Nature of partial sigma bond.

This study investigates the formation of partial sigma (σ) covalent bonds in experimentally synthesizable biradicals formed from hydrogenated and fluorinated C8, C20, and C60 cage structures, by assessing their stability, geometry, and bonding character in singlet and triplet states using restricted B3LYP-D3/6-31+G(d,p) theory, natural bond orbital (NBO) analysis, and complete active space self-consistent field (CASSCF) method. The results show that these partial σCC bonds have Wiberg bond orders of 0.38 to 0.48 and bond lengths ranging from 2.62 Å to 5.93 Å. Cage size influences the characteristics of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), with electrons favoring more antibonding orbitals in smaller cages where electrons reside more on the exterior of the cage and favoring bonding orbitals in larger ones where electrons are more in the interior. Fluorination enhances electron density on bonding orbitals. The analysis further clarified that the differentiation between antibonding and bonding features of HOMOs and LUMOs extends beyond merely electron transfer from s- to p-atomic orbitals, also noting possible interactions of the same symmetry repel. The study also introduces hyperconjugation from α-position CH bonds as a factor in stabilizing partial σ-bond formation. The results also caution against the use of broken symmetry methodology in unrestricted SCF wavefunctions for biradicals, such as those in this study as it may cause large spin contamination and thus errors in the calculated electronic properties results.

Atom-Based Machine Learning Model for Quantitative Property-Structure Relationship of Electronic Properties of Fusenes and Substituted Fusenes.

This study presents the development of machine-learning-based quantitative structure-property relationship (QSPR) models for predicting electron affinity, ionization potential, and band gap of fusenes from different chemical classes. Three variants of the atom-based Weisfeiler-Lehman (WL) graph kernel method and the machine learning model Gaussian process regressor (GPR) were used. The data pool comprises polycyclic aromatic hydrocarbons (PAHs), thienoacenes, cyano-substituted PAHs, and nitro-substituted PAHs computed with density functional theory (DFT) at the B3LYP-D3/6-31+G(d) level of theory. The results demonstrate that the GPR/WL kernel methods can accurately predict the electronic properties of PAHs and their derivatives with root-mean-square deviations of 0.15 eV. Additionally, we also demonstrate the effectiveness of the active learning protocol for the GPR/WL kernel methods pipeline, particularly for data sets with greater diversity. The interpretation of the model for contributions of individual atoms to the predicted electronic properties provides reasons for the success of our previous degree of π-orbital overlap model.

Computational Design of a Lantern Organic Framework.

This study employed a computational quantum chemistry approach to design lantern organic framework (LOF) materials. Using the density functional theory method with the B3LYP-D3/6-31+G(d) level theory, novel lantern molecules ranging from two to eight bridges made of sp3 and sp carbon atoms to connect circulene bases that have phosphorous or silicon as anchor atoms were made. It was found that five-sp3-carbon and four-sp-carbon bridges are optimal candidates for constructing the lantern framework in the vertical direction. Although circulenes can be stacked vertically, their resulting HOMO-LUMO gaps remain relatively unchanged, indicating their potential applications as porous materials and for host-guest chemistry. The electrostatic potential surface maps reveal that LOF materials are relatively electrostatically neutral overall.

Machine Learning-Based Quantitative Structure-Property Relationships for the Electronic Properties of Cyano Polycyclic Aromatic Hydrocarbons.

In this study, quantitative structure-property relationships (QSPR) based on a machine learning (ML) methodology and the truncated degree of π-orbital overlap (DPO) to predict the electronic properties, namely, the bandgaps, electron affinities, and ionization potentials of the cyano polycyclic aromatic hydrocarbon (CN-PAH) chemical class were developed. The level of theory B3LYP/6-31+G(d) of density functional theory (DFT) was used to calculate a total of 926 data points for the development of the QSPR model. To include the substituents effects, a new descriptor was added to the DPO model. Consequently, the new ML-DPO model yields excellent linear correlations to predict the desired electronic properties with high accuracy to within 0.2 eV for all multi-CN-substituted PAHs and 0.1 eV for the mono-CN-substituted PAH subclass.

