Thiosemicarbazone Complexes Research Articles

In Vitro and In Vivo of Triphenylamine-Appended Fluorescent Half-Sandwich Iridium(III) Thiosemicarbazones Antitumor Complexes.

Half-sandwiched structure iridium(III) complexes appear to be an attractive organometallic antitumor agents in recent years. Here, four triphenylamine-modified fluorescent half-sandwich iridium(III) thiosemicarbazone (TSC) antitumor complexes were developed. Because of the "enol" configuration of the TSC ligands, these complexes formed a unique dimeric configuration. Aided by the appropriate fluorescence properties, studies found that complexes could enter tumor cells in an energy-dependent mode, accumulate in lysosomes, and result in the damage of lysosome integrity. Complexes could block the cell cycle, improve the levels of intrastitial reactive oxygen species, and lead to apoptosis, which followed an antitumor mechanism of oxidation. Compared with cisplatin, the antitumor potential in vivo and vitro confirmed that Ir4 could effectively inhibit tumor growth. Meanwhile, Ir4 could avoid detectable side effects in the experiments of safety evaluation. Above all, half-sandwich iridium(III) TSC complexes are expected to be an encouraging candidate for the treatment of malignant tumors.

Bismuth(III) halide complexes of aromatic thiosemicarbazones: Synthesis, structural characterization and biological evaluation

Four new bismuth(III) thiosemicarbazone complexes, {BiCl3(η1-S-Hacptsc)3} (1), {[BiBr3(η1-S-Hacptsc)3]·CH3OH} (2), {[BiI2(µ2-I](η1-S-Hacptsc)]2} (3) and {[BiCl2(µ2-Cl)(η1-S-Hbztsc)2]2} (4), were prepared with the ligands acetophenone thiosemicarbazone (Hacptsc) and benzaldehyde thiosemicarbazone (Hbztsc). The complexes were characterized by a series of spectroscopic techniques. The crystal structures of 1–4 were also determined by X-ray diffraction. To the best of our knowledge, complexes 1–4 are the first examples of bismuth(III) halide aromatic thiosemicarbazones. Hirshfeld surface analysis studies show that H…H and X…H/H…X interactions of complexes 1–4 play an important role in the formation of supramolecular aggregation. Complexes 1–4 have been tested for their in vitro cytotoxic activity against human breast adenocarcinoma (MCF-7) cells. The toxicity of 1–4 has been evaluated on normal human fetal lung fibroblast cells (MRC-5). Complexes 1–4 appeared to show low cytotoxic activity and low toxicity. The antibacterial activity of 1–4 and their ligands was evaluated against the Gram negative species Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli) and Gram positive ones Staphylococcus epidermidis (S. epidermidis) and Staphylococcus aureus (S. aureus) by the Inhibition Zone (IZ) method. The influence of 1–4 on the catalytic peroxidation of linoleic acid by the enzyme lipoxygenase (LOX) has been determined experimentally. The IC50 values reveal that the synthesized bismuth(III) aromatic thiosemicarbazone complexes have good potential to inhibit lipoxygenase, with values better than the free aromatic thiosemicarbazone ligands and cisplatin.

Bis{N'-[3-(4-nitro-phen-yl)-1-phenyl-prop-2-en-1-yl-idene]-N-phenyl-carbamimido-thio-ato}zinc(II): crystal structure, Hirshfeld surface analysis and computational study.

The title zinc bis-(thio-semicarbazone) complex, [Zn(C22H17N4O2S)2], comprises two N,S-donor anions, leading to a distorted tetra-hedral N2S2 donor set. The resultant five-membered chelate rings are nearly planar and form a dihedral angle of 73.28 (3)°. The configurations about the endocyclic- and exocyclic-imine bonds are Z and E, respectively, and that about the ethyl-ene bond is E. The major differences in the conformations of the ligands are seen in the dihedral angles between the chelate ring and nitro-benzene rings [40.48 (6) cf. 13.18 (4)°] and the N-bound phenyl and nitro-benzene ring [43.23 (8) and 22.64 (4)°]. In the crystal, a linear supra-molecular chain along the b-axis direction features amine-N-H⋯O(nitro) hydrogen bonding. The chains assemble along the 21-screw axis through a combination of phenyl-C-H⋯O(nitro) and π(chelate ring)-π(phen-yl) contacts. The double chains are linked into a three-dimensional architecture through phenyl-C-H⋯O(nitro) and nitro-O⋯π(phen-yl) inter-actions.

