Quinoline Ligands Research Articles

Synthesis, characterization, antibacterial, antioxidant and molecular docking studies of Zn(II) complexes with imine quinoline derivative ligand

The efficacy of metal complexes with bioactive ligands for pharmaceutical purposes is increasingly gaining clinical and commercial importance for treating infectious diseases. This research aimed to synthesize new Zn(II) complexes, assess their potential applications in antibacterial and antioxidant properties, and explore their molecular docking properties. The synthesis was done by condensing 7-chloro-2-hydroxyquinoline-3-carbaldehyde and 2,2′-thiodianiline with Zn(II) metal complexes. A range of spectroscopic techniques, such as 1H and 13C NMR, FTIR, TG/DTA, pXRD, and UV–Vis, were employed to characterize both the ligand and its complexes. Imine quinoline ligand (L), ZnL, and ZnL2 all had average crystallite diameters of 13.28, 21.19, and 16.26 nm, respectively, according to pXRD analysis, which confirmed that the synthesized ligand and its Zn(II) complexes showed polycrystalline properties. Based on the results, an octahedral geometry was proposed for the complexes. A very good agreement was obtained between the experimental and the TD-DFT calculated absorption peaks. Their biological potency against Gram-positive (Staphylococcus aureus ATCC 25926) and Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 248) bacterial strains as well as antioxidant properties were tested. The ZnL complex showed a maximum growth inhibition of 9.50 ± 0.41 mm against S. aureus ATCC 25926; whereas the maximum growth inhibition of the ZnL2 complex was 9.67 ± 0.47 mm and 9.33 ± 0.47 mm against ATCC 25926, respectively. With an IC50 of 167.3 ± 1.04 mg/mL, ZnL had the strongest antioxidant activity against DPPH radicals. All the complexes had strong binding affinities according to the molecular docking investigation: L (−11.31 kcal/mol), ZnL (−11.38 kcal/mol), and ZnL2 (−13.51 kcal/mol) against the active sites of S. aureus and (−7.92, −8.07, and −8.92) kcal/mol, respectively, against the active sites of E. coli. The Zn(II) complexes had the highest potency of biological activity.

Ruthenium-p-Cymene Complexes Incorporating Substituted Pyridine–Quinoline Ligands with –Br (Br-Qpy) and –Phenoxy (OH-Ph-Qpy) Groups for Cytotoxicity and Catalytic Transfer Hydrogenation Studies: Synthesis and Characterization

Organometallic ruthenium complexes with p-cymene = 1-methyl-4-(1-methylethyl)-benzene and N^N = bidentate polypyridyl ligands constitute interesting candidates with biological and catalytic properties. Towards this aim, we have synthesized four ruthenium(II)–arene complexes of the type [Ru(η6-p-cymene)(N^N)Cl][X] (N^N = Br-Qpy = 6-bromo-4-phenyl-2-pyridin-2-yl-quinoline, X = Cl− (1a); PF6− (1b); N^N = OH-Ph-Qpy = 4-(4-phenyl-2-(pyridin-2-yl)quinolin-6-yl)phenol, X = Cl− (2a); PF6− (2b)). This is the first report of ruthenium(II) p-cymene complexes incorporating substituted pyridine–quinoline ligands, with –Br and –C6H4OH groups in the 6-position of quinoline. We also refer to the cytotoxicity of the ligands and their possible effect of modulating the activity of the ruthenium(II) complexes. These were characterized by a combination of spectroscopic methods (ATR-IR, UV–Vis, multinuclear NMR), elemental analysis, and conductivity measurements. The solid-state structure of 2b, determined by single-crystal X-ray diffraction, reveals a three-legged piano-stool geometry. The in vitro cytotoxic activities of the new complexes were evaluated in HEK293T (human embryonic kidney cells) and in HeLa cells (cervical cancer cells), via the MTT assay. Poor in vitro anticancer activities were observed for the HeLa cancer cell line, with 2a being the most potent (IC50 = 75 μΜ). The cytotoxicity of Br-Qpy in HEK293T is comparable to that of cisplatin. Both complexes 1a and 1b successfully catalyze the transfer hydrogenation of benzophenone to benzhydrol by 2-propanol at 82 °C. The catalytic performance of 1a in the ratio of S:Cat:B = 400:1:40 (S = substrate, Cat = catalyst, B = base = KOiPr) leads to a conversion of 94%, within 3 h of reaction. Presumably, catalytic transformation takes place via ruthenium(II) hydride species being the active catalyst.

