errors, no disorder, R < 0.05) is unconstrained in the sense that the HO group is free to hydrogen bond itself. The syn conformer has the torsion of 0° and it has a distinct preponderance over the anti isomer (180°). There is the first hint that the most probable C=C distance for the syn isomer may be longer than that for the anti, but this is not yet entirely convincing.
To try to make it so, a constrained search is now performed, in which only structures where the HO group has no contact (hydrogen bonding) interaction are included. This is achieved using a “Boolean” search;

The number of hits approximately halves, but the proportion of syn examples increases considerably. There is an interesting double “hot-spot” distribution, which amplifies the lengthening of the C=C bond compared to the anti orientation.

The next constraint added is that the data collection must be <100K (to reduce thermal noise) which reduces the hits considerably but now shows the lengthening of the C=C bond for the syn isomer very clearly.

A final plot is of the C=C length vs the C-O length (no temperature, but HO interaction constraint). If there were no correlation, the distribution would be ~circular. In fact it clearly shows that as the C=C bond lengthens, the C-O bond contracts.

Now for some calculations (ωB97XD/Def2-TZVPP, DOI: 10.14469/hpc/2429) which reveal the following:

  1. The free energy of the syn isomer is 1.2 kcal/mol lower than that of the syn. The effect is small, and hence easily masked by other interactions such as hydrogen bonding to the OH group. Hence the reason why removing such interactions from the search above increased the syn population compared to anti.
  2. The syn C=C bond length (1.325Å) is longer than the anti (1.322Å). 
  3. The syn isomer has one unique σO-Lp/σ*C-C NBO orbital interaction (below) with a value of E(2) 7.7 kcal/mol, which is absent in the anti form. As it happens, a πO/π*C=C interaction is present in both forms but is also stronger in the syn isomer (E(2)= 46.8 vs 44.2 kcal/mol).
    unoccupied NBO, σ*C-C
    Occupied NBO, σO-Lp
  4. The overlap of the filled σO-Lp with the empty σ*C-C orbital is shown below (blue overlaps with purple, red overlaps with orange).

    To view the overlap in rotatable 3D, click on any of the colour diagrams above.‡

It is nice to see how experiment (crystal structures) and theory (the calculation of geometries and orbital interactions) can quickly and simply be reconciled. Both these searches and the calculations can be done in just one day of “laboratory time” and I think it would make for an interesting undergraduate chemistry lab experiment.

‡ This visualisation uses Java. Increasingly this browser plugin is becoming more onerous to activate (because of increased security) and some browsers do not support it at all. The macOS Safari browser is one that still does, but you do have to allow it via the security permissions.

Tags:, , , , , , , , , , , , , ,
Posted in crystal_structure_mining, reaction mechanism | 2 Comments »

First, hexacoordinate carbon – now pentacoordinate nitrogen?

Saturday, March 25th, 2017

A few years back I followed a train of thought here which ended with hexacoordinate carbon, then a hypothesis rather than a demonstrated reality. That reality was recently confirmed via a crystal structure, DOI:10.5517/CCDC.CSD.CC1M71QM[1]. Here is a similar proposal for penta-coordinate nitrogen.

First, a search of the CSD (Cambridge structure database) for such nitrogen. There are only three hits[2], [3], [4] all of which relate to RN bonded to four borons as part of a boron cage. There are none which relate to RN bonded to four carbon atoms. 

The original argument was based on cyclopentadienyl anion and its symmetric coordination to RC3+ to achieve six coordination for one carbon. Morphing C to the iso-electronic N+ gets one to the ligand RN4+ and this can now be coordinated to the di-anion of cyclobutadiene, also iso-electronic in the 6π sense to cyclopentadienyl mono-anion.

The optimised structure of the methylated system (ωB97XD/Def2-TZVPP) as shown below (DOI: 10.14469/hpc/2348) is a true minimum and reveals a 5-coordinate nitrogen. It is the dication of an isomer of pentamethyl pyrrole.

One of the normal modes for this molecule is the so-called Kekule vibration, which elongates two C-C bonds and shortens the other two. The value (1266 cm-1) is typical of aromatic systems.

A QTAIM analysis shows four line (bond) critical points (LCP, magenta) connecting the 4-carbon base of the system and four further LCPs connecting each carbon to the nitrogen. Significantly, the four carbons are not themselves characterised by a ring critical point (RCP, green), these being confined to the rings formed between two carbons and the nitrogen. The value of the electron density ρ(r) at the basal bond is typical of a single bond; the value to the nitrogen indicates the bond has a smaller order.

An ELF (electron localisation function) analysis is similar, showing basal C-C electron basins of 2.12e and C-N basins of 1.25e.

In hunting for examples of hyper-coordination in the second row of the periodic table, the focus has tended largely towards identifying carbon examples. Perhaps that might now right-shift to the adjacent element nitrogen?

