Intercalative Binding Mode Research Articles

Antibacterial and ct-DNA binding studies of new synthesized ruthenium (III) hydroxamate complexes: Design, synthesis, DFT calculations and in-vitro study

Ruthenium (III) complexes (1–5) with general composition [Ru(L1–4)3] and [Ru(HL5)3Cl3] where L1 = benzohydroximato (1), L2 = salicylhydroximato (2), L3 = acetohydroximato (3), L4 = hydroxyureato (4), HL 5 = N‑hydroxy-N-phenylbenzamide (5) were synthesized by reacting RuCl3·3H2O with respective hydroxamic acids in 1:3 molar ratio . The complexes were characterized using various techniques including ruthenium metal analysis, elemental analysis, UV–Vis, FT-IR, NMR (1H and 13C), and mass spectrometry. Antibacterial activity of the complexes was evaluated using the agar well diffusion method against ten pathogenic strains. The complexes showed significant inhibition zones and were more active than their corresponding ligands. DNA binding studies indicated intercalative binding mode, with hypochromism and red shift observed. Computational and structural parameters were determined using Frontier Molecular Orbital (FMO) energies and Density Functional Theory (DFT) calculations. The complexes demonstrated favorable molecular geometry, chemical reactivity, and biological activity.

X-ray structures, density functional theory study, DNA binding ability and micellization behaviour of decavanadates anions containing cationic organic moieties

Reported here synthesis, structure, DNA binding ability of three decavanadates complexes containing cationic organic moieties, 2-methylimidazolium (1), 4-dimethylaminopyridinium (2) and protonated 3-pyridiniumcarboxamide (3). Compounds are stable solids, characterized by elemental analyses, spectroscopic, single-crystal X-ray diffraction and theoretical studies. X-ray diffraction analysis indicates, the molecular structures of the compounds are composed of ion pairs formed by decavanadate ion [H2V10O28]4− and the corresponding cationic organic moieties. Complex 1 composed of decavanadate anion in combination with cationic 2-methylimidazolium and 2 contains decavanadate moiety with counter cation protonated 4-dimethylaminopyridine, two DMSO molecules. The structure of 3 consists of [H2V10O28]4−, protonated 3-pyridinecarboxamide, two co-crystallized neutral organic moieties with two molecules of water. The effective interaction of the ion-pair and hydrogen bonding interaction resulted in the cohesion, stabilization of solid state structure of the complexes. In solid state, compounds present interesting assemblies through the formation of H-bonds analyzed using DFT calculations and quantum theory of “atoms in molecules” (QTAIM). Interaction of the compounds with CT-DNA studied by absorption and fluorescence spectroscopy, show moderately strong intercalative mode of binding. Additionally micellization behaviour of the complexes using surfactant CTAB was studied by conductance measurements and absorption spectroscopy. The complexes show an increased solubility on addition of the surfactant.

Comprehensive investigation of Co(II), Ni(II) and Cu(II) complexes derived from a novel Schiff base: Synthesis, characterization, DNA interactions, ADME profiling, molecular docking, and in-vitro biological evaluation

Here, anisidine-based ligand (HL) and its cobalt (1a), nickel (1b) and copper (1c) complexes were synthesized and characterized by various spectroscopic techniques such as NMR, mass, IR, UV–visible, magnetic moments, ESR and TGA. The synthesized [Ni(L)2] and [Cu(L)2] complexes demonstrated square planar geometry around the metal centers, while the cobalt complex [Co(L)2(H2O)2] adopted six coordinated octahedral geometries. The DNA interaction studies of the complexes revealed an intercalative mode of binding, as evidenced by UV absorption, emission, and viscosity experiments, and the binding constant (Kb) follows the order of 1c > 1a > 1b. When exposed to oxidative and photolytic methods, the complexes demonstrated better efficacy in cleaving double-stranded pBR322 DNA compared to their parent Schiff base. When tested for cytotoxicity against A549 and MCF7 cell lines, complexes showed more activity than their parent ligand. In-vitro studies of the complexes' antimicrobial and antioxidant properties shown that they are far more effective than the parent ligand. Further, the biological efficiency of the ligand (HL) and complexes were verified by computational methods, including molecular docking (against protein data bank PDB ID: 2ADO.pdb) and pharmacokinetic studies, both the ligand (HL) and complexes have demonstrated significant potency. This promising result indicated their potential as therapeutic agents for treating pathogen-induced deformities.

