Synthesis, and Characterization and In-Silico Analysis Against SARS CoV-2 of Novel Benzimidazolium Salts

N-heterocyclic carbene molecules are often used as the main scaffold in pharmaceutical chemistry, and one of the most important of these is benzimidazoles. Severe Acute Respiratory Syndrome Coronavirus Disease-2 is the cause of the ongoing pandemic, and a drug should be developed against this virus. Scientists have been investigated the antiviral effects of many not only known molecules but also new molecules. In this study, reactivity and anti-coronavirus disease properties of new benzimidazole derivative molecules were investigated by theoretical methods. Three new benzimidazole derivative molecules were synthesized and fully characterized by FT-IR, 1H NMR and, 13C{1H} NMR spectroscopies for this purpose. Density Functional Theory-based calculation methods were used for optimization and frontier orbitals analysis. Also, the interactions of the molecules were evaluated with coronavirus disease main protease, and severe acute respiratory syndrome coronavirus main peptidase and the results were compared with the results of well-known anti-viral drugs by molecular docking methods. According to the results, 1-allyl-3-(3-chlorobenzyl-5,6-dimethylbenzimidazolium chloride represent the best result against both main protease and main peptidase enzyme with -6.36 kcal/mol and -8.87 kcal/mol, respectively. Additionally, three of the molecules were give better binding results than the well-known anti-viral drugs

Solvent Effects on Frontier Orbitals and Electronic Transitions of Manganese Carbonyl Complexes: A DFT/TDDFT Study

Metal carbonyl complexes constitute a molecular family that is widely used in chemical processes since their discovery. Recently, one of the most popular applications of these molecules is storage/transport of CO. It is known that CO is not only an ordinary toxic gas but also a gasotransmitter. It is synthesized endogenously and the amount of CO increases in healing periods. This knowledge provides strong motivation for using metal carbonyl complexes as CO-releasing molecules for therapeutic purposes. However, the solvent that is used in analyzing CO-releasing properties causes quantitative discrepancies and this is a disadvantage for progression of studies. Nevertheless, it is extremely difficult to analyze the activity differences of bioactive molecules depending upon solvent type due to time/source restrictions. Herein, we show that theoretical analysis with DFT/TDDFT approaches could be a good alternative for determining the solvent effect. In this study, we analyzed the molecular orbital diagrams and electronic transitions of [Mn(CO)3(bpy)(L)]+ type complexes for various solvents. DOI: http://dx.doi.org/10.17807/orbital.v10i7.1157 </p

A new approach to predicting the carbonyl stretching frequencies of Co₂(CO)₈ with D₃d symmetry

1388-1392This paper describes a method for determining C-O stretching frequencies of dicobalt octacarbonyl belonging to D₃d point group. The method is based on the variation of fundamental C-O stretching frequencies and C-O stretching force constants of axially substituted X₃MCo(CO)₄ (M=Si, Ge, Sn and Pb; X=Cl, Ph and Et) molecules with the dipole moment of X₃M-Co(CO)₄ bond. Frequencies of a1ɡ⁽¹⁾, a₂ս⁽²⁾ and ℯս modes have been evaluated from the graph of frequency versus dipole moment, and the frequencies of a1g⁽²⁾ and ℯɡ modes determined from the equations derived by using the CO-factored force field. The calculated frequencies have been found to be consistent with the experimental values. With the use of the calculated frequencies, the C-O factored force constants of Co₂(CO)₈ with D₃d symmetry have been calculated. In addition, frequencies of mono-¹³CO substituted species of Co₂(CO)₈ have been estimated and compared with observed frequencies of the species

Manganese(I) tricarbonyl complexes: UV-dependent antioxidant activity, electrochemistry, and DFT/TDDFT calculation

