Wednesday, June 12, 2019

Vibrational Signatures of Chirality Recognition Between α-Pinene and Alcohols for Theory Benchmarking

Medel, R.; Stelbrink, C.; Suhm, M. A., Angew. Chem. Int. Ed. 2019, 58, 8177
Contributed by Steven Bachrach
Reposted from Computational Organic Chemistry with permission

Can vibrational spectroscopy be used to identify stereoisomers? Medel, Stelbrink, and Suhm have examined the vibrational spectra of (+)- and (-)-α-pinene, (±)-1, in the presence of four different chiral terpenes 2-5.1 They recorded gas phase spectra by thermal expansion of a chiral α-pinene with each chiral terpene.

For the complex of 4 with (+)-1 or (-)-1 and 5 with (+)-1 or (-)-1, the OH vibrational frequency is identical for the two different stereoisomers. However, the OH vibrational frequencies differ by 2 cm-1 with 3, and the complex of 3/(+)-1 displays two different OH stretches that differ by 11 cm-1. And in the case of the complex of α-pinene with 2, the OH vibrational frequencies of the two different stereoisomers differ by 11 cm-1!

The B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1 complexes are shown in Figure 2, and some subtle differences in sterics and dispersion give rise to the different vibrational frequencies.


Figure 2. B3LYP-D3(BJ)/def2-TZVP optimized geometry of the 2/(+)-1 and 2/(-)-1

Of interest to readers of this blog will be the DFT study of these complexes. The authors used three different well-known methods – B3LYP-D3(BJ)/def2-TZVP, M06-2x/def2-TZVP, and ωB97X-D/def2-TZVP – to compute structures and (most importantly) predict the vibrational frequencies. Interestingly, M06-2x/def2-TZVP and ωB97X-D/ def2-TZVP both failed to predict the vibrational frequency difference between the complexes with the two stereoisomers of α-pinene. However, B3LYP-D3(BJ)/def2-TZVP performed extremely well, with a mean average error (MAE) of only 1.9 cm-1 for the four different terpenes. Using this functional and the larger may-cc-pvtz basis set reduced the MAE to 1.5 cm-1 with the largest error of only 2.5 cm-1.

As the authors note, these complexes provide some fertile ground for further experimental and computational study and benchmarking.


1. Medel, R.; Stelbrink, C.; Suhm, M. A., “Vibrational Signatures of Chirality Recognition Between α-Pinene and Alcohols for Theory Benchmarking.” Angew. Chem. Int. Ed. 201958, 8177-8181, DOI: 10.1002/anie.201901687.


(-)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m0/s1
(+)-1, (-)-α-pinene: InChI=1S/C10H16/c1-7-4-5-8-6-9(7)10(8,2)3/h4,8-9H,5-6H2,1-3H3/t8-,9-/m1/s1
2, (-)borneol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(9,3)8(11)6-7/h7-8,11H,4-6H2,1-3H3/t7-,8+,10+/m0/s1
3, (+)-fenchol: InChI=1S/C10H18O/c1-9(2)7-4-5-10(3,6-7)8(9)11/h7-8,11H,4-6H2,1-3H3/t7-,8-,10+/m0/s1
4, (-1)-isopinocampheol: InChI=1S/C10H18O/c1-6-8-4-7(5-9(6)11)10(8,2)3/h6-9,11H,4-5H2,1-3H3/t6-,7+,8-,9-/m1/s1
5, (1S)-1-phenylethanol: InChI=1S/C8H10O/c1-7(9)8-5-3-2-4-6-8/h2-7,9H,1H3/t7-/m0/s1

This work is licensed under a Creative Commons Attribution-NoDerivs 3.0 Unported License.