Mechanochemical synthesis of a red luminescent coordination polymer from a polydentate quinoline ligand with large conjugation

Abstract A red luminescent coordination polymer has been prepared from a polydentate 8-hydroxyquinoline ligand via mechanochemical synthesis. The obtained coordination polymer is micro/nano spherical and can suspend stably in organic solvents after ultrasonic treatment. Due to the large conjugation of the ligand with a strong polar s-triazine core, the coordination polymer shows a largely red-shifted emission relative to the ligand. The photoluminescence peak of the coordination polymer in organic solvent is at 613 nm, while a largely red-shifted photoluminescence peak at 675 nm and a shoulder peak at 770 nm are found in the photoluminescence spectrum of the coordination polymer in solid due to the strong interchain interaction.

Effect of Red Emissive Ligand Number on Dendronized Solution‐Processable Iridium(III) Complexes for Organic Light‐Emitting Diodes

AbstractTris‐bidentate iridium(III) complexes used in organic light‐emitting diodes (OLEDs) are typically homoleptic or heteroleptic with three or two identical emissive ligands, respectively. Herein red phosphorescence emitting dendrimers composed of first generation biphenyl dendrons, 2‐ethylhexyloxy surface groups and an iridium(III) complex core with three, two or one emissive [4‐phenyl]−2‐[thiophen‐2‐yl]quinoline ligands are reported. The dendrimers have similar photoluminescence quantum yields (PLQYs) in solution (84–88%), neat film (23–25%) and when blended with tris(4‐carbazoyl‐9‐ylphenyl)amine (72–73%), enabling the effect of the number of emissive ligands on OLED performance to be determined. The external quantum efficiency (EQE) of OLEDs composed of neat dendrimer films increased with decreasing number of emissive ligands, with the device composed of the dendrimer having a single emissive ligand having an EQE of 9.2%, which is almost double that expected from a bottom emitting device and a film PLQY of 25 ± 3.6%. The emission is Lambertian and the higher‐than‐expected EQE is ascribed to alignment of the single emissive ligand being optimal for light‐outcoupling. The EQE of OLEDs containing the blend film also increased with decreasing emissive number of ligands (maximum EQE = 15.4%).

Cytotoxic Cu(II) Complexes with a Novel Quinoline Derivative Ligand: Synthesis, Molecular Docking, and Biological Activity Analysis.

The utilization of metallodrugs as a viable alternative to organic molecules has gained significant attention in modern medicine. We hereby report synthesis of new imine quinoline ligand (IQL)-based Cu(II) complexes and evaluation of their potential biological applications. Syntheses of the ligand and complexes were achieved by condensation of 7-chloro-2-hydroxyquinoline-3-carbaldehyde and 2,2'-thiodianiline, followed by complexation with Cu(II) metal ions. The synthesized ligand and complexes were characterized using UV-vis spectroscopy, TGA/DTA, FTIR spectroscopy, 1H and 13C NMR spectroscopy, and pXRD. The pXRD diffractogram analysis revealed that the synthesized ligand and its complexes were polycrystalline systems, with nanolevel average crystallite sizes of 13.28, 31.47, and 11.57 nm for IQL, CuL, and CuL 2 , respectively. The molar conductivity confirmed the nonelectrolyte nature of the Cu(II) complexes. The biological activity of the synthesized ligand and its Cu(II) complexes was evaluated with in vitro assays, to examine anticancer activity against the MCF-7 human breast cancer cell line and antibacterial activity against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. The CuL complex had the highest cytotoxic potency against MCF-7 breast cancer cells, with an IC50 of 43.82 ± 2.351 μg/mL. At 100 μg/mL, CuL induced the largest reduction of cancer cell proliferation by 97%, whereas IQL reduced cell proliferation by 53% and CuL 2 by 28%. The minimum inhibitory concentration for CuL was found to be 12.5 μg/mL against the three tested pathogens. Evaluation of antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl revealed that CuL exhibited the highest antioxidant activity with IC50 of 153.3 ± 1.02 μg/mL. Molecular docking results showed strong binding affinities of CuL to active sites of S. aureus, E. coli, and estrogen receptor alpha, indicating its high biological activity compared to IQL and CuL 2 .

