Copper Thiosemicarbazone Complexes Research Articles

Co-modification of engineered cellulose surfaces using antibacterial copper-thiosemicarbazone complexes and flame retardants

Lyocell fibers, the most successful regenerated cellulose fibers, have already attracted much attention. However, the use of traditional Lyocell fibers in the field of personal protective equipment (PPE) is limited, due to the lack of antibacterial properties. Additionally, the flame-retardant properties of Lyocell fibers are also required for the specific applications. Here, we co-conjugated phosphorus flame retardants and copper-thiosemicarbazone complexes with antibacterial performance on Lyocell fibers through chemical crosslinkers. The chemical composition and morphology of our engineered Lyocell fibers were fully characterized, and their mechanical properties were also maintained. Flame retardants can import flame-retardant properties (LOI: 25.0 % - 25.7 %) to Lyocell fibers, which also show promising antibacterial activity, suppressing Escherichia coli (GIR: 20.51 % - 66.67 %) and Staphylococcus aureus (GIR: 74.19 % - 93.54 %). Such an improved sustainable formulation can be used to produce the next-generation of Lyocell-based PPE, to meet the demand for the antibacterial and flame-retardant properties of fibers in special applications.

Proving the Antimicrobial Therapeutic Activity on a New Copper-Thiosemicarbazone Complex.

The misuse and overdose of antimicrobial medicines are fostering the emergence of novel drug-resistant pathogens, providing negative repercussions not only on the global healthcare system due to the rise of long-term or chronic patients and inefficient therapies but also on the world trade, productivity, and, in short, to the global economic growth. In view of these scenarios, novel action plans to constrain this antibacterial resistance are needed. Thus, given the proven antiproliferative tumoral and microbial features of thiosemicarbazone (TSCN) ligands, we have here synthesized a novel effective antibacterial copper-thiosemicarbazone complex, demonstrating both its solubility profile and complex stability under physiological conditions, along with their safety and antibacterial activity in contact with human cellular nature and two most predominant bacterial strains, respectively. A significant growth inhibition (17% after 20 h) is evidenced over time, paving the way toward an effective antibacterial therapy based on these copper-TSCN complexes.

Copper thiosemicarbazone modified electrode for hydrazine electrocatalytic oxidation

The major barrier in electro-oxidation of hydrazine hydrate involves usage of expensive, precious noble metal catalysts (Platinum, Palladium, Ruthenium and etc) along with complex reaction mechanism & sluggish kinetics. In this work, a novel copper thiosemicarbazone complex (Cu2L2) is synthesised and characterised by various spectroscopic techniques & proposed as a new electrocatalyst for hydrazine oxidation. Electrocatalytic efficiency of the modified catalyst with metal complex (Cu2L2) have been studied using several potentiostatic & potentiodynamic techniques. Fundamental cyclic voltammeteric investigation reveal sharp & irreversible oxidation peak at 0.3 V vs Ag/AgCl (Sat.KCl) electrode for the direct oxidation of hydrazine with fast electrochemical kinetics using the modified electrode approach & thus it can be an excellent platform for oxidising hydrazine in neutral, basic & acidic medium. The sensing ability of modified electrode for hydrazine is demonstrated using chronoamperometric technique with the detection limit of 0.5 μM with linearity range from 0.5 μM to 27 μM. In addition, Modified electrodes are specific and selective towards the precise oxidation of hydrazine in presence of other interfering organic compounds and inorganic ions. Thus, present modified electrode approach opens the possibility of using such new class of copper thiosemicarbazone complex as an electrocatalyst for direct electrochemical oxidation of hydrazine which can be further extended in the application of direct hydrazine fuel cells (DHFC).