Wednesday, May 29, 2019

Activity-Based Screening of Homogeneous Catalysts through the Rapid Assessment of Theoretically Derived Turnover Frequencies

Matthew D. Wodrich, Boodsarin Sawatlon, Ephrath Solel, Sebastian Kozuch, and Clémence Corminboeuf (2019)
Highlighted by Jan Jensen

Figure 1. Adapted from images in the preprint posted under the CC-BY-NC-ND 4.0 license

LFESRs linearly relate the reaction energies of barrier heights to a single reaction energy. In this work the all the barriers and reaction energies in Figure 1a is computed via the free energy difference between 1 and 4 [ΔG(4)]

The volcano plot is then obtained by plotting the largest free energy difference in the cycle as a function of ΔG(4). In this particular case that is the barrier between 1 and 4 when ΔG(4) is small and the energy difference between 2 and 3 when  ΔG(4) is large. The optimum catalysts is the one with a ΔG(4) for which these two lines meet and one can screen for such catalyst by computing a single free energy difference.

One problem with thus approach is that the largest free energy difference in the cycle is not always directly related to the turn over frequency (TOF), which is what is measured experimentally. In principle, the TOF should be determined by microkinetic modeling for each value of ΔG(4) to find the maximum TOF. But in this work TOFs are efficiently estimated by the energy span model, which basically considers all energy differences in the cycle (e.g. also between 1 and 3).

Using the TOF plot different energy differences between important and the optimum ΔG(4) value decreases (Figure 1b). The points in Figure 1b show the corresponding TOFs computed without the LFESRs and demonstrate the accuracy of this approach.

Monday, April 29, 2019

Exploration of Chemical Compound, Conformer, and Reaction Space with Meta-Dynamics Simulations Based on Tight-Binding Quantum Chemical Calculations

Highlighted by Jan Jensen

The paper describes a new way to search for conformers, chemical reactions, and estimate barriers using the semiempirical GFNn-XTB method using meta-dynamics. A force term is included that scales exponentially with the Cartesian RMSD from previously found structures, thereby forcing the MD explore new areas of phase space. For simulations with more than one molecule it is necessary to add a constraining potential so that the RMSD cannot be increased simply by increasing the distance between molecules. Each individual MD can be relatively short and most of the CPU time is actually spend on energy minimising the snapshots that are saved.

The results depend on a few hyperparameters, so several MD simulations with different values are run in parallel. Because of the extra force the temperature is also a hyperparameters so the method doesn't necessarily tell you what reactions are most likely to occur at, say, 300K.

The conformational search is tested on 22 (mostly) organic molecules and includes the GFN2-xTB energies of the lowest energy conformer for each molecules. This is a valuable benchmark set for other conformational search algorithms designed to find the global minimum.

This work is licensed under a Creative Commons Attribution 4.0 International License.

Wednesday, April 10, 2019

Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity

Xue, X.-S.; Jamieson, C. S.; Garcia-Borràs, M.; Dong, X.; Yang, Z.; Houk, K. N., J. Am. Chem. Soc. 2019, 141, 1217
Contributed by Steven Bachrach
Reposted from Computational Organic Chemistry with permission

A major topic of this blog has been the growing body of studies that demonstrate that dynamic effects can control reaction products (see these posts). Often these examples crop up with valley ridge inflection points. Another cause can be bispericyclic transition states, first discovered by Caramello et al for the dimerization of cyclopentadiene.1 The Houk group now reports on the first trispericyclic transition state.2

Using ωB97X-D/6-31G(d), they examined the reaction of the tropone derivative 1 with dimethylfulvene 2. Three possible products can arrive from different pericyclic reactions: 3, the [4+6] product; 4, the [6+4] product; and 5, the [8+2] product. The thermodynamic product is predicted to be 5, but it is only 1.2 kcal mol-1 lower in energy than 4 and 6.2 kcal mol-1 lower than 3.

They identified one transition state originating from the reactants TS1. Hypothesizing that it would be trispericyclic, they performed a molecular dynamics study with trajectories starting from TS1. They ran a total of 142 trajectories, and 87% led to 3, 3% led to 4, and 3% led to 5. This demonstrates the unusual nature of TS1 and the dynamic effects on this reaction surface.



Figure 1. ωB97X-D/6-31G(d) optimized geometries of TS1-TS3.

Additionally, there are two different Cope rearrangements (through TS2 and TS3) that convert 3 into 4 and 5. Some trajectories can pass from TS1 and then directly through either TS2 or TS3 and these give rise to products 4 and 5. In other words, some trajectories will pass from a trispericyclic transition state and then through a bispericyclic transition state before ending in product.


