Machine learning enabling prediction of the bond dissociation enthalpy of hypervalent iodine from SMILES

Machine learning to create models on the basis of big data enables predictions from new input data. Many tasks formerly performed by humans can now be achieved by machine learning algorithms in various fields, including scientific areas. Hypervalent iodine compounds (HVIs) have long been applied as useful reactive molecules. The bond dissociation enthalpy (BDE) value is an important indicator of reactivity and stability. Experimentally measuring the BDE value of HVIs is difficult, however, and the value has been estimated by quantum calculations, especially density functional theory (DFT) calculations. Although DFT calculations can access the BDE value with high accuracy, the process is highly time-consuming. Thus, we aimed to reduce the time for predicting the BDE by applying machine learning. We calculated the BDE of more than 1000 HVIs using DFT calculations, and performed machine learning. Converting SMILES strings to Avalon fingerprints and learning using a traditional Elastic Net made it possible to predict the BDE value with high accuracy. Furthermore, an applicability domain search revealed that the learning model could accurately predict the BDE even for uncovered inputs that were not completely included in the training data.

Structure-antioxidant Activity (Oxygen Radical Absorbance Capacity) Relationships of Phenolic Compounds

Antioxidant capacity is the extent to which a compound can eliminate reactive oxygen species, and in vitro methods for its chemical evaluation have been proposed. Among these methods, the oxygen radical absorbance capacity (ORAC) assay comes close to the oxidation reaction in the living body because it generates radical species that mimic the lipid peroxyl radical involved in the peroxidation reaction of biological components and react in a phosphate buffer. In this study, PM7, a semi-empirical molecular orbital method, was used to calculate the thermodynamic properties (bond dissociation enthalpy, ionisation potential, and proton affinity) associated with ORAC. We also applied the clusterwise linear regression analysis as a statistical method for grouping the antioxidants by structure. By analysing the data for antioxidants, the trend in the hydrophilic ORAC values was determined using the calculated structures and bond dissociation enthalpies of the groups classified according to the presence or absence of oxygen functional groups in the ortho position of phenol. Further studies of indicators other than bond dissociation enthalpy are needed to predict the ORAC of other antioxidants such as flavonoids and indoles.

Exploring the Antioxidant Activity of Thiaflavan Compounds: a Quantum Chemical Study

Density functional theory calculations at B3LYP level are performed to theoretically investigate the antioxidant properties of 30 thiaflavan compounds. The main theoretical parameters, such as bond dissociation enthalpy, ionization potential,...

Solvent Effect on Bond Dissociation Enthalpy (BDE) of Tetrahydrocurcumin: A Theoretical Study

Solvent effect on bond dissociation enthalpy (BDE) of different functional groups of tetrahydrocurcumin is investigated. This is to evaluate how the polarity of a medium affect BDE and to clarify which functional groups hold the key role in its antioxidant activity through hydrogen transfer. We occupy density functional theory to calculate BDE through geometrical optimization and frequency calculation at six sites of tetrahydrocurcumin in water, methanol and chloroform solvents. The solvents represent polar and non-polar medium. Our result shows that BDE is lower in non-polar medium and hydrogen transfer is favored in this medium. A phenolic group is responsible for the antioxidant activity of tetrahydrocurcumin.

THERMOCHEMICAL PARAMETERS OF ERGOTHIONEINE: A DFT STUDY USING M06, WB97XD AND TPSSTPSS METHODS

Antioxidant properties of ergothioneine (ESH) have been investigated via hydrogen atomtransfer (HAT), single electron transfer-proton transfer (SET-PT) and sequential proton losselectron transfer (SPLET) mechanisms. Three new DFT methods including M06, WB97XD andTPSSTPSS at the 6-311++G(2df,2p) basis set were used to compute the thermochemicalparameters of ESH in the gas phase. Based on these methods, bond dissociation enthalpy (BDE),ionization energy (IE), proton dissociation enthalpy (PDE), proton affinity (PA) and electrontransfer enthalpy (ETE) were calculated. The results were also compared with the valuesobtained by B3LYP method. The calculated results show that ergothioneine plays a role as apotential antioxidant via HAT mechanism.

Calculated antioxidant activity of selected phenolic compounds

Determination of the corresponding bond dissociation enthalpy, ionization potential and proton affinity, dipole moment values, highest occupied molecular orbital eigenvalues, and spin density along with the bioactivity score is central to the antioxidant activity evaluation in this paper. Molecular geometries were optimized with DFT using B3LYP and UB3LYP for parent, ionic, and radical species and 6-311+G(d,p) basis set. Bioactivity, drug likeness, and drug scores were calculated using freely available cheminformatics programs for data visualization and analysis. Overall, the values revealed two structures as promising molecules because of good reaction enthalpies (ΔHr). Lipinski rules were fully satisfied for all molecules.

Theoretical Study about the Effect of Halogen Substitution on the Reactivity of Antitumor 3-Formylchromones and Their Free Radicals

The mandatory presence of a chlorine atom on the aromatic ring of 6-hydroxy-3-formyl angular chromones, on the respiration inhibition of mammary carcinoma mouse, is explained through a computational study of these compounds. This study analyzes the reactivity of the neutral molecules and their free radicals, in gas phase and with water solvation, incorporated by the polarizable continuum medium (PCM) approach. Electrophilic reactivities were evaluated using Fukui (f+) and Parr (P+) functions. The stabilities of radical species formed by the abstraction of a hydrogen atom from the O-H bond were evaluated by bond dissociation enthalpy (BDE) and spin density (SD) calculations. This study has potential implications for the design of chromone analogues as anticancer compounds.

Gallic acid: thermodynamics of the homolytic and heterolytic phenolic O—H bonds splitting-off

The DFT study of primary antioxidant action of gallic acid and its carboxylic anion is presented in the gas-phase, benzene and water. Corresponding reaction enthalpies for three possible mechanisms was calculated using B3LYP/6-311++G** method. Bond dissociation enthalpy (BDE) and proton dissociation enthalpy (PDE) of 4-OH group was found to be the lowest in gas-phase as well as in both solvents approximated by IEF-PCM model. Ionization potentials (IPs) were higher than BDEs in all cases. Deprotonation of carboxylic group result in increased antioxidant potency as drop in BDE, proton affinities (PAs) and IPs was indicated in all environments.