Selectivity Switch in Non‐Directed Palladium‐Catalyzed C−H Olefination of Chlorobenzene Derivatives

AbstractA palladium(II)‐catalyzed oxidative C−H olefination of chlorobenzene derivatives, which favored the functionalization at the ortho‐to‐chlorine position, was reported. The catalytic system employed a commercially available quinoline ligand to access a wide panel of olefinated aryl chlorides in moderate to high yields from feedstock chemicals (42 examples, 28 to 93% yields). The synthetic utility of the method was further demonstrated by the coupling of various bio‐relevant acrylate partners offering straightforward access to structurally diverse complex molecules. A computational study of the reaction allowed us to confirm that the C−H activation step, occurring through a Concerted Metalation‐Deprotonation mechanism, determined the site‐selectivity of the transformation. The regioselectivity was controlled by the pKa of the C−H bond (more acidic position) and the lower distortion of chlorobenzene in the key transition structure.

Position of substituents directs the electron transfer properties of entatic state complexes: new insights from guanidine-quinoline copper complexes.

In a previous study, we showed that the properties and the ability as an entatic state model of copper guanidine quinoline complexes are significantly influenced by a methyl or methyl ester substituent in the 2-position. To prove the importance of the 2-position of the substituent, two novel guanidine quinoline ligands with a methyl or methyl ester substituent in the 4-position and the corresponding copper complexes were synthesized and characterized in this study. The influence of the substituent position on the copper complexes was investigated with various experimental and theoretical methods. The molecular structures of the copper complexes were examined in the solid state by single-crystal X-ray diffraction (SCXRD) and by density functional theory (DFT) calculations indicating a strong dependency on the substituent position compared to the systems substituted in the 2-position from the previous study. Further, the significantly different influence on the donor properties in dependency on the substituent position was analyzed with natural bond orbital (NBO) calculations. By the determination of the redox potentials, the impact on the electrochemical stabilization was examined. With regard to further previously analyzed guanidine quinoline copper complexes, the electrochemical stabilization was correlated with the charge-transfer energies calculated by NBO analysis and ground state energies, revealing the substituent influence and enabling a comparatively easy and accurate possibility for the theoretical calculation of the relative redox potential. Finally, the electron transfer properties were quantified by determining the electron self-exchange rates via the Marcus theory and by theoretical calculation of the reorganization energies via Nelsen's four-point method. The results gave important insights into the dependency between the ability of the copper complexes as entatic state model and the type and position of the substituent.

Low-dimensional compounds containing bioactive ligands. Part XXIII: A comprehensive study of the preparation and cytotoxic activities of zirconium(IV) complexes with 8-hydroxyquinoline and its derivatives

