Chemical Reactivity Indices Research Articles

Antitumor neodymium(III) complex with 1,10-phenanthroline and nitrate ligands: A comprehensive experimental-theoretical study, in silico pharmacokinetic and cytotoxic properties

Here we report the crystallization of the tris(nitrate-O,O')-bis(1,10-phenanthroline-N,N')-neodymium(III) complex by the slow solvent evaporation method. Structural, electronic, thermal, and vibrational properties have been explored and discussed. Additionally, all vibrational modes were carefully assigned, and geometric parameters and chemical reactivity indices were obtained from the results of density functional theory (DFT) calculations including solvation effects in dimethylformamide and water, as well as in vacuum. Moreover, a computational study using Hirshfeld surfaces identified and quantified the intermolecular interactions that stabilize the crystal lattice. X-ray powder diffraction results showed that the system has monoclinic symmetry with C2/c-space group and four monomers per unit cell (Z = 4). The thermoanalytical measurements revealed that the material has high thermal stability (≈ 300°C) and the experimental Raman and FT-IR spectroscopic data showed good correlation with the spectra calculated via DFT, where it was confirmed the influence of the solvents on the structure of the complex. Finally, cell viability assays showed that the neodymium(III) complex has cytotoxic activity and selectivity against MCF-7 (breast) and SiHa (cervical) cancer cells, with a potent biological effect. Complementary, a computational study of the pharmacokinetic profile was performed to support the experimental biological data via absorption, distribution, metabolism and elimination (ADME), and druglikeness.

Spectral, optical, thermal, dielectric, micro hardness analysis and computational calculations of a novel crystal, 2-amino-3-methylpyridinium 2, 4-dinitrobenzoate

By adapting slow evaporation technique novel single crystals of 2-Amino-3- Methylpyridinium 2, 4-Dinitrobenzoate (AMPD) were synthesized. The grown crystal was subjected to Single crystal X‒Ray Diffraction technique to explicate the crystal structure. The spectral analyses were carried out to identify the vibrational modes of various functional groups. To explore the optical transparency of the synthesized crystal UV‒Visible study has been performed and its cut-off wavelength was found to be 209 nm. By Kurtz‒Perry powder technique, the assessment of second harmonic generation efficiency of the crystal has been calculated. Using TG/DTA analysis, the thermal behavior of the crystal was studied. The mechanical strength of the crystal was examined by Vicker′s micro hardness test and the work hardening coefficient was 3.59, affirming that the grown crystal belongs to soft material category. Optimized structural geometry, vibrational wavenumbers, frontier molecular orbitals energy, chemical reactivity indices and density of states were also computed using DFT method. Nonlinear optical property of the molecule was explored by the first‒order hyperpolarizability calculation. These experimental and theoretical studies reveal that the molecules can be suitable to use in optoelectronic devices.

Analyzing a series of ligands against malaria through the application of molecular docking, molecular quantum similarity, and reactivity indices

Background The primary goal of this research is to underscore the significance of molecular docking in the context of malaria drug discovery. Molecular docking plays a crucial role in comprehending the interactions between prospective drugs and the target proteins found in Plasmodium parasites. The study delves into the docking interactions of various compounds, emphasizing the necessity of stabilizing the active site to formulate potent and selective drugs. Methods The research focuses on highlighting compound-specific interactions with residues, stressing the importance of stabilizing the active site to design drugs tailored to specific target proteins. Inhibiting the function of these target proteins disrupts the life cycle of the malaria parasite. Quantum Similarity Analysis, utilizing Overlap and Coulomb operators, is employed to identify electronic similarities. The resulting quantum similarity values guide subsequent chemical reactivity analysis. Global reactivity indices such as chemical potential, hardness, softness, and electrophilicity contribute to drug design by showcasing compound-specific indices that underscore the significance of stability and electrophilicity. Fukui functions are utilized to visualize regions for stabilization, providing insights crucial for potential malaria treatment. Results The enhancement of drug-target binding affinity is observed through stabilizing interactions in the active site. Understanding electrophilicity at the active site emerges as a critical factor in drug design and selectivity. The rational manipulation of electrophilic interactions holds promise for developing potent and selective drugs against malaria. Consequently, the integration of molecular docking, quantum similarity analysis, and chemical reactivity indices offers a comprehensive approach to malaria drug discovery. Conclusions The study identifies potential lead compounds, emphasizing the crucial role of stabilizing the active site. Additionally, it sheds light on electronic considerations vital for the design of effective and resistance-resistant drugs. The insights provided by Fukui functions into regions susceptible to -H bond formation make these compounds promising candidates for malaria treatment.