Synthesis and antioxidant activities of new nickel(II) complexes derived from 4-benzyloxysalicylidene-S-methyl/propyl thiosemicarbazones.

Six nickel(II) complexes of the N2O2 chelating thiosemicarbazones were synthesized using N1-4-benzyloxysalicylidene-S-methyl/propyl thiosemicarbazone and methoxy-substitute-salicylaldehydes in the presence of Ni(II) ion by template reaction. The structures of thiosemicarbazones and nickel(II) complexes were characterized by elemental analysis, UV-Vis, IR, and 1H-NMR spectroscopies. The structure of the N1-4-benzyloxysalicylidene-S-propyl thiosemicarbazone ( 2 ) was determined by X-ray single-crystal diffraction method. The total antioxidant capacities of synthesized compounds were evaluated by using cupric reducing antioxidant capacity (CUPRAC) method. The thiosemicarbazones exhibited more potent antioxidant capacity than Ni(II) complexes. Trolox equivalent antioxidant capacity (TEAC) of 1c was found highest in tested nickel(II) complexes. In addition, antioxidant activities of tested compounds were evaluated by using the hydroxyl radical, DPPH radical, and ABTS radical scavenging abilities of these compounds.

Novel thiosemicarbazone complexes as single coordinated precursors for noble metal modified nickel oxide nanophotocatalysts

Pd2+, Pt2+, Ni2+ and Cu2+ complexes of N-ethyl-2-(2-hydroxybenzylidene) hydrazine-1-carbothioamide (H2L) have been prepared and fully characterized via SCXRD, FTIR, CHNS, UV–Vis, GC-MS, TGA and NMR. Ni2+, Pd2+ and Pt2+ complexes were used as novel single precursors for the preparation of noble metal/metal oxide nanoparticles via solid state thermal decomposition method based on their thermal characteristics. For the first time, one pot preparation of Pd/NiO and Pt/NiO nanoparticles (NPs) was achieved via this method. The prepared nanoparticles were characterized using XRD, TEM, XPS and UV–Vis analytical techniques. The photocatalytic activities of bare and noble metal modified NiO NPs were assessed toward the photodegradation of Methylene Blue dye (MB) under natural solar radiation. The tight contact between noble metals and NiO in addition to the lack of aggregation gave preference to this method. The nanoparticles demonstrated high photocatalytic activities with the following trend Pt/NiO (91.3%)˃Pd/NiO(84.5%)˃NiO (45.0%). The enhanced photocatalytic efficiency in the presence of noble metals was attributed to lower charge carrier's recombination rate and the fermi level energies of noble metal nanoparticles. Total organic carbon (TOC) analysis was performed to assess the mineralization ability of the Pt/NiO nanoparticles (90.7% TOC Removal). For in-depth understanding the reasons behind Pt/NiO nanoparticles photo-reactivity, the revealing of reactive oxidative species (ROS) was achieved through scavenging trapping experiments.

Binding Models of Copper(II) Thiosemicarbazone Complexes with Human Serum Albumin: A Speciation Study.

Copper(II) complexes of thiosemicarbazones (TSCs) often exhibit anticancer properties, and their pharmacokinetic behavior can be affected by their interaction with blood transport proteins. Interaction of copper(II) complexes of an {N,N,S} donor α-N-pyridyl TSC (Triapine) and an {O,N,S} donor 2-hydroxybenzaldehyde TSC (STSC) with human serum albumin (HSA) was investigated by UV–visible and electron paramagnetic resonance spectroscopy at physiological pH. Asp-Ala-His-Lys and the monodentate N-methylimidazole were also applied as binding models. Conditional formation constants were determined for the ternary copper(II)-TSC complexes formed with HSA, DAHK, and N-methylimidazole based on the spectral changes of both charge transfer and d-d bands. The neutral N-methylimidazole displays a similar binding affinity to both TSC complexes. The partially negatively charged tetrapeptide binds stronger to the positively charged Triapine complex in comparison to the neutral STSC complex, while the opposite trend was observed for HSA, which demonstrates the limitations of the use of simple ligands to model the protein binding. The studied TSC complexes are able to bind to HSA in a fast process, and the conditional constants suggest that their binding strength is only weak-to-moderate.

