Henry Rzepa's blog

Deltamethin is a pyrethroid insecticide for control of malaria which has been used for a little while. Perhaps inevitably, mosquitoes are developing resistance to it. So what could be done about countering this? Well, perhaps surprisingly, form a polymorph![1] These crystal structure isomers are often highly undesirable; thus Ritonavir, which changed its polymorphic form during manufacture to become far less active (due it has to be said to insolubility). Now a polymorph of Deltamethin has been discovered, which when applied as a powder, increases its effectiveness more than 10 times against Anopheles mosquitoes and provides a potentially new affordable malaria control solution for countries that are loosing protection.

You can view this new polymorph at DOI: 10.5517/ccdc.csd.cc24mrxg and 10.5517/ccdc.csd.cc24mryh. The two structures differ in the torsion angle around the O-C(CN) bond, resulting in differing anomeric interactions between the ester oxygen and the C-CN group.

The anomeric effect can be quantified by the dihedral angle between a donor oxygen lone pair and the accepting (in this case C-CN) bond. The position of the lone pair itself can be localised using the ELF (electron localisation function) method. For one polymorph, this has a torsion angle of 127° and O-C and C-CN lengths of 1.455 and 1.480Å. The other form has an almost orthogonal (i.e. non-interacting) torsion of 79° with lengths of 1.461 and 1.477Å. The first form exhibits some electron pair donation into the C-O bond, shortening it slightly, accompanied by transfer of C-CN bond electrons onto the N, weakening the C-N bond. A very similar effect was noted for a herbicide[2] which resulted in very differing stabilities for two stereoisomers in water.

Just such aqueous hydrolytic stability was indeed reported for Deltamethrin[3] and its other 7 stereoisomers in water (3 stereocentres, 2³ = 8). Persistence of any chemical applied to the soil is a very important aspect of its properties; recollect that a now banned insecticide, DDT, suffered from very long soil persistence. The article[3] looks at what happens to Deltamethrin (labelled compound 1) in water in the dark. As it goes, a new isomer labelled 2′ appears and then too decays, all in a period of ~5 days. This new isomer was found to be inactive as an insecticide.

So what is 2′? Well here is a table of all 8 stereoisomers, where 1 is labelled as α-S,1R cis and 2′ is labelled as α-S,1S cis. Here we have only one of the three stereocentres labelled using Cahn-Ingold-Prelog (CIP) notation, the 1-R/S carbon (the convention is to use italics for CIP). The cis designation implies that the 3-position is also S and the cyano carbon remains S. This cis label however conflicts with the abstract to the article, which indicates that the dark water isomerisation is subject to cis/trans isomerisation. So we have a water-induced isomerisation which inverts the configuration of 1R,3R in molecule 1 to apparently 1S,3S in molecule 2′?  

Changes in stereochemistry in Deltamethrin are likely to be the result of forming planar enols and so one might judge the hydrolytic stability by the ease of forming such an enol. Just such a process was the topic of a post on the undesired epimerisation of thalidomide in water. Time for calculations (FAIR data doi: 10.14469/hpc/8020 ) at the B3LYP+GD3+BJ/Def2-TZVPP/SCRF=water computational level. Firstly, the free energy of the enol form on the cyclopropane by relocation of the proton at C-1 is 32.0 kcal/mol higher. However, forming the enol by relocating the proton on the carbon bearing the CN group to the nitrogen is only 20.0 kcal/mol higher in energy. With a small further barrier for the TS for proton removal expected, this latter enol is within an accessible energy range for room temperature reaction, whereas the previous enol is not. So the hypothesis is that 2′ is actually the stereoisomer labelled 2 in Table 1, ie R,R,R and not S,S,S. The free energy of this R,R,R diastereoisomer is calculated 1.1 kcal/mol higher than 1 itself, which would represent about 13% of this isomer at equilibrium.

I have shown here how uncertainty caused by how to reconcile the stereochemistry of eg  Figure 4 and Table 1[4] in modern terms can perhaps be lessened by performing “reality check” calculations on possible multiple interpretations to reduce them to the most probable. We also find that a relatively old and much used bioactive compound can have surprises lurking around the corner, in this case by a simple recrystallisation that results in a new form being discovered without having to do any other chemistry.  Still, how much longer will pyrethroid insecticides be used?

