Molecular Docking Study Of Complexes Research Articles

Structural investigations of new tridentate-phenylacetohydrazide Schiff base metal chelates: X-ray diffraction, Hirshfeld surface analyses, DFT, antibacterial and molecular docking studies

The coordination complexes of a tridentate-phenylacetohydrazide Schiff base (2-hydroxybenzylidene-2-phenylacetohydrazide, HL) with metal ions, namely, iron(II), zinc(II), palladium (II), silver(I) and cadmium(II), were synthesized and investigated using various analytical and spectroscopic techniques. A single-crystal X-ray diffraction analysis was performed on the silver derivative. The HL ligand and Ag complex were also characterized via Hirshfeld surface analyses. Both X-ray and Hirshfeld surface analysis revealed intriguing structure and geometric characteristics, as well as remarkably intramolecular and intermolecular hydrogen bonding. All metal ions, with the exception of palladium one, bonded to two molecules of ligand without deprotonation of the hydroxyl moieties. In addition, 1H NMR studies of the diamagnetic complexes and X-ray analysis of the silver complex revealed the presence of the unprotonated OH. DFT-B3LYP calculations were used to determine the energy-minimized molecular geometric arrangements of the Pd(II), Ag(I), and Cd(II) derivatives. Quantum global reactivities of the complexes were also computed. Antibacterial and molecular docking studies of complexes were carried out to examine the potential applications of derivatives as therapeutic reagents. The Ag(I) complex showed the highest antibacterial inhibition towards the tested bacteria with zone diameter = 21.7, 21.0, 19.3 and 15.7 mm. Molecular docking analysis revealed that the complexes have high binding affinities against the selected receptors (PDB: 1BNA and 5AEP) and demonstrated different DNA binding potencies.

Liquid-assisted mechanochemical synthesis, crystallographic, theoretical and molecular docking study on HIV instasome of novel copper complexes: (µ-acetato)-bis(2,2'-bipyridine)-copper and bromidotetrakis(2-methyl-1H-imidazole)-copper bromide.

In the present work the two new Cu(II) complexes, (µ-acetato)-bis(2,2'-bipyridine)-copper [Cu(bpy)2(CH3CO2)] and bromidotetrakis(2-methyl-1H-imidazole)-copper bromide [Cu(2-methylimid)4Br]Br have been synthesized by liquid assisted mechanochemical method. The [Cu(bpy)2(CH3CO2)] complex (1) and [Cu(2-methylimid)4Br]Br complex (2) characterised by IR and UV-visible spectroscopy and the structure are confirmed by XRD diffraction studies. Complex (1) crystallized in the Monoclinic with the space group of C2/c where a = 24.312(5)Å, b = 8.5892(18)Å, c = 14.559(3)Å, α = 90°, β = 106.177(7)° and γ = 90° and Complex (2) crystallized in the Tetragonal with the space group of P4nc, a = 9.9259(2)Å, b = 9.9259(2)Å, c = 10.9357(2)Å, α = 90°, β = 90° and γ = 90°. The complex (1) has distorted octahedral geometry where the acetate ligand showed bidentate bridging with the central metal ion and complex (2) has slightly deformed square pyramidal geometry. The HOMO-LUMO energy gap value and the low chemical potential showed that the complex (2) is stable and difficult to polarize compare to complex (1). The molecular docking study of complexes with the HIV instasome nucleoprotein showed the binding energy values -7.1 and -5.3kcal/mol for complex (1) and complex (2) respectively. The negative binding energy values showed the complexes have affinity to bind with HIV instasome nucleoproteins. The in-silico pharmacokinetic study of the complex (1) and complex (2) showed non AMES toxicity, non-carcinogens and low honey Bee toxicity but weakly inhibit Human Ether-a-go-go-related gene.