<p>As important catalysts, metal carbonyl complexes have received considerable attention in recent years owing to their ability to store and transport carbon monoxide that have been proven to function as antiinflammatory, antiapoptotic, and antiproliferative agents. In addition, imidazole/benzimidazole derivative molecules have been known to be bioactive owing to their antihypertensive, antiinflammatory, and antimicrobial properties. Combining these two bioactive species could be a good idea for possible synergistic effect. In this study, [Mn(CO)₃(bpy)L]X (bpy =2,2-bipyridyl; X = PF₆, SO₃CF₃, L = imidazole, N-methylimidazole, benzimidazole, N-benzylbenzimidazole, N-4-chlorobenzylbenzimidazole) complexes have been characterized electrochemically and related to CO-releasing properties. The molecules have been theoretically analyzed in terms of electronic transitions and spin-density plot in water, acetonitrile, and gas phase for having insight that promote CO-releasing and electroactivity characteristics. Antioxidant activity of the complexes has also been analyzed in order to gain a possible relationship with CO-releasing properties of the complexes.</p

Silver(I) Complexes Based on Oxadiazole-Functionalized &alpha;-Aminophosphonate: Synthesis, Structural Study, and Biological Activities

Two silver(I) complexes, bis{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-&kappa;N3:&kappa;N4-amino) (4-trifluoromethylphenyl)methyl]phosphonate-(tetrafluoroborato-&kappa;F)}-di-silver(I) and tetrakis-{diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-&kappa;N3-amino)(4-trifluoromethylphenyl)methyl]phosphonate} silver(I) tetrafluoroborate, were prepared starting from the diethyl[(5-phenyl-1,3,4-oxadiazol-2-yl-amino)(4-trifluoromethylphenyl)methyl]phosphonate (1) ligand and AgBF4 salt in Ag/ligand ratios of 1/1 and 1/4, respectively. The structure, stoichiometry, and geometry of the silver complexes were fully characterized by elemental analyses, infrared, single-crystal X-ray diffraction studies, multinuclear NMR, and mass spectroscopies. The binuclear complex ([Ag2(1)2(BF4)2]; 2) crystallizes in the monoclinic asymmetric space group P21/c and contains two silver atoms adopting a {AgN2F} planar trigonal geometry, which are simultaneously bridged by two oxadiazole rings of two ligands, while the mononuclear complex ([Ag(1)4]BF4; 3) crystallizes in the non-usual cubic space group Fd-3c in which the silver atom binds to four distinct electronically enriched nitrogen atoms of the oxadiazole ring, in a slightly distorted {AgN4} tetrahedral geometry. The &alpha;-aminophosphonate and the monomeric silver complex were evaluated in vitro against MCF-7 and PANC-1 cell lines. The silver complex is promising as a drug candidate for breast cancer and the pancreatic duct with half-maximal inhibitory concentration (IC50) values of 8.3 &plusmn; 1.0 and 14.4 &plusmn; 0.6 &mu;M, respectively. Additionally, the interactions of the ligand and the mononuclear complex with Vascular Endothelial Growth Factor Receptor-2 and DNA were evaluated by molecular docking methods

Synthesis, characterization and antimicrobial properties of silver complexes derived from 5,6-Dimethylbenzimidazol-2-ylidene

Benzimidazoles are considered as a class of bioactive heterocyclic compounds that exhibit many biological activities such as antimicrobial. Benzimidazole-silver complexes also have strong antimicrobial activity, sometimes even higher than that of conventionally used silver antimicrobials. In this study, six new 5,6-dimethylbenzimidazolium ligand precursors which were functionalized by using 2-naphthylmethyl and their silver complexes were synthesized. All molecules were characterized by elemental analysis, 1H NMR, 13C NMR, and IR spectroscopy techniques. Additionally, µ-Dichloro-bis{[1-(2-naphthylmethyl)-3-(benzyl)-5,6-dimethylbenzimidazol-2-ylidene]silver(I)} was characterized structurally in the solid state by X-ray crystallography which was found to be dimeric with two bridging chlorides. In vitro antimicrobial activity of the synthesized compounds investigated in this work was tested against the reference strains: Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (ATCC 27853), Candida albicans (ATCC MYA-2876) and Candida glabrata (ATCC 2001). Some of these new compounds have been found to display significant effectiveness. Also, the molecular docking analysis was performed for all optimized ligands and complexes against Sar

