Global and local reactivity descriptors based on quadratic and linear energy models for α,β‐unsaturated organic compounds

Abstract

Global and local descriptors of chemical reactivity can be derived from conceptual density functional theory. Their explicit form, however, depends on how the energy is defined as a function of the number of electrons. Within the existing interpolation models, here, the quadratic and the linear energy model were used to derive global descriptors as the electrophilicity and nucleophilicity (defined as the negative of the ionization potential) and local descriptors employing either the corresponding condensed Fukui function in the linear model or the local response of the global descriptor in the quadratic model. The ability of these descriptors to predict the reactivity of molecules with more than one reactive site was first studied on a set of α, β-unsaturated ketones, where experimental rate constants for the nucleophilic attack is known. With the validated descriptors the reactivity of α, β-unsaturated carboxylic compounds with different heteroatoms as α, β-unsaturated thioesters, esters, and amides was addressed as alternative substrates for enzymatic CO 2 fixation.Carbon dioxide fixation involves the reduction of the neutral α, β-unsaturated carboxylic compounds by a nucleophilic attack of a hydride anion from NADPH and the following electrophilic attack by carbon dioxide. It was found that condensed values of the linear Fukui function within the fragment of molecular response approximation describe best the reactivity of α, β-unsaturated ketones. For the two relevant processes involved in CO 2 fixation the amides present the largest reactivity in vacuum and in aqueous solution compared to the esters and thioesters and may, therefore, serve as alternative substrates of carboxylases. K E Y W O R D SFukui function, linear and quadratic energy models, reactivity descriptors, α,β-unsaturated compounds

Atom-Condensed Fukui Function in Condensed Phases and Biological Systems and Its Application to Enzymatic Fixation of Carbon Dioxide

“…In our previous study, we have shown that the condensed Fukui functions under the fragment molecular response (FMR) approach with the Hirshfeld-I partitioning method correctly describe the reactivity of α,βunsaturated systems such as the crotonyl thioester. 33 Recently, our findings were further independently confirmed by others. 34,35 Here we use the validated local reactivity descriptor to analyze the crotonyl test system in different conformations and molecular environments such as a vacuum, aqueous solution, and the enzyme.…”

“…For each configuration of the atoms the reactivity of the crotonyl thioester as the enzyme substrate model was studied with atom-condensed local reactivity descriptors based on conceptual DFT. In our previous study, we compared several global and local reactivity descriptors for this family of molecules with the result that the atom-condensed Fukui function − within the linear energy model best reproduces the experimental electrophilicity and nucleophilicity of α,β-unsaturated esters, amides, and thioesters …”

Methyl Trifluoroacetate as a Methylation Reagent for N−H, O−H, and S−H Functionalities under Mild Conditions

“…In addition, conceptual DFT (Figure S3, Table S2 and S3) of MTFA was calculated . The condensed values of the Fukui functions f + showed carbonyl carbon display a larger value with respect to the methyl carbon, illustrating that carbonyl carbon of MTFA is more electrophilic . Therefore, the carbonyl carbon possesses higher positive charge than methyl carbon, and the carbonyl group of MTFA is a harder electrophile and the methyl group represents softer electrophile.…”

Machine learning activation energies of chemical reactions

“…Electronic properties of the reactants and TSs were calculated with the B3LYP/6-31+G(d) level of theory and used as features for the models. Reactant features were ionization energies; electron attachment energies 222 ; the surface electrostatic potential and electrostatic potentials at reactive nuclei 223,224 ; local and global descriptors of nucleophilicity and electrophilicity 225 ; atomic charges; bond orders; solvent accessible surface areas 226 ; and a descriptor for dispersion. 227 TS features were the activation barrier of the reaction as calculated with the ωB97X-D/6-311+G(d,p) level of theory; TS atomic charges; TS bond orders; and TS nuclear electrostatic potentials.…”