References

1. J. Yang, B. Erriah, C.T. Hu, E. Reiter, X. Zhu, V. López-Mejías, I.P. Carmona-Sepúlveda, M.D. Ward, and B. Kahr, "A deltamethrin crystal polymorph for more effective malaria control", Proceedings of the National Academy of Sciences, vol. 117, pp. 26633-26638, 2020. https://doi.org/10.1073/pnas.2013390117
2. P. Camilleri, D. Munro, K. Weaver, D.J. Williams, H.S. Rzepa, and A.M.Z. Slawin, "Isoxazolinyldioxepins. Part 1. Structure–reactivity studies of the hydrolysis of oxazolinyldioxepin derivatives", J. Chem. Soc., Perkin Trans. 2, pp. 1265-1269, 1989. https://doi.org/10.1039/p29890001265
3. R.J. Maguire, "Chemical and photochemical isomerization of deltamethrin", Journal of Agricultural and Food Chemistry, vol. 38, pp. 1613-1617, 1990. https://doi.org/10.1021/jf00097a039

For obvious reasons, anti-viral molecules are very much in the news at the moment. Thus Derek Lowe highlights Molnupiravir which is shown as a hydroxylamine, the representation originating from the Wikipedia page on the molecule.

I like stereocentres more clearly identified using eg R/S notation and so I went to another source of information, SciFinder, which represents the molecule in a different way. There you get the stereocentres unambiguously identified for you, but the hydroxylamine is now replaced by an oxime! 

The Reaxys database renders it differently again as below (note the different rotamer for the hydroxylamine):

Are they all talking about the same molecule? Well yes, since the hydroxylamine and the oxime are related by tautomerism, but it takes a bit of effort to fully reconcile these three representations with each other. So the next question is does it matter which tautomer is selected to represent a molecule? Since they differ by proton transfers between acidic atoms (N,O) the presumption is that the equilibrium between the tautomers is fast and so the predominant species is determined by the position of the equilibrium. The tautomer matters in another sense. This molecule clearly interacts with DNA, and very probably by paired hydrogen bonding. It is this hydrogen bonding that was crucial in helping Watson and Crick to postulate the first successful model of DNA itself,[1] famously enabled by them using the correct tautomeric form of the component DNA bases! So the tautomers do matter!

Time for some calculations (B3LYP+GD3BJ/Def2-TZVPP/SCRF=water, using integral=(acc2e=14,grid=superfinegrid). The FAIR DOI for the collection is 10.14469/hpc/7990

In the diagram above, the non-aromatic valence representation is shown at the top, followed by a reorganisation of the electrons into an aromatic form below. These aromatic forms are all ionic with charge separation and so the question here arises: does the aromatic stabilisation energy outweigh the destabilisation caused by charge separation? 

The calculated free energies (ΔG₂₉₈) show that the oxime is 3.2 kcal/mol more stable than the next most stable, the hydroxylamine tautomer (calculated for a water continuum solvation model).The third tautomer is not far behind, being a nitrone! A 3D model is shown below illustrating the internal hydrogen bonds (I hope it is clear why I wanted the four stereocentres unambiguously identified, and why the simple perspective diagram shown on the Wikipedia page is not definitive). This model was obtained after also experimenting with hydroxyl rotamers to ensure the lowest energy was obtained.

So how “aromatic” are the two lowest energy species? The oxime has two sets of charge separation, whilst the hydroxylamine only one. One measure of aromaticity is the NICS magnetic index. For the oxime it is -0.1ppm, very clearly non-aromatic. Separating two sets of charges clearly is not compensated by aromatic stabilisation. The next most stable hydroxylamine has NICS -1.8ppm, which shows slightly more signs of aromaticity (benzene on this scale is ~ -10 ppm), perhaps because it only separates one pair of charges. 

What about crystal structures? NETGEY is a model which removes the sugar unit and with an N-Me replacing the NH (thus preventing tautomerism and locking the molecule into the oxime form). MHCYTC protonates the hydroxylamine on the imine nitrogen OR the oxime on its imine nitrogen thus rendering the two tautomers identical.

