Quantum Mechanical Modeling Unveil the Effect of Substitutions on the Activation Barriers of the Diels-Alder Reactions of an Antiviral Compound 7H-Benzo[a]phenalene

Density functional theory has been utilized for exploring the mechanism of Diels-Alder reaction between 7H-benzo[a]phenalene and maleic anhydride. 7H-Benzo[a]phenalene is an antiviral compound and information available about its cycloaddition reactions with possible reaction path and mechanism is scarce. In order to work on the synthesis of its further potential derivatives, the mechanism of its reaction with all aspects should be well understood. Two novel intermediates involved in this reaction have been reported. Diels-Alder reaction of maleic anhydride has found many applications in the synthesis of wide range of useful products. The major concern of this work is to evaluate the consequences of introducing electron donating and electron withdrawing substituents on the reactivity of maleic anhydride towards 7H-benzo[a]phenalene. Thermodynamic parameters, activation parameters, energies of frontier orbitals, global reactivity indices and global electron density transfer (GEDT) have been determined for all the reactions. Fukui functions are computed for each reactant in order to identify the most reactive sites. All the reactions have been found to proceed via normal electron demand having polar nature. The substituents with opposite electronic properties were expected to affect the reactivity of dienophile in an inverse manner, however, the results are not according to this assumption. Rather, both kinds of substituents increased the activation barrier of the reaction. This behavior has been explained in the light of various parameters such as the stability of reacting species, gap of frontier molecular orbitals etc. Experimental studies reported previously are in agreement with these results.

Solvent effect on the Molecular structure and Global, Local and Dual Descriptors: A Density Functional Theory Study

This study aims to explore the effects of solvent polarity on the geometry, energy of solvation, dipole moment, polarizability, charge distribution, frontier molecular orbital analysis, and global, local, and dual descriptors for β Carboline. The effects of eight solvents were treated using a conductor-like polarized continuum model. Density Functional Theory calculations were performed at B3LYP level at 6-311++g (d,p) basis set. The computed results showed that the dipole moment, polarizability, the solvation free energy, and atomic charge of β Carboline increased with the increasing polarity of the solvent. Also, the solvation modified the values of the reactivity descriptors as a result of the interaction between the solvent and β Carboline. The dual descriptor provided a clearer difference between electrophilic and nucleophilic attack at specific atomic site than presented by Fukui functions of β Carboline.

Molecular Structure, Interactions and Antimicrobial Properties of Curcumin-PLGA Complexes – A DFT Study

Density functional calculations are performed to study the molecular structure, interactions, and antimicrobial activity of curcumin-poly Lacto glycolic acid (Cur-PLGA) complexes. The calculations are performed on curcumin, Glycolic acid (SSC and AAT conformers), Lactic acid (LA), Cur-SSC, Cur-AAT, Cur-LA, and Cur-PLGA complexes using dispersion corrected M06-2X functional with 6–31 + G* basis set. The condensed Fukui functions of curcumin are calculated to identify the favorable reactive sites. Inter- and intramolecular H–bond interactions are analyzed in detail through natural bond orbital, Atoms in Molecule, and Reduced density gradient analyses. The interaction energy values indicate that the interaction between curcumin and AAT is stronger than the other studied complexes. Further, our calculations show that the PLGA interacted with curcumin is having lower LUMO energy and density values. This indicates that the antimicrobial activity is high in this complex.

Teaching a neural network to attach and detach electrons from molecules

Interatomic potentials derived with Machine Learning algorithms such as Deep-Neural Networks (DNNs), achieve the accuracy of high-fidelity quantum mechanical (QM) methods in areas traditionally dominated by empirical force fields and allow performing massive simulations. Most DNN potentials were parametrized for neutral molecules or closed-shell ions due to architectural limitations. In this work, we propose an improved machine learning framework for simulating open-shell anions and cations. We introduce the AIMNet-NSE (Neural Spin Equilibration) architecture, which can predict molecular energies for an arbitrary combination of molecular charge and spin multiplicity with errors of about 2–3 kcal/mol and spin-charges with error errors ~0.01e for small and medium-sized organic molecules, compared to the reference QM simulations. The AIMNet-NSE model allows to fully bypass QM calculations and derive the ionization potential, electron affinity, and conceptual Density Functional Theory quantities like electronegativity, hardness, and condensed Fukui functions. We show that these descriptors, along with learned atomic representations, could be used to model chemical reactivity through an example of regioselectivity in electrophilic aromatic substitution reactions.

Study of Reactivity and Molecular Stability by the Density Functional Theory Method on 2,3-Dihydro -1H-Perimidine: Comparative Analysis

Numerous studies have been carried out on the structure of 2,3-dihydro-1H-perimidine substituted as compounds with various biological activities. Researchers have found that these compounds exhibit characteristics potentially useful in medicinal chemistry research and have many therapeutic applications. In this work, we carried out a study using descriptors of the conceptual DFT in order to determine the atoms responsible for the chelation of certain metals (zinc, copper, iron ...) in order to propose new stable molecules complexed with these metals. Calculations were performed to determine the local reactivity of substituted 2,3-dihydro-1H-perimidine using Fukui functions by the Natural Population Analysis method. Overall parameters were also determined to predict the relative stability and reactivity of substituted 2,3-dihydro-1H-perimidine. This work was carried out at the calculation level B3LYP / 6-311G (d, p). Compound 2 with an energy difference from the frontier orbitals of ΔEgap = 4.031 eV is the most polarizable. Also, the study of frontier orbitals locates HOMO on the function of substituted 2,3-dihydro-1H-perimidine. Analysis of local reactivity indices as well as of the dual descriptor revealed that nitrogen N17 and N19 are the most favorable sites for electrophilic attack.