Copper-thiosemicarbazone complexes conjugated-cellulose fibers: Biodegradable materials with antibacterial capacity

Personal protective equipment (PPE) is vital in battling bacteria crisis, but conventional PPE materials lack antimicrobial activities and environmental friendliness. Our work focused on developing biodegradable and antibacterial fibers as promising bioprotective materials. Here, we grafted highly effective antibacterial copper-thiosemicarbazone complexes (CT1–4) on cellulose fibers via covalent linkages. Multiple methods were used to characterize the chemical composition or morphology of CT1–4 conjugated-fibers. Conjugation of CT1–4 maintains the mechanical properties (Breaking strength: 2.35–2.45 cN/dtex, Breaking elongation: 7.19 %–7.42 %) and thermal stability of fibers. CT1 can endow cellulose fibers with the excellent growth inhibition towards Escherichia coli (E. coli) (GIR: 61.5 % ± 1.28 %), Staphylococcus aureus (S. aureus) (GIR: 85.7 % ± 1.93 %), and Bacillus subtilis (B. subtilis) (GIR: 87.6 % ± 1.44 %). We believe that the application of CT1 conjugated-cellulose fibers is not limited to the high-performance PPE, and also can be extended to various types of protective equipment for food and medicine safety.

Catalytic Reduction of Oxygen by a Copper Thiosemicarbazone Complex

The new copper(II) thiosemicarbazone complex CuL (H2L = 4‐{bis[4‐(p‐methoxyphenyl)‐thiosemicarbazone]}‐2,3‐butane) was synthesized and structurally characterized. Its electrochemical behavior in N,N‐dimethylformamide (DMF) was examined. This complex proved active for homogeneous oxygen reduction reaction (ORR) in DMF in the presence of organic acids. The activity and selectivity for ORR were found to be dependent on the nature of the proton source (phenol or acetic acid). This study confirms the previously reported free energy linear correlation between selectivity and overpotential requirement [Passard et al., J. Am. Chem. Soc. 2016, 138, 2925–2928] and suggests that additional descriptors are required for a full understanding of the catalytic ORR behaviour.

Anti-Prostate Cancer Activity of 8-Hydroxyquinoline-2-Carboxaldehyde-Thiosemicarbazide Copper Complexes by Fluorescent Microscopic Imaging.

Copper 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide(CuHQTS) and copper 8-hydroxyquinoline-2-carboxaldehyde-4,4-dimethyl-3-thiosemicarbazide (CuHQDMTS) are two copper thiosemicarbazone complexes with potent anticancer activity on cisplatin-resistant neuroblastoma cells. This study aimed to evaluate anti-prostate cancer activity of these two copper complexes in vitro. Both CuHQTS and CuHQDMTS inhibited proliferation of prostate cancer cells and showed cytotoxicity on prostate cancer cells carrying green fluorescent protein (GFP) by fluorescent microscopic imaging. The findings of this study demonstrated anti-prostate cancer activity of CuHQTS and CuHQDMTS and suggested that GFP-carrying prostate cancer cells might be used for testing anticancer activity of copper complexes by fluorescent microscopic imaging.

Increased generation of intracellular reactive oxygen species initiates selective cytotoxicity against the MCF-7 cell line resultant from redox active combination therapy using copper-thiosemicarbazone complexes.

The combination of cytotoxic copper-thiosemicarbazone complexes with phenoxazines results in an up to 50-fold enhancement in the cytotoxic potential of the thiosemicarbazone against the MCF-7 human breast adenocarcinoma cell line over the effect attributable to drug additivity-allowing minimization of the more toxic copper-thiosemicarbazone component of the therapy. The combination of a benzophenoxazine with all classes of copper complex examined in this study proved more effective than combinations of the copper complexes with related isoelectronic azines. The combination approach results in rapid elevation of intracellular reactive oxygen levels followed by apoptotic cell death. Normal fibroblasts representative of non-cancerous cells (MRC-5) did not display a similar elevation of reactive oxygen levels when exposed to similar drug levels. The minimization of the copper-thiosemicarbazone component of the therapy results in an enhanced safety profile against normal fibroblasts.

Mechanisms underlying reductant-induced reactive oxygen species formation by anticancer copper(II) compounds

Intracellular generation of reactive oxygen species (ROS) via thiol-mediated reduction of copper(II) to copper(I) has been assumed as the major mechanism underlying the anticancer activity of copper(II) complexes. The aim of this study was to compare the anticancer potential of copper(II) complexes of Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone; currently in phase II clinical trials) and its terminally dimethylated derivative with that of 2-formylpyridine thiosemicarbazone and that of 2,2'-bipyridyl-6-carbothioamide. Experiments on generation of oxidative stress and the influence of biologically relevant reductants (glutathione, ascorbic acid) on the anticancer activity of the copper complexes revealed that reductant-dependent redox cycling occurred mainly outside the cells, leading to generation and dismutation of superoxide radicals resulting in cytotoxic amounts of H(2)O(2). However, without extracellular reductants only weak intracellular ROS generation was observed at IC(50) levels, suggesting that cellular thiols are not involved in copper-complex-induced oxidative stress. Taken together, thiol-induced intracellular ROS generation might contribute to the anticancer activity of copper thiosemicarbazone complexes but is not the determining factor.