NETGEY	MHCYTC

The crystal structure of Molnupiravir itself has not been reported, so there is no definitive answer to the most stable tautomer in the solid state. But the calculation above does suggest that it is the oxime (and hence SciFinder’s representation) that is the probable dominant form in aqueous solutions. If one is trying to build a model to show how this small molecule interacts with DNA, this might be useful information (in the same way that picking the correct tautomer of the original DNA bases worked for Watson and Crick!). 

References

1. J.D. WATSON, and F.H.C. CRICK, "Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid", Nature, vol. 171, pp. 737-738, 1953. https://doi.org/10.1038/171737a0

The last post addressed the concept of “steric clashes” in a pericyclic reaction transition state as an extension of the time honoured practice of building molecular models to analyse reaction outcomes. A modern computer generated model might express this in terms of a NCI (non-covalent-interaction) surface. A few posts ago, I had looked at some “molecules of the year” for 2020, one of which was a “figure-eight” twisted dodecaporphyrin in which an aspect of the reported[1] geometry had struck me as potentially lacking features due to the so-called non-covalent dispersion or van der Waals attractions. So I am revisiting here by adding the NCI surface for this molecule and one other.

The molecule in question has 720 atoms and can be regarded as a [162]-annulene (4n+2, n=40) with a linking number Lk =2π.[2] The NCI surface is ideally computed from a “self-consistent-field or SCF density” and so in this instance I used the PM7 SCF-density, which is derived from the valence shell only and does not include the core shells. That hardly matters since the non-covalent NCI surface does not use the core shells!

You can see from the above that the porphyrin-stacking region has a very dense NCI green surface (arrow), indicating a lot of stabilisation is originating there; something lacking in the original proposed structure. There are lots of other features and so I do encourage you to explore the 3D model.

The second (hypothetical) molecule is a simpler CH-based [144]-annulene,[3] comprising a twisted coil of 144 CH= units with a linking number Lk = 18π (the largest such ever proposed for a molecule!). The SCF-NCI surface (derived from an ωB97XD/6-31G(d,p) calculation) is contiguous all the way around the circuit and must be the ultimate π-π stacked molecule!

I should end with a brief tutorial on how to generate these surfaces. You need a density matrix (e.g. DOI: 10.14469/ch/16967). In programs such as Gaussian 16, this can be obtained from the checkpoint file, which contains it. A progam called cubgen is used by (e.g.) Gaussian to create a 3D cube of electron density values (as well as other interesting properties). To get good resolution (~ 0.044Å) the file will be between 500 – 800 Mbyte in size. If a resolution of ~ 0.088Å is used it will be eight times smaller. For cube files less than ~105 Mbyte in size, you can use this Web-based tool (DOI: 10.14469/hpc/7864) to get the NCI surface. For the larger files you will need the Jmol application which can sustain files up to ~1 Gbyte (or larger, but I have not tested) and where you will run the following script: 

load density.cub;isosurface parameters [0.5 1 0.0005 0.05 0.95 1.00] NCI "";color isosurface "bgyor" range -0.04 0.04;write density.xyz;write density.jvxl;

(where this script assumes that the file density.cub file is in the same folder as the Jmol.java application).

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Postscript: The NCI analysis is based on computing the total density of the molecule. Close inspection of the top molecule as computed using the semi-empirical method PM7 reveals some interesting features extending beyond the C-H bonds. Analysis of this reveals it to be an artefact of the computed density, itself traced back to differences in how overlaps are handled in computing the density for this particular method. This error is not present for the MNDO semi-empirical method. When evaluated using MNDO, but at the geometry computed by PM7, these artefacts are removed. The NCI feature in the π-π stacking shown above however remains and hence is not an artefact.