Multi-spectroscopic, calorimetric and molecular dynamics evaluation on non-classical intercalation of antiviral drug Molnupiravir with DNA

The interaction of an antiviral drug Molnupiravir (MOL) with calf thymus DNA (CT-DNA) was investigated using a series of biophysical techniques. A significant hyperchromism with a blue shift nm in the UV-Vis spectra indicated a high binding affinity of MOL for CT-DNA with binding constants in the order of 105 M−1. Competitive fluorescent dye displacement assays with ethidium bromide (EB) and Hoechst 33258 suggested an intercalative mode of binding of MOL with CT-DNA. Thermodynamic profiles determined using fluorescence titration and isothermal titration calorimetric (ITC) analysis matched well with each other. The negative free energy change revealed that the MOL/CT-DNA complexation is a spontaneous process. The negative values of enthalpy and entropy changes indicated that H-bonding and van der Walls interactions play dominant roles in stabilizing the complex. A decrease in viscosity of CT-DNA solution upon adding MOL indicated a partial intercalation mode of binding which was well supported by circular dichroism (CD) spectral and effect of KI and denaturation studies. Molecular docking and metadynamics simulation studies clearly showed the partial intercalation of the pyrimidine ring of MOL into the base pairs of DNA. Free energy surface (FES) contour indicated that the drug/DNA complex is stabilized by H-bonding and pi-pi/pi-cation interactions. Communicated by Ramaswamy H. Sarma

Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies.

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2-4) were obtained (45-92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(μ-CO){μ-η1:η3-C(Ph)═C(Ph)C(═O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η5-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1-3 by HBF4 afforded the corresponding μ-alkenyl derivatives 5-7, in 40-86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry (1, 2, 5, 7) and single-crystal X-ray diffraction (5, 7) analyses were performed on representative compounds. Complexes 5-7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5-7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru2Cp2(CO)x scaffold (x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.

Synthesis and characterization of nanoscale level mono/bi-ligated metal(II) complexes

A series of nanoscale level metal complexes with bidentate (N2MCl2) and tetradentate (MN) chromophores as cisplatin analogues and intercalating agents of, [M(phen)Cl2] (1- 3), [M(bpy)Cl2] (4-6), [M(phen)2] (7-9) and [M(bpy)2] (10-12) (where respectively M = Cu(II), Ni(II) or Zn(II); phen = 1,10-phenanthroline and bpy = 2,2’-bipyridine) respectively were prepared in the present investigation. These complexes were prepared by sonochemical technique and characterized using elemental, spectral, and electrochemical techniques. Their nanorod or stick morphologies and crystalline nature were evaluated with scanning electron microscopy (SEM). Metal complexes, 1-6 are existing with two labile chlorides similar to the chemotherapeutic inorganic drug cisplatin, which may anticipate binding covalently with herring sperm DNA, While, complexes, 7-12 may undergo an intercalative mode of binding due to their structural differences relative to 1-6.

Gemcitabine drug intercalation with ds-DNA at surface of ds-DNA/Pt–ZnO/SWCNTs/GCE biosensor: A DNA-biosensor for gemcitabine monitoring confirmed by molecular docking study

Herein, a facile and highly sensitive electroanalytical tool for monitoring and quantifying the antineoplastic drug gemcitabine in real sample was provided. In this regard, a novel DNA-biosensor based on Pt-doped ZnO decorated single walled carbon nanotubes (Pt–ZnO/SWCNTs) hybrid nanomaterial modification of glassy carbon electrode (GCE) was fabricated. Ds-DNA (Calf Thymus), as a biological recognition element, was decorated onto nanomaterial-modified GCE via layer-by-layer fabrication strategy to attain ultimate biosensor ds-DNA/Pt–ZnO/SWCNTs/GCE. The characterizations confirmed the successful fabrication of hybrid nanomaterial, as well as the modification of electrode surface by fabricated nanomaterial. The electrochemical impedance spectroscopy (EIS) analysis revealed that the nanomaterial modification of GCE surface enhanced the electrical conductivity thanks to the synergistic effects of Pt–ZnO and SWCNTs structures, thereby boosted the electrocatalytic activity of the resultant biosensor. The electrochemical characterization results showed that the suggested biosensor is capable of detecting gemcitabine in a wide concentration range of 0.01–30.0 μM, with a detection limit of 5.0 nM. The intercalation binding mode of Gemcitabine inside guanine and cytosine rich region of DNA receptor was approved by molecular docking study. The results of the experimental data were well congruent with the molecular docking analysis, which showed that the binding mode of gemcitabine drug with ds-DNA was intercalation.