Antibacterial [Zn(nicotinamide)2Cl2] complex for the treatment of skin conditions: An experimental-theoretical study of physicochemical, microbiological and in silico pharmacokinetic properties

A dichlorobis(nicotinamide)zinc(II) complex, [Zn(nicotinamide)2Cl2], was crystallized through the slow evaporation method, and its vibrational, electronic, structural, and thermal properties have been characterized. Density functional theory (DFT) was used for the accurate analysis of intramolecular vibrational modes, obtaining chemical reactivity indices and comparative studies of geometric and electronic parameters, including solvation effects in methanol, ethanol, and water, as well as in vacuum. Additionally, the nature and strength of the bonds associated with the coordination sphere (Cl–Zn and N–Zn) were elucidated from the quantum theory of atoms in molecules and natural bond orbital analyses. Powder X-ray diffraction showed that the coordination compound belongs to a monoclinic symmetry with P21/a (C2h5) space group. Thermal analyses revealed that the material is stable up to 200 °C. From DFT calculations, the complex is chemically more stable in solvents compared to vacuum conditions, with the aqueous medium offering greater stability. The chemical stability was also analyzed by infrared and Raman spectroscopy, with the results showing spectral changes mainly for the vibrational spectra obtained in methanol, ethanol, and water against those obtained in vacuum. Biological experiments showed the complex antibacterial activity against Gram-positive and Gram-negative bacteria, mainly against the Cutibacterium acnes ATCC 6919 strain. A computational study of the absorption, distribution, metabolism, excretion (ADME), and drug-likeness were calculated to support the experimental data.

Study anti-viral drugs for their efficiency against multiple SARS CoV-2 drug targets within molecular docking, molecular quantum similarity, and chemical reactivity indices frameworks

The study focused on drug discovery for COVID-19, emphasizing the challenges posed by the pandemic and the importance of understanding the virus’s biology. The research utilized molecular docking and quantum similarity analyses to explore potential ligands for SARS-CoV-2 RNA-dependent RNA polymerase. Docking Results Docking outcomes for various ligands, including Oseltamivir, Prochloraz, Valacyclovir, Baricitinib, Molnupiravir, Penciclovir, Famciclovir, Lamivudine, and Nitazoxanide, were presented. Interactions between ligands and specific residues in the RNA-dependent RNA polymerase were analyzed. Reactivity Descriptors Global parameters, such as electronic chemical potential, chemical hardness, global softness, and global electrophilicity, were computed for the ligands. For the local reactivity descriptors, the Fukui Functions were used. Fukui functions, representing electrophilic and nucleophilic sites, were calculated for selected ligands (Valacyclovir and Penciclovir). Nucleophilic character assignments for specific molecular regions were discussed, providing insights into potential charge-donating interactions. Results and Discussion Challenges in COVID-19 drug discovery, such as virus mutability, rapid evolution, and resource limitations, were summarized. Progress in vaccine development and the need for ongoing research to address variants and breakthrough cases were emphasized. Overlap Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.5742) indicates structural and electronic similarity. Lowest MQSM between Oseltamivir and Prochloraz (0.2233) implies structural dissimilarity. Coulomb Operator Analysis Higher MQSM between Lamivudine and Molnupiravir (0.9178) suggests both structural and electronic similarity. Lowest MQSM between Baricitinib and Famciclovir (0.6001) indicates greater structural diversity. Measurements above 0.5 in Table 3 suggest electronic similarity, emphasizing the electronic aspects in molecular analysis. In this sense, it study employed a multi-faceted approach combining molecular docking, quantum similarity analyses, and chemical reactivity assessments to explore potential drug candidates for COVID-19. The findings provide valuable insights into ligand interactions, reactivity patterns, and the challenges associated with drug discovery in the context of the global pandemic.