References

1. M. Rickhaus, M. Jirasek, L. Tejerina, H. Gotfredsen, M.D. Peeks, R. Haver, H. Jiang, T.D.W. Claridge, and H.L. Anderson, "Global aromaticity at the nanoscale", Nature Chemistry, vol. 12, pp. 236-241, 2020. https://doi.org/10.1038/s41557-019-0398-3
2. S.M. Rappaport, and H.S. Rzepa, "Intrinsically Chiral Aromaticity. Rules Incorporating Linking Number, Twist, and Writhe for Higher-Twist Möbius Annulenes", Journal of the American Chemical Society, vol. 130, pp. 7613-7619, 2008. https://doi.org/10.1021/ja710438j
3. R.J.F. Berger, "Prediction of a Cyclic Helical Oligoacetylene Showing Anapolar Ring Currents in the Magnetic Field", Zeitschrift für Naturforschung B, vol. 67, pp. 1127-1131, 2012. https://doi.org/10.5560/znb.2012-0189

Last May, I wrote an update to the story sparked by the report of the chemical synthesis of C₂.[1] This species has a long history of spectroscopic observation in the gas phase, resulting from its generation at high temperatures.[2] The chemical synthesis however was done in solution at ambient or low temperatures, a game-changer as they say. Here I give another update to this unfolding story.

Key to the story is the precursor labelled 11 in the scheme above and the suggestion[1] that it is unimolecular decomposition of 11 that results in C₂. A question that had not been posed however was whether 11 itself could participate in any bimolecular reactions and whether these could be lower in free energy than its unimolecular decomposition. That has now been addressed in a recent pre-print, DOI: 10.26434/chemrxiv.13560260.v1[3] Here I will show just one of the possible bimolecular reactions investigated, that of 11 with itself. 

The reaction has a low barrier (ΔG^‡ 15.4 kcal/mol for a standard state of 0.044 molar, approximately the concentration the original experiments were conducted for) which means it will be very rapid at room temperatures.^♥ The product of this reaction can itself react with more 11 ((ΔG^‡ 16.9 kcal/mol) and so on to form polymeric chains or clusters of carbon, eventually resulting in C₆₀ and other forms of carbon. Low energy barriers for a number of other possible bimolecular reactions of 11 with species such as the chemical traps used in the original experiment are also reported,[3] most of which are lower in free energy than that predicted for the unimolecular fragmentation of 11, despite the entropic penalty.

So the enigma is thus: Does species 11 truly fragment to C₂, or are the products of this reaction really bimolecular reactions of 11? It does seem as if 11 itself can have a rich and fascinating room temperature chemistry, the scope of which has only started to be explored.

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^♥The potential energy surface is unusual, in that initially two products are possible, depending on where the C₄ unit ends up attached. The potential energy valley only bifurcates into two valleys resulting in the final product at a late stage (~ IRC -5). Put another way, the initial symmetry is C_2h, but this breaks/bifurcates into two valleys each leading to different outcomes for the C₄ unit. This is very much like the famous potential energy surface for the dimerisation of cyclopentadiene.

References

1. K. Miyamoto, S. Narita, Y. Masumoto, T. Hashishin, T. Osawa, M. Kimura, M. Ochiai, and M. Uchiyama, "Room-temperature chemical synthesis of C2", Nature Communications, vol. 11, 2020. https://doi.org/10.1038/s41467-020-16025-x
2. T.W. Schmidt, "The Spectroscopy of C₂: A Cosmic Beacon", Accounts of Chemical Research, vol. 54, pp. 481-489, 2021. https://doi.org/10.1021/acs.accounts.0c00703
3. H. Rzepa, "No Free C2 Is Involved in the DFT-Computed Mechanistic Model for the Reported Room-Temperature Chemical Synthesis of C2.", 2021. https://doi.org/10.26434/chemrxiv.13560260.v1

In the previous post, I showed the geometries of three large cyclic porphyrins, as part of an article[1] on exploring the aromaticity of large 4n+2 cyclic rings. One of them had been induced into a “figure-eight” or lemniscular conformation, as shown below.