Synthesis, Characterization, DFT Studies of Novel Cu(II), Zn(II), VO(II), Cr(III), and La(III) Chloro-Substituted Schiff Base Complexes: Aspects of Its Antimicrobial, Antioxidant, Anti-Inflammatory, and Photodegradation of Methylene Blue.

A new chlorobenzylidene imine ligand, (E)-1-((5-chloro-2-hydroxybenzylidene)amino) naphthalen-2-ol (HL), and its [Zn(L)(NO3)(H2O)3], [La(L)(NO3)2(H2O)2], [VO(L)(OC2H5)(H2O)2], [Cu(L)(NO3)(H2O)3], and [Cr(L)(NO3)2(H2O)2], complexes were synthesized and characterized. The characterization involved elemental analysis, FT-IR, UV/Vis, NMR, mass spectra, molar conductance, and magnetic susceptibility measurements. The obtained data confirmed the octahedral geometrical structures of all metal complexes, while the [VO(L)(OC2H5)(H2O)2] complex exhibited a distorted square pyramidal structure. The complexes were found to be thermally stable based on their kinetic parameters determined using the Coats-Redfern method. The DFT/B3LYP technique was employed to calculate the optimized structures, energy gaps, and other important theoretical descriptors of the complexes. In vitro antibacterial assays were conducted to evaluate the complexes' potential against pathogenic bacteria and fungi, comparing them to the free ligand. The compounds exhibited excellent fungicidal activity against Candida albicans ATCC: 10231 (C. albicans) and Aspergillus negar ATCC: 16404 (A. negar), with inhibition zones of HL, [Zn(L)(NO3)(H2O)3], and [La(L)(NO3)2(H2O)2] three times higher than that of the Nystatin antibiotic. The DNA binding affinity of the metal complexes and their ligand was investigated using UV-visible, viscosity, and gel electrophoresis methods, suggesting an intercalative binding mode. The absorption studies yielded Kb values ranging from 4.40 × 105 to 7.30 × 105 M-1, indicating high binding strength to DNA comparable to ethidium bromide (value 107 M-1). Additionally, the antioxidant activity of all complexes was measured and compared to vitamin C. The anti-inflammatory efficacy of the ligand and its metal complexes was evaluated, revealing that [Cu(L)(NO3)(H2O)3] exhibited the most effective activity compared to ibuprofen. Molecular docking studies were conducted to explore the binding nature and affinity of the synthesized compounds with the receptor of Candida albicans oxidoreductase/oxidoreductase INHIBITOR (PDB ID: 5V5Z). Overall, the combined findings of this work demonstrate the potential of these new compounds as efficient fungicidal and anti-inflammatory agents. Furthermore, the photocatalytic effect of the Cu(II) Schiff base complex/GO was examined.

Electro-organic synthesis of C-5 sulfenylated amino uracils: Optimization and exploring topoisomerase-I based anti-cancer profile

Cancer is spreading worldwide and is one of the leading causes of death. The use of existing chemotherapeutic agents is frequently limited due to side effects. As a result, it is critical to investigate new agents for cancer treatment. In this context, we developed an electrochemical method for the synthesis of a series of thiol-linked pyrimidine derivatives (3a-3p) and explored their anti-cancer potential. The biological profile of the synthesized compounds was evaluated against breast (MDAMB-231 and MCF-7) and colorectal (HCT-116) cancer cell lines. 3b and 3d emerged to be the most potent agents, with IC50 values ranging between 0.98 to 2.45 µM. Target delineation studies followed by secondary anticancer parameters were evaluated for most potent compounds, 3b and 3d. The analysis revealed compounds possess DNA intercalation potential and selective inhibition towards human topoisomerase (hTopo1). The analysis was further corroborated by DNA binding studies and in silico-based molecular modeling studies that validated the intercalating binding mode between the compounds and the DNA.

