International Journal of Quantum Chemistry最新文献

Fluorine is commonly incorporated into pharmaceuticals to enhance properties such as metabolic site blocking. However, the Smoothened receptor (SMO) inhibitor, 2,4-Difluoro-benzylphthalazine derivative, undergoes metabolism by CYP450 to generate toxic quinone species. A combination of reactivity and accessibility is employed to demonstrate that the quinone production involves hydrogen abstraction from benzyl instead of the phenyl epoxidation mechanism. The main metabolite of fluorine-containing benzylphthalazine derivatives is benzyl hydroxylation derivatives, which corroborates well with experimental observations. The rate-determining step in the epoxidation process is a CO bond formation, leading to the production of a radical species instead of a carbocation intermediate. The substitution of F with groups such as CF₃ or CN can increase the energy barrier associated with CO bond formation, thereby augmenting the difficulty in producing quinones. The present study provides a theoretical foundation for the drug metabolism and drug design of pharmaceuticals containing fluorine atoms.

Two bromodomains BRD4-BD1 and BRD4-BD2 of BRD4 play a critical role in the design of inhibitors targeting various diseases such as inflammatory diseases and cancers. In the present study, multiple computational methods, including molecular docking, multiple replica MD simulations, and binding free energy calculations, were utilized to study the selective binding of three novel inhibitors, 21r, Lpd22, and XY221, to the two bromodomains BRD4-BD1 and BRD4-BD2, respectively. When these three inhibitors interact with BRD4-BD1 and BRD4-BD2, they exert distinct effects on their internal dynamics, leading to changes in their interaction patterns with critical residues of BRD4. Residues Trp81/Trp374, Pro82/Pro375, Val87/Val380, Leu92/Leu385, Leu94/Leu387, Asn140/Asn433, and Ile146/Val439 in BRD4-BD1 and BRD4-BD2 play a critical role in the selectivity binding to these three inhibitors. Meanwhile, electrostatic interactions and nonpolar interactions are the main driving factors influencing their interactions. This provides theoretical guidance for the rational design of selective inhibitors targeting these two bromodomains of BRD4.

A computational study of dihydrogen-bonded complexes formed by LiH⋯HX (X = F, Cl, CN, or CCH) at the DFT, MP2, and CCSD theoretical levels along with Pople's and Dunning's basis sets is presented. One of our main goals was to establish a direct correlation between interaction strength and the stretching frequencies of the proton donors shifted to red and blue. To this end, NBO and ChElPG atomic charge calculations were performed to quantify intermolecular charge transfers. Considering the wide range of formalisms for atomic charge calculations, the theoretical levels employed, as well as the types of intermolecular bound systems studied in this work, the application of an unsupervised statistical pattern recognition method was required. Furthermore, NCIPlot graphic visualization and QTAIM topological descriptors have characterized all dihydrogen bonds and the intermolecular covalency profile could be discussed in terms of contributions from kinetic and potential energy densities. Additionally, SAPT energy partitioning was used to evaluate the interaction strength and the trend associated with the manifestation of intermolecular covalency.

The development of high-performance n-type thermoelectric materials for application in aerospace energy harvesting systems is the main objective of this work. We present an innovative synthesis approach for ZnAlGaO-based semiconductors, utilizing a refined sol–gel technique with water-based precursor solutions and the inclusion of glacial acetic acid to facilitate gelation. The process carefully controls solution pH and turbidity through precise instrumentation, ensuring the formation of uniform gels. Following gelation, the xerogel undergoes an optimized drying procedure at 200°C to remove residual compounds. High-purity ZnAlGaO materials are then created by calcining the resultant powders at 600°C. A novel thermal process at 1350°C for 36 h was implemented to improve the bulk thermoelectric characteristics of the material. Detailed characterization techniques, including DTA-TG, SEM, FTIR, XRD, XPS, and thermoelectric measurements, confirm the superior performance of the fabricated materials. The n-type ceramics exhibit a remarkable thermoelectric figure of merit of 0.172 at 800°C, making them promising candidates for thermoelectric generator applications in aerospace technologies.

Anthocyanidins are natural compounds soluble in water and known for their various biological activities. They show potent antioxidant activity towards free radicals. Herein, we investigate the effects of different types of polar and nonpolar solvents on the antioxidant activity of pelargonidin 3-glucoside. Density functional theory calculation has been performed using the hybrid functional M052X and the basis set 6-31+G(d,p). The solvent effects were considered implicitly by using IEFPCM formalism where acetone, aniline, benzene, water, methanol, chloroform, and cyclohexane are the attested solvents. The antioxidant activity is evaluated by calculating bond dissociation enthalpies of different OH groups (BDEs) and ionization potentials (IP) of pelargonidin 3-glucoside. In addition, the dipole moment and gap energy in different solvents were determined. The results show that the antioxidant activity of the pelargonidin 3-glucoside increases with polarity and that water is the favored media for free radical scavenging. The results show that an exponential potential decays of ionization potential with the dielectric constant of the tilted solvent. The favorable mechanism involved in free radical scavenging of free radicals by anthocyanidin pelargonidin 3-glucoside may depend on both the environment and the reactants. Herein, the effect of the solvent polarity on the stability of the transition state, activation, and the rate constant of the PC-ET mechanism of OOCH3 free radical scavenging by the pelargonidin 3-glucoside have been investigated. The obtained results showed that the free radical scavenging by 3-glucoside may be strongly affected by the environmental media and the type of solvents, that is, polar or nonpolar solvents.