Any initial inspection of the geometries of these systems suggests they have a high level of symmetry, and the molecule above does have the potential for D₂ symmetry, typical of such leminscates.[2] The coordinates provided as part of the article however[1] had no symmetry and in the previous post, I asked myself if the coordinates could be symmetrised. That proved possible for the first two molecules shown, and here I ask myself it it can be done for the molecule shown above. My method for symmetrising was to use the PM7 semi-empirical method.[3] For the first time in the PM-series, this latest extension includes a Grimme-style dispersion attraction correction, one that grows in magnitude with the size of the molecule. Since this is a large molecule (720) atoms, dispersion might well have an important role to play. The coordinates provided[1] were obtained using the LC-ωhPBE/6-31G* method, a functional which in its latest form does not include a built-in dispersion term, although one can be added to the earlier LC-ωPBE version of the functional. We may presume that the calculation used to obtain the coordinates shown above does not include such a dispersion term.

Here is the PM7 optimised version. Firstly, it has C₂-symmetry only and not the higher D₂. The reason is that the four porphyrin rings at the point of the ring crossover, which in the original version show no ring-ring stacking, now indeed show stacking of a pair of porphyrin rings when dispersion is included in the calculation.

Whether such stacking, which does significantly perturb the overall geometry has any impact on the inferred aromaticity, remains to be established. But it reinforces the conclusion that when dealing with large molecules, it is absolutely essential to include a good quality dispersion correction, otherwise the geometries so obtained may differ significantly from reality.

References

1. M. Rickhaus, M. Jirasek, L. Tejerina, H. Gotfredsen, M.D. Peeks, R. Haver, H. Jiang, T.D.W. Claridge, and H.L. Anderson, "Global aromaticity at the nanoscale", Nature Chemistry, vol. 12, pp. 236-241, 2020. https://doi.org/10.1038/s41557-019-0398-3
2. H.S. Rzepa, "A Double-Twist Möbius-Aromatic Conformation of [14]Annulene", Organic Letters, vol. 7, pp. 4637-4639, 2005. https://doi.org/10.1021/ol0518333
3. J.J.P. Stewart, "Optimization of parameters for semiempirical methods VI: more modifications to the NDDO approximations and re-optimization of parameters", Journal of Molecular Modeling, vol. 19, pp. 1-32, 2012. https://doi.org/10.1007/s00894-012-1667-x

Here is another of the “large” molecules in the c&e news shortlist for molecule-of-the-year, 2020. This one is testing the Hückel 4n+2 rule out to a value never before seen (n = 40, or 162 π-electrons).[1] The take-home message is that this rule seems to behave well in predicting global aromaticity even at this sort of scale!

The smallest and largest of the 34 examples for which coordinates are provided are shown below. The smallest example has “only” 300 atoms, whilst the largest has 1008,^‡ which is certainly something for which the wavefunction would be analysed for its NICS aromaticity indices.

A point of interest is the symmetry of these systems. My attempt to “symmetrise” the provided coordinates did not succeed, probably because the structure provided was insufficiently symmetric to succumb to this.^♥ Initially at least it seems the larger “bicycle-wheel” structure might have as much as twelve-fold symmetry, with twelve zinc porphyrin units in the outer ring. But with the coordinates displayed in a rotatable 3D model, I quickly noticed one pyridyl ring acting as a spoke and ringed in red. Its orientation is different from all the others! Is this significant? You decide for yourself by clicking on either of the images above to load the 3D coordinates.

I also include a fascinating Möbius “lemniscular” version, which has a linking number Lk=2 and so also follows the 4n+2 rule.[2],[3]

Postscript A note on symmetrization. If a geometry is approaching symmetry, one can try an automatic algorithm in the molecular display programs to complete the process. But if the symmetry is still some way off, other methods based on energy minimisation must be tried. Molecular Mechanics in this instance is problematic, since all the bond types for the force field to be used must be set, and symmetrically at that. That is a big task. Far better to use a quantum mechanical method, which does not rely on bond types. Given the sizes of the molecules, I here select the PM7 semi-empirical procedure. It can handle in excess of 1000 atoms with no real difficulty and this version of the AM/PM series has the added advantage that it contains a dispersion attraction correction. This might be expected to be important in these types of molecule. Firstly c-P6e6_neutral, for which C₆-symmetry can be achieved. A full PM7 optimisation takes ~10 minutes. This reveals that the distance between adjacent ortho-hydrogen atoms on the pyridyl spoke is 2.21Å, which is typical of a dispersion attraction (and a distance for which inclusion of a dispersion term is vital). The original coordinates have values ranging from 2.7 – 3.4Å.

