Realization of Coronavirus Testing Kit Using a Combination of a Triangular Photonic Crystal (PhC) Structure and a 412 nm Laser Beam

The design of a Covid-19 testing kit is proposed in this research using a photonic crystal structure (PhC) and a violet laser beam. The basic principle of this structure relies on the phenomenon of absorbance reflectance and transmission at the signal of a 412 nm laser beam. Finally, the transmitted light energy through the PhC structure is the conclusive factor to detect the types of virus which is the function of the reflectance and absorbance. The reflected light energy is computed by plane wave expansion (PWE) whereas the absorbance of light energy is obtained through numerical computation. The notable advantages of this technique are that the virus related to Covid-19 can be recognized by observing the colour of transmitted energy through a photo energy meter. Finally, the outcomes of the research affirm that the sample could be Covid-19 if the output energy would be infrared (IR). Similarly, the sample could be a normal coronavirus, if the output energy would lie within the visible regime.

A phenoxy-bridged trinuclear Ni(ii) complex: synthesis, structural elucidation and molecular docking with viral proteins

A novel phenoxy-bridged trinuclear nickel(ii) complex [Ni3(mu-L)2(bipy)3](1) (where H3L= (E)-2-hydroxy-N-(2-hydroxy-3,5-diiodophenyl)-3,5-diiodobenzohydrazonic acid, bipy = 2,2'-bipyridyl) has been designed and synthesized as a potential antivirus drug candidate. The trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) was fully characterized via single crystal X-ray crystallography. The unique structure of the trinuclear nickel(ii) complex crystallized in a trigonal crystal system with P3221 space group and revealed distorted octahedral coordination geometry around each Ni(ii) ion. The X-ray diffraction analysis established the existence of a new kind of trinuclear metal system containing nickel(ii)-nickel(ii) interactions with an overall octahedral-like geometry about the nickel(ii) atoms. The non-bonded Ni-Ni distance seems to be 3.067 and 4.455 A from the nearest nickel atoms. The detailed structural analysis and non-covalent supramolecular interactions are also investigated by single crystal structure analysis and computational approaches. Hirshfeld surfaces (HSs) and 2D fingerprint plots (FPs) have been explored in the crystal structure to investigate the intermolecular interactions. The preliminary analysis of redox and magnetic characterization was conducted using cyclic voltammetry measurements and a vibrating sample magnetometer (VSM), respectively. This unique structure shows good inhibition performance for SARS-CoV-2, Omicron and HIV viruses. For insight into the potential application of the Ni(ii) coordination complex as an effective antivirus drug, we have examined the molecular docking of the trinuclear Ni(ii) complex [Ni3(mu-L)2(bipy)3](1) with the receptor binding domain (RBD) from SARS-CoV-2 (PDB ID: 7MZF), Omicron BA.3 variant spike (PDB ID: 7XIZ), and HIV protease (PDB ID: 7WCQ) viruses. This structure shows good inhibition performance for SARS-CoV-2, Omicron S protein and HIV protease viruses;the binding energies (DELTAG) and the respective Ki/Kd (inhibition/dissociation constants) correlation values are -8.9 (2.373 muM or 2373 nM), -8.1 (1.218 muM or 1218 nM) and -7.9 (0.874 muM or 874 nM), respectively. The results could be used for rational drug design against SARS-CoV-2 Omicron variant and HIV protease viruses.Copyright © 2023 The Royal Society of Chemistry.

Structure-Based Design of Potent Peptidomimetic Inhibitors Covalently Targeting SARS-CoV-2 Papain-like Protease.