Anthocyanidins are natural compounds soluble in water and known for their various biological activities. They show potent antioxidant activity towards free radicals. Herein, we investigate the effects of different types of polar and nonpolar solvents on the antioxidant activity of pelargonidin 3-glucoside. Density functional theory calculation has been performed using the hybrid functional M052X and the basis set 6-31+G(d,p). The solvent effects were considered implicitly by using IEFPCM formalism where acetone, aniline, benzene, water, methanol, chloroform, and cyclohexane are the attested solvents. The antioxidant activity is evaluated by calculating bond dissociation enthalpies of different OH groups (BDEs) and ionization potentials (IP) of pelargonidin 3-glucoside. In addition, the dipole moment and gap energy in different solvents were determined. The results show that the antioxidant activity of the pelargonidin 3-glucoside increases with polarity and that water is the favored media for free radical scavenging. The results show that an exponential potential decays of ionization potential with the dielectric constant of the tilted solvent. The favorable mechanism involved in free radical scavenging of free radicals by anthocyanidin pelargonidin 3-glucoside may depend on both the environment and the reactants. Herein, the effect of the solvent polarity on the stability of the transition state, activation, and the rate constant of the PC-ET mechanism of OOCH3 free radical scavenging by the pelargonidin 3-glucoside have been investigated. The obtained results showed that the free radical scavenging by 3-glucoside may be strongly affected by the environmental media and the type of solvents, that is, polar or nonpolar solvents.

We present a modification of our recently described method for learning potential energy surfaces (PES) via the bond-order charge-density matrix (CDM) formalism which makes use of the Hartree-Fock expression for the electronic energy. The modified approach also employs permutationally invariant polynomials (PIP) as a fitting basis for the individual CDM elements P_μν with μ and ν as Cartesian components. The key difference introduced presently is in the representation of P_μν as linear combinations of orientation-independent intrinsic density elements weighted by the bond direction cosines forming a complete basis, in contrast to the direct space-fixed Cartesian representation employed by us previously. The new approach identically preserves PES's rotational invariance and has the same root-mean-square error as the original formulation with ∼2.2 times fewer linear variational parameters. We demonstrate its efficiency on the fitting quality of the PESs of cyclo[10]carbon singlet and linear triplet states in full permutational symmetry space.

We present a modification of our recently described method for learning potential energy surfaces (PES) via the bond-order charge-density matrix (CDM) formalism which makes use of the Hartree-Fock expression for the electronic energy. The modified approach also employs permutationally invariant polynomials (PIP) as a fitting basis for the individual CDM elements P_μν with μ and ν as Cartesian components. The key difference introduced presently is in the representation of P_μν as linear combinations of orientation-independent intrinsic density elements weighted by the bond direction cosines forming a complete basis, in contrast to the direct space-fixed Cartesian representation employed by us previously. The new approach identically preserves PES's rotational invariance and has the same root-mean-square error as the original formulation with ∼2.2 times fewer linear variational parameters. We demonstrate its efficiency on the fitting quality of the PESs of cyclo[10]carbon singlet and linear triplet states in full permutational symmetry space.

The global diabatic potential energy surfaces (PESs) of the BH₂ system were constructed using neural network method in conjunction with a specific function based on 11 553 ab initio points. We have carefully examined the diagonal elements V₁₁, V₂₂ and the off-diagonal element V₁₂ of the diabatic PESs matrix and compared them with the ab initio points. The theoretical results show that the diagonal elements V₁₁ and V₂₂ can reasonably describe the non-adiabatic processes between the electronic states. The shape of the off-diagonal element V₁₂ is regular and can satisfy the group symmetry operations. To clarify the influence of non-adiabatic effects in B(2p²P) + H₂ reaction, both adiabatic and non-adiabatic dynamics calculations were performed based on the newly constructed diabatic PESs. In addition, the adiabatic dynamical results are compared with the non-adiabatic ones. The results show that the non-adiabatic effects play an important role in the reaction process, while the adiabatic dynamical results are not reliable.

The pharmacological potential of marine alkaloids is enormous due to their diverse bioactivities. In this work, we performed a comprehensive computational analysis of marine alkaloids, including Calcardine C, Ernstine A, Naamine H, Naamine I, Naamidine J, Naamidine K, Phorbatopsin D, and Phorbatopsin E, in connection with Mycothiol S-conjugate amidase (MycoSCoA), an essential enzyme for Mycobacterium tuberculosis metabolism. Frontier molecular orbital (FMO) analysis and geometry optimization show that Naamidine J is the most stable compound; its low HOMO–LUMO gaps suggest high reactivity. According to electrostatic potential mapping, Naamidine K has the highest charge distribution, which is in line with a higher binding potential. The strong intramolecular charge transfer of the lead compounds was further confirmed by Natural Bond Orbital (NBO) analysis. Molecular docking studies show that Naamidine K and Naamidine J have the highest binding affinities with MycoSCoA (−10.6 and −9.3 kcal/mol, respectively). These substances use a range of hydrophobic and hydrogen bonding interactions to create stable complexes. It is noteworthy that Naamidine J exhibited superior binding to 4EWL (−9.3 kcal/mol), which was sustained by a network of hydrogen bonds and π-interactions. The selectivity of the marine alkaloids was highlighted by the weakest interactions, which were shown by BOG and GOL. This in silico study highlights Naamidine K and J as promising candidates for further anti-tuberculosis drug development in general.