Synthesis, characterization, cytotoxicity evaluation, and molecular docking with DNA, bovine serum albumin, and SARS‐Cov‐2 of copper complexes bearing tris‐(2‐pyridyl)‐pyrazolyl borate ligand

Four copper (II) complexes bearing tris‐(2‐pyridyl)‐pyrazolyl borate (Tppy) ligand with corresponding chloride (Cu‐1), aqua (Cu‐2), azide (Cu‐3), and thiocyanide (Cu‐4) substitutions were synthesized and characterized by spectroscopic and analytical methods. Spectroscopic and molecular docking studies were employed to investigate the interactions of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA). The results inferred intercalation binding mode of the complexes with DNA. All the complexes exhibited good binding with BSA as well. In addition, the binding efficacy of the Cu (II) complexes with SARS‐Cov‐2 was tested in silico. Further, in vitro anticancer activity of the complexes was investigated against the HeLa‐cervical, HepG2‐liver and A549‐lung cancer, and one normal (L929‐fibroblast) cell line. IC50 values unveiled that the complexes were more active than cisplatin against all three cancer cells. It was understood that complex Cu‐3 containing azide substitution displayed the highest activity on the HeLa cell line (IC50 = 6.3 μM). More importantly, TppyCu (II) complexes were not active against the normal cell line. Lastly, the acridine orange/ethidium bromide (AO/EB) and 4′,6‐diamidino‐2‐phenylindole staining assays indicated that Cu‐3 induced cell death in HeLa cells at the late apoptotic stage. This complex also efficiently generated ROS in HeLa cells promoting apoptosis as understood from the DCFH‐DA assay.

Pyrazole derivatives of pyridine and naphthyridine as proapoptotic agents in cervical and breast cancer cells

Cancer is one of the leading causes of death worldwide. The increasing prevalence and resistance to chemotherapy is responsible for driving the search of novel molecules to combat this disease. In search of novel compounds with pro-apoptotic potential, pyrazolo-pyridine and pyrazolo-naphthyridine derivatives were investigated against cervical cancer (HeLa) and breast cancer (MCF-7) cells. The anti-proliferative activity was determined through the MTT assay. Potent compounds were then analyzed for their cytotoxic and apoptotic activity through a lactate dehydrogenase assay and fluorescence microscopy after propidium iodide and DAPI staining. Flow cytometry was used to determine cell cycle arrest in treated cells and pro-apoptotic effect was verified through measurement of mitochondrial membrane potential and activation of caspases. Compounds 5j and 5k were found to be most active against HeLa and MCF-7 cells, respectively. G0/G1 cell cycle arrest was observed in treated cancer cells. Morphological features of apoptosis were also confirmed, and an increased oxidative stress indicated the involvement of reactive oxygen species in apoptosis. The compound-DNA interaction studies demonstrated an intercalative mode of binding and the comet assay confirmed the DNA damaging effects. Finally, potent compounds demonstrated a decrease in mitochondrial membrane potential and increased levels of activated caspase-9 and -3/7 confirmed the induction of apoptosis in treated HeLa and MCF-7 cells. The present work concludes that the active compounds 5j and 5k may be used as lead candidates for the development of lead drug molecules against cervical and breast cancer.

Interaction of an anticancer benzopyrane derivative with DNA: Biophysical, biochemical, and molecular modeling studies

BackgroundSIMR1281 is a potent anticancer lead candidate with multi- target activity against several proteins; however, its mechanism of action at the molecular level is not fully understood. Revealing the mechanism and the origin of multitarget activity is important for the rational identification and optimization of multitarget drugs. MethodsWe have used a variety of biophysical (circular dichroism, isothermal titration calorimetry, viscosity, and UV DNA melting), biochemical (topoisomerase I & II assays) and computational (molecular docking and MD simulations) methods to study the interaction of SIMR1281 with duplex DNA structures. ResultsThe biophysical results revealed that SIMR1281 binds to dsDNA via an intercalation-binding mode with an average binding constant of 3.1 × 106 M−1. This binding mode was confirmed by the topoisomerases' inhibition assays and molecular modeling simulations, which showed the intercalation of the benzopyrane moiety between DNA base pairs, while the remaining moieties (thiazole and phenyl rings) sit in the minor groove and interact with the flanking base pairs adjacent to the intercalation site. ConclusionsThe DNA binding characteristics of SIMR1281, which can disrupt/inhibit DNA function as confirmed by the topoisomerases' inhibition assays, indicate that the observed multi-target activity might originate from ligand intervention at nucleic acids level rather than due to direct interactions with multiple biological targets at the protein level. General significanceThe findings of this study could be helpful to guide future optimization of benzopyrane-based ligands for therapeutic purposes.