The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a critical role in the proteolytic processing of viral polyproteins and the dysregulation of the host immune response, providing a promising therapeutic target. Here, we report the structure-guide design of novel peptidomimetic inhibitors covalently targeting SARS-CoV-2 PLpro. The resulting inhibitors demonstrate submicromolar potency in the enzymatic assay (IC50 = 0.23 µM) and significant inhibition of SARS-CoV-2 PLpro in the HEK293T cells using a cell-based protease assay (EC50 = 3.61 µM). Moreover, an X-ray crystal structure of SARS-CoV-2 PLpro in complex with compound 2 confirms the covalent binding of the inhibitor to the catalytic residue cysteine 111 (C111) and emphasizes the importance of interactions with tyrosine 268 (Y268). Together, our findings reveal a new scaffold of SARS-CoV-2 PLpro inhibitors and provide an attractive starting point for further optimization.

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, H-1 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(L-2)(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.

Synthesis, theoretical calculations, X-ray, HS and energy framework analysis, molecular docking of amino pyrazole containing azo dye and its inhibition activity of COVID-19 main protease

The synthesis and characterization of 5-Amino-4-Phenylazo-3-Methyl-1-(2-hydroxyethyl) Pyrazole (AD2a) were investigated in our study. The novel synthesized pyrazole-based disperse diazo dye has been elucidated by using UV–Vis, FT-IR, elemental analysis, LC/MS-MS, NMR and X-ray analysis. The AD2a molecule containing pyrazole and phenyl rings, hydroxy‑ethyl and azo group moieties crystallized in the orthorhombic space group Pbca. The crystal structures of AD2a are consolidated by N(3)-H(3A)⋯O(1) and O(1)-H(1)⋯N(5) intermolecular hydrogen bonds. The geometry of AD2a has been optimized with the DFT calculation B3LYP/6–31G(d,p) level and it has been observed that the obtained results give very good results with the X-ray diffraction data. The theoretical vibrational analysis, frontier orbital energies, electronic absorption spectrum, electronic properties, global reactivity descriptors and other theoretical parameters were obtained by using the same DFT method. Additionally, Hirshfeld surface analysis (HSA) with 2D fingerprint plots (FP) was performed to estimate contacts and the energy framework diagrams of AD2a (Eele, Edis and Etot) were determined. The inhibitor-receptor relationship established by the molecular docking study confirmed the inhibition activity of the AD2a construct against COVID-19. It showed that the AD2a molecule, shown as a drug candidate, binds strongly to SARS-CoV-2 (Mpro) (-6.5 kcal/mol) receptors.

Structural and Computational Studies of Cobalt(II) and Copper(II) Complexes with Aromatic Heterocyclic Ligand

Two coordination complexes, a cobalt(II) complex tris(1,10-phenanthroline)-cobalt perchlorate hydrate, [Co(phen)3]·(ClO4)2·H2O(1), and a copper(II) complex tris(1,10-phenanthroline)-copper perchlorate 4-bromo-2-{[(naphthalene-1-yl)imino]methyl}phenol hydrate, [Cu(phen)3]·(ClO4)2·HL·[O] (2), [where, phen = 1,10-phenathroline as aromatic heterocyclic ligand, HL = 4-bromo-2-((Z)-(naphthalene-4-ylimino) methyl) phenol] have been synthesized and structurally characterized. Single crystal X-ray analysis of both complexes has revealed the presence of a distorted octahedral geometry around cobalt(II) and copper(II) ions. density functional theory (DFT)-based quantum chemical calculations were performed on the cationic complex [Co(phen)3]2+ and copper(II) complex [Cu(phen)3]2+ to get the structure property relationship. Hirshfeld surface and 2-D fingerprint plots have been explored in the crystal structure of both the metal complexes. To find potential SARS-CoV-2 drug candidates, both the complexes were subjected to molecular docking calculations with SARS-CoV-2 virus (PDB ID: 7BQY and 7C2Q). We have found stable docked structures where docked metal chelates could readily bound to the SARS-CoV-2 Mpro. The molecular docking calculations of the complex (1) into the 7C2Q-main protease of SARS-CoV-2 virus revealed the binding energy of −9.4 kcal/mol with a good inhibition constant of 1.834 µM, while complex (2) exhibited the binding energy of −9.0 kcal/mol, and the inhibition constant of 1.365 µM at the inhibition binding site of receptor protein. Overall, our in silico studies explored the potential role of cobalt(II) complex (1), and copper(II) complex (2) complex as the viable and alternative therapeutic solution for SARS-CoV-2.