1. Caramella, P.; Quadrelli, P.; Toma, L., “An Unexpected Bispericyclic Transition Structure Leading to 4+2 and 2+4 Cycloadducts in the Endo Dimerization of Cyclopentadiene.” J. Am. Chem. Soc. 2002124, 1130-1131, DOI: 10.1021/ja016622h
2. Xue, X.-S.; Jamieson, C. S.; Garcia-Borràs, M.; Dong, X.; Yang, Z.; Houk, K. N., “Ambimodal Trispericyclic Transition State and Dynamic Control of Periselectivity.” J. Am. Chem. Soc. 2019141, 1217-1221, DOI: 10.1021/jacs.8b12674.


1: InChI=1S/C10H6N2/c11-7-10(8-12)9-5-3-1-2-4-6-9/h1-6H
2: InChI=1S/C8H10/c1-7(2)8-5-3-4-6-8/h3-6H,1-2H3
3: InChI=1S/C18H16N2/c1-11(2)17-15-7-8-16(17)14-6-4-3-5-13(15)18(14)12(9-19)10-20/h3-8,13-16H,1-2H3
4: InChI=1S/C18H16N2/c1-18(2)13-6-8-14(12(10-19)11-20)15(9-7-13)16-4-3-5-17(16)18/h3-9,13,15-16H,1-2H3
5: InChI=1S/C18H16N2/c1-12(2)13-8-9-16-17(13)14-6-4-3-5-7-15(14)18(16,10-19)11-20/h3-9,14,16-17H,1-2H3/t14?,16-,17-/m1/s1

This work is licensed under a Creative Commons Attribution-NoDerivs 3.0 Unported License.

Wednesday, March 27, 2019

A Universal Density Matrix Functional from Molecular Orbital-Based Machine Learning: Transferability across Organic Molecules

Highlighted by Jan Jensen

Figure 3c from the paper, showing results for MP2 correlation energies

Some years ago I wrote about the ∆-ML approach where ML is used to estimate the energy difference between expensive and cheap methods based on the molecular structure. I remember wondering at the time whether additional information could be extracted from the cheap method and used as descriptors. 

This has now been tested for correlation energies and it does indeed lead to a significant improvement in accuracy. The method uses Fock, Coulomb, and exchange matrix elements in an LMO basis (which makes me wonder why it's called a density matrix functional) and Gaussian process regression (GPR) to machine learn the LMO contributions to MP2, CCSD, and CCSD(T) correlation energies.

Using just 140 molecules with 7 heavy atoms the MOB-ML method can be trained to give reasonably accurate results for molecules with 13 heavy atoms (see figure above), and offer a significant improvement over the ∆-ML approach. An MAE of 0.25 mH/heavy atom translates into an MAE of roughly 2 kcal/mol for a molecule with 13 heavy atoms, which can translate into 4 kcal/mol ∆E-errors depending on the sign, so the method may not be quite accurate enough for many purposes yet. Unfortunately, it doesn't look like training on more molecules leads to additional improvements for transferability to larger molecules, but this is definitely a promising step in the right direction.

Planar rings in nano-Saturns and related complexes

Bachrach, S. M., Chem. Commun. 2019, 55, 3650-3653
Contributed by Steven Bacharach
Reposted from Computational Organic Chemistry with permission

For the past twelve years, I have avoided posting on any of my own papers, but I will stoop to some shameless promotion to mention my latest paper,1 since it touches on some themes I have discussed in the past.

Back in 2011, Iwamoto, et al. prepared the complex of C60 1 surrounded by [10]cycloparaphenylene 2 to make the Saturn-like system 3.2 Just last year, Yamamoto, et al prepared the Nano-Saturn 5a as the complex of 1 with the macrocycle 4a.3 The principle idea driving their synthesis was to utilize a ring that is flatter than 2. The structures of 3 and 5b (made with the parent macrocycle 4b) are shown in side view in Figure 1, and clearly seen is the achievement of the flatter ring.



Figure 1. Computed structures of 3, 5, and 7.

