Chapter 6. Quantum Chemical Topology: on Descriptors, Potentials and Fragments

J. Chem. Theory Comput.

2014

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Present computing power enables novel ways of modeling polarization. Here we show that the machine learning method kriging accurately captures the way the electron density of a topological atom responds to a change in the positions of the surrounding atoms. The success of this method is demonstrated on the four aromatic amino acids histidine, phenylalanine, tryptophan, and tyrosine. A new technique of varying training set sizes to vastly reduce training times while maintaining accuracy is described and applied to each amino acid. Each amino acid has its geometry distorted via normal modes of vibration over all local energy minima in the Ramachandran map. These geometries are then used to train the kriging models. Total electrostatic energies predicted by the kriging models for previously unseen geometries are compared to the true energies, yielding mean absolute errors of 2.9, 5.1, 4.2, and 2.8 kJ mol(-1) for histidine, phenylalanine, tryptophan, and tyrosine, respectively.

Section: Background and Methodsmentioning

confidence: 99%

Section: Background and Methodsmentioning

confidence: 99%

Prediction of Intramolecular Polarization of Aromatic Amino Acids Using Kriging Machine Learning

Fletcher

Davie

J. Chem. Theory Comput.

2014

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“…To summarize, an authentic understanding of the cause of the gauche effect in 1,2-difluoroethane can be obtained from IQA and QTAIM. Both approaches share the idea of real-space partitioning by a gradient vector field, which together are part of the overarching approach of quantum chemical topology (QCT). − IQA has been successfully used to gain meaningful insight into a growing number of chemical systems ranging from proton-transfer reactions to intramolecular bond paths between electronegative atoms to hydrogen–hydrogen interactions with respect to the torsional barrier in biphenyl over short-range electrostatic potentials across torsional barriers to CO 2 trapping by adduct formation, atom–atom repulsion, and the diastereoselective allylation of aldehydes, to name a few.…”

Section: Introductionmentioning

confidence: 99%

Fluorine Gauche Effect Explained by Electrostatic Polarization Instead of Hyperconjugation: An Interacting Quantum Atoms (IQA) and Relative Energy Gradient (REG) Study

Thacker

2018

J. Phys. Chem. A

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We present an interacting quantum atoms (IQA) study of the gauche effect by comparing 1,2-difluoroethane, 1,2-dichloroethane, and three conformers of 1,2,3,4,5,6-hexafluorocyclohexane. In the 1,2-difluoroethane, the gauche effect is observed in that the gauche conformation is more stable than the anti, whereas in 1,2-dichloroethane the opposite is true. The analysis performed here is exhaustive and unbiased thanks to using the recently introduced relative energy gradient (REG) method [ Thacker , J. C. R. ; Popelier , P. L. A. Theor. Chem. Acc . 2017 , 136 , 86 ], as implemented in the in-house program ANANKE. We challenge the common explanation that hyperconjugation is responsible for the gauche stability in 1,2-difluoroethane and instead present electrostatics as the cause of gauche stability. Our explanation of the gauche effect is also is seen in other molecules displaying local gauche conformations, such as the recently synthesized "all-cis" hexafluorocyclohexane and its conformers where all the fluorine atoms are in the equatorial positions. Using our extension of the traditional IQA methodology that allows for the partitioning of electrostatic terms into polarization and charge transfer, we propose that the cause of gauche stability is 1,3 C···F electrostatic polarization interactions. In other words, if a number of fluorine atoms are aligned, then the stability due to polarization of nearby carbon atoms is increased.

“…This approach capitalises on the fact that the electron density of any system (molecule or assembly thereof, or condensed matter) naturally falls apart into space-filling atoms, only by applying the gradient vector to the electron density. All approaches that extract (chemically useful) information from the wave function, using only the gradient vector operating on a corresponding property density, are bundled under the name quantum chemical topology (QCT) [20,21]. To date, there are at least ten approaches [17] that resort under the umbrella of QCT.…”

Section: Introductionmentioning

confidence: 99%

The ANANKE relative energy gradient (REG) method to automate IQA analysis over configurational change

Thacker

2017

Theor Chem Acc

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dimer). Although applied only for the water dimer in this work, the method is general and able to explain the gauche effect, the torsional barrier in biphenyl, the arrow-pushing scheme of an enzymatic reaction (peptide hydrolysis in the HIV-1 Protease active site), and halogen-alkane nucleophilic substitution (S N 2) reactions. Those applications will appear elsewhere as separate and elaborated case studies; here we focus on the details of the ANANKE method and its justification, using the water dimer as a concrete case.