Synthesis and characterization of new copper thiosemicarbazone complexes with an ONNS quadridentate system: cell growth inhibition, S-phase cell cycle arrest and proapoptotic activities on cisplatin-resistant neuroblastoma cells

Two new copper thiosemicarbazone complexes with an ONNS quadridentate system were synthesized and evaluated for anticancer activity on cisplatin-resistant neuroblastoma cells. Among these two copper complexes, the substituted 8-hydroxyquinoline-2-carboxaldehyde-4,4-dimethyl-3-thiosemicarbazide (CuHQDMTS) exhibited stronger cell growth inhibition activity than the unsubstituted copper 8-hydroxyquinoline-2-carboxaldehyde thiosemicarbazide complex (CuHQTS). Both CuHQTS and CuHQDMTS showed dose-dependent cell growth inhibition, cell cycle arrest and apoptosis induction activities on the SK-N-DZ neuroblastoma cells. Increased expression of p53 protein molecules was detected in the SK-N-DZ cells treated with CuHQTS. The data obtained in this study suggest that CuHQDMTS and CuHQTS hold potential as new, effective drugs for treatment of refractory neuroblastoma in children.

Preparation of [ 61Cu]-2-acetylpyridine thiosemicarbazone complex as a possible PET tracer for malignancies

Due to the interesting anti-proliferative properties of copper–thiosemicarbazone complexes, the production of a 61Cu-labeled thiosemicarbazone, i.e. 2-acetylpyridine thiosemicarbazone (APTS) was investigated. Copper-61 ( T 1 / 2 = 3.33 h ) was produced via the 64Zn(p,α) 61Cu nuclear reaction using a natural zinc target irradiated with 22 MeV protons for 500 μAh. The 61Cu was separated from the irradiated target material by a two-step method and converted to acetate; this yielded a final activity of 222 GBq (6.0 Ci), with a radiochemical yield of >95%. The 61Cu–acetate was mixed with 2-acetylpyridine thiosemicarbazone for 30 min at room temperature to yield [ 61Cu]APTS with a radiochemical yield of more than 80%. Colorimetric methods showed that residual chemical impurities in the product were below the accepted limits. Radio thin layer chromatography (RTLC) showed a radiochemical purity of more than 99% after C 18 column chromatography. A specific activity of about 370–740 MBq/mmol (10–20 Ci/mmol) was obtained. The stability of the final product was checked in the absence and presence of human serum at 37 °C for up to 3 h. The partition coefficient of the final complex was also determined.

Oxidative stress induced by a copper-thiosemicarbazone complex

Copper thiosemicarbazones cause considerable oxidative stress. This effect may be related to their cytotoxicity. In the present work, the chemical and cellular properties of a new ligand, pyridoxal thiosemicarbazone (H2T), and its copper(II) chelate (CuT) are assessed. CuT is toxic to cultured Ehrlich ascites tumor cells, producing nearly complete cell kill at drug/cell ratios of 2.5-4 nmol/10(5) cells in a monolayer culture over a 48-h treatment period. This concentration is at least 1 order of magnitude lower than those required for a similar degree of cytotoxicity by H2T or CuCl2. The following observations support the view that activated oxygen species are generated by interaction of CuT with Ehrlich cells: (1) Room-temperature electron spin resonance spectroscopy and atomic absorption measurements show rapid cellular uptake and CuT-thiol adduct formation. (2) Cellular thiol content is reduced. (3) High levels of DNA strand scission result from 1-h treatments of cells by concentrations of CuT that cause growth inhibition and toxicity. (4) The extent of strand scission can be increased by addition of superoxide dismutase and decreased by catalase or DMSO in the treatment medium. Catalase and DMSO do not inhibit the toxic effect of CuT. This suggests that DNA damage is not responsible for inhibition of cell proliferation by CuT.