However, the encompassing ring is not flat, with dihedral angles between the anthrenyl groups of 35°. This twisting is due to the steric interactions of the ortho-ortho’ hydrogens. A few years ago, my undergraduate student David Stück and I suggested that selective substitution of a nitrogen for one of the C-H groups would remove the steric interaction,4 leading to a planar poly-aryl system, such as making twisted biphenyl into the planar 2-(2-pyridyl)-pyridine (Scheme 1)

Scheme 1.

Following this idea leads to four symmetrical nitrogen-substituted analogues of 4b; and I’ll mention just one of them here, 6.

As expected, 6 is perfectly flat. The ring remains flat even when complexed with (as per B3LYP-D3(BJ)/6-31G(d) computations), see the structure of 7 in Figure 1.

I also examined the complex of the flat macrocycle 6 (and its isomers) with a [5,5]-nanotube, 7. The tube bends over to create better dispersion interaction with the ring, which also become somewhat non-planar to accommodate the tube. Though not mentioned in the paper, I like to refer to 7 as Beyoncene, in tribute to All the Single Ladies.
Figure 2. Computed structure of 7.

My sister is a graphic designer and she made this terrific image for this work:


1. Bachrach, S. M., “Planar rings in nano-Saturns and related complexes.” Chem. Commun. 201955, 3650-3653, DOI: 10.1039/C9CC01234F.
2. Iwamoto, T.; Watanabe, Y.; Sadahiro, T.; Haino, T.; Yamago, S., “Size-Selective Encapsulation of C60 by [10]Cycloparaphenylene: Formation of the Shortest Fullerene-Peapod.” Angew. Chem. Int. Ed. 201150, 8342-8344, DOI: 10.1002/anie.201102302
3. Yamamoto, Y.; Tsurumaki, E.; Wakamatsu, K.; Toyota, S., “Nano-Saturn: Experimental Evidence of Complex Formation of an Anthracene Cyclic Ring with C60.” Angew. Chem. Int. Ed. 2018 57, 8199-8202, DOI: 10.1002/anie.201804430.
4. Bachrach, S. M.; Stück, D., “DFT Study of Cycloparaphenylenes and Heteroatom-Substituted Nanohoops.” J. Org. Chem. 201075, 6595-6604, DOI: 10.1021/jo101371m


4b: InChI=1S/C84H48/c1-13-61-25-62-15-3-51-33-75(62)43-73(61)31-49(1)50-2-14-63-26-64-16-4-52(34-76(64)44-74(63)32-50)54-6-18-66-28-68-20-8-56(38-80(68)46-78(66)36-54)58-10-22-70-30-72-24-12-60(42-84(72)48-82(70)40-58)59-11-23-71-29-69-21-9-57(39-81(69)47-83(71)41-59)55-7-19-67-27-65-17-5-53(51)35-77(65)45-79(67)37-55/h1-48H
6: InChI=1S/C72H36N12/c1-2-38-14-44-20-45-25-67(73-31-50(45)13-37(1)44)57-9-4-39-15-51-32-74-68(26-46(51)21-61(39)80-57)58-10-5-40-16-52-33-75-69(27-47(52)22-62(40)81-58)59-11-6-41-17-53-34-76-70(28-48(53)23-63(41)82-59)60-12-7-42-18-54-35-77-71(29-49(54)24-64(42)83-60)72-78-36-55-19-43-3-8-56(38)79-65(43)30-66(55)84-72/h1-36H

This work is licensed under a Creative Commons Attribution-NoDerivs 3.0 Unported License.

Thursday, March 21, 2019

More DFT benchmarking

Contributed by Steven Bacharach
Reposted from Computational Organic Chemistry with permission

Selecting the appropriate density functional for one’s molecular system at hand is often a very confounding problem, especially for non-expert or first-time users of computational chemistry. The DFT zoo is vast and confusing, and perhaps what makes the situation worse is that there is no lack of benchmarking studies. For example, I have made more than 30 posts on benchmark studies, and I made no attempt to be comprehensive over the past dozen years!

One such benchmark study that I missed was presented by Mardirossian and Head-Gordon in 2017.1 They evaluated 200 density functional using the MGCDB84 database, a combination of data from a number of different groups. They make a series of recommendations for local GGA, local meta-GGA, hybrid GGA, and hybrid meta-GGA functionals. And when pressed to choose just one functional overall, they opt for ωB97M-V, a range-separated hybrid meta-GGA with VV10 nonlocal correlation.