Nine zirconium(IV) complexes, [Zr(8-HQ)4]·DMF·H2O (1), [Zr(dClQ)4]·EtOH (2), [Zr(ClNQ)4]·EtOH (3a), [Zr(ClNQ)4]·DMF (3b), [Zr(BrQ)4] (4), [Zr(dBrQ)4]·DME (5), [Zr(2-MedBrQ)4]·2DMF (6), [Zr2Cl2(CQ)4µ2-O(DMF)2]·0.33DMF (7), and [Zr2Cl2(ClBrQ)4µ2-O(DMF)2]·DMF (8) (DME = 1,2-dimethoxyethane, H8-HQ = 8-hydroxyquinoline, HdClQ = 5,7-dichloro-8-hydroxyquinoline, HClNQ = 5-chloro-7-nitro-8-hydroxyquinoline, HBrQ = 7-bromo-8-hydroxyquinoline, HdBrQ = 5,7-dibromo-8-hydroxyquinoline, H2-MedBrQ = 2-methyl-5,7-dibromo-8-hydroxyquinoline, HCQ = 5-chloro-7-iodo-8-hydroxyquinoline, HClBrQ = 5-chloro-7-bromo-8-hydroxyquinoline), have been prepared and characterized by elemental, single crystal X-ray structure analysis and IR spectroscopy. Complexes 1 – 6 are mononuclear complexes with Zr(IV) atoms octacoordinated by four bidentate quinoline ligands. Complexes 7 and 8 are binuclear complexes in which two Zr(IV) atoms are coordinated by two bidentate quinoline, one DMF and one chloro ligands, and the seventh coordination place occupies an oxygen atom bridging both complex species. The stability of complexes soluble in a DMSO was verified by NMR spectroscopy. In vitro cytotoxic properties of complexes 1, 2, 4, 5, and 6, and corresponding ligands were studied against 8 cancer cell lines, and their selectivity was verified on BJ-5ta non-cancerous cell line. The most potent complexes are 1 and 4 with the smallest quinoline ligands.

Preparation, characterization and electrochemical properties of ruthenium carbonyl octaethylporphyrins with axial quinoline and quinine ligands

Preparation, characterization and electrochemical properties of ruthenium carbonyl octaethylporphyrins with axial quinoline and quinine ligands

Synthesis and crystal structure of bis-(9-mesityl-9,10-di-hydro-10-aza-9-borabenzo[h]quinolinato-κ2N1,N10)zinc(II).

The title compound, [Zn(C20H18BN2)2] (Zn L 2), is an overall uncharged chelate that consists of two units of an NH-deprotonated 10-aza-9-borabenzo[h]quinoline ligand (L) per ZnII center. It was synthesized in two steps by treating the protonated ligand HL with lithium bis-(tri-methyl-sil-yl)amide and further conversion with di-ethyl-zinc. Its asymmetric unit comprises one ZnL fragment; the mol-ecule is completed by application of inversion symmetry at Zn. Due to the fourfold coordination with nitro-gen atoms, the zinc(II) ion is located in a distorted tetra-hedral environment. Besides the relatively short N-Zn bonds, Zn L 2 is characterized by the significant protrusion of the central ion from the plane of the ligand backbone. The crystal structure is consolidated by intra- and inter-molecular π-π stacking inter-actions, while the polarized B-N bond is barely involved in any close atom contacts.

Synthesis and characterization of a new azo quinoline ligand and its metal complexes with spectrophotometric determination and biological efficacy study of its Hg(II) complex

ABSTRACT. An azo quinoline ligand, (E)-2-((4-iodophenyl)diazenyl)-8-hydroxyquinoline (IPDHQ), was synthesized by the coupling reaction of 4-iodoaniline diazonium salt with 8-hydroxyquinoline. The synthesized ligand and its Cd(II), Pd(II), Cu(II) and Hg(II) complexes were spectrally characterized by UV‒Vis spectrophotometry, FT-IR, mass spectral analysis, 1H-NMR, magnetic sensitivity and molar conductivity. The general formula of the Cd(II), Cu(II) and Hg(II) complexes is [M(L)2].Cl2.H2O with octahedral geometry, while the general formula of the Pd(II) complex is [M(L).Cl2].H2O with square planer geometry. A simple and rapid spectrophotometric procedure was suggested for the determination of Hg(II) using the synthesized ligand as a spectrophotometric reagent. By measuring the absorbance for the resulting orange complex at 430 nm, the linearity range was 0.5-15 µg mL-1, and the interfering effect was also studied. The synthesized azo ligand and its Hg(Ⅱ) complex were tested for their biological activity against four bacterial strains.
 KEY WORDS: Azo quinoline ligand, 8-Hydroxy quinoline, 4-Iodoaniline, Azo metal complexes, Spectrophotometric determination, Biological efficacy study
 Bull. Chem. Soc. Ethiop. 2023, 37(6), 1459-1470. DOI: https://dx.doi.org/10.4314/bcse.v37i6.13