New Heterocyclic Organo-Chalcogenide Compounds: Synthesis, Physicochemical Characterization, and Evaluation of Anticancer Activity against Breast Cancer Cells

This work aimed to synthesize, characterize and evaluate the thermal stability of new sulfur and selenium organochalcogenide derivatives and to test the cytotoxic activity against breast adenocarcinoma cell line (MCF-7) through conducting MTT assay and AO/EB dual staining-technique. Two series of ten organo-chalcogen compounds: 4-(substituted)phenylthiomorpholine-3,5-dione and 4-(substituted)phenylselenomorpholine-3,5-dione were prepared by the reaction of Na2S·3H2O and NaHSe with N-(substituted)phenyl-2-chloro-N-(2-chloroacetyl)acetamide, respectively, under nitrogen atmosphere to give the corresponding cyclic chalcogenide ligands. All new compounds were characterized by melting point, FTIR, elemental analysis, UV-Visible, 1H-NMR and 13C-NMR. Meanwhile, TG/DTA analysis of some of these ligands was conducted to evaluate the thermal stability, kinetic, and characteristic thermodynamic parameters. Absorption spectroscopy was used to investigate these compounds with human DNA. The experimental results investigated a hypochromic effect via intercalation binding mode. The role of the prepared ligands in breast cell lines has been investigated by conducting MTT assay via spectroscopic techniques on HBL100 and MCF-7, normal and cancer breast cell lines, respectively. Cell death was seen after AO/EB dye staining method employing the fluorescence microscopy technique. The results revealed that these compounds possess cytotoxic activity on the MCF-7 and HBL-100 cell lines at a fixed concentration.

Exploring the binding of mitoxantrone to DNA using optical tweezers.

Mitoxantrone (MTX) is a synthetic anti-cancer drug that displays intercalation binding mode with DNA. It has been widely studied using conventional methods, but not using single molecule techniques which can provide molecular level details of the interactions. Here we explored the binding of MTX with DNA using optical tweezers. Our optical tweezers set-up uses two counter propagating lasers to trap and manipulate a single DNA molecule that is stretched to measure the force response as a function of extension. The DNA stretching was repeated in the presence of various nano-molar concentrations of MTX at different pulling rates. Stretching at much slower pulling rates exhibited closer to binding equilibrium, indicating MTX is a slow binder with the time scale of seconds compared to classical intercalators which have microsecond binding kinetics. This will provide more detail about the binding mechanism of MTX that can be used to better understand the binding of MTX and also develop similar drug designs.

Cancer cells inhibition by cationic carbon dots targeting the cellular nucleus

Nucleus targeting is tremendously important in cancer therapy. Cationic carbon dots (CCDs) are potential nanoparticles which might enter cells and penetrate nuclear membranes. Although some CCDs have been investigated in nucleus targeting and applied in nuclear imaging, the CCDs derived from drugs, that are able to target the nucleus, bind with DNA and inhibit the growth of cancer cells have not been reported. In this project, 1, 2, 4, 5-benzenetetramine (Y15, a focal adhesion kinase inhibitor) derived cationic carbon dots (Y15-CDs) were prepared via a hydrothermal approach utilizing Y15, folic acid and 1,2-ethylenediamine as precursors. Based on the structural, optical, and morphologic characterizations, Y15-CDs possess rich amine groups and nitrogen in structure, an excitation-dependent photoluminescence emission, and a small particle size of 2 to 4 nm. The DNA binding experiments conducted through agarose gel electrophoresis, UV–vis absorption, fluorescence emission, and circular dichroism spectroscopies, prove that Y15-CDs might bind with DNA via electrostatic interactions and partially intercalative binding modes. In addition, the cell imaging and cytotoxicity studies in human foreskin fibroblasts (HFF), prostate cancer (PC3) and osteosarcoma cells (U2OS) indicate the nucleus targeting and anticancer abilities of Y15-CDs. Most interestingly, Y15-CDs exhibit a higher cytotoxicity to cancer cells (PC3 and U2OS) than to normal cells (HFF), inferring that Y15-CDs might be potentially applied in cancer therapy.