The symmetrisation of c-P12b12_T6ef to C₆ is also possible using prior PM7 optimisation, with non-bonded H…H contacts now all as pairs of 2.504 and 2.352Å each originating from a different central dendrimer unit. The original coordinates had H…H contacts as short as 1.6Å, which is very unreasonable.

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^‡A common format for expressing coordinates is the so-called MDL Molfile. This has one advantage over the much more simple XYZ file as provided in the supplementary information of the article in that it defines atom and bond types. This in turn sets the coordinates up for a molecular mechanics optimisation of the geometry. But the molfile, which originated decades ago, does not work for molecules with 1000 atoms or more! Why? Because at the top of the file are two indices, the number of atoms and the number of connected bonds. For this molecule, these strings look like 10081128. In other words because each can carry only three integers, they flow together without an intervening space and end up confusing programs. I used the Sybyl Mol2 format for these coordinates, which does not have this issue. ^♥The non-bonded closed H…H contacts are now shown as labels on the 3D model, and you can see for yourself the asymmetry.

References

1. M. Rickhaus, M. Jirasek, L. Tejerina, H. Gotfredsen, M.D. Peeks, R. Haver, H. Jiang, T.D.W. Claridge, and H.L. Anderson, "Global aromaticity at the nanoscale", Nature Chemistry, vol. 12, pp. 236-241, 2020. https://doi.org/10.1038/s41557-019-0398-3
2. S.M. Rappaport, and H.S. Rzepa, "Intrinsically Chiral Aromaticity. Rules Incorporating Linking Number, Twist, and Writhe for Higher-Twist Möbius Annulenes", Journal of the American Chemical Society, vol. 130, pp. 7613-7619, 2008. https://doi.org/10.1021/ja710438j
3. C.S.M. Allan, and H.S. Rzepa, "Chiral Aromaticities. AIM and ELF Critical Point and NICS Magnetic Analyses of Möbius-Type Aromaticity and Homoaromaticity in Lemniscular Annulenes and Hexaphyrins", The Journal of Organic Chemistry, vol. 73, pp. 6615-6622, 2008. https://doi.org/10.1021/jo801022b

The title derives from an article[1] which was shortlisted for the annual c&en molecule of the year 2020 awards (and which I occasionally cover here). In fact this year’s overall theme is certainly large molecules, the one exception being a smaller molecule with a quadruple bond to boron, a theme I have already covered here.

To illustrate a main theme of many of these award-winning molecules, I often look to showing either a computed property (such as each of the localised orbitals for the quadruple bond to boron) or the actual 3D coordinates. In this example, they were there in the supporting information and are presented here as rotatable 3D models without any further transformation. The authors of the article encourage the reader to spot the different types of knot that can be tied in the three molecules reported, but to show how difficult it can be to get a good perception of this, I illustrate the standard journal presentation of a static 2D projection of the 3D structure. It can be a nightmare to try to find the optimum such projection for larger molecules and so often they are reduced to much simpler schematics to get the message across. Well, below you can see three (unoptimized) projections, but you can covert them to 3D form by clicking on the scheme and then select your own projection.

Synthesized molecules with knots and the like have been around since about 1967, but they have certainly come on a pace since then. It would be interesting to see if any have properties unique to knots that have seen spectacular uses!

References

1. D.A. Leigh, F. Schaufelberger, L. Pirvu, J.H. Stenlid, D.P. August, and J. Segard, "Tying different knots in a molecular strand", Nature, vol. 584, pp. 562-568, 2020. https://doi.org/10.1038/s41586-020-2614-0

Cyclopropenylidene must be the smallest molecule to be aromatic due to π-electrons, with just three carbon atoms and two hydrogen atoms. It has now been detected in the atmosphere of Titan, one of Saturn’s moons[1] and joining benzene, another aromatic molecule and the protonated version of cyclopropenylidene, C₃H₃⁺ there.