Structure property relationship in two thiazole derivatives: Insights of crystal structure, Hirshfeld surface, DFT, QTAIM, NBO and molecular docking studies

Detailed structural and noncovalent interactions in two thiazole derivatives (N-(4-Bromophenyl)-2-(methylthio)thiazole-5-carboxamide and Ethyl-5-((4-bromophenyl)carbamoyl)thiazole-4-carboxylate) are investigated by single crystal X-ray diffraction study and computational approaches. The structure investigation revealed that various interactions like C-H…O, N-H…O, and N-H…N hydrogen bonds and Br…Br interactions are involved in constructing ring motifs to stabilize the crystal packing. Hirshfeld surface analysis and fingerprint plots were carried out to study the differences and similarities in the relative contribution of noncovalent interactions in both the molecules. The FMOs and other global reactive parameters are analyzed for thiazole derivatives. The strength and nature of weak interactions present in the molecule were characterized by RDG-based NCI and QTAIM analyses. Natural bond orbital (NBO) analysis unravels the importance of non-covalent and hyperconjugative interactions for the stability of the molecules in their solid state. Further, molecular docking of N-(4-Bromophenyl)-2-(methylthio)thiazole-5-carboxamide and Ethyl-5-((4-bromophenyl)carbamoyl)thiazole-4-carboxylate with SARS-Covid-19 have been carried out. © 2023 Taylor & Francis Group, LLC.

Computational study of 2D photonic crystal based biosensor for SARS-COV-2 detection

A computational study to design a 2D-photonic crystal (PC) structure with a fluorescence-based biosensor has been demonstrated for the detection of the severe acute respiratory syndrome corona virus 2 (SARS-COV-2) virus in the lungs. The proposed sensor can detect the different concentrations of the virus without any pretreatment of the sample. The virus detection is performed by measuring the mid-gap wavelength from the dispersion diagram and a redshift in the mid-gap wavelength has been observed as the concentration of virus increases in the lung tissue. The plane wave expansion method is used to determine the dispersion diagram of the proposed PC. The interaction of incident light with the proposed PC-based biosensor has been analyzed to evaluate the shift in the mid-gap wavelength. A maximum sensitivity of about 1459.3 nm/RIU is obtained for r/a = 0.45 with a mid-gap wavelength shift of 145.93 nm at n net = 1.49 concentration of SARS-COV-2. Moreover, a very small detection time has been observed with the proposed device as compared to conventional methods. This study provides a simple process to detect the presence of a virus within a short period and could be helpful in the development of a direct and easy-to-use portable detection kit in the future. © 2023 IOP Publishing Ltd.

A quinoline-benzotriazole derivative: Synthesis, crystal structure and characterization by using spectroscopic, DFT and molecular docking methods