Gagones A-F: Six prenylated chalcones from the heartwood of Mansonia gagei.

Six undescribed prenylated chalcones gagones A-F were isolated from the acetone fraction of Mansonia gagei heartwood. Their structures were unambiguously established based on spectroscopic analysis (HRESIMS, 1D and 2D NMR), as well as comparison to literature data. Their absolute configurations were elucidated using DP4 and electronic circular dichroism calculations. Isolated compounds were evaluated for their inhibitory activity against α-glucosidase and DPPH assay. All of the tested compounds exhibited better activity than that of acarbose (IC50 93.6 ± 0.5 µM). Among them, gagone D exhibited the highest α-glucosidase inhibitory with the IC50 value of 3.6 ± 0.4 µM. For antioxidant activity, gagones A-C, and E showed more active than that of ascorbic acid (IC50 30.2 ± 0.5 µM) with the IC50 values of 13.2 ± 0.7, 20.1 ± 0.4, 19.3 ± 0.5 and 12.8 ± 0.2 µM, respectively.

Computational Study on the Nature of Bonding between Silver Ions and Nitrogen Ligands.

In this paper, the nature of silver ion-nitrogen atom bonding in the complexation with ammonia, azomethine, pyridine, and hydrogen cyanide from one to four coordinations is studied at the B97-1 level of density functional theory. The results indicate that the two-coordinated complex of the silver ion with different nitrogen ligands representing sp, sp2, and sp3 orbital hybridizations is the most stable form having the shortest Ag+-N bond distance, highest vibrational frequencies, largest bond order, and favorable Gibbs free energy of formation. Natural bond orbital analyses further show that σ-donation from the nitrogen lone pair to the silver empty 5s orbital is dominant in the dative metal-ligand bonding character with N-sp3 having the largest contribution among the different N atomic orbital hybridizations. Natural energy decomposition analyses further show that the two-coordinated complexes have enhanced electrostatic interaction and charge transfer energies over other coordination types leading them to be more stable. For this reason, the two-coordinated complexes would be a better representation for studying bonding and interaction in silver ion complexes.

Application of Machine Learning in Developing Quantitative Structure-Property Relationship for Electronic Properties of Polyaromatic Compounds.

The degree of π orbital overlap (DPO) model has been demonstrated to be an excellent quantitative structure-property relationship (QSPR) that can map two-dimensional structural information of polycyclic aromatic hydrocarbons (PAHs) and thienoacenes to their electronic properties, namely, band gaps, electron affinities, and ionization potentials. However, the model suffers from significant limitations that narrow its applications due to inefficient manual procedures in parameter optimization and descriptor formulation. In this work, we developed a machine learning (ML)-based method for efficiently optimizing DPO parameters and proposed a truncated DPO descriptor, which is simple enough that can be automatically extracted from simplified molecular-input line-entry system strings of PAHs and thienoacenes. Compared with the result from our previous studies, the ML-based methodology can optimize DPO parameters with four times fewer data, while it can achieve the same level of accuracy in predictions of the mentioned electronic properties to within 0.1 eV. The truncated DPO model also has similar accuracy to the full DPO model. Consequently, the ML-based DPO approach coupled with the truncated DPO model enables new possibilities for developing automatic pipelines for high-throughput screening and investigating new QSPR for new chemical classes.

Quantum Mechanical-Based Quantitative Structure-Property Relationships for Electronic Properties of Two Large Classes of Organic Semiconductor Materials: Polycyclic Aromatic Hydrocarbons and Thienoacenes.