Synthesis, Antiproliferative and Antimalarial Activities of Dinuclear Silver(I) Complexes with Triphenylphosphine and Thiosemicarbazones Ligands

A series of six sulfur-bridged dinuclear silver(I) thiosemicarbazone complexes were synthesized through the reaction of silver(I) nitrate with 4-phenyl-3-thiosemicarbazone derivatives together with triphenylphosphine (PPh3) (in a 1:1:2 molar ratio). Following structural characterizations using various techniques such as elemental analysis, Fourier-transform infrared (FTIR) spectroscopy, as well as 1H, 13C, 31P{1H}s, COSY, and 1H-13C nuclear magnetic resonance (NMR) spectroscopy, it was found that the thiosemicarbazone ligand exists in the form of a thione rather than thiol tautomer. Subsequently, MDA-MB-231 and MCF-7 breast cancer cell lines, as well as the HT-29 colon cancer cell lines, were used to investigate the in vitro antiproliferative activities of these complexes. In all cases, the IC50 values were in the potent micromolar range. Besides, the aforementioned complexes also had good antiplasmodial activity against chloroquine-resistant P. falciparum, as per the results of histidine-rich protein 2 (HRP2) assays and cytotoxicity evaluations of MDBK cells.

Complex formation of an estrone-salicylaldehyde semicarbazone hybrid with copper(II) and gallium(III): Solution equilibria and biological activity

The solution chemical properties such as proton dissociation, complex formation with copper(II) and gallium(III) ions in addition to antibacterial and antitumor activity of a novel tridentate salicyaldehyde semicarbazone-estrone hybrid (estrone-SC) and a related bicyclic compound (thn-SC) were investigated. The crystal structure of complex [Cu(thn-SCH−1)Cl] was studied by single crystal X-ray diffraction method. Estrone-SC and thn-SC form mono-ligand complexes with Cu(II) characterized by relatively high stability, however, they are much less stable than their thiosemicarbazone analogues. The neutral Cu(II) complexes with (O−,N,O−)(H2O) coordination mode predominate at physiological pH. Estrone-SC and thn-SC are more efficient Ga(III) binders in comparison with thiosemicarbazones, although the complexes also suffer dissociation at pH 7.4. The Cu(II) complex of estrone-SC displayed significant cytotoxicity in A549, SW480 and CH1/PA cancer cells, and moderate apoptosis induction and ROS formation. The semicarbazone compounds did not exhibit antibacterial effect; unlike the related Cu(II)-thiosemicarbazone complexes represented by the fairly low MIC values (3–50 μM) obtained on the Gram-positive Staphylococcus aureus and Enterococcus faecalis bacteria.

New Mononuclear and Binuclear Cu(II), Co(II), Ni(II), and Zn(II) Thiosemicarbazone Complexes with Potential Biological Activity: Antimicrobial and Molecular Docking Study.

Herein, we report the synthesis of eight new mononuclear and binuclear Co2+, Ni2+, Cu2+, and Zn2+ methoxy thiosemicarbazone (MTSC) complexes aiming at obtaining thiosemicarbazone complex with potent biological activity. The structure of the MTSC ligand and its metal complexes was fully characterized by elemental analysis, spectroscopic techniques (NMR, FTIR, UV-Vis), molar conductivity, thermogravimetric analysis (TG), and thermal differential analysis (DrTGA). The spectral and analytical data revealed that the obtained thiosemicarbazone-metal complexes have octahedral geometry around the metal center, except for the Zn2+-thiosemicarbazone complexes, which showed a tetrahedral geometry. The antibacterial and antifungal activities of the MTSC ligand and its (Co2+, Ni2+, Cu2+, and Zn2+) metal complexes were also investigated. Interestingly, the antibacterial activity of MTSC- metal complexes against examined bacteria was higher than that of the MTSC alone, which indicates that metal complexation improved the antibacterial activity of the parent ligand. Among different metal complexes, the MTSC- mono- and binuclear Cu2+ complexes showed significant antibacterial activity against Bacillus subtilis and Proteus vulgaris, better than that of the standard gentamycin drug. The in silico molecular docking study has revealed that the MTSC ligand could be a potential inhibitor for the oxidoreductase protein.