In silico design of a new Podophyllotoxin derivative with potent anti-tubulin activity

Nowadays, there is an increasing focus on cancer as a major cause of death. Therefore, comprehending the chemical reactivity, geometric and electronic structures of inhibitors can aid in the development of better quality and more efficient drugs. In this study, we propose a hybrid compound of Podophyllotoxin (PPT) and vitamin C (VC) as an anti-cancer agent. The PPT and its derivatives are well-known for their anti-tubulin properties. The geometry optimisation and calculation of global chemical reactivity indices (µ = −3.836 eV, η = 2.402 eV, S = 0.416 eV, and ω = 3.061 eV) were performed using the M06/6-311++G (d, p) level of theory. The global reactivity descriptors predict that the PPT-VC compound has more nucleophilic properties compared to Etoposide and Teniposide compounds. Furthermore, the PPT-VC compound exhibits a lower HOMOPPT-VC–LUMOSWCNT gap and a higher adsorption energy (−37.4 kJ mol−1) in the encapsulation process than other derivatives into SWCNT, providing additional evidence of its nucleophilic nature as an effective anti-tubulin agent. Therefore, the PPT-VC@SWCNT compound can be considered a reliable drug delivery system (DDS). Molecular docking analysis reveals that the best cavity of tubulin has an interaction energy of −102.1 kJ mol−1, involving both bonding and non-bonding interactions.

Understanding the high electronic quantum similarity of a series of ligands used as inhibitors of the SARS-CoV-2 virus by molecular mechanics and density functional theory approaches

Background A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: Darunavir (Daru), Dexamethasona (Dexame), Dolutegravir (Dolu), Fosamprenavir (Fosam), Ganciclovir (Gan), Insoine (Inso), Lopinavir (Lop), Ritonavir (Rito) and Tipranavir (Tipra). Methods These ligands were analyzed using molecular docking, molecular quantum similarity using four similarity indices like overlap, Coulomb and their Euclidean distances. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LYS621, ARG555 and ASP623, CYS622, ASP760, among others. In the molecular quantum similarity, the highest indices have been obtained in the electronic similarity in comparison with the structural similarity. Conclusions These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Application of Quantum Chemical Reactivity Index Analysis—Synthesis and Mechanism of Lithium Dimethyl Sulfide

Application of Quantum Chemical Reactivity Index Analysis—Synthesis and Mechanism of Lithium Dimethyl Sulfide

Analyzing the Synthesis of 4,4-Diphenylbutyronitrile by Quantum Chemical Reactivity Index

Analyzing the Synthesis of 4,4-Diphenylbutyronitrile by Quantum Chemical Reactivity Index

Effect of solvent and pH on the stability and chemical reactivity of the delphinidin molecule

The study of the stability in different solvents and its effect on the chemical reactivity for the delphinidin molecule is presented, using molecular modeling as a tool. The structural modeling of delphinidin in the different solvents (water, methanol, ethanol and acetone) was carried out based on the predominant structures of delphinidin in different pHs (1, 4.5, 5.5 and 7). Quantum mechanical studies were performed using density functional theory (DFT) with a B3LYP level and a base set 6-11+g(d,p). The solvation energies of the delphinidin molecule were obtained, finding that methanol is where the molecule dissolves best. Besides, The chemical reactivity indices for the molecule were obtained due to the effect of the solvent, finding that when it is found in water as a solvent, it acquires a lower hardness, making it more susceptible, that is, more reactive. The results also showed that at pH < 2 using methanol as solvent, the hydrogen atom of the hydroxyl group attached to the 4' carbon is the most prone to donate hydrogen.

New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices

Background The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, molecular quantum similarity, and chemical reactivity indices defined within a conceptual density functional theory framework. Results The analysis of molecular quantum similarity indices on inhibitors showed a high number of differences from a structural point of view. However, they are quite similar in their electronic density, obtaining the highest values in the electronic similarity index. Global and local chemical reactivity indices were analyzed. Conclusions These studies allowed for the identification of the main stabilizing interactions using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical reactivity descriptors provide novel insights into these ligands that can be used in the design of new COVID-19 treatments.