Synthesis, characterization and biological evaluation of piperazine embedded copper complexes

In this paper, we report the synthesis, and characterization of three piperazine based multidentate ligands and their copper complexes. Ligands and complexes were characterized by UV–Vis, FT–IR, 1H NMR and mass spectra along with EPR spectra, molar conductance and thermogravimetric analysis (TGA). The metal complexes showed peaks corresponding to ligand to Cu(II) LMCT transition in UV–Vis spectrum. Molar conductance values of all complexes studied in water and DMSO indicated nonionic nature of complexes. TGA derivative curve represented the initial loss of water, which was in agreement of coordinated water in the proposed complexes. Four coordinated copper complexes were proposed on the basis of spectral data and supported by mass fragmentation pattern, isotopic distribution pattern, EPR, molar conductance and TGA. Ligands and complex geometries were optimized using DFT calculations and TDDFT studies of ligands were performed to corroborate the experimental UV–Vis spectrum. These ligands and complexes were tested for antibacterial activity and all complexes showed higher activity as compared to ligands. Antioxidant behavior of complexes was investigated by DPPH (2,2-diphenyl-1-picrylhydrazyl) method, and percentage inhibition data suggested two complexes Cu2L1 and Cu2L3 to hold fair antioxidant potential. In vitro cytotoxic studies of complexes performed on breast cancer cell line (MCF–7) using MTT calorimetric assay and IC50 value indicated good cytotoxic potential. BSA binding studies and DNA binding studies with CT-DNA were performed using UV–Vis titrimetric methods and were supported by molecular docking studies of complexes to investigate available binding interactions sites.

Synthesis and characterization of new metal complexes containing Triazino[5,6–b]indole moiety: In vitro DNA and HSA binding studies

The present study reports the synthesis, structural characterization of Ni(II) (1,3) and Cu(II) (2,4) metal complexes of Schiff-base (L) derived from 5H-[1,2,4]triazino[5,6-b]indol-3-amine and salicylaldehyde moiety. The coordination sphere of Cu(II)/Ni(II) was completed by tethering secondary ligand 2,2′–Bipyridine and 1,10 phenanthroline to obtain the final complexes 1–4, respectively. The spectral analysis of complexes 1 and 3 suggested square planar geometry while complexes 2 and 4 acquire the octahedral geometry around the metal centers. In vitro DNA binding profiles of the newly synthesized metal complexes 1–4 with calf thymus DNA (CT DNA) were explored by employing electronic absorption titrations and fluorescence spectral studies. The results revealed that complexes 1–4 bind to DNA through electrostatic surface binding mode along with partial intercalation in the minor groove. Moreover, complexes 3 and 4 have stronger DNA binding propensity with higher intrinsic binding constant Kb values of 1.9 × 104 and 4.8 × 104 M–1, respectively. Additionally, HSA binding studies of ligand L and metal complexes 1–4 support the static quenching mechanism and alterations in the microenvironment around Trp–214 residues causing conformational distortions in the HSA secondary structure. Furthermore, molecular docking studies of complexes 3 and 4 with DNA and HSA confirms that both specifically binds in G–C rich regions of the DNA minor groove and subdomain IIA pocket of HSA near the Trp–214 residue.

Syntheses, characterization, crystal structures and Jack bean urease inhibitory activities of ZnII, CoII/III and NiII complexes derived from reduced Schiff base ligand

A series of new ZnII, CoII/III and NiII complexes derived from reduced Schiff base 6,6′-((propane-1,3-diylbis(azanediyl))bis(methylene))bis(2-ethoxyphenol) (H2L), [Zn3L2(N3)2] (1), [Co2L(N3)2(CH3COO)]·CH3OH (2) and [Ni(HL)(OH2)(CH3OH)]·ClO4 (3), were prepared and characterized by physico-chemical methods. Crystal structures of the complexes were determined by single crystal X-ray diffraction. Complex 1 is a trinuclear zinc(II) compound. Complex 2 is a dinuclear cobalt(II/III) compound. Complex 3 is a mononuclear nickel(II) compound. The cobalt complex and the nickel complex have effective urease inhibitory activities, with IC50 values of 19.8 and 11.6 μmol·L−1, respectively. However, the zinc complex 1 has no such activity. Molecular docking study of complexes 2 and 3 with the active center of Jack bean urease was studied.