Thioether-based novel transition metal complexes: Synthesis, DNA interaction, in vitro biological assay, DFT calculations, and molecular docking studies

A novel Schiff base ligand 2-(((2-(benzylthio)phenyl)imino)methyl)-4-chlorophenol and its cobalt, nickel, copper, and zinc metal complexes were prepared. Using B3LYP/6–31++G(d,p) method with LanL2DZ as basis set, the molecular structure of metal complexes has been optimized, and their parameters have been explored. The distorted octahedral geometries have been observed in cobalt, nickel, and copper complexes. In contrast, zinc complex exhibited distorted tetrahedral geometry indicating the coordination of metal ions with ligands through ONS binding sites, which are confirmed by various spectroscopic techniques, magnetic measurements, molar conductivity, elemental analysis, and DFT studies. The intercalative binding mode between CT-DNA and synthesized metal complexes has been determined by absorption and fluorescence spectroscopy. The binding constant values of metal complexes found to be varied from 5.28 × 103 M−1 to 9.18 × 104 M−1. Furthermore, several methods have been used to scrutinize the bioactivities, such as in vitro anti-diabetic, anti-inflammatory, and antioxidant. From the obtained results, it can be concluded that zinc metal complex exhibited excellent anti-inflammatory and anti-diabetic activity compared to others. However, the copper complex has good antioxidant property. Besides deducing the prospective binding energies of inhibitors, molecular docking simulations have also been conducted utilizing the enzyme structures of B-DNA, 6-COX, α-amylase, and α-glucosidase.

Novel copper (II) binary complexes with N,O-donor isoxazole Schiff base ligands: Synthesis, characterization, DPPH scavenging, antimicrobial, and DNA binding and cleavage studies

Cu(II) binary complexes of the type [Cu(Ln)2], where n = 1–3, HL1 = 2-((E)-(3,5-dimethylisoxazol-4-ylimino)methyl)-6-tert-butylphenol (C1), HL2 = 2-((E)-(3,5-dimethylisoxazol-4-ylimino)methyl)-4-bromo-6-methoxyphenol (C2), HL3 = 2-((E)-(3,5-dimethylisoxazol-4-ylimino)methyl)-5-methylphenol (C3) have been synthesized and characterized by analytical, structural, and spectral methods. The antioxidant studies of novel Cu(II) complexes revealed, significant activity against DPPH radical. The synthesized compounds were monitored for antimicrobial activities and the results of these studies indicated that the complexes exhibit a good antimicrobial efficiency compared to ligands. The interaction of CT–DNA with the Cu(II) complexes has been explored using absorption and emission spectral techniques. Spectral evidence showed the intercalative mode of DNA binding with the complexes. Agarose gel electrophoresis results revealed that all Cu(II) complexes induced double strand breaks of pBR 322 plasmid DNA in the presence of H2O2 and UV light.

Synthesis, characterization, X-ray crystal structure, antioxidant, antimicrobial, and DNA binding interaction studies of novel copper (II)-isoxazole binary complexes

Cu (II) binary complexes of the type [Cu(HLx)2], where x = 1–3, HL1 = 2-((E)-(3,5-dimethylisoxazol-4-ylimino)methyl)-6-methylphenol (C1), HL2 = 2-((E)-(3,5-dimethylisoxazol-4-ylimino)methyl)-6-ethoxyphenol (C2) and HL3 = 2-((E)-(3,5-dimethylisoxazol-4-ylimino)methyl)-4,6-di-tert-butylphenol (C3) have been synthesized and characterized by various analytical, structural, and spectral methods. Single crystal X–ray diffraction analysis of ligand HL1, complexes C2 &C3 revealed that the compounds are crystallized in monoclinic crystal system with the space groups of P1 21/c1 for HL1 &C2, and P1 21/n1 for C3. The antioxidant studies of the synthesized Cu(II) complexes were carried out and it was shown as significant activity against DPPH radical. The synthesized Schiff bases and Cu(II) complexes were explored for antimicrobial activities and the complexes exhibited better potency against diverse microorganisms compared to Schiff bases as ligands. The interaction of Cu(II) complexes with CT–DNA has been explored with absorption and emission spectral techniques and the obtained results were evidence to the intercalative mode of DNA binding. The study of Agarose gel electrophoresis was resulted in three Cu(II) complexes stimulate the double strand breakage of pBR 322 plasmid DNA in the presence and absence of H2O2.