Gold(III) complexes with thiosemicarbazonate ligands as potential anticancer agents: Cytotoxicity and interactions with biomolecular targets

Gold(III) complexes have been studied for the past years due to their anticancer properties and great affinity to biotargets, such as enzymes and proteins, which support their pharmacological applications. Within this scope, in this work the antiproliferative activities of two Au(III)-thiosemicarbazonate complexes, [AuClL1] (1, L1: (E,Z)-N-ethyl-N'-(3-nitroso-kN)butan-2-ylidene)carbamohydrazonothioato-k2N2,S) and [Au(Hdamp)L2]Cl (2, L2: N-(N'',N''-diethylaminothiocarbonyl)-N'(N''', N'''-dimethylcarbothioamide)benzamidineto-kN,k2S and Hdamp: 2-(N,N-dimethylaminomethyl)-phenyl-C1), and their affinities to possible biological targets were investigated. Three different tumor cell lines were used to perform the cytotoxicity assays, including one cisplatin-resistant model, and the results showed lower EC50 for 1 over 2 in every case: B16F10 (4.1 μM and 15.6 μM), A431 (4.0 μM and >50 μM) and OVCAR3 (4.2 μM and 24.5 μM). However, a lower toxicity to fibroblast 3T3 cell line was observed for 2 (30.58 μM) when compared to 1 (7.17 μM), resulting in comparable therapeutic indexes. Both complexes presented strong affinity to HSA: they distorted the secondary structure of the protein, as verified by circular dichroism, but 1 additionally presented the apparent fluorescence quenching constant (Kapp) ten times greater than 2, which was probably due to the fact of 1 being able to denature HSA. The ethidium bromide displacement assay showed that neither 1 nor 2 are strong DNA intercalators, which is in agreement with what was observed through the UV-vis titration. In both cases, the 260 nm band presented hyperchromism, which can indicate ionic interactions or DNA damage. In fact, 1 was able to damage the pGEM plasmid, similarly to cisplatin, as verified by agarose gel electrophoresis and Atomic Force Microscopy. Biophysical studies in cancer cells model membranes were also performed in order to investigate the interaction of the gold complexes to lipid bilayers and revealed that the compounds interact with the membranes by exhibiting partition coefficients of 103 order of magnitude. Overall, both complexes were found to be promising candidates for the development of a future anticancer drug against low sensitive or cisplatin resistant tumors.

Synthesis, Characterization, Antibacterial, Antifungal and Antimalarial Study of Mixed Ligand Metal Complexes Derived from Azo Quinoline with Thiosemicarbazone

Mixed ligand metal complexes of azo quinoline and thiosemicarbazone with Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) metal ions were synthesized. The structure and possible geometry of all the metal(II) complexes were analyzed and supported by IR, mass spectrum, elemental analysis, TG-DTA, electronic spectra (UV), magnetic susceptibility and molar conductance. The synthesized compounds were studied for their antibacterial, antifungal and antimalarial activities. The antimicrobial activity was carried out against bacteria (two Gram-positive bacteria and two Gram-negative bacteria), three fungal strain and one malarial pathogen

Thiosemicarbazone Complexes of Uranium(IV)

AbstractThe first homoleptic thiosemicarbazone complexes of uranium were isolated by reacting uranium tetrachloride in a salt metathesis or acid‐base reaction with four equivalents of Na(BzTSC) or H(BzTSC) (BzTSC=benzylthiosemicarbazone), carrying a non‐methylated (L1), monomethylated (L2) or dimethylated (L3) terminal amino group, in moderate yields. [U(BzTSCNH2)4] (1), [U(BzTSCNH(CH3))4] (2) and [U(BzTSCN(CH3)2)4] (3) show a remarkable stability towards air, with oxidation potentials in THF between +0.43 and +0.53 V and reduction potentials between −2.53 and −2.67 V vs. ferrocene/ferrocenium. The simple methylation of the terminal amino group of the ligand allows for controlled changes in the coordination environments of the complexes. Thermogravimetric analyses indicate that the complexes are stable up to 155 °C.