Cyclometalated Ir(III) Complexes as Lysosome-Targeted Photodynamic Anticancer Agents.

We have designed and synthesized two Ir(III) complexes (Ir1 and Ir2) coordinated with an 8-sulfonamidoquinoline derivative ligand as photosensitizers, which exhibit strong red phosphorescence emission and a long phosphorescence lifetime. The Ir(III) complexes exhibit a high population of triplet states, which enable red phosphorescence and efficient singlet oxygen generation. Ir1 and Ir2 rapidly enter the cancer cells and accumulate in lysosomes, producing large amounts of intracellular singlet oxygen when exposed to light irradiation, eventually leading to cancer cell death, and the phototoxic indexes of complexes Ir1 and Ir2 against cancer cells are in the range of 76-228. Overall, our studies indicate that the synthesized Ir(III) complexes with quinoline ligands exhibit photosensitizing properties, effectively inducing cancer cell death when exposed to light. These promising results suggest their potential application in photodynamic therapy.

Paper-based fluorescent sensors from quinoline ligands for distance-based quantification of Zn2+

A series of aminoquinoline derivatives with different N-alkyl substituents were synthesized and used in the development of paper-based fluorescent sensors. In aqueous solutions, the quinoline ligands show strong green fluorescence selectively upon binding to Zn2+ that is clearly observed by naked eyes under blacklight illumination. The paper-based sensors were prepared by depositing the amidoquinoline derivatives in wax-printed channels on filter paper. Developing of Zn2+ samples, deposited below the ligand spots, with an aqueous buffer solution creates green fluorescent lines suitable for distance measurement. The ligands with a tertiary amino group showed better-defined fluorescent lines than those of ligands containing primary and secondary amino groups. The length of the fluorescent lines increases linearly with the amounts of Zn2+ in the range of 2.5–80 nmol that can be easily determined by naked-eye observation or an image processing software. The increase in hydrophobicity of the ligands results in a wider dynamic concentration range of the detection. The paper-based sensor can accurately and conveniently quantify Zn2+ in drinking water, dietary supplement, and fertilizer samples.

Platinum(II) Complexes with Phenylpyridine, Benzo[h]quinoline, and NHC Ligands: Exploration of Ligand Effects on Photophysical Properties

AbstractPlatinum(II) complexes with one cyclometalated phenylpyridine or benzo[h]quinoline (C^N) ligand and an N-heterocyclic carbene (NHC) ligand are a robust and readily available class of sky-blue to green phosphorescent triplet emitters. They can be used as a benchmark system to investigate the influence of different ligands on the emissive properties of these [Pt(C^N)(NHC)I] complexes. This new class of compounds was fully characterized by standard techniques. Additionally a solid-state structure could be obtained. Photoluminescence measurements at room temperature revealed the strong emissive behavior of these compounds with quantum yields of up to 80%. The effect of electron-withdrawing and -donating groups on the photophysical properties was examined and rationalized by density functional theory calculations (PBE0/6-311G(d)).

Sulfur-bridging the gap: investigating the electrochemistry of novel copper chelating agents for Alzheimer's disease applications.

