Theoretical Chemistry Accounts最新文献

The COVID-19 is recognized as one of the deadly disease in the history of human life. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first case appeared in December 2019 in Wuhan, China, number of COVID-19 cases are still growing worldwide, till now number of confirmed COVID-19 cases reported globally are 594 million and number of fatalities are 6.29 million. It creates panic situation on every individual as well as put an extraordinary challenge on every country, especially on the health care system. The ruthlessness of the disease and its noxious complexities need development of suitable and effective drug on urgent basis to prevent as well as treat COVID-19. Though specific drug with proper efficacy is not yet found, a number of research and clinical trials are still going on to check the suitability and effectiveness of existing drug, i.e. repurposed drug to treat patients of COVID-19. In this article, repurposed drug—arbidol, baricitinib, favipiravir, galidesivir and ribavirin are reported by using Conceptual Density Functional Theory (CDFT) approach. Optimization energy, spin multiplicity, zero point energy correction, CDFT-based descriptors, optical and thermochemical properties of these repurposed drugs are computed and analysed. Result signify that favipiravir is the most reactive compound whereas ribavirin is found as the most stable among these molecular species. Favipiravir has the lowest thermal energy, heat capacity and entropy, whereas arbidol has the maximum thermal energy, heat capacity and entropy. There is an interesting correlation found between optimization energy, zero point energy correction, polarizability and thermochemical properties of these repurposed drugs.

The heats of formation of forty-six molecules containing sodium, lithium and magnesium atoms have been calculated using G3X-CEP, G3X(CCSD)-CEP, G4, EnAt1, EnAt2, G3B3, G3MP2B3, CBS-QB3 and functionals using the atomization. The discrepancies between the predicted and the reported heats of formation vary in the range of 0.0–85 kcal mol⁻¹. The best agreement with experimental data was achieved by using Gn and Gn-CEP multilevel techniques. It was found that the best performance among density functional theory (DFT) methods within the atomization approach demonstrated the long range corrected LC-wPBE and BMK level theory. Composite methods presented the best results when compared with DFT. The G4, which was recently reported as a very accurate method for calculating enthalpies of formation, presented the best results when compared with DFT and other composite methods.

Abstract

The nitration reaction was applied to synthesize new substituted coumarin derivatives which undergo a reduction reaction to give the corresponding amino-coumarins. The structures of the nitro-coumarins and amino-coumarins were elucidated by ¹H, ¹³C NMR and infrared spectroscopy. The reactivity indices of the target molecules were computed with conceptual density functional theory framework using DFT/B3PW91/6-31G(d, p). The computed data in terms of ¹H NMR and IR of all the synthesized nitro-coumarins (N1–N3) and amino-coumarins (A1–A3) were compared to the experimental data. Nitro-coumarin (N1) is the least hyperpolarizable of the compound among understudied compounds, making it the most stable and least responsive to nonlinear optics (NLO), while (A1) has the highest hyperpolarizability, making it the least stable and most NLO responsive. Every synthesized compound shows a significant three-dimensional delocalization of the pi-electron, which is crucial for explaining responses to nonlinear optics.

Supramolecular systems may be used to stabilize otherwise unstable isomers to find alternative synthetic pathways. It has been reported that cucurbit[8]uril can stabilize trans-I and trans-II Cu(^{{textrm{II}}}) cyclam, whereas trans-III is the only non-substituted trans Cu(^{{textrm{II}}}) cyclam diastereoisomer found outside of the host molecule experimentally. Quantum chemistry methods can provide valuable insight into the intermolecular interactions involved in these inclusion complexes. All five possible trans diastereoisomers of Cu(^{{textrm{II}}}) cyclam were studied within the host molecule to calculate the interaction energy and free energy of association for each complex. The relative free energies of the five free cyclams confirm that trans-I and trans-II are the most energetically accessible diastereoisomers from the initial trans-III starting point. Energy decomposition analysis was used to identify the attractive and repulsive interactions between cyclam and cucurbit[8]uril and showed that trans-II encounters repulsive forces almost three times greater than trans-I, which may explain the 7:3 ratio of trans-I to trans-II within cucurbit[8]uril that occurs experimentally. Optimized complex geometries with trans-III, IV, and V show that the cyclams protrude out of cucurbit[8]uril, whereas trans-I and trans-II become more encapsulated and elongate the host, suggesting that the position of the cyclam is extremely important when forming non-covalent interactions. Our results agree with the experimental findings and provide greater insight into why the most stable isolated cyclam diastereoisomer, trans-III, does not form a complex.