In this research, FT-IR, NMR (1H & 13C), mass spectrometry and single-crystal X-ray diffraction has been used to characterize the synthesized 5-((1H-benzo[d][1,2,3]triazol-1-yl)methyl)quinolin-8-ol (DD2) derivative. B3LYP calculations with the 6-31G* and 6–311++G** basis sets have shown that the most stable C2 structure in gas phase and aqueous solution is in agreement with the experimental determined by X-ray diffraction. Higher dipole moments for C2 in aqueous solution, predicted with both methods, are probably related to its higher stability resulting higher volume contraction (ΔV −1.0 Å3) in solution with the B3LYP/6-31G* method. Similar behaviours in the Mulliken and NPA charges but different from MK charges are observed. Bond orders studies reveal that the O15-H16···N17 bonds are present in both media, as was experimentally observed in the solid state. MEP surfaces have evidenced nucleophilic sites on N of triazol ring while weak electrophilic ones on aromatic H of three rings being the H atom of OH the most labile. Gap values support a lower reactivity of C2 in solution, in agreement with the higher stability evidenced by AIM analyses. The higher electronic density on triazol ring could justify that C2 is unstable in solution, as revealed by NBO analyses. Complete assignments of 93 expected vibration normal modes of C2 and a set of scaled force constants were obtained in both media by using harmonic force fields. Comparisons between experimental and theoretical infrared and 1H- and 13C NMR spectra show reasonable concordances. Intermolecular interactions in the crystal packing of DD2 were studied by using Hirshfeld surface analysis. Furthermore, DD2 was investigated against two targets of SARS-CoV-2 (PDB ID: 6WCF and PDB ID: 6Y84) by using molecular docking studies. Finally, drug likeness and ADME properties of DD2 were researched and compared with hydroxychloroquine, remdesivir, oseltamivir, lopinavir, ritonavir molecules associated as SARS-CoV-2 inhibitors. © 2023 The Authors

A new short synthesis route for favipiravir and its analogue: Their tautomerization behaviour

The study of tautomerism in biologically relevant heterocycles is essential, as it directly affects their chemical properties and biological function. Lactam-lactim tautomerization in pyridine/pyrazine derivatives is such a phenomenon. Favipiravir, a pyrazine derivative, is an essential antiviral drug molecule having notable performance against SARS-CoV-2. Along with a better yielding synthetic method for favipiravir, we have also investigated the lactam-lactim tautomerization of favipiravir and its analogous molecules. Most of these molecules were crystalized and studied for various interactions in their lattice. Many interesting supramolecular interactions such as hydrogen bonding, pi-pi stacking and halogen bonding were revealed during the analysis. Some of these structures show interesting F-F halogen bonding and water channels in their solid state.Copyright © 2022 The Royal Society of Chemistry.

Broad-spectrum coronavirus 3C-like protease peptidomimetic inhibitors effectively block SARS-CoV-2 replication in cells: Design, synthesis, biological evaluation, and X-ray structure determination.

Despite the approval of vaccines, monoclonal antibodies and restrictions during the pandemic, the demand for new efficacious and safe antivirals is compelling to boost the therapeutic arsenal against the COVID-19. The viral 3-chymotrypsin-like protease (3CLpro) is an essential enzyme for replication with high homology in the active site across CoVs and variants showing an almost unique specificity for Leu-Gln as P2-P1 residues, allowing the development of broad-spectrum inhibitors. The design, synthesis, biological activity, and cocrystal structural information of newly conceived peptidomimetic covalent reversible inhibitors are herein described. The inhibitors display an aldehyde warhead, a Gln mimetic at P1 and modified P2-P3 residues. Particularly, functionalized proline residues were inserted at P2 to stabilize the ß-turn like bioactive conformation, modulating the affinity. The most potent compounds displayed low/sub-nM potency against the 3CLpro of SARS-CoV-2 and MERS-CoV and inhibited viral replication of three human CoVs, i.e. SARS-CoV-2, MERS-CoV, and HCoV 229 in different cell lines. Particularly, derivative 12 exhibited nM-low µM antiviral activity depending on the virus, and the highest selectivity index. Some compounds were co-crystallized with SARS-CoV-2 3CLpro validating our design. Altogether, these results foster future work toward broad-spectrum 3CLpro inhibitors to challenge CoVs related pandemics.