Georigk and Mehta2 just recently offer a review of the density functional zoo. Leaning heavily on benchmark studies using the GMTKN553 database, they report a number of observations. Of no surprise to readers of this blog, their main conclusion is that accounting for London dispersion is essential, usually through some type of correction like those proposed by Grimme.

These authors also note the general disparity between the most accurate, best performing functional per the benchmark studies and the results of the DFT poll conducted for many years by Swart, Bickelhaupt and Duran. It is somewhat remarkable that PBE or PBE0 have topped the poll for many years, despite the fact that many newer functionals perform better. As always, when choosing a functional caveat emptor.


1.  Mardirossian, N.; Head-Gordon, M., “Thirty years of density functional theory in computational chemistry: an overview and extensive assessment of 200 density functionals.” Mol. Phys. 2017115, 2315-2372, DOI: 10.1080/00268976.2017.1333644.
2. Goerigk, L.; Mehta, N., “A Trip to the Density Functional Theory Zoo: Warnings and Recommendations for the User.” Aust. J. Chem. 2019, ASAP, DOI: 10.1071/CH19023.
3. Goerigk, L.; Hansen, A.; Bauer, C.; Ehrlich, S.; Najibi, A.; Grimme, S., “A look at the density functional theory zoo with the advanced GMTKN55 database for general main group thermochemistry, kinetics and noncovalent interactions.” Phys. Chem. Chem. Phys. 201719, 32184-32215, DOI: 10.1039/C7CP04913G.

This work is licensed under a Creative Commons Attribution-NoDerivs 3.0 Unported License.

Tuesday, March 19, 2019

Artificial Intelligence Assists Discovery of Reaction Coordinates and Mechanisms from Molecular Dynamics Simulations

Contributed by Jesper Madsen

Here, I highlight a recent preprint describing an application of Artificial Intelligence/Machine Learning (AI/ML) methods to problems in computational chemistry and physics. The group previously published the intrinsic map dynamics (iMapD) method, which I also highlighted here on Computational Chemistry Highlights. The basic idea in the previous study was to use an automated trajectory-based approach (as opposed to a collective variable-based approach) to explore the free-energy surface a computationally expensive Hamiltonian that describes a complex biochemical system.

Fig 1: Schematic flow chart of the AI-assisted MD simulation algorithm.

The innovation in their current approach is the combination of the sampling scheme, statistical inference, and deep learning to construct a framework where sampling and mechanistic interpretation happens simultaneously – an important milestone towards completely “autonomous production and interpretation of MD simulations of rare events,” as the authors themselves remark.

It is reassuring to see that the method correctly identifies known results for benchmark cases (the alanine dipeptide and LiCl dissociation) and out-competes traditional approaches such as transition path sampling in terms of efficiency. In these simple model cases, however, complexity is relatively low and sampling is cheap. I will be looking forward to seeing the method applied to a much more complex problem in the future; E.g. a problem where ergodicity is a major issue other challenges, such as hysteresis, plays a significant role.

Another much appreciated aspect of general interest in this paper that I am emphasizing is the practical approach to interpretation of the constructed neural networks. All in all, there are many useful comments and observations in this preprint and I would recommend reading it thoroughly for those who seek to use modern AI-based methods on molecular simulations.

Wednesday, February 27, 2019

Ultra-large library docking for discovering new chemotypes

Jiankun Lyu, Sheng Wang, Trent E. Balius, Isha Singh, Anat Levit, Yurii S. Moroz, Matthew J. O’Meara, Tao Che, Enkhjargal Algaa, Kateryna Tolmachova, Andrey A. Tolmachev, Brian K. Shoichet, Bryan L. Roth & John J. Irwin (2019)
Highlighted by Jan Jensen