Abstract

An extension of the use of the linear response function to interpret non-covalent interactions is put forward. Due to its computational intricacies, most applications until now have been done on isolated atoms or molecules using coupled perturbed Hartree–Fock or Kohn–Sham theory, thereby adopting the simplest level for the LRF evaluation, the independent particle approximation. The previously presented possibilities for extension (the random phase and the “full” expression) are scrutinised, thereby highlighting the intricacies in the evaluation of the exchange-correlation term in the case of meta-GGAs and hybrid functionals, and implemented. A set of 25 hydrogen bonded and 11 halogen bonded systems, selected from Hobza S66 and X 40 compilations, were used to investigate the correlation between the stabilisation energy due to these non-covalent interactions and the relevant atom–atom-condensed LRF matrix element. The lack of a relevant correlation in the case of hydrogen bonding is contrasted with the excellent result for the halogen bonds. The correlation between the full option and the IPA is high providing support for our previous work using the IPA as is also the case for the previously used iterative Hirshfeld condensation and the more advanced FOHI method making use of fractional occupation numbers. The fundamental difference between hydrogen and halogen bond behaviour and the retrieval of the stability sequence within the halogen bonds series are traced back to the nature of the LRF as a response function for perturbations in the external potential putting polarisation effects and the polarisability of the atoms of the donor–acceptor couple at the forefront. The extension to the use of the softness kernel is advocated and already invoked to rectify the behaviour of two deviating complexes involving S as second row halogen bond acceptor atom.

The effects of hybrid functionals and solvents (nonpolar, polar aprotic, and polar protic) on the results of calculating the photochemical transformations of unsubstituted spirooxazine (TMINSO) in solution were analyzed. A preliminary selection of functionals showed that the predominant S₀→S₁ transition observed in the experiment for the closed form gives BMK, CAM-B3LYP, LC-ωHPBE, M052X, M062X, M08HX, M11, MN15, SOGGA11X, ωB97, ωB97X, and ωB97XD functionals in each of the three solvents considered (cyclohexane, acetonitrile, methanol). The functionals that did not break the C_spiro-O bond upon TMINSO excitation (LC-ωHPBE, M11, and SOGGA11X in all solvents considered, and ωB97 in the methanol) nonetheless weakened it. Most of the functionals that provided the photoinduced breaking of the C_spiro-O bond in all three solvents under consideration gave excited intermediate X* forms in which the indoline and naphthoxazine units are approximately perpendicular to each other. The exceptions were M052X and ωB97XD in both polar solvents. The outcome of X*→X relaxation is determined by the X* conformation, which, in turn, is the interplay of the used functional and the solvent. For intense photobleaching in a nonpolar solvent, the excitation of the planar merocyanine form must be accompanied by its twisting into the X* form, causing the C_spiro and O atoms to approach each other, which, in turn, makes it possible to recover the C_spiro-O bond. In polar solvents, TMINSO photobleaching, on the contrary, is weak, which corresponds to the preservation of the planar excited open structure. Therefore, functionals giving both of these effects (M052X and ωB97XD) are recommended for modeling the phototransformations of spirooxazine in polar and nonpolar solvents. The possibility of recovering the C_spiro-O bond does not depend directly on the distance between these atoms but on the electron densities on them and the conformation of the linker connecting the aromatic systems in the X form. Three solvating methanol molecules for most of the used functionals stabilize the closed form of TMINSO. Preservation of the planar MC structure during its excitation in the composition of the solvated complex gives only the M052X functional, so it is recommended for modeling the excitation of spirooxazine in methanol. The effect of excitation on the H-bonds of spirooxazine with methanol in the solvated complex was also analyzed.