There is currently an unmet demand for multi-functional precision treatments for Alzheimer's disease (AD) after several failed attempts at designing drugs based on the amyloid hypothesis. The focus of this work is to investigate sulfur-bridged quinoline ligands that could potentially be used in chelation therapies for a subpopulation of AD patients presenting with an overload of labile copper ions, which are known to catalyze the production of reactive oxygen species (ROS) and exacerbate other markers of AD progression. The ligands 1-(2'-thiopyridyl)isoquinoline (1TPIQ) and 2-(2'-thiopyridyl)quinoline (2TPQ) were synthesized and characterized before being electrochemically investigated in the presence of different oxidizing and reducing agents in solution with a physiological pH relevant to the brain. The electrochemical response of each compound with copper was studied by employing both hydrogen peroxide (H2O2) as an oxidizing agent and ascorbic acid (AA) as an antioxidant during analysis using cyclic voltammetry (CV). The cyclic voltammograms of each quinoline were compared with similar ligands that contained aromatic N-donor groups but no sulfur groups to provide relative electrochemical properties of each complex in solution. In a dose-dependent manner, it was observed that AA exerted dual-efficacy when combined with these chelating ligands: promoting synergistic metal binding while also scavenging harmful ROS, suggesting AA is an effective adjuvant therapeutic agent. Overall, this study shows how coordination by sulfur-bridged quinoline ligands can alter copper electrochemistry in the presence of AA to limit ROS production in solution.

Enhancing Substrate-Metal Catalyst Affinity via Hydrogen Bonding: Pd(II)-Catalyzed β-C(sp3)-H Bromination of Free Carboxylic Acids.

The achievement of sufficient substrate-metal catalyst affinity is a fundamental challenge for the development of synthetically useful C-H activation reactions of weakly coordinating native substrates. While hydrogen bonding has been harnessed to bias site selectivity in existing C(sp2)-H activation reactions, the potential for designing catalysts with hydrogen bond donors (HBDs) to enhance catalyst-substrate affinity and, thereby, facilitate otherwise unreactive C(sp3)-H activation remains to be demonstrated. Herein, we report the discovery of a ligand scaffold containing a remote amide motif that can form a favorable meta-macrocyclic hydrogen bonding interaction with the aliphatic acid substrate. The utility of this ligand scaffold is demonstrated through the development of an unprecedented C(sp3)-H bromination of α-tertiary and α-quaternary free carboxylic acids, which proceeds in exceedingly high mono-selectivity. The geometric relationship between the NHAc hydrogen bond donor and the coordinating quinoline ligand is crucial for forming the meta-macrocyclophane-like hydrogen bonding interaction, which provides a guideline for the future design of catalysts employing secondary interactions.

Abnormal NHC Palladium(II) Complex Containing CNN Pincer Skeleton and Its Application to Suzuki‐Miyaura Coupling of Aryl Chlorides in Water

AbstractThe excellent catalytic activities of abnormal NHC carbene complexes, where the C2 position remains unaffected, and coordination occurs at the C4 or C5 position of the imidazolium ring, is still a fascinating but scarce area of research. This present work reports a palladium complex (LPdBr) bearing abnormal NHC with CNN pincer architecture. It is synthesized from imidazolium‐based quinoline ligand (LH) with Pd(OAc)2 via ‐NH and carbene deprotonation. The complex was fully characterized by NMR spectroscopy (1D and 2D) and high‐resolution mass spectrometry (HRMS). The structure and abnormal coordination modes of the complex are further confirmed with the help of single‐crystal X‐ray diffraction. The studies revealed the abnormal coordination mode in LPdBr where C5 carbon of the imidazolium ring participates in bonding, leaving the C2 position unaffected. The catalytic potential of complex LPdBr was investigated in the Pd‐catalyzed Suzuki‐Miyaura coupling of various aryl/heteroaryl chlorides with different aryl/naphthyl/phenanthryl boronic acids. The catalyst LPdBr successfully activated various less‐activated aryl chloride substrates. LPdBr also exhibited good catalytic activity at 1 mol% Pd loading under microwave irradiation and in green solvent water. The mechanism of the catalytic cycle is investigated and proposed by HRMS.