References

  1. M. Malischewski, and K. Seppelt, "Crystal Structure Determination of the Pentagonal‐Pyramidal Hexamethylbenzene Dication C<sub>6</sub>(CH<sub>3</sub>)<sub>6</sub><sup>2+</sup>", Angewandte Chemie International Edition, vol. 56, pp. 368-370, 2016. https://doi.org/10.1002/anie.201608795
  2. U. Doerfler, J.D. Kennedy, L. Barton, C.M. Collins, and N.P. Rath, "Polyhedral azadirhodaborane chemistry. Reaction of [{RhCl2(η5-C5Me5) }2] with [EtH2NB8H11NHEt] to give contiguous ten-vertex [1-Et-6,7-(η5-C5Me5)2- closo-6,7,1-Rh2NB7H7 ]", Journal of the Chemical Society, Dalton Transactions, pp. 707-708, 1997. https://doi.org/10.1039/a700132k
  3. L. Schneider, U. Englert, and P. Paetzold, "Die Kristallstruktur von Aza‐<i>closo</i>‐decaboran NB<sub>9</sub>H<sub>10</sub>", Zeitschrift für anorganische und allgemeine Chemie, vol. 620, pp. 1191-1193, 1994. https://doi.org/10.1002/zaac.19946200711
  4. M. Mueller, U. Englert, and P. Paetzold, "X-ray Crystallographic Structure of a 7-Aza-nido-undecaborane Derivative: (NB2tBu3H)NB10H12", Inorganic Chemistry, vol. 34, pp. 5925-5926, 1995. https://doi.org/10.1021/ic00127a034

Tags:, , , , , ,
Posted in Bond slam, crystal_structure_mining, Hypervalency, Interesting chemistry | 1 Comment »

How does methane invert (its configuration)?

Thursday, March 16th, 2017

This is a spin-off from the table I constructed here for further chemical examples of the classical/non-classical norbornyl cation conundrum. One possible entry would include the transition state for inversion of methane via a square planar geometry as compared with e.g. NiH4 for which the square planar motif is its minimum. So is square planar methane a true transition state for inversion (of configuration) of carbon?

The history of this topic is nicely told as far back as 1993[1], when square planar methane was shown to be a 4th-order saddle point (i.e. four negative force constants) and not the first order one required of a transition state. A true transition state was located,‡ and here I show it as part of an animated IRC (intrinsic reaction coordinate). Go to DOI: 10.14469/hpc/2288 for the calculation outputs.

To convince yourself that the configuration really does invert, focus on the CIP rule. With atom 1 pointing behind, atoms 2 → 3  → 4 rotate in a clockwise direction. Now focus on the final point at the end of the IRC, when 2 → 3  → 4 rotate anti-clockwise. The configuration has inverted! The barrier as can be seen below is ~118 kcal/mol. At this value the half-life for the process would be far longer than the age of the universe.

The process can be described as an interesting variation on pseudorotation, for which the classic example is of course PF5.† Alternatively it can be thought of as the partial extrusion of H2 to give carbene, followed by re-addition of the H2 to reform methane. Partial because the extrusion is never fully achieved.

I have to say I did not expect anything quite so interesting to be associated with methane;  one can learn from the simplest of molecules!

‡ It was not entirely trivial to recover appropriate coordinates for recomputing this TS from the article. But it is in fact an easy one to find from scratch. Hopefully with the files at 10.14469/hpc/2288 to help, this will not be an issue here.

†There are many kinds of pseudo-rotations. For others see here.[2] and [3]

References

  1. M.S. Gordon, and M.W. Schmidt, "Does methane invert through square planar?", Journal of the American Chemical Society, vol. 115, pp. 7486-7492, 1993. https://doi.org/10.1021/ja00069a056
  2. H.S. Rzepa, and M.E. Cass, "A Computational Study of the Nondissociative Mechanisms that Interchange Apical and Equatorial Atoms in Square Pyramidal Molecules", Inorganic Chemistry, vol. 45, pp. 3958-3963, 2006. https://doi.org/10.1021/ic0519988
  3. H.S. Rzepa, and M.E. Cass, "In Search of the Bailar and Rây−Dutt Twist Mechanisms That Racemize Chiral Trischelates:  A Computational Study of Sc<sup>III</sup>, Ti<sup>IV</sup>, Co<sup>III</sup>, Zn<sup>II</sup>, Ga<sup>III</sup>, and Ge<sup>IV</sup> Complexes of a Ligand Analogue of Acetylacetonate", Inorganic Chemistry, vol. 46, pp. 8024-8031, 2007. https://doi.org/10.1021/ic062473y

Tags:, , , , , ,
Posted in reaction mechanism | 2 Comments »

« Older Entries