The molecule has two π-electrons in the three membered ring and a carbene lone pair in the σ-framework. As with the cyclopropenium cation (C₃H₃⁺), these two electrons make it π-aromatic, as indicated by Hückel’s 4n+2 rule (n=0). I thought it might be fun to show the molecular orbitals containing these two pairs of electrons and then to show the result of a double excitation of the carbene lone pair into the π-system to make a anti-aromatic isomer with four π-electrons. This species is a whopping 209.3 kcal/mol higher in free energy, made up of the double electronic excitation energy topped up by conversion of the stabilizing aromaticity into destabilizing anti-aromaticity. Because of this antiaromaticity, the excited state is in fact a second order saddle point, avoiding anti-aromaticity by asymmetric distortion back down to the ground state and resymmetrisation.

Ground state of Cyclopropenylidene
Click to view 3D model of NBO 10	Click to view 3D model of NBO 8
Doubly excited anti-aromatic state of Cyclopropenylidene
Click to view 3D model of NBO 10	Click to view 3D model of NBO 8

It might be a tiny molecule, but to chemists at least it is very interesting in a historical sense at least. Curiously, the astrophysicists describe it as a “complex molecule”!

References

1. C.A. Nixon, A.E. Thelen, M.A. Cordiner, Z. Kisiel, S.B. Charnley, E.M. Molter, J. Serigano, P.G.J. Irwin, N.A. Teanby, and Y. Kuan, "Detection of Cyclopropenylidene on Titan with ALMA", The Astronomical Journal, vol. 160, pp. 205, 2020. https://doi.org/10.3847/1538-3881/abb679

Way back in 2010, I was writing about an experience I had just had during an organic chemistry tutorial, which morphed into speculation as to whether a carbon atom might sustain a quadruple bond to nitrogen. A decade on, and possibly approaching 100 articles by many authors on the topic, quadruple bonds to carbon continue to fascinate. Now an article as appeared[1] repeating this speculation for a carbon to iron quadruple bond, in the very simple species C⩸Fe(CO)₃. This is particularly exciting because of the very real prospect of synthesising this species and perchance getting a crystal structure (something not possible with most of the other quadruply bonded carbon systems studied to date).

They authors report[1] that this sytem is well described by a single-configurational wavefunction and hence that a M062X/Def2-TZVPP calculation is a good description of the bonding. In the article you will find the valence molecular orbitals shown, which by their nature show a lot of delocalisation. Because the more localised NBOs are not shown in the article, I illustrate them here, as 3D rotatable models. The DOI for the calculation can be found at 10.14469/hpc/7537.

CFe(CO)3
NBO 37 π	NBO 36 π
Click to view 3D model of NBO 37	Click to view 3D model of NBO 36
NBO 33 σ	NBO 23 σ
Click to view 3D model of NBO 33	Click to view 3D model of NBO 23

These NBOs show very clearly that the two higher energy orbitals are orthogonal π-bonds to carbon from Fe and the two lower energy orbitals are both σ-bonds to carbon from Fe. Exactly the same picture appears for C₂, which has been often mentioned on this blog.

All that remains is that some inspired synthetic chemist sets out to make C⩸Fe(CO)₃ and to report back on its properties. I fancy the last has not yet been heard about quadruple bonds to carbon!

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Postscript: Here are the analogous orbitals for the species N⩸Mn(CO)₃ to illustrate their evolution across an isoelectronic series.

NMn(CO)3
NBO 35	NBO 34
Click to view 3D model of NBO 35	Click to view 3D model of NBO 34
NBO 33	NBO 20
Click to view 3D model of NBO 33	Click to view 3D model of NBO 20

NBO 33 (the higher in energy of the two σ-type bonds) has an interesting structure. Here it is at a slightly lower threshold:

It has an inner compact σ-bond running along the axis of the bond and an outer “wrap” of different phase. A two layer σ-bond if you like!

References

1. A.J. Kalita, S.S. Rohman, C. Kashyap, S.S. Ullah, and A.K. Guha, "Transition metal carbon quadruple bond: viability through single electron transmutation", Physical Chemistry Chemical Physics, vol. 22, pp. 24178-24180, 2020. https://doi.org/10.1039/d0cp03436c