Preliminary Study of The Structure of Hesperidin and Neohesperidin as a Potential Inhibitor of SARS-CoV-2 by using The DFT Method

The discovery of drugs as COVID-19 antivirals has been intensively carried out by researchers as an effort to reduce the number of victims of the COVID-19 pandemic in 2020. The discovery of main protease (Mpro) which plays a role in protein replication and transcription helped researchers identify virus inhibitors. This research has examined the potency of the bioflavonoid compounds hesperidin and the flavanon glycosides neohesperidin and their structural stability as potential inhibitors of SARS-CoV-2 by DFT computation. The first method used is the calculation of density functional theory (DFT) on hesperidin and neohesperidin molecules to optimize the geometry of the molecular structure, analysis of frontier molecular orbitals (FMO), chemical reactivity index, and map electrostatic potential (MEP).

Effect of coal tar pitch on highly reactive coke properties and microstructure

ABSTRACT Highly reactive and high-strength cokes are important for developing and producing hydrogen-rich blast furnaces. The work aimed to produce cokes with high reactivity and high post-reaction strength. The coal tar pitch (CP) was added to improve the post-reaction strength of cokes on the premise of adding alkali metals or alkaline earth metals to improve the reactivity of cokes. The chemical reactivity index of coke samples generally decreases by about 1%, while the post reaction strength of coke samples shows a significant improvement after the addition of coal tar pitch, with coke rich in CaO increasing by about 6% and coke rich in K2CO3 and Na2CO3 increasing by about 3% after adding the CP. Besides, the structural strength and micro strength of coke samples from the composite CP were improved. The microstructure analysis of the coke samples before and after the composite CP showed that the addition of the CP could weaken the originally developed pore structure of the coke samples and reduce the surface area of the gasification reaction of coke samples. Therefore, the gasification reaction of coke samples was inhibited. Moreover, the CP reduced the damage of alkali or alkaline earth metals to the dense aromatic-ring structure in the carbon matrix during the carbonization process of coking coal. It increased the amount of qualitative carbon in the coke samples and the order of carbon microcrystals. The effect of the CP on coke samples varied due to differences in coking coal and catalyst types.

Philicity scales using molecular quantum similarity and chemical reactivity indices within density functional theory

AbstractIn this manuscript, we postulate a possible relationship of philicity within a molecular set of electrocyclic reactions. Philicity has been studied by Chattaraj and co‐workers (J. Phys. Chem. A. 2003, 107, 25). This important concept was obtained using the electrophilicity index and Fukui functions. Recently, the present author has published a possible way to quantify philicity using molecular quantum similarity and chemical reactivity indices (see, J. Math. Chem. 2023, 61, 165). In this work, philicity was related with the molecular quantum similarity framework to obtain a possible way to relate philicity using 21 electrocyclic reactions using the cyclobutene reaction as a reference. The main idea is to postulate philicity scales. This methodology can open up a possible path to find systematic relationships in each molecular ensemble using the selectivity defined in the density functional theory context. With these scales, we can relate the effect of the substituent on the electrocyclic opening reaction on the molecular set.

New findings on ligand series used as SARS-CoV-2 virus inhibitors within the frameworks of molecular docking, molecular quantum similarity and chemical reactivity indices