DNA binding and in vitro anticancer activity of 2‐((1H‐benzimidazol‐2‐yl)methylamino)acetic acid and its copper(II) mixed‐polypyridyl complexes: Synthesis and crystal structure

New copper(II) ternary complexes formulated as [Cu(N‐N)BIG]ClO4, where BIG is deprotonated 2‐((1H‐benzimidazol‐2‐yl)methylamino)acetic acid and N‐N represents 2,2′‐bipyridine (1) or 4,4′‐dimethyl‐2,2′‐bipyridine (2) or 5,5′‐dimethyl‐2,2′‐bipyridine (3) or 1,10‐phenanthroline (4) or 4,5‐diazafluoren‐9‐one (5) or dipyridylamine (6), were synthesized and characterized using analytical and spectral methods. Complex 1 was characterized using single‐crystal X‐ray diffraction analysis and found to be monomeric in nature with distorted square pyramidal geometry. The binding interactions of 1–6 with calf thymus DNA were studied using UV–visible absorption and emission spectroscopy and viscosity measurements. The DNA cleavage ability of 1–6 with pUC19 DNA shows that the complexes can cleave DNA without any external agents. The ligand and complexes were investigated for their in vitro antibacterial activity against Bacillus subtilis and Staphylococcus aureus. The complexes showed enhanced antibacterial activities compared to the free ligand. Molecular docking studies of complexes 1–6 were made using Genetic Optimization of Ligand Docking (GOLD) software. The study indicated that LEU23, ASP25, ILE84, ASN144 and ARG87 of COX‐2 were important for strong hydrogen bonding interaction with the complexes. Among the complexes, 2 showed the best docking result with COX‐2. Cytotoxicity assay was performed using MTT reagent against human cervical cancer cells, human breast cancer cells and human lung cancer cells. The complexes were found to show moderate anticancer activity.

Theoretical, biological and in silico studies of pendant-armed heteroleptic copper(II) phenolate complexes

A new series of pendant-armed heteroleptic copper(II) phenolate complexes of the type [CuL1−3(diimine)] (1–6) have been synthesized by the reaction of pendant-armed ligands 2,2'-(benzoyliminodiethylene)bissalicylidene (H2L1), 2,2'-(4-nitrobenzoyliminodiethylene)bissalicylidene (H2L2) or 2,2'-(3,5-dinitrobenzoyliminodiethylene)bissalicylidene (H2L3) with coligands (diimine; 2,2′-bipyridyl (bpy) or 1,10-phenanthroline (phen)) in the presence of copper(II) chloride, and characterized by spectroscopic techniques. The seven coordinated pentagonal-bipyramidal geometry around the copper(II) center was inferred from the electronic spectra of the complexes. The bond length, bond angle and HOMO-LUMO energy gap calculations were carried out by DFT studies, using Gaussian 03 program. Electrochemical studies of the mononuclear complexes evidenced one-electron irreversible reduction wave in the cathodic region (Epc = −0.61 to −0.65 V). Experimental and in silico molecular docking studies support groove mode of binding with DNA. Further, the molecular docking studies of complexes with B-DNA indicate the binding of the guanine-cytosine residues in the minor groove of the DNA. Molecular docking studies also revealed the interaction of complexes with protein ERK2 kinase and significant topoisomerase (Topo-I) inhibitory activity. All the complexes display pronounced cleavage activity against supercoiled pBR322 DNA in the presence of H2O2. In vitro cytotoxicity of the complexes was tested against liver cancer cell line (HepG2) by MTT reduction assay.