In this study, the degree of the π-orbital overlap (DPO) model proposed earlier for polycyclic aromatic hydrocarbons (PAH) was employed to develop quantitative structure-property relationships (QSPRs) for band gaps, ionization potentials, and electron affinities of thienoacenes. DPO is based on two-dimensional topological draw of aromatic molecules. The B3LYP/6-31+G(d) level of density functional theory (DFT) was used to provide chemical data for developing QSPRs. We found that the DPO model is able to capture the correct physics of electronic properties of aromatic molecules so that with only six nonzero topological parameters (four for PAH and additional two for thienoacenes), the DPO model yields the linear dependence of electronic properties of both the PAH and thienoacenes classes by a single set of QSPRs with the accuracy to within 0.1 eV of the DFT results. The results suggest that within the DPO framework, all aromatic molecules can share the same set of QSPRs.

On-the-fly kinetics of hydrogen abstraction from polycyclic aromatic hydrocarbons by methyl/ethyl radicals.

This work provides a rigorous procedure, within the framework of the Reaction Class Transition State Theory (RC-TST) and the Structure-Activity Relationship (SAR), for predicting reliable thermal rate constants on-the-fly for hydrogen abstraction reactions by methyl/ethyl radicals from Polycyclic Aromatic Hydrocarbons (PAHs) in a temperature range of 300-3000 K. All necessary RC-TST parameters were derived from ab initio calculations for a representative set of 36 reactions on which different error analyses and comparisons with available literature data were carried out. In addition to the good agreement between the RC-TST rate constants and the literature data, the detailed error analyses show that RC-TST/SAR, utilizing either the Linear Energy Relationship (LER) where only the reaction energy is needed or Barrier Height Grouping (BHG) where no additional data is needed, can predict the thermal rate constants for any reaction in the title reaction class with an average systematic error of less than 50% when compared to the explicit rate calculations. Therefore, the constructed RC-TST procedure can be confidently used to obtain reliable rate constants on the fly in an attempt to effectively construct detailed kinetic mechanisms for PAH-related fuels.

Quantitative Structure-Property Relationships for the Electronic Properties of Polycyclic Aromatic Hydrocarbons.

This study presents a development in quantitative structure-property relationships (QSPRs) for research in organic semiconductor materials by introducing a new structural descriptor called "degree of π-orbital overlap" based on two-dimensional structure information of aromatic molecules. Application of this method to predict the electronic properties of polycyclic aromatic hydrocarbon (PAH) molecules, which are known to be the core component of many organic semiconductor materials, is presented. Results demonstrated that QSPRs based on the new descriptor can predict rather accurate band gaps, ionization potentials and electron affinities for a large number of PAHs compared to those explicitly calculated by density functional theory method. This research opens new possibilities for developing QSPRs for other organic semiconductor classes in future.

Density functional theory study of mechanism of epoxy-carboxylic acid curing reaction.

A comprehensive picture on the mechanism of the epoxy-carboxylic acid curing reactions is presented using the density functional theory B3LYP/6-31G(d,p) and simplified physical molecular models to examine all possible reaction pathways. Carboxylic acid can act as its own promoter by using the OH group of an additional acid molecule to stabilize the transition states, and thus lower the rate-limiting barriers by 45 kJ/mol. For comparison, in the uncatalyzed reaction, an epoxy ring is opened by a phenol with an apparent barrier of about 107 kJ/mol. In catalyzed reaction, catalysts facilitate the epoxy ring opening prior to curing that lowers the apparent barriers by 35 kJ/mol. However, this can be competed in highly basic catalysts such as amine-based catalysts, where catalysts can enhance the nucleophilicity of the acid by forming hydrogen-bonded complex with it. Our theoretical results predict the activation energy in the range of 71 to 94 kJ/mol, which agrees well with the reported experimental range for catalyzed reactions. © 2017 Wiley Periodicals, Inc.

Performance of First-Principles-Based Reaction Class Transition State Theory.