Effective Binding Affinity of Inhibitor - [3-(Carbamoylamino) Phenyl] Acetamide Against the SARS-CoV-2 NSP13 Helicase

The ongoing outbreak of COVID-19 has become a global health emergency. The SARS-CoV-2 NSP13 helicase plays an important role in SARS-Co V-2 replication and could serve as a target for antivirals to develop potential COVID-19 treatment. The objective of the study is to used Homology modeling and docking analysis of SARS-CoV-2 NSP13 helicase as drug target. The results of this study establish N-[3-( carbamoylamino) phenyl] acetamide as a valuable lead molecule with great potential for SARS-CoV-2 NSP13 helicase inhibitor. The structure and function of SARS-CoV- 2 NSP13 helicase predicted by in silica modeling studies. The SWISS-MODEL Structure Assessment tool was used for homology modeling and visual analysis of the crystal structure of the protein. The validation for structure models was performed using PROCHECK. Model quality estimates based on the QMEAN and ProSA. The MCULE-1-Click docking and InterEvDock-2.0 server were used for proteinlig and docking.The SARS-CoV-2 NSP13 helicase model corresponds to probability confirmation with 90.9% residue of the core section that specifies the accuracy of the predicted model. ProS A Z-score of -9.17;indicates the good quality of the model. Inhibitor N-[3-(carbamoylamino) phenyl] acetamide exhibited effective binding affinity against the NSP13 helicase. The docking results revealed the Lys-146, Leu-147, Ile-151, Tyr-185, Lys-195, Tyr-224, Val-226, Leu- 227, Ser-229 residues exhibit good binding interactions with inhibitor ligand.

The impact of the COVID-19 pandemic on the structure of radiation diagnostics and collective doses of the population of the Russian Federation under medical irradiation in 2020.

Computed tomography has become the main method of early diagnostics of COVID-19 during the pandemic of the novel coronavirus infection. Based on results of computed tomography of the chest it is possible to diagnose viral pneumonia associated with COVIS-19, to quickly assess the lung damage volume and severity of changes, to perform quick routing of patients and to start antiviral treatment. Hence, 2020 was associated with a rapid increase in the number of computed tomography examinations with corresponding changes in the structure of X-ray diagnostics. The aim of the current study was to evaluate the impact of the pandemic of the novel coronavirus infection on the structure of X-ray diagnostics and collective doses from medical exposure in the Russian Federation in 2019-2020. The study was based on the results of analysis of the federal state statistical surveillance forms 3-DOZ and 30 as well as on the data on Covid-19 morbidity in the regions of the Russian Federation. The results of the study indicate that there were no significant changes in the structure of X-ray diagnostics in 2020 compared to 2019 except for the increase in the number of computed tomography examinations. Their contribution to the total number of X-ray examinations has increased to 8,2% in 2020 compared to 4,6% in 2019. Contribution of other imaging modalities to the total number of X-ray examinations has not changed significantly. In 2020 the number of X-ray examinations decreased by 20% in average, varying from 6% for diagnostic nuclear medicine to 42% for interventional examinations. At the same time, the number of computed tomography examinations has rapidly increased by 60%. The structure of collective dose from medical exposure has significantly changed in 2020. Contribution of computed tomography to the collective dose in 2020 accounted for to 74% compared to 57% in 2019. Contribution of other imaging modalities has decreased by the factor of 1,5-2. Contribution of radiography examinations has decreased to 10,5% compared to 19% in 2019. Collective doses have correspondingly decreased by 20-30% for all imaging modalities except for computed tomography. Collective dose from computed tomography has increased by 71% compared to 2019. The number of all X-ray examinations in the Russian Federation has decreased by 12%: from 294 million in 2019 to 258 million in 2020. Collective dose from medical exposure has rapidly increased in 2020 by 30% to 115 thousand man.-Sv compared to 88 thousand man.-Sv in 2019. In average, in regions of the Russian Federation in 2020 each second computed tomography examination has been performed as a part of COVID-19 diagnostics with 2,3 computed tomography examinations per person infected with COVID.Copyright © 2022, Saint-Petersburg Research Institute of Radiation Hygiene after Professor P.V. Ramzaev. All rights reserved.

