The influence of thioether-substituted ligands in dicopper(II) complexes: Enhancing oxidation and biological activities.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm-1 and -5.01 cm-1, respectively, H = -2JS1S2) and ferromagnetic coupling for 2 (J = 5.72 cm-1). Broken symmetry DFT calculations attribute this behavior to a major contribution from the dz2 orbitals for 1 and 3, and from the dx2-y2 orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with kcat of (90.79 ± 2.90) × 10-3 for 1, (64.21 ± 0.99) × 10-3 for 2 and (14.20 ± 0.32) × 10-3 s-1 for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

Equilibrium Studies of Iron (III) Complexes with Either Pyrazine, Quinoxaline, or Phenazine and Their Catecholase Activity in Methanol.

Currently, catalysts with oxidative activity are required to create valuable chemical, agrochemical, and pharmaceutical products. The catechol oxidase activity is a model reaction that can reveal new oxidative catalysts. The use of complexes as catalysts using iron (III) and structurally simple ligands such as pyrazine (pz), quinoxaline (qx), and phenazine (fz) has not been fully explored. To characterize the composition of the solution and identify the abundant species which were used to catalyze the catechol oxidation, the distribution diagrams of these species were obtained by an equilibrium study using a modified Job method in the HypSpec software. This allows to obtain also the UV-vis spectra calculated and the formation constants for the mononuclear and binuclear complexes with Fe3+ including: [Fe(pz)]3+, [Fe2(pz)]6+, [Fe(qx)]3+, [Fe2(qx)]6+, [Fe(fz)]3+, and [Fe2(fz)]6+. The formation constants obtained were log ß110 = 3.2 ± 0.1, log ß210 = 6.9 ± 0.1, log ß110 = 4.4 ± 0.1, log ß210 = 8.3 ± 0.1, log ß110 = 6.4 ± 0.2, and log ß210 = 9.9 ± 0.2, respectively. The determination of the catechol oxidase activity for these complexes did not follow a traditional Michaelis-Menten behavior.

Effect of structural variation on enzymatic activity in tetranuclear (Cu4) clusters with defective cubane core.

The stimulus to the modeling of enzyme functioning sites comes from their potential to give insight into the natural enzyme's mechanistic pathways, ascertain the role of that different metal ion in the active site and construct better catalysts motivated by nature. The presence of metal ion leads to the activation of molecular oxygen in the metalloenzymes. The metalloenzymes such as the catechol oxidase (CO) enzyme that oxidizes the catechol to corresponding quinones which eventually protect damage tissues from plant and pathogen. Thus, the design and characterization of catalysts used as selectively and efficiently oxidation reactions have grown to be unique challenges for modern inorganic chemists. In this work, two novel tetranuclear complexes (1 and 2) have been synthesized in excellent yield. The complexes were characterized using various spectroscopic techniques such as FTIR, UV-Visible and PXRD pattern. The structure of 1 and 2 was elucidated by SC-XRD (single crystal X-ray diffraction) analysis. The magnetic study reveals the presence of the antiferromagnetic nature of 1 and 2. Both 1 and 2 shows a very good catecholase-like activity by oxidizing the catechol to analogous quinone in methanolic solution. Thus, a structure-activity relationship can further help us design other substituted tetranuclear complexes with enhanced catecholase like activity.Communicated by Ramaswamy H. Sarma.

Synthesis of Novel Tetra(µ3-Methoxo) Bridged with [Cu(II)-O-Cd(II)] Double-Open-Cubane Cluster: XRD/HSA-Interactions, Spectral and Oxidizing Properties.

A new double-open-cubane core Cd(II)-O-Cu(II) bimetallic ligand mixed cluster of type [Cl2Cu4Cd2(NNO)6(NN)2(NO3)2].CH3CN was made available in EtOH/CH3CN solution. The 1-hydroxymethyl-3,5-dimethylpyrazole (NNOH) and 3,5-dimethylpyrazole (NNH) act as N,O-polydentate anion ligands in coordinating the Cu(II) and Cd(II) centers. The structure of the cluster in the solid state was proved by XRD study and confirmed in the liquid state by UV-vis analysis. The XRD result supported the construction of two octahedral and one square pyramid geometries types around the four Cu(II) centers and only octahedral geometry around Cd(II) two centers. Interestingly, NNOH ligand acts as a tetra-µ3-oxo and tri-µ2-oxo ligand; meanwhile, the N-N in NNH acts as classical bidentate anion/neutral ligands. The interactions in the lattice were detected experimentally by the XRD-packing result and computed via Hirschfeld surface analysis (HSA). The UV-vis., FT-IR and Energy Dispersive X-ray (EDX), supported the desired double-open cubane cluster composition. The oxidation potential of the desired cluster was evaluated using a 3,5-DTB-catechol 3,5-DTB-quinone as a catecholase model reaction.

Dinuclear copper(II) complexes with derivative triazine ligands as biomimetic models for catechol oxidases and nucleases.