Performance of the Reaction Class Transition State Theory (RC-TST) for prediction of rates constants of elementary reactions is examined using data from its previous applications to a number of different reaction classes. The RC-TST theory is taking advantage of the common structure denominator of all reactions in a given family combined with structure activity relationships to provide a rigorous theoretical framework to obtain rate expression of any reaction within a reaction class in a simple and cost-effective manner. This opens the possibility for integrating this methodology with an automated mechanism generator for "on-the-fly" generation of accurate kinetic models of complex reacting systems.

Density functional theory study on mechanisms of epoxy-phenol curing reaction.

A comprehensive picture on the mechanism of the epoxy-phenol curing reactions is presented using the density functional theory B3LYP/ 6-31G(d,p) and simplified physical molecular models to examine all possible reaction pathways. Phenol can act as its own promoter by using an addition phenol molecule to stabilize the transition states, and thus lower the rate-limiting barriers by 27.0-48.9 kJ/mol. In the uncatalyzed reaction, an epoxy ring is opened by a phenol with an apparent barrier of about 129.6 kJ/mol. In catalyzed reaction, catalysts facilitate the epoxy ring opening prior to curing that lowers the apparent barriers by 48.9-50.6 kJ/mol. However, this can be competed in highly basic catalysts such as amine-based catalysts, where catalysts are trapped in forms of hydrogen-bonded complex with phenol. Our theoretical results predict the activation energy in the range of 79.0-80.7 kJ/mol in phosphine-based catalyzed reactions, which agrees well with the reported experimental range of 54-86 kJ/mol.

Discover binding pathways using the sliding binding-box docking approach: application to binding pathways of oseltamivir to avian influenza H5N1 neuraminidase.

Drug binding and unbinding are transient processes which are hardly observed by experiment and difficult to analyze by computational techniques. In this paper, we employed a cost-effective method called "pathway docking" in which molecular docking was used to screen ligand-receptor binding free energy surface to reveal possible paths of ligand approaching protein binding pocket. A case study was applied on oseltamivir, the key drug against influenza a virus. The equilibrium pathways identified by this method are found to be similar to those identified in prior studies using highly expensive computational approaches.

Effects of amine organic groups as lattice in ZSM-5 on the hydrolysis of dimethyl ether.

The effects of doping amine to ZSM-5 on its catalytic activity for hydrolysis of dimethyl ether (DME) have been studied theoretically using Density Functional Theory with the embedded cluster ONIOM(M06/6-31G(d,p):UFF) model. Doping by amine to ZSM-5 yields two new active centers, namely the protonated Z[NH2] and non-protonated Z[NH] amine sites in addition to the normal Brønsted acid Z[OH] site. The reaction has two possible stepwise and concerted channels. The stepwise channel consists of two elementary steps; (i) the demethylation followed by (ii) the hydrolysis while the concerted channel involves in the demethylation and hydrolysis in a single step. We found that the reaction favors to proceed via the concerted channel at all three active centers. The results predict that the Z[OH] shows the best catalytic performance for the studied reaction. The Z[NH2] is not catalytically active due to the activation barriers are extremely high for both stepwise and concerted pathways. The demethylation step is energetically favorable over the Z[NH] site, however, the product methylamonium surface intermediate is too stable to be further converted to methanol.

Kinetics of the C-C bond beta scission reactions in alkyl radical reaction class.

Kinetics of the ß-scission in alkyl radical reaction class was studied using the reaction class transition state theory (RC-TST) combined with the linear energy relationship (LER) and the barrier height grouping (BHG) approach. All necessary parameters were derived from first-principle density functional calculations for a representative set of 21 reactions. Different error analyses and comparisons with available literature data were made. Direct comparison with available experimental data indicates that the RC-TST/LER, where only reaction energy is needed, can predict rate constants for any reaction in this reaction class with excellent accuracy. Specifically for this reaction class, the RC-TST/LER method has less than 60% systematic errors on average in the predicted rate constants when compared to explicit rate calculations.