Impact of Drug Repurposing on SARS-Cov-2 Main Protease

Abstract: The recent emergence of the severe acute respiratory disease caused by a novel coronavirus remains a concern posing many challenges to public health and the global economy. The resolved crystal structure of the main protease of SARS-CoV-2 or SCV2 (Mpro) has led to its identification as an attractive target for designing potent antiviral drugs. Herein, we provide a comparative molecular impact of hydroxychloroquine (HCQ), remdesivir, and β-D-N4-Hydroxycytidine (NHC) binding on SCV2 Mpro using various computational approaches like molecular docking and molecular dynamics (MD) simulation. Data analyses showed that HCQ, remdesivir, and NHC binding to SARS-CoV-2 Mpro decrease the protease loop capacity to fluctuate. These binding influences the drugs' optimum orientation in the conformational space of SCV2 Mpro and produce noticeable steric effects on the interactive residues. An increased hydrogen bond formation was observed in SCV2 Mpro–NHC complex with a decreased receptor residence time during NHC binding. The binding mode of remdesivir to SCV2 Mpro differs from other drugs having van der Waals interaction as the force stabilizing protein–remdesivir complex. Electrostatic interaction dominates in the SCV2 Mpro−HCQ and SCV2 Mpro–NHC. Residue Glu166 was highly involved in the stability of remdesivir and NHC binding at the SCV2 Mpro active site, while Asp187 provides stability for HCQ binding. © 2022, Pleiades Publishing, Ltd.

Cu(II)(PhOMe-Salophen) Complex: Greener Pasture Biological Study, XRD/HAS Interactions, and MEP

Abstract: PhOMe-salophen (1b) (salophen is N,N-bis(salycilidene)-1,2-phenylenediamine with two tert-butyl on each ring) and Cu(II) complex with PhOMe-salophen (1c) have been synthesized and characterized using various tools, including X-ray diffraction for the Cu(II)-complex (1c, C43H52CuN2O3)). The copper complex has been obtained by Cu2+ templated approach using 1b. PhOMe-salophen (1b) has been obtained in reasonably high yield using a mixture of the Schiff-base, 1a, Pd(OAc)2, PPh3, Na2CO3, 4-methoxyphenylboronic acid in benzene. We focus in this research work on the electronic and structural properties of the Cu–Schiff base complex. The tetra-coordinate τ4 index was calculated, indicating almost a perfect square planner in agreement with X-ray diffraction results. MEP reveals the maximum positive regions in 1/-associated with the azomethine and methoxyphenyl C–H bonds with an average value of 0.03 a.u. Hirshfeld surface analysis (HSA) was also studied to highlight the significant inter-atomic contacts and their percentage contribution through 2D Fingerprint plot. In a fair comparative molecular docking study, 1b and 1c were docked together with N-[{(5-methylisoxazol-3-yl)-carbonyl}alanyl}-l-valyl]-N1-((1R,2Z)-4-(benzyloxy)-4-oxo-1-[{(3R)-2-oxopyrrolidin-3-yl}methyl]but-2-enyl)-l-leucinamide, N3 against main protease Mpro, (PDB code 7BQY) using the same parameters and conditions. Interesting here to use the free energy, in silico, molecular docking approach, which aims to rank our molecules with respect to the well-known inhibitor, N3. The binding scores of 1b, 1c, N3 are –7.8, –9.0, and –8.4 kcal/mol, respectively. These preliminary results propose that ligands deserve additional study in the context of possible remedial agents for COVID-19. © 2022, Pleiades Publishing, Ltd.

The Potential Impact of Ayurvedic Traditional Bhasma on SARS-CoV-2-Induced Pathogenesis

