Efficient prediction of reaction paths through molecular graph and reaction network analysis

Yeonjoon Kim, Jin Woo Kim, Zeehyo Kim and Woo Youn Kim (2017)

Highlighted by Jan Jensen

Figure 2 from the paper. Reproduced under the CC-BY licence.

The paper presents an interesting approach to generating the most important intermediates given reactants and products. 

1. The reactants and products are mapped to atom connectivity (AC) matrices, where the presence and absence of bonds are represented by 1's and 0's. 

2. Intermediates are then enumerated by changing the matrix elements using simple rules and constraints are employed to keep the number of intermediates manageable: the change in bonding is limited to a maximum of two per steps and only changes to bonds involving "active atoms" (atoms with different bonding in reactants and products) are considered. Identifying active atoms involves mapping reactant atoms to product atoms, using the method proposed by Floudas and co-workers.  The AC matrices are converted to SMILES strings and 3D coordinates to ensure that they correspond to chemically reasonable molecules.

3. A reaction network is then constructed by finding intermediates that best connect reactants and products by computing "chemical distances (CDs)" between AC matrices and identifying intermediates with CDs to reactant and product that are similar to the CD between the reactant and product themselves. The CDs are then used to find the shortest path to reactant and product for each intermediate to yields a minimal reaction network.

4. Finally, TSs connecting the structures in the minimal reaction are found using conventional QM methods.

The method is applied to Claisen ester condensation and Cobalt-catalyzed hydroformylation. The method is implemented in a python program called ACE-Reaction but the availability of this program is unclear.  

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

A Zwitterionic, 10 π Aromatic Hemisphere

Hafezi, N.; Shewa, W. T.; Fettinger, J. C.; Mascal, M., Angew. Chem. Int. Ed. 2017, 56, 14141-14144
Contributed by Steven Bacharach

Reposted from Computational Organic Chemistry with permission

The range of aromatic compounds seems limitless. Mascal and co-workers have prepared the azatriquinacene 1 in a remarkably simple fashion.¹ The molecule is a zwitterion, with the carbon atoms forming a 9-center, but 10 π-electron ring, and the quaternary nitrogen sitting above it. The carbon ring satisfies Hückel’s rule (4n+2) and so should be aromatic. The capping nitrogen should help to keep the carbon ring fixed in a shallow bowl.

As expected, the molecule in fact turns out to possess an aromatic 10 π-electron ring. The B3LYP/6-311++G(d,p) geometry is shown in Figure 1. There is little bond alternation among the C-C distances: the mean deviation is only 0.015 Å with the largest difference only 0.024 &Aring. The x-ray crystal structure shows the same trends. The NICS(1) value is -12.31 ppm, larger even than that of benzene (-10.22 ppm).

Figure 1. B3LYP/6-311++G(d,p) geometry of 1.

References

1) Hafezi, N.; Shewa, W. T.; Fettinger, J. C.; Mascal, M., "A Zwitterionic, 10 π Aromatic Hemisphere." Angew. Chem. Int. Ed. 2017, 56, 14141-14144, DOI: 10.1002/anie.201708521.

InChIs

1: InChI=1S/C10H9N/c1-11-8-2-3-9(11)6-7-10(11)5-4-8/h2-7H,1H3
InChIKey=ZXZPLDVSQUVKTH-UHFFFAOYSA-N

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Heavy-Atom Tunneling Calculations in Thirteen Organic Reactions: Tunneling Contributions are Substantial, and Bell’s Formula Closely Approximates Multidimensional Tunneling at ≥250 K

Doubleday, C.; Armas, R.; Walker, D.; Cosgriff, C. V.; Greer, E. M., Angew. Chem. Int. Ed. 2017, 56, 13099-13102
Contributed by Steven Bacharach
Reposted from Computational Organic Chemistry with permission

Though recognized to occur in organic systems, the breadth of involvement of heavy-atom tunneling has not been established. Doubleday, Greer and coworkers have examined 13 simple organic reactions sampling pericyclic reactions, radical rearrangements and S_N2 reactions for heavy-atom tunneling.¹ A few of these reactions are shown below.

Reaction rates were obtained using the small curvature tunneling approximation (SCT), computed using Gaussrate. Reaction surfaces were computed at B3LYP/6-31G*. The tunneling correction to the rate was also estimated using the model developed by Bell: k_Bell = (u/2)/sin(u/2) where u = hν^‡/RT and ν^‡ is the imaginary frequency associated with the transition state. The temperature was chosen so as to give a common rate constant of 3 x 10^-5 s^-1. Interestingly, all of the examined reactions exhibited significant tunneling even at temperatures from 270-350 K (See Table 1). The tunneling effect estimated by Bell’s equation is very similar to that of the more computationally demanding SCT computation.

Table 1. Tunneling contribution to the rate constant

Reaction	% tunneling
	35
	17
	28
	95
CN– + CH3Cl → CH3CN + Cl– (aqueous)	45

This study points towards a much broader range of reactions that may be subject to quantum mechanical tunneling than previously considered.

References

1. Doubleday, C.; Armas, R.; Walker, D.; Cosgriff, C. V.; Greer, E. M., "Heavy-Atom Tunneling Calculations in Thirteen Organic Reactions: Tunneling Contributions are Substantial, and Bell’s Formula Closely Approximates Multidimensional Tunneling at ≥250 K." Angew. Chem. Int. Ed. 2017, 56, 13099-13102, DOI: 10.1002/anie.201708489.

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