The epidermal growth factor receptor (EGFR) plays a key role in the pathogenesis of cancers of different types. It has been shown that EGFR and EGF-like peptides are often overexpressed in human carcinomas and that these proteins can cause cell transformation both in vivo and in vitro. In order to design a new apoptotic EGFR inhibitor, we used the essential pharmacophoric structural properties of EGFR inhibitors. We started with the natural alkaloid, theobromine, to get a new semisynthetic N-cyclohexyl acetamide derivative (T-1-NCA). T-1-NCA was extensively examined computationally for its potential against the EGFR protein. We initially performed deep density functional theory (DFT) computations to validate its 3D structure. The electrostatic potential, global reactive indices, and total density of states anticipating a high degree of reactivity were also indicated by the DFT analyses. Second, T-1-NCA's propensity to bind and inhibit the EGFR protein was investigated and verified using structure-based computational investigations such as molecular docking against EGFR^WT, molecular dynamics (MD) over 100 ns, MM-GPSA, and PLIP experiments. T-1-NCA's computational ADME and toxicity profiles were examined before the synthesis, and its safety and general drug-likeness were anticipated. As a consequence, T-1-NCA was semi-synthesized to examine the proposed design and the in silico findings. In comparison with erlotinib, T-1-NCA suppressed EGFR^WT in vitro with an IC₅₀ value of 24.25 nM. (5.87 nM). Furthermore, T-1-NCA suppressed the proliferation of A549 and HCT-116 malignant cell lines with IC₅₀ values of 40.20 and 34.05 µM, respectively, as compared to erlotinib, which had IC₅₀ values of 17.13 and 17.32 µM. Interestingly, T-1-NCA’s selectivity indices were 3.29 and 3.89 against the two cancer cell lines indicating its general safety. Finally, the apoptotic effects of T-1-NCA were confirmed by flow cytometry and RT-PCR through the significant increase of the levels BAX, Casp3, and Casp9 in addition to the significant decrease of Bcl-2 level.

In this study, we investigate the adsorption behavior of three benzophenone derivatives, namely 2,4-Dihydroxybenzophenone (benzophenone-1; BP-1), 2,2′,4,4′-tetrahydroxybenzophenone (benzophenone-2; BP-2), and 2-hydroxy-4-methoxybenzophenone (benzophenone-3; BP-3) on the surfaces of graphene oxide (GO) using density functional theory method. The geometric optimization of the unaltered structures of GO adsorbent, benzophenone derivatives, and their respective complexes was conducted via the M052X/6-311 + G* level of theory. The optimal temperature for the interaction between the GO adsorbent and BPs pollutants in the aqueous phase was found to be 298.15 K. The adsorption process was found to be spontaneous, exothermic, and irreversible based on the calculated values of adsorption energy, Gibbs free energy (ΔG_ad), and enthalpy (ΔH_ad). The negative values of the calculated chemical potential for all structures indicated that the studied structures were thermodynamically stable. The adsorption of BP-2 pollutant on the surface of GO results in a highest dipole moment (μ_d = 28.22 D) compared to the corresponding unadsorbed molecule (μ_d = 7.93 D). The adsorption efficiency of GO–BPs complexes follows an increasing trend of GO–BP-2 (−1009.75 kcal/mol) > GO–BP-3 (−1006.31 kcal/mol) > GO–BP-1(−1000.65 kcal/mol). Moreover, infrared (IR) frequency calculations confirmed the feasibility of the structures, showing true local minima. The recovery time values indicate that GO is a highly effective adsorbent in removing organic BP-2 pollutants ((tau =) 3.158 ms) from aqueous media rather than BP-3 ((tau =) 2.120 ms) and BP-1 ((tau =) 1.831 ms) counterparts. Other key parameters engaged in the adsorption behavior of considered molecules, including charge capacity, electrophilicity, band gap, chemical potential, and chemical hardness, were also deliberated.

Different standard VPT2 codes employ Cartesian coordinates for the computation of rotational and vibrational spectroscopic parameters. However, curvilinear internal coordinates offer a number of advantages provided that a general non-redundant set of coordinates can be built and employed in an unsupervised workflow. In the present paper I summarize the main results and perspectives of a general engine employing curvilinear internal coordinates and perturbation theory for the computation of rotational and vibrational spectroscopic parameters of large molecules beyond the conventional rigid rotor/harmonic oscillator model. Some examples concerning biomolecule building blocks are discussed in some detail in order to better analyze the performance of the proposed strategy.