The mass casualties caused by the delta variant and the wave of the newer "Omicron" variant of SARS-COV-2 in India have brought about great concern among healthcare officials. The government and healthcare agencies are seeking effective strategies to counter the pandemic. The application of nanotechnology and repurposing of drugs are reported as promising approaches in the management of COVID-19 disease. It has also immensely boomed the search for productive, re-liable, cost-effective, and bio-assimilable alternative solutions. Since ancient times, the traditional-ly employed Ayurvedic bhasmas have been used for diverse infectious diseases, which are now employed as nanomedicine that could be applied for managing COVID-19-related health anomalies. Like currently engineered metal nanoparticles (NPs), the bhasma nanoparticles (BNPs) are also packed with unique physicochemical properties, including multi-elemental nanocrystalline compo-sition, size, shape, dissolution, surface charge, hydrophobicity, and multi-pathway regulatory as well as modulatory effects. Because of these conformational and configurational-based physico-chemical advantages, Bhasma NPs may have promising potential to manage the COVID-19 pandemic and reduce the incidence of pneumonia-like common lung infections in children as well as age-related inflammatory diseases via immunomodulatory, anti-inflammatory, antiviral, and adju-vant-related properties.Copyright © 2023 Bentham Science Publishers.

Synthesis, crystal structure, DFT calculations, and Hirshfeld surface analysis of an NNN pincer type compound

The novel benzamide derivative NNN pincer type, N,N'-(azanediylbis(2,1-phenylene))bis(3-chlorobenzamide) (H3L), was synthesized from bis(2-nitrophenyl)amine starting material. The pincer ligand was characterized by 1H NMR, 13C NMR, COSY, HMQC, and FT-IR techniques. The geometry of pincer ligand was also confirmed by a single-crystal X-ray diffraction analysis. Structural analysis demonstrate that H3L is monoclinic and space group P21/n with Z = 4. It was find out the molecular conformation of the structure is promoted by intramolecular (N[sbnd]H⋅⋅⋅O, N[sbnd]H⋅⋅⋅N, and C[sbnd]H⋅⋅⋅O) and intermolecular (N(2)-H(2)⋅⋅⋅O(2)i, symmetry code (i) = 1/2 + x, 3/2-y, 1/2 + z) hydrogen bonds. The theoretical study of H3L was performed in the gaseous phase by B3LYP/6-311G(d,p) method to determine the structural properties of the title molecule, as a consequence the obtained data showed that the considerable agreement between the experimental and theoretical results. The reactivity and stability of the molecule were evaluated by calculating the HOMO–LUMO energy gap which was found as 6.5163 eV. In addition, FMO, NBO, NLO, DOS, RDG, MEP surface, and Mulliken atomic charge analyses were carried out. Hirshfeld surface analysis and two-dimensional fingerprint plots were investigated and the obtained data exposed that the most significant contributions to the crystal packing are from C···H/H···C (33.2%), H···H (31.5%), and H···Cl/Cl··H (18.9%) contacts. Furthermore, the molecular docking studies were performed to reveal the binding affinity between the title compound and the main protease (6LU7) of COVID-19 coronavirus. © 2023 Elsevier B.V.

Low-Dimensional Compounds Containing Bioactive Ligands. Part XX: Crystal Structures, Cytotoxic, Antimicrobial Activities and DNA/BSA Binding of Oligonuclear Zinc Complexes with Halogen Derivatives of 8-Hydroxyquinoline

Two tetranuclear [Zn4Cl2(ClQ)6]·2DMF (1) and [Zn4Cl2(ClQ)6(H2O)2]·4DMF (2), as well as three dinuclear [Zn2(ClQ)3(HClQ)3]I3 (3), [Zn2(dClQ)2(H2O)6(SO4)] (4) and [Zn2(dBrQ)2(H2O)6(SO4)] (5), complexes (HClQ = 5-chloro-8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline and HdBrQ = 5,7-dibromo-8-hydroxyquinoline) were prepared as possible anticancer or antimicrobial agents and characterized by IR spectroscopy, elemental analysis and single crystal X-ray structure analysis. The stability of the complexes in solution was verified by NMR spectroscopy. Antiproliferative activity and selectivity of the prepared complexes were studied using in vitro MTT assay against the HeLa, A549, MCF-7, MDA-MB-231, HCT116 and Caco-2 cancer cell lines and on the Cos-7 non-cancerous cell line. The most sensitive to the tested complexes was Caco-2 cell line. Among the tested complexes, complex 3 showed the highest cytotoxicity against all cell lines. Unfortunately, all complexes showed only poor selectivity to normal cells, except for complex 5, which showed a certain level of selectivity. Antibacterial potential was observed for complex 5 only. Moreover, the DNA/BSA binding potential of complexes 1–3 was investigated by UV-vis and fluorescence spectroscopic methods.