A Comparative Analysis of the Global Electrophilicity Power of Some Cationic Dyes. Understanding Selective Removal Dyes From Mixture Solution

Some bibliographic findings of dyes' adsorption from a mixture state suggest that certain dyes are more likely to be adsorbed first on the adsorbent surface than others, and therefore attracted strongly to the adsorbent surface. To explain the phenomenon, DFT calculations are applied. In this fact, the global electrophilicity index ω of some cationic dyes has been evaluated. The results show that, for studied electrophilic dyes, the molecule with the greatest global electrophilicity power is favored to be adsorbed on the surface's anionic sites. In addition, local electrophilic Parr and Fukui functions were introduced to characterize the most reactive adsorption sites properly and indicate successfully the same adsorption centers. The success of DFT calculations in explaining and predicting the selective dye was assessed.

DFT Calculations and Molecular Docking Studies on a Chromene Derivative

Chromenes and their derivatives have been considered as an important class of oxygen-containing heterocycles. There has been an increasing interest in the study of chromenes due to their biological activity. Herein, the structural, electronic, and vibrational properties of a chromene derivative, entitled 2‐amino‐5‐oxo‐4‐phenyl‐4,5‐dihydropyrano[3,2‐c]chromene‐3‐carbonitrile and abbreviated as Chrom-D, have been reported. The FT-IR, UV-vis, and 1H-NMR and 13C-NMR chemical shifts’ measurements were recorded. The molecular geometry and the vibrational frequencies are computed in the frame of density functional theory at the B3LYP/6-311++G(d,p) level of theory. The noncovalent interactions in the crystal lattice which are responsible to the 3D crystal structure of Chrom-D are investigated based on Hirshfeld surfaces and topological reduced density gradient (RDG) analysis. Molecular electrostatic potential surface, Mulliken charges, and Fukui functions are computed in order to find out the electrophilic and nucleophilic sites. The electronic properties of the title compound have been studied based on the TD-DFT calculations. Finally, Chrom-D has been evaluated as a multifunctional agent against Alzheimer’s disease (AD).

Density Functional Theory Reactivity Studies on X3N@C80 (X = Sc, Gd, Lu) Fullerenes

Density functional theory studies have been performed to reveal the reactivity of the sites in Sc3N@C80, Gd3N@C80 and Lu3N@C80 endohedral fullerenes. The condensed Fukui functions have been calculated using Mulliken atomic charges. The calculations show that the carbon atom sites are in direct contact with the endohedral cluster favourable nucleophilic attack. Similarly, the carbon atoms which are away from the direct bonding with the cluster are favourable for the electrophilic attack. This is also confirmed from the charge transfer analysis. It is noted that the spin multiplicity decides the reactivity sites and stability of the Gd3N@C80 system. The HOMO-LUMO gap value indicates that Gd3N@C80 with S = 7 is stable than the S = 21 system. Finally, present studies indicate that the charge transfer between the C80 cage and X3N plays a major role to determine the reactivity of the sites in the C80 cage.

Theoretical Study of closo-Borate Anions [BnHn]2− (n = 5–12): Bonding, Atomic Charges, and Reactivity Analysis

This study has focused on the structure, bonding, and reactivity analysis of closo-borate anions [BnHn]2− (n = 5–12). Several descriptors of B–H interactions have been calculated. It has been found that the values of electron density and total energy at bond critical point are the most useful descriptors for investigation of B–H interactions. Using results from the descriptor analysis, one may conclude that orbital interactions in [BnHn]2− increase with increasing the boron cluster size. Several approaches to estimate atomic charges have been applied. Boron atoms in apical positions have more negative values of atomic charges as compared with atoms from equatorial positions. The mean values of boron and hydrogen atomic charges tend to be more positive with the increasing of boron cluster size. Global and local reactivity descriptors using conceptual density functional theory (DFT) theory have been calculated. Based on this theory, the closo-borate anions [BnHn]2− (n = 5–9) can be considered strong and moderate electrophiles, while the closo-borate anions [BnHn]2− (n = 10–12) can be considered marginal electrophiles. Fukui functions for electrophilic attack have been calculated. Fukui functions correlate well with atomic charges of the closo-borate anions. Boron atoms in apical positions have the most positive values of Fukui functions.

Quantum Computational, Spectroscopic and Molecular Docking Studies on N-(4-Hydroxyphenyl)picolinamide

In this work, the quantum computations of newly synthesized N-(4-hydroxyphenyl)picolinamide (4-HPP) is focused. Density functional theory (DFT) was used to perform the quantum calculations. The optimized molecular geometry was obtained using the B3LYP and MP2 methods employing 6-311++G(d,p) basis set, which served as the foundation for all subsequent calculations. The experimental data was compared with the calculated vibrational frequencies and NMR spectra. With the use of the molecular electrostatic potential surface (MEP) and the Fukui functions, the charge distribution, reactive regions and electrostatic potential were displayed. The chemical activity of the 4-HPP was evaluated by the energy difference between HOMO and LUMO. For better understanding of the intermolecular charge transfer (ICT), natural bond order analysis (NBO) was used. At various temperatures, thermodynamic parameters such as Gibb’s free energy, enthalpy and entropy were determined. The electrophilicity index was used to portray the molecule’s bioactivity and molecular docking was used to show the interaction between the ligand and the protein. The nature of the molecule was determined by drug similarity when expecting its application for medical purposes.