Figure 3a from the paper. (c) Nature

This paper has already been thoroughly highlighed several places, such as here and here, so I'll just summarise what the main take-home messages are for me.
  • The size of the libraries (99 and 138 million) that are screened are truly impressive, especially when you realise that they sampled 280 conformations for each molecule! This required 1.2 calendar days on 1,500 cores.
  • The libraries where made from 70,000 commercially available building blocks, which where combined using 130 known reactions. The molecules in the library should therefore be easy to synthesise
  • Indeed, for one target they selected 589 molecules for synthesis and successfully made 549, for which they measured affinities.
  • The selected molecules spanned the whole range of docking score, which results in a thorough test of the accuracy. As shown in the figure above, the scores can only really be used to weed out the very weak binders.
  • As Derek Lowe notes "That definitely argues for setting up these virtual libraries according to expected ease of synthesis, because otherwise you could spend a lot of time making tough compounds that don’t do anything. People have."
Very commendably, the authors have made the libraries available as a public database.

This work is licensed under a Creative Commons Attribution 4.0 International License.


Xiao, Y.; Mague, J. T.; Schmehl, R. H.; Haque, F. M.; Pascal Jr., R. A., Angew. Chem. Int. Ed. 2019, 58, 2831-2833
Contributed by Steven Bacharach
Reposted from Computational Organic Chemistry with permission

The Pascal group has synthesized dodecaphenyltetracene 1.1

While this paper has little computational work, it is of interest to readers of this blog since I have discussed many aspect of aromaticity. This new tetracene is notable for its large twisting along the tetracene axis: about 97° in the x-ray structure. I have optimized the structure of 1 at B3LYP-D3(BJ)/6-311G(d) and its structure is shown in Figure 1. It is twisted by about 94°. The computed and x-ray structures are quite similar, as seen in Figure 2. Here the x-ray structure is shown with red balls, the computed structure with gray balls, and hydrogens have been removed for clarity.

Figure 1. B3LYP-D3(BJ)/6-311G(d) optimized structure of 1.

Figure 2. Comparison of the x-ray (red) and computed (gray) structures of 1. (Hydrogens omitted for clarity.)

The authors note that this molecule is chiral, having near D2 symmetry. (The optimized structure has D2symmetry.) They performed AM1 computations to estimate a very low barrier for racemization of only 17.3 kcal mol-1, leading to a half-life of less than one second at RT.

A notable aspect of the molecule is that aromaticity can adapt to significant twisting yet retain aromatic character. For example, the molecule is stable even surviving boiling off of chloroform (61 °C) to form crystals and the majority of the C-C bonds in the tetracene portion have distances typical of aromatic systems (~1.4 Å).


1) Xiao, Y.; Mague, J. T.; Schmehl, R. H.; Haque, F. M.; Pascal Jr., R. A., “Dodecaphenyltetracene.” Angew. Chem. Int. Ed. 201958, 2831-2833, DOI: 10.1002/anie.201812418.


1: InChI=1S/C90H60/c1-13-37-61(38-14-1)73-74(62-39-15-2-16-40-62)78(66-47-23-6-24-48-66)86-82(70-55-31-10-32-56-70)90-84(72-59-35-12-36-60-72)88-80(68-51-27-8-28-52-68)76(64-43-19-4-20-44-64)75(63-41-17-3-18-42-63)79(67-49-25-7-26-50-67)87(88)83(71-57-33-11-34-58-71)89(90)81(69-53-29-9-30-54-69)85(86)77(73)65-45-21-5-22-46-65/h1-60H

This work is licensed under a Creative Commons Attribution-NoDerivs 3.0 Unported License.

Wednesday, January 30, 2019

Discovery of conical intersection mediated photochemistry with growing string methods

Cody Aldaz, Joshua A. Kammeraad and Paul M. Zimmerman (2018)
Highlighted by Jan Jensen

Photochemistry is becoming an increasing important synthetic tool but is significantly harder to study computationally than thermal chemistry. Zimmerman and co-workers have developed a new tool that promises to help change that.

The method uses a growing string method (usually used to find TSs) to locate minimum energy conical intersections (MECI), the lowest energy point where the excited state PES intersects the ground state PES. Ground state geometry optimisation starting from the MECI structures are then used to identify the products of the photochemical reaction. Crucially, the method doesn't just find the MECI closest to the reactant structure, but considers several search directions.