Cytotoxic properties of fac-Re(CO)3 complexes with quinoline coligands: Insights on the mode of cell death and DNA fragmentation

Four tricarbonyl rhenium(I) complexes featuring quinoline ligands (1–4) were examined for their potential cytotoxicity properties against three malignant cell lines and one normal cell line of different origins. The most cytotoxic compound among the synthesized complexes was complex 2, which was formed when [ReBr(CO)3(N∧O)] (N∧O = quinoline-2-carboxaldehyde) (1) and para-amino phenol reacted. Its IC50 values are in the range of 26.05–30.33 μg/mL. Complex 4, decorated with benzimidazole moiety, has been demonstrated to be harmless to normal mice splenocytes. The cellular localization of 1–4 was investigated using fluorescence microscopy to provide insight into their biotargets, cellular localization, and modes of action. Among the evaluated malignant cell lines, complex 2 exhibited the highest levels of apoptotic and necrotic alterations in the MCF-7 cell line. Re(I) complexes appeared to gather inside intercellular connections and around cellular membranes, as seen in the fluorescence microscopy images. Along the cell membrane, the compounds accumulated as well, anticipating their entry.

Quinoline analogue as a potential inhibitor of SARS-CoV-2 main protease: ADMET prediction, molecular docking and dynamics simulation analysis

The novel coronavirus (COVID-19) has triggered a major human turmoil worldwide by posing challenges regarding infection prevention, disease diagnosis, and treatment. Several drugs including remdesivir (RDV), hydroxychloroquine (HCQ), and others are being used to treat COVID-19, although these are not specifically proven drugs. Thus, it is very critical to understand COVID-19 drug targets and their interactions with candidate drugs. Here, we attempted in silico screening of ten quinoline analogs (Q1-Q10) against the five main proteases of SARS-CoV-2 by docking and dynamics analysis. The prediction of the ADMET profile showed that the best docked quinolines are safe and possess drug-like properties. The molecular interaction and binding affinity of these small molecules were determined with respect to the five protease (Mpro) targets of SARS-CoV-2 (PDB ID: 6LU7, 6W63, 6M03, 6Y84 and 6YB7). The study indicated that the quinoline ligands Q4, Q5, Q6, Q7, Q8, Q9, and Q10as probable inhibitors against SARS-CoV-2 Mpro and showed favorable binding interaction with the amino acid Glu166 of 6Y84, 6LU7and 6M03. Furthermore, Q9 has a highly significant docking score and binding affinity with all fiveCOVID-19 receptors having a minimum of two H-bonds, which is remarkable compared to HCQ, RDV, and other quinolines. The dynamics simulation analysis of this potent drug candidate Q9 with 6LU7 indicated high stability of the complex. In conclusion, our findings indicate that all of these quinolines in general possess good binding affinity and Q9 can serve as a good quinoline scaffold for the design of new antiviral agents to target the active site of SARS-CoV-2 MPro.

Pd-Catalyzed TBHP-Mediated Selective Wacker-Type Oxidation and Oxo-acyloxylation of Olefins Using a 2-(1H-Indazol-1-yl)quinoline Ligand.

Pd(II)-catalyzed oxidation of terminal olefins to methyl ketones has emerged as an attractive strategy for organic synthesis. Here we report the Pd(II)-catalyzed selective oxidation of olefins using tert-butyl hydroperoxide as the oxidant and 2-(1H-indazol-1-yl)quinoline as the ligand. A wide range of olefins were well tolerated in this reaction system to provide methyl ketones, whereas the presence of Ac2O initiated the oxo-acyloxylation to afford the α-acetoxyacetone products. Isotope labeling studies and active-intermediate-capture experiments were performed to elucidate the underlying selective reaction mechanism. Notably, the generation of α-acetoxyacetone products involves the palladium enolate intermediate while the methyl ketone products were generated through the most commonly proposed alkylperoxide intermediates, followed by 1,2-hydride migration.