Molecular dynamics simulations suggest that electrostatic funnel directs binding of Tamiflu to influenza N1 neuraminidases.

Oseltamivir (Tamiflu) is currently the frontline antiviral drug employed to fight the flu virus in infected individuals by inhibiting neuraminidase, a flu protein responsible for the release of newly synthesized virions. However, oseltamivir resistance has become a critical problem due to rapid mutation of the flu virus. Unfortunately, how mutations actually confer drug resistance is not well understood. In this study, we employ molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, as well as graphics processing unit (GPU)-accelerated electrostatic mapping, to uncover the mechanism behind point mutation induced oseltamivir-resistance in both H5N1 "avian" and H1N1pdm "swine" flu N1-subtype neuraminidases. The simulations reveal an electrostatic binding funnel that plays a key role in directing oseltamivir into and out of its binding site on N1 neuraminidase. The binding pathway for oseltamivir suggests how mutations disrupt drug binding and how new drugs may circumvent the resistance mechanisms.

Kinetics of thermoneutral intermolecular hydrogen migration in alkyl radicals.

High pressure limits of thermal rate constants of intramolecular hydrogen migrations, particularly 1,3 to 1,6 H-shift in propyl, butyl, pentyl and hexyl radicals, respectively, were calculated using the canonical variational transition state theory (CVT) with a multi-dimensional small-curvature tunneling (SCT) correction over the temperature range of 300-3000 K. The CCSD(T)/cc-pVDZ//BH&HLYP/cc-pVDZ method was used to provide necessary potential energy surface information. Rate constants for these reactions were used to extrapolate rate constants for reactions of larger alkyls where experimental data are available using the Reaction Class Transition State Theory (RC-TST). Excellent agreement with experimental data confirms the validity of the RC-TST methodology and the accuracy of the calculated kinetic data in this study.

Explicitly solvated ligand contribution to continuum solvation models for binding free energies: selectivity of theophylline binding to an RNA aptamer.

To provide more accurate computational estimates of binding free energies in solution from molecular dynamics (MD) simulations, a separate solvation contribution for the binding ligand is determined from a linear response treatment. We use explicit water coordinates for this term and combine with MM-PBSA (molecular mechanics, Poisson-Boltzmann, and surface area contributions) in a new approach (MM-PB/LRA-SA). To assess this method, application to the binding between theophylline and its derivatives to an RNA aptamer was performed and compared with experimental binding affinities. Explicitly solvated MD trajectories were generated with the same parameter set used in the previous work by Gouda et al., who compared the relative binding of these molecules by both the MM-PBSA and thermodynamic integration methods. Substituting the linear response term for the ligand in the MM-PB/LRA-SA approach led to an improvement upon MM-PBSA when compared with experimental and thermodynamic integration results at approximately twice the computational cost. The balance between accuracy and computational expense achieved using this method suggests potential advantages in applying it in the virtual drug-screening process.

Kinetics of the hydrogen abstraction C2H3* + alkane --> C2H4 + alkyl radical reaction class.

This paper presents an application of the reaction class transition state theory (RC-TST) to predict thermal rate constants for hydrogen abstraction reactions of the type C(2)H(3) + alkane --> C(2)H(4) + alkyl radical. The linear energy relationship (LER) was proven to hold for both noncyclic and cyclic hydrocarbons. We have derived all parameters for the RC-TST method from rate constants of 19 representative reactions, coupling with LER and the barrier height grouping (BHG) approach. Both the RC-TST/LER, where only reaction energy is needed, and the RC-TST/BHG, where no other information is needed, can predict rate constants for any reaction in this reaction class with satisfactory accuracy for combustion modeling. Our analysis indicates that less than 90% systematic errors on the average exist in the predicted rate constants using the RC-TST/LER or RC-TST/BHG method, while in comparison to explicit rate calculations, the differences are within a factor of 2 on the average.