The research reported herein focuses on the synthesis of two new Cu(II) complexes {[Cu2(2-X-4,6-bis(di-2-picolylamino)-1,3,5-triazine], with X = butane-1,4-diamine (2) or N-methylpyrenylbutane-1,4-diamine (3)}, the latter with a pyrene group as a possible DNA intercalating agent. The structure of complex (3) was determined by X-ray crystallography and shows the dinuclear {CuII(µ-OCH3)2CuII} unit in which the CuII···CuII distance of 3.040 Å is similar to that of 2.97 Å previously found for 1, which contains a {CuII(µ-OH)2CuII} structural unit. Complexes (2) and (3) were also characterized in spectroscopic and electrochemical studies, and catecholase-like activity were performed for both complexes. The kinetic parameters obtained for the oxidation of the model substrate 3,5-di-tert-butylcatechol revealed that the insertion of the spacer butane-1,4-diamine and the pyrene group strongly contributes to increasing the catalytic efficiency of these systems. In fact, Kass becomes significantly higher, indicating that these groups influence the interaction between the complex and the substrate. These complexes also show DNA cleavage under mild conditions with moderate reaction times. The rate of cleavage (kcat) indicated that the presence of butane-1,4-diamine and pyrene increased the activity of both complexes. The reaction mechanism seems to have oxidative and hydrolytic features and the effect of DNA groove binding compounds and circular dichroism indicate that all complexes interact with plasmid DNA through the minor groove. High-resolution DNA cleavage assays provide information on the interaction mechanism and for complex (2) a specificity for the unpaired hairpin region containing thymine bases was observed, in contrast to (3).

A novel Cu(II) distorted cubane complex containing Cu4O4 core as the first tetranuclear catalyst for temperature dependent oxidation of 3,5-di-tert-butyl catechol and in interaction with DNA & protein (BSA).

The tri-dentate Schiff base ligand 3-(2-hydroxyethylimino)-1-phenylbut-1-en-1-ol (L) produced the tetra-nuclear Cu(II) distorted cubane complex which contain Cu4O4 core, upon reaction with Cu(II)acetate.H2O. The complex was structurally characterized by X-ray crystallography and found that, in this tetrameric and tetra-nuclear distorted cubane structure, each two-fold deprotonated Schiff base ligand coordinated to a Cu(II) center with their alcoholic oxygens and imine nitrogens and formed six and five-membered chelate rings. At the same time, each ligand bridged to a neighboring Cu(II) atom by its alcoholic oxygen, thus the metal centers became penta-coordinated. The copper(II) complex with µ-ɳ2-hydroxo bridges and Cu….Cu distance about 3 Šwas structurally similar to the active site of natural catechol oxidase enzyme and exhibited excellent catecholase activity in aerobic oxidation of 3,5-di-tert-butyl catechol to its o-quinone. The kinetics and mechanism of the oxidation of 3, 5-DTBCH2 catalyzed by [CuL]4 complex, were studied at four different temperatures from 283 to 313K by UV-Vis spectroscopy. Interaction of [CuL]4 complex with FS-DNA was investigated by UV-Vis and fluorescence spectroscopy, viscosity measurements, cyclic voltammetry (CV), circular dichroism (CD) and agarose gel electrophoresis. The main mode of binding of the complexes with DNA was intercalation. The interaction between [CuL]4 complex and bovine serum albumin (BSA) was studied by UV-Vis, fluorescence and synchronous fluorescence spectroscopic techniques. The results indicated a high binding affinity of the complex to BSA. In vitro anticancer activity of the complex was evaluated against A549, Jurkat and Ragi cell lines by MTT assay. The complex was remarkably active against the cell lines and can be a good candidate for an anticancer drug. Theoretical docking studies were performed to further investigate the DNA and BSA binding interactions.

Phenotypic Characterization and Synthesis of Extracellular Catecholase from a Newly Isolated Bacterium Pseudomonas sp. BSC-6

Abstract Catecholase (EC 1.10.3.1), an oxidoreductase enzyme is a key member of polyphenol oxidase family which catalyze the degradation of catechol. This enzyme possesses vast applications in diverse areas and is found in bacteria, fungi, mushrooms, higher plants, arthropods, amphibians and mammals. Catechol, a phenolic compound, is used as a starting material in the synthesis of various industrial compounds such as inhibitors, antioxidants, pesticides etc. The release of this phenolic compound in the environment causes toxicity to both flora and fauna. In the present studies, emphasis has been laid on isolation, screening and characterization of catechol degrading bacterium coupled with synthesis of catecholase enzyme. Further, the selected isolated strain was phenotypically characterized and was found to be member of genus Pseudomonas. Among all the isolates, BSC-6 was found as best isolate with maximum extracellular catecholase activity of 152.32 IU/L obtained after scale up studies. The herein synthesized bacterial catecholase may be employed for wide applications particularly in bioremediation of phenol enriched polluted sites.