DFT, ADMET, molecular docking and molecular dynamics studies of pyridoxal

We report in silico studies of pyridoxal, which is of interest both as a precursor for further functionalization due to the presence of the aldehyde functionality, as well as a bioactive compound. So far, the crystal structure of pyridoxal has not been reported and, thus, we have optimized its structure both under water solvation and in gas phase using the DFT calculations. Under water solvation conditions the optimized structure of pyridoxal is 7.62 kcal/mol more favorable in comparison to that in gas phase. The DFT calculations were also applied to verify optical and electronic properties of the optimized structure of pyridoxal in water. The HOMO and LUMO were revealed to subtract a set of descriptors of the so-called global chemical reactivity as well as to probe pyridoxal as a potential corrosion inhibitor for some important metals used in implants. The title compound exhibits the best electron charge transfer from the molecule to the surface of Ni and Co. Some biological properties of pyridoxal were evaluated using the respective on-line tools. Molecular docking was additionally applied to study interaction of pyridoxal with some SARS-CoV-2 proteins as well as one of the monkeypox proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with nonstructural protein 15 (endoribonuclease) and Omicron Spike protein of SARS-CoV-2. Pyridoxal was found to be also active against the studied monkeypox protein. Interaction of pyridoxal with nonstructural protein 15 (endoribonuclease) was further studied using molecular dynamics simulation.Copyright © 2023 Indian Chemical Society

N'-isonicotinoylpicolinohydrazonamide: Synthesis, crystal structure, DFT and ADMET studies, and in silico inhibition properties toward a series of COVID-19 proteins

In this work, synthesis as well as detailed structural and computational analyses of the novel isoniazid derivative, namely N'-isonicotinoylpicolinohydrazonamide (1), are reported. The obtained compound was examined by microanalysis, IR, 1H NMR spectroscopy and single crystal X-ray diffraction. The crystal packing was studied by the Hirshfeld surface analysis. Molecules in the crystal structure of 1 are linked through N–H⋯O and N–H⋯N hydrogen bonds, and π⋯π interactions, yielding a 1D supramolecular chain. According to the Hirshfeld surface analysis, crystal packing of 1 is primarily dictated by H⋯H, H⋯C, H⋯N and H⋯O contacts, of which the latter three contacts are highly favoured. The crystal packing is further characterized by highly favoured C⋯C contacts. Compound 1 was also studied using DFT in gas phase, which revealed its pronounced electrophilic features. The most electron-rich (nucleophilic) sites were revealed for the carbonyl oxygen atom, and 4-pyridyl and imine nitrogen atoms, while the most electron-deficient (electrophilic) sites were found for the NH and NH2 hydrogen atoms. Compound 1 was predicted to belong to a fourth class of toxicity and exhibits negative blood–brain barrier penetration and positive gastrointestinal absorption property. In silico molecular docking was applied to probe 1 as a potential inhibitor of a series of the SARS-CoV-2 proteins and it was found that 1 is potentially active against all the applied proteins with the best activity against Nonstructural protein 3 (Nsp3_range 207–379-MES). It was also established that the best docking scores for 1 were found for the cavities, where initial ligands were located, except for the Papain-like protease (PLpro). The best binding affinity of the latter protein with 1 was revealed for the other cavity with about 0.8 kcal/mol being more efficient. Molecular dynamics simulations were also applied to evaluate the stability of complexes PLproI–1, PLproII–1 and Nsp_range 207–379-MES–1. Complex PLproI–1 was found to be highly unstable, while complexes PLproII–1 and Nsp_range 207–379-MES–1 are stable. © 2023 Elsevier Ltd