Synthesis, Cytotoxicity and Molecular Docking Study of Complexes Containing Thiazole Moiety

The ligand 5-methyl-2-phenyl-4-[(E)-1,3-thiazol-2-yldiazenyl]-2,4-dihydro-3H-pyrazol-3-one (Dy) has been synthesized by diazo coupling reactions of 5-methyl-2-phenyl- 2,4-dihydro-3H-pyrazol-3-one with 2-aminothiazole and ferric hydrogen sulfate (FHS), as a catalyst, under solvent-free conditions. A series of complexes of the ligand with Co(II), Ni(II), Cu(II), and Zn(II) ions are synthesized and structurally characterized by 1H NMR, FTIR, and UV–Visible spectral techniques. The cytotoxic activity of the complexes and the uncoordinated ligand against human breast cancer (MCF-7) and chronic myelogenous leukemia cell line (human erythroleukemia) (K-562) cell lines exhibits good viability in the range of 50.16–55.16% at a concentration of >100-110 µg/mL as compared to the inhibition in the untreated cells. Further, the metal complexes and ligand were screened against antibacterial strains of S. typhi, S. aureus, and E. coli. Both the cytotoxicity and antioxidant studies are correlated with computational docking analysis and powder XRD studies reviles that all complexes are in crystalline nature.

Synthesis of mononuclear copper(II) complexes of N3O2 and N4O2 donors containing Schiff base ligands: Theoretical and biological observations

A new series of six mononuclear copper(II) complexes were synthesized from N3O2 and N4O2 donors containing Schiff base ligands, and characterized by various spectral methods. The geometry of the complexes was determined using UV–Vis, EPR and DFT calculations. The complexes of N3O2 donors (1–3) adopted square pyramidal geometry and the remaining complexes of N4O2 donors (4–6) show distorted octahedral geometry around copper(II) nuclei. Redox properties of the complexes show a one-electron irreversible reduction process in the cathodic potential (Epc) region from −0.74 to −0.98 V. The complexes show potent antioxidant activity against DPPH radicals. Molecular docking studies of complexes showed σ–π interaction, hydrogen bonding, electrostatic and van der Waals interactions with VEGFR2 kinase receptor. In vitro cytotoxicity of the complexes was tested against human breast cancer (MDA-MB-231) cell lines and one normal human dermal fibroblasts (NHDF) cell line through MTT assay. The morphological assessment data obtained by Hoechst 33258 and AO/EB staining revealed that the complexes induce apoptosis pathway of cell death.

Enantiomeric in vitro DNA binding, pBR322 DNA cleavage and molecular docking studies of chiral l- and d-ternary copper(II) complexes of histidine and picolinic acid

Novel chiral ternary Cu(II) and Ni(II) complexes of l/d-histidine and picolinic acid, 1 and 2(a and b) were synthesized and characterized by elemental analysis, molar conductance and spectroscopic data (IR, NMR, EPR, UV–vis). In vitro DNA binding profile of both Cu(II) and Ni(II) complexes have been investigated by UV–vis titrations, while fluorescence spectroscopy, circular dichroism and viscosity measurements were carried out for Cu(II) complexes 1(a and b). Both the enantiomers of 1 and 2(a and b) bind to CT DNA via electrostatic interactions and the intrinsic binding constant, Kb values for complexes 1 and 2(a and b) were found to be 5.6×104, 9.8×103, 8.2×103 and 6.7×103M−1, respectively suggesting greater binding propensity of l-form of Cu(II) complex 1a. The DNA cleavage activity of complexes 1(a and b), investigated by agarose gel electrophoresis suggested an oxidative pathway for DNA cleavage. Further, the molecular docking studies of complexes 1(a and b) were carried out with B-DNA revealing that the complexes bind to the adenine–thymine residues in the minor groove of the DNA. The resulting binding energies of docked metal complexes 1(a and b) were found to be −265.1 and −218.9KJmol−1, respectively. Furthermore, enantiomeric complexes 1 and 2(a and b) were screened for in vitro antimicrobial activity.