One has to define a driving coordinate but this can be automatically determined by generating several possible products, e.g. using Zimmerman's ZStruct method. As far as I know the molecule is not in thermal equilibrium on the excited state PES, so I am not sure one can use the relative energies of the MECIs to predict a product distribution.  Still, an important step forward.

This work is licensed under a Creative Commons Attribution 4.0 International License.

Saturday, January 26, 2019

Exceptionally Long C−C Single Bonds in Diamino-o-carborane as Induced by Negative Hyperconjugation

Li, J.; Pang, R.; Li, Z.; Lai, G.; Xiao, X.-Q.; Müller, T., Angew. Chem. Int. Ed. 2019, 58, 1397-1401
Contributed by Steven Bacharach
Reposted from Computational Organic Chemistry with permission

Chemists are constantly checking the limits of theories, and the limits of bonding is one that has been subject to many tests of late. I have posted on two recent papers (herehere) that probe just how long a C-C bond can be, and now Li, Müller, and co-workers report a structure that pushes that limit even further out.1

They prepared and obtained the x-ray structure of five derivatives of o-carborane, namely compounds 12a3a3b and 4. In all of these, the C-C bond in the carborane is stretched well beyond that of a typical C-C bond (see Table 1). The longest case is in 3b where the C-C bond length is a whopping 1.931 Å (see Figure 1), which obliterates the previous record holder at 1.798 Å.2 B3PW91-D3/cc-pVTZ computations corroborate these structures and the long C-C bond.

Scheme 1: Carboranes with long C-C bonds (highlighted in blue)
Table 1. C-C bond distance (Å)
cmpdr(C-C) exptr(C-C) DFT
Figure 1. B3PW91-D3/cc-pVTZ optimized structure of 3b.

Topological electron density analysis locates a bond path between the two carbons in all five structures. The Wiberg bond index is small, with a value of only 0.34 in 3b. Natural bond orbital (NBO) analysis identifies a negative hyperconjugation interaction between the nitrogen lone pair and the σ*C-C orbital. This rationalizes both the very long C-C bond and the very short C-N bonds, and the trends associated with the variation between 1° amine, 2° amine and imine.


1. Li, J.; Pang, R.; Li, Z.; Lai, G.; Xiao, X.-Q.; Müller, T., “Exceptionally Long C−C Single Bonds in Diamino-o-carborane as Induced by Negative Hyperconjugation.” Angew. Chem. Int. Ed. 201958, 1397-1401, DOI: 10.1002/anie.201812555.
2. Ishigaki, Y.; Shimajiri, T.; Takeda, T.; Katoono, R.; Suzuki, T., “Longest C–C Single Bond among Neutral Hydrocarbons with a Bond Length beyond 1.8 Å.” Chem 20184, 795-806, DOI: 10.1016/j.chempr.2018.01.011.


3b: InChI=1S/C22H28B10N2/c1-13-7-15(3)19(16(4)8-13)11-33-21-22(34-12-20-17(5)9-14(2)10-18(20)6)25(21)23-27(21)24-30(23,25)28(22,25)29(22)26(21,22,27)31(24,27,29)32(24,28,29)30/h7-10,33-34H,11-12H2,1-6H3

This work is licensed under a Creative Commons Attribution-NoDerivs 3.0 Unported License.

Monday, January 21, 2019

Understanding Combustion of H/O Gases inside Nanobubbles Generated by Water Electrolysis Using Reactive Molecular Dynamic Simulations.

S. Jain and L. Qiao, The Journal of Physical Chemistry A,122, 5261 2018
Highlighted by Tina Mihm, Colleen Lasar, Matthew Emerson

Abstract Image

It was found (by accident) that nanobubbles containing both H2 and O2 gas would form during the electrolysis of water and spontaneously combust. This is surprising because at smaller scales, the surface-to-volume ratio is large enough that heat loss becomes a real factor when trying to create and sustain a combustion reaction. Jain et al. believe this nanobubble combustion reaction is due to the low temperature and high pressure zone that takes place in the bubble. The initial thought with this discovery was that the combustion reaction inside said nanobubbles could be used to produce energy. However, most of the temperature from the reaction was found to be lost to the walls of the bubbles indicating low energy yields.