Oxadiazole Schiff Base as Fe3+ Ion Chemosensor: "Turn-off" Fluorescent, Biological and Computational Studies.

Compound, (E)-5-(4-((thiophen-2-ylmethylene)amino)phenyl)-1,3,4-oxadiazole-2-thiol (3) was synthesized via condensation reaction of 5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol with thiophene-2-carbaldehyde in ethanol. For the synthesis and structural confirmation the FT-IR, 1H, 13C-NMR, UV-visible spectroscopy, and mass spectrometry were carried out. The long-term stability of the probe (3) was validated by the experimental as well as theoretical studies. The sensing behaviour of the compound 3 was monitored with various metal ions (Ca2+, Cr3+, Fe3+, Co2+, Mg2+, Na+, Ni2+, K+) using UV- Vis. and fluorescence spectroscopy techniques by various methods (effect of pH and density functional theory) which showing the most potent sensing behaviour with iron. Job's plot analysis confirmed the binding stoichiometry ratio 1:1 of Fe3+ ion and compound 3. The limit of detection (LOD), the limit of quantification (LOQ), and association constant (Ka) were calculated as 0.113µM, 0.375µM, and 5.226 × 105 respectively. The sensing behavior was further confirmed through spectroscopic techniques (FT-IR and 1H-NMR) and DFT calculations. The intercalative mode of binding of oxadiazole derivative 3 with Ct-DNA was supported through UV-Vis spectroscopy, fluorescence spectroscopy, viscosity, cyclic voltammetry, and circular dichroism measurements. The binding constant, Gibb's free energy, and stern-volmer constant were find out as 1.24 × 105, -29.057kJ/mol, and 1.82 × 105 respectively. The cleavage activity of pBR322 plasmid DNA was also observed at 3 × 10-5M concentration of compound 3. The computational binding score through molecular docking study was obtained as -7.4kcal/mol. Additionally, the antifungal activity for compound 3 was also screened using broth dilution and disc diffusion method against C. albicans strain. The synthesized compound 3 showed good potential scavenging antioxidant activity against DPPH and H2O2 free radicals.

Purine-based Schiff base Co(II), Cu(II), and Zn(II) complexes: Synthesis, characterization, DFT calculations, DNA binding study, and molecular docking

A series of metal complexes of Co(II), Zn(II), and Cu(II) of purine base Schiff base ligand L1 6,6′-((1E,1′E)-((7H-purine-2,6-diyl)bis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenol) and L2 3,3′-((1E,1′E)-((7H-purine-2,6-diyl)bis(azanylylidene))bis (methanylylidene))bis(4H-chromen-4-one) were synthesized. The characterization of synthesized compounds was investigated through elemental analysis, UV–vis, FT-IR, NMR, and mass spectrometry. The spectroscopic and DFT studies validate the coordination of ligand to the metal centers along with their structural details. In complexes of L1 and L2, the N and O atoms coordinate to metal centers of zinc, cobalt, and copper. However, in the case of L1 complexes the binding mode of oxygen is through phenolic –OH of vanillin moiety. In contrast, complexes of L2 the binding mode of oxygen source is carbonyl oxygen of chromone carboxaldehyde moiety. The stability order follow- ZnL1 < CoL1 < CuL1 < CuL2 < CoL2 < ZnL2. The CT-DNA binding activity of all synthesized complexes with the help of UV–vis absorption titration, fluorescence titration, and viscosity measurement was studied. In both cases, cobalt complexes of L1 and L2 showed high DNA binding activity. The binding constant values are in the order of 105 via intercalation mode of binding. The molecular docking study was performed to speculate on the active binding site between metal complexes and CT-DNA.