Background: The severe acute respiratory syndrome coronavirus (SARS-CoV)-2 virus causes an infectious illness named coronavirus disease 2019 (COVID-19). SARS-CoV is a positive-sense single-stranded RNA virus from the Betacoronavirus genus. The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) has an important role in the viral life cycle and its active site is a very accessible region, thus a potential therapeutic approach may be to target this region to study the inhibition of viral replication. Various preexisting drugs have been proposed for the treatment of COVID-19 and the use of existing antiviral agents may reduce the time and cost of new drug discoveries, but the efficacy of these drugs is limited. Therefore, the aim of the present study was to evaluate a number of ligands used as SARS-CoV-2 virus inhibitors to determine the suitability of them for potential COVID-19 treatment. Methods: In this study, we selected a series of ligands used as SARS-CoV-2 virus inhibitors such as: abacavir, acyclovir, amprenavir, ascorbic acid vitamin C, azithromycin, baloxavir, boceprevir, cholecalciferol vitamin D, cidofovir, edoxudine, emtricitabine, hydroxychloroquine and remdesivir. These ligands were analyzed using molecular docking, molecular quantum similarity, and chemical reactivity indices defined within a conceptual density functional theory framework. Results: The analysis of molecular quantum similarity indices on inhibitors showed a high number of differences from a structural point of view. However, they are quite similar in their electronic density, obtaining the highest values in the electronic similarity index. Global and local chemical reactivity indices were analyzed. Conclusions: These studies allowed for the identification of the main stabilizing interactions using the crystal structure of SARS-CoV-2 RdRp. The molecular quantum similarity and chemical reactivity descriptors provide novel insights into these ligands that can be used in the design of new COVID-19 treatments.

Production of highly reactive cokes by adding alkali metals and alkaline earth metals and their effect mechanism

The influence of alkali metals and alkaline earth metals on coke reactivity and coke microstructure was studied by the mechanical mixing method to produce metallurgical cokes with high reactivity. The Gasification kinetics of coke samples was further studied to clarify the catalytic mechanism of alkali metals and alkaline earth metals on cokes, which provided a basis and guidance for the production of hydrogen-rich blast furnace charge. The chemical reactivity index of cokes increased significantly after adding alkali metals or alkaline earth metals. Meanwhile, CaO had little effect on the structural strength of cokes, while the structural strength of cokes added with K2CO3 and Na2CO3 decreased. The microstructure analysis of different coke samples showed that cokes produced new pores after adding alkali metals or alkaline earth metals, with increased contact area and decreased disorder of cokes. These were the main reasons for the increased reactivity index of cokes. The addition of alkali metals or alkaline earth metals increased the positive reaction rate constant and the effective diffusion coefficient inside cokes by analyzing the kinetic behavior of cokes after adding alkali metals or alkaline earth metals. Furthermore, it reduced gasification reaction resistance and internal-diffusion mass transfer resistance.

Design a New D-π-A Formation Dyes as Dye-sensitized Solar Cells Applications/ a DFT and TD-DFT Study.

Dye-sensitized solar cells (DSSCs) have garnered significant interest among researchers in the field of photovoltaics due to their promising performance, low cost and easy process of fabrication. In this study, we have designed new D-π-A systems as derivatives of the reference (Ref. A) D-A-D scaffold, incorporating different π-bridges to enhance and optimize their efficiency as sensitizing dyes for DSSCs applications. Density functional theory (DFT) and time-dependent DFT (TD-DFT) methods were employed to investigate the geometrical and electronic structures, chemical reactivity indices, optical properties, exciton binding energy, and electrochemical properties of these dyes. We also examined the preferred adsorption process of the two selected dyes on a (TiO2)15 cluster model. The results demonstrate that all the dyes exhibit improved open-circuit photovoltage, enhanced light-harvesting efficiencies, higher electron injection efficiency, and excellent photovoltaic efficiency. Moreover, there is evidence of electron injection occurring from each studied dye to the conduction band of TiO2, followed by efficient regeneration. The introduced bridges in the molecular systems play a crucial role in facilitating electron transfer from the donor to the acceptor region. Comparatively, the D-π-D systems exhibit superior performance in DSSCs compared to Ref. A, which can be attributed to their higher energy levels of the lowest unoccupied molecular orbital and larger oscillator strengths for the most excited states involving intramolecular electron transfer and the electron injection process occurring from each examined molecule to the conduction band of TiO2, followed by subsequent regeneration. Overall, the results of our study highlight the potential of all the D-π-A systems as promising sensitizers for DSSCs applications, owing to their favorable optical and electronic properties and impressive photovoltaic parameters.

Receptor-Based Pharmacophore Modelling of a series of ligands used as inhibitors of the SARS-CoV-2 virus by complementary theoretical approaches, molecular docking, and reactivity descriptors.