Synthesis of Novel 1,3,4-Oxadiazole-Derived <i>α</i>-Aminophosphonates/<i>α</i>-Aminophosphonic Acids and Evaluation of Their In Vitro Antiviral Activity against the Avian Coronavirus Infectious Bronchitis Virus

An efficient and simple approach has been developed for the synthesis of eight dialkyl/aryl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(aryl)methyl]phosphonates through the Pudovik-type reaction of dialkyl/arylphosphite with imines, obtained from 5-phenyl-1,3,4-oxadiazol-2-amine and aromatic aldehydes, under microwave irradiation. Five of them were hydrolyzed to lead to the corresponding phosphonic acids. Selected synthesized compounds were screened for their in vitro antiviral activity against the avian bronchitis virus (IBV). In the MTT cytotoxicity assay, the dose-response curve showed that all test compounds were safe in the range concentration of 540–1599 µM. The direct contact of novel synthesized compounds with IBV showed that the diethyl[(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethoxyphenyl)methyl]phosphonate (5f) (at 33 µM) and the [(5-phenyl-1,3,4-oxadiazol-2-ylamino)(4-trifluoromethylphenyl)methyl] phosphonic acid (6a) (at 1.23 µM) strongly inhibited the IBV infectivity, indicating their high virucidal activity. However, virus titers from IBV-infected Vero cells remained unchanged in response to treatment with the lowest non-cytotoxic concentrations of synthesized compounds suggesting their incapacity to inhibit the virus replication inside the host cell. Lack of antiviral activity might presumably be ascribed to their polarity that hampers their diffusion across the lipophilic cytoplasmic membrane. Therefore, the interactions of 5f and 6a were analyzed against the main coronavirus protease, papain-like protease, and nucleocapsid protein by molecular docking methods. Nevertheless, the novel 1,3,4-oxadiazole-based α-aminophosphonic acids and α-amino-phosphonates hold potential for developing new hygienic virucidal products for domestic, chemical, and medical uses

CO-releasing properties and anticancer activities of manganese complexes with imidazole/benzimidazole ligands

<p>Carbon monoxide (CO) is an important signaling molecule which plays significant roles in the pathogenesis of cancer. CO is produced by enzymatic degradation of heme in mammals. Heme oxygenase 1 (HO-1) catalyzes the breakdown of heme into CO, ferrous iron, and biliverdin. CO induces HO-1 and inhibits cell proliferation. Cancer cells exposed to several stress factors (hypoxia, reactive oxygen species, cis-platin, and oxidative stress), and HO-1 displays cytoprotective role against oxidative stress and inhibits apoptosis, metastases, angiogenesis, and cell proliferation processes. Therefore, metal containing CO-releasing molecules (CORMs) have been designed as an effective cancer treatment strategy. CORMs are responsible for releasing controlled amounts of CO to cells and tissues. Thus, we synthesized [Mn(CO)₃(bpy)L]X manganese containing CORMs [bpy = 2,2′-bipyridine, X = hexafluorophosphate (PF₆), trifluoromethanesulfonate (OTf), L = imidazole, methylimidazole, benzimidazole, N-benzylbenzimidazole, N-(4-chlorobenzyl)benzimidazole] to release CO in human invasive ductal breast (MCF-7) cell line. <i>In vitro</i> experiments indicated that the compounds inhibited cell proliferation and exhibited cytotoxic effect on breast cancer cells. Moreover, side groups of the compounds enhanced the anticancer effects in MCF-7 cell line. These manganese containing CORMs gave promising results and may be used as a drug template for effective treatment of invasive ductal breast carcinoma.</p