The reaction mechanism is as follows: 2 H2(g) + O2(g)  →  2 H2O(g). Both experimental and older computational methods have looked into the temperature changes and kinetics of this reaction, however, the mechanism has not been looked into in detail. Jain et al. uses molecular dynamic simulations to explore the mechanism of this phenomenon. They explored the characteristics of H2/O2 reactions at high pressure and low temperature as a function of Hydrogen radical concentration and found that H2O2 was the dominant species produced instead of the expected H2O.

In the simulations, they used a force field designed specifically to investigate the reaction kinetics of H2/O2 system at high pressures and low temperatures. Specifically, the first-principles derived reactive force field ReaxFF was employed, as implemented in the open-source molecular dynamics simulation code LAMMPS.  After thermalizing the system to 300 K with a Nose-Hoover thermostat, production runs  of 100 fs were carried out, using a 0.1 fs time step. The model was then validated using existing more generalized force fields that were not designed for the H2/O2 system. They also found that increasing the concentration of H radical or the system pressure increased reactivity. While this result was initially thought to be able to increase energy output, it was found that most of the energy from the reaction was found to be lost to the walls of the combustion chamber. If this happened in an automobile, the engine would become so hot that the hood would melt off.

In conclusion, it was found that hydrogen and oxygen gas in nano bubbles formed during electrolysis of water and would spontaneously combust. The mechanism for this reaction was investigated using reactions at high pressure and low temperature as a function of Hydrogen radical concentration and found that H2O2 was the dominant species produced instead of the expected H2O. The increase in reactivity due to increased pressure and H radical concentration during simulation was thought to increase energy output, and, therefore, create a source of clean energy. However, further computational simulations found that most of the heat was lost to the walls of the bubbles, greatly decreasing energy output, making a lousy nano-engine.

Thursday, January 17, 2019

SERS, XPS and DFT investigation on palladium surfaces coated with 2,2′-bipyridine monolayers

M. Muniz-Miranda, F. Miranda-Muniz, S. Caporali, N. Calisi, P. Alfonso, Applied Surface Science, 457, 98-103 2018
Highlighted by Michaella Raglione, Sajeewani Kumarage, and Glorianne Dorce

Palladium (II) chloride complexes containing diimine ligands like what is shown in Figure 1 have been widely used as a reaction catalyst. One application of a palladium catalyst is the Heck reaction, which utilizes a Palladium (II) complex intermediate to activate the reaction of an unsaturated halide with an alkene in the presence of a base. Often, palladium is used in a suspension, but it lacks the colloidal stability to maintain a homogeneous mixture, which can lower its efficiency. Furthermore, heterogenous catalysis provides high yield, and facilitates the reusability of catalysts compared to homogeneous catalysis. Thus, Muniz-Miranda et al. recently investigated the use of Palladium coated with 2,2’-bipyridine monolayers for heterogenous catalysis.

Figure 1. Crystal structure of byp-PdCl2 from Table S1 supplementary material.

Their experiments centered around Palladium plate which was wetted with 2,2’-bipyridine (bpy). In order to test their work, Muniz-Miranda et al. utilized the surface plasmon effect of Ag nanoparticles (nps) to enhance their surface enhance Raman signal (SERS). The Ag nps were obtained through laser ablation in the bpy solution without free chloride anions. To determine the resulting complex, DFT calculations were performed using GAUSSIAN 09 software with a B3LYP/6-311++G(d,p) for non-metal atoms, and Lanl2DZ for palladium basis sets. To ensure their experimental methods would work, byp-PdCl2 was collected and the Raman spectra was compared to the calculated spectra.

Muniz-Miranda et al.  have made bpy-PdX, and by comparing the resulting calculated Raman active modes to the experimental bpy-PdR (R=O,O2,(OH)2)  revealed that they created bpy-Pd(OH)2.

Due to similar structural and spectroscopic characteristics of the bpy-Pd(OH)2 and bpy-PdCl2, the catalysts are expected to function similarly. The similarities in these catalysts opens the possibility of utilization of the much simpler heterogenous nucleation of the bpy-Pd(OH)2 complex for reaction mechanisms. This suggests that combined benefits of both heterogenous and homogenous nucleation can be achieved: improved yield and reusability as well as selectivity control.