Background: A coronavirus identified in 2019, SARS- CoV- 2, has caused a pandemic of respiratory illness, called COVID- 19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: the Zidovudine, Tromantadine, Pyramidine, Oseltamivir, Hydroxychoroquine, Cobicistat, Doravirine (Pifeltro), Dolutegravir, Boceprevir, Indinavir, Truvada, Trizivir, Trifluridine, Sofosbuvir and Zalcitabine. Methods: These ligands were analyzed using molecular docking, Receptor-Based Pharmacophore Modelling. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LEU141, GLN189, GLU166 and GLY143, HIE41, among others. Also was development an electrostatic potential comparison using the global and local reactivity indices. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Understanding the high electronic quantum similarity of a series of ligands used as inhibitors of the SARS-CoV-2 virus by molecular mechanics and density functional theory approaches

Background: A coronavirus identified in 2019, SARS-CoV-2, has caused a pandemic of respiratory illness, called COVID-19. Most people with COVID-19 experience mild to moderate symptoms and recover without the need for special treatments. The SARS‑CoV‑2 RNA‑dependent RNA polymerase (RdRp) plays a crucial role in the viral life cycle. The active site of the RdRp is a very accessible region, so targeting this region to study the inhibition of viral replication may be an effective therapeutic approach. For this reason, this study has selected and analysed a series of ligands used as SARS-CoV-2 virus inhibitors, namely: Darunavir (Daru), Dexamethasona (Dexame), Dolutegravir (Dolu), Fosamprenavir (Fosam), Ganciclovir (Gan), Insoine (Inso), Lopinavir (Lop), Ritonavir (Rito) and Tipranavir (Tipra). Methods: These ligands were analyzed using molecular docking, molecular quantum similarity using four similarity indices like overlap, Coulomb and their Euclidean distances. On the other hand, these outcomes were supported with chemical reactivity indices defined within a conceptual density functional theory framework. Results: The results show the conformations with the highest root-mean-square deviation (RMSD), have π-π stacking interaction with residue LYS621, ARG555 and ASP623, CYS622, ASP760, among others. In the molecular quantum similarity, the highest indices have been obtained in the electronic similarity in comparison with the structural similarity. Conclusions: These studies allow the identification of the main stabilizing interactions using the crystal structure of SARS‑CoV‑2 RNA‑dependent RNA polymerase. In this order of ideas, this study provides new insights into these ligands that can be used in the design of new COVID-19 treatments. The studies allowed us to find an explanation supported in the Density Functional Theory about the chemical reactivity and the stabilization in the active site of the ligands.

Novel oxazolidinone zinc(II) complexes as antibacterial and anti-SARS-CoV-2 agents: synthesis, characterization, DFT calculations, ADMET, in silico molecular docking and biological activities

A series of Zn(II) complexes with oxazolidinone derivatives has been synthesized and characterized using spectroscopic techniques: IR, 1H NMR, UV-Vis spectroscopy, and TGA/DTG thermal investigation. Theoretical computations were carried out using B3LYP/6-31G(d) and B3LYP/LanL2DZ to analyze the vibrational properties, NBO charges, global chemical reactivity indices and to illustrate the FOMs. TD-DFT calculations using WB97XD functional were realized with 6-31 G(d) and LAN2DZ basis set on oxazolidinone ligands and their zinc complexes. The pharmacokinetic properties and toxicity of the investigated compounds were predicted using in silico ADMET studies. Moreover, the S. aureus, E. coli, S. pneumoniae, ribosome 50S subunit, SARS-Cov-2 spike protein and ACE2 human receptor were selected for molecular docking study. The docking study shows that HL4 and ZnL4 bind better to the spike protein and hACE2 receptor. The redox properties were also studied for ligands and their corresponding complexes using cyclic voltammetry. Finally, antioxidant activity studies using DPPH radical scavenging showed efficiency for HL2 and [Zn(L2)2] with low values of IC50 compared to ascorbic acid. The antimicrobial activity against B. subtilis (ATCC 9372), E. faecalis (ATCC 29212), S. aureus (ATCC 6538), E. coli (ATCC 4157), bacteria strains, C. albicans (ATCC 24433) and A. niger fungi strains were evaluated.