Copper bis(thiosemicarbazone) Complexes with Pendent Polyamines: Effects of Proton Relays and Charged Moieties on Electrocatalytic HER

AbstractA series of new bis(thiosemicarbazonato) Cu(II) complexes with pendent polyamines, diacetyl‐(N, ‐dimethylethylenediaminothiosemicarbazonato)‐(N’‐methyl‐3‐thio‐semicarbazonato)butane‐2,3‐diimine)‐copper(II) (Cu‐1), diacetyl‐bis(N‐dimethylethylenediamino‐3‐thiosemicarbazonato)butane‐2,3‐diimine)‐copper(II) (Cu‐3), and their cationic derivatives Cu‐2 and Cu‐4, have been synthesized and fully characterized by spectroscopic, electrochemical, and X‐ray diffraction methods. Complexes Cu‐1–Cu‐4 are analogues of Cu(ATSM), which contains a similar N2S2 donor core with terminal non‐coordinating amines. Substitution of the methyl group(s) of the terminal amines of H2ATSM with N,N‐dimethylethylenediamine followed by alkylation generates a charged quaternary amine in the ligand framework. The charged site tunes the redox potentials of the complexes with minimal changes in their physical and electronic properties. The HER activity of all four copper complexes were evaluated in acetonitrile with glacial acetic acid. All of the complexes have lower HER overpotentials than Cu(ATSM), which is attributed to charge effects. The pendent amines of Cu‐1 and Cu‐3 have the lowest HER overpotential as the pendent tertiary amine also serves as a proton relay to enhance proton rearrangement under catalytic conditions. Complex Cu‐3 showed the highest activity with a TOF of 12 × 103 s−1, an overpotential of 0.65 V, and faradaic efficiency of 100 %.

Synthesis, characterization and biological activity of Pt(II) complexes with steroidal thiosemicarbazones

In this work, Pt(II) complexes of previously synthesized steroidal thiosemicarbazones were synthesized and characterized. The ligands and their metal complexes were studied by analytical and spectroscopic data (elemental analysis, IR, 1D-NMR and 2D-NMR, HSQC, HMBC, NOESY, COSY), the analysis of which enabled complete 1H and 13C assignments of each compound including E and Z isomers. All the synthesized ligands and complexes were screened for their cytotoxic and antimicrobial activity. The results demonstrate that the new steroidal thiosemicarbazone complexes were significantly less cytotoxic than the corresponding steroidal thiosemicarbazones. In addition, complexes showed lower antimicrobial activity than the standard drugs, similar to the activity of the starting thiosemicarbazones.

Two nickel (II) complexes of 2-acetylpyrazine thiosemicarbazones: Synthesis, crystal structures and biological evaluation

In this article, two nickel complexes of 2-acetylpyrazine thiosemicarbazone formulated as [Ni(L1)2]·CH3OH (1) and [Ni2(L2)3]ClO4·C2H5OH (2) (HL1 = 2-acetylpyrazine N4-methylthiosemicarbazone, HL2 = 2-acetylpyrazine N4-dimethylthiosemicarbazone), have been synthesized and structurally characterized. The antibacterial activities of the two complexes and ligands were studied. It is found that the ligand HL2 and its corresponding complex displayed effective antimicrobial activity against the tested bacterial. Besides, the growth inhibition assays indicated that complex 2 and the two proligands are capable of showing inhibitory activity against the human hepatocellular carcinoma HepG2 cells, and the subsequent toxicity study on normal QSG7701cells showed that complex 2 has the highest tumor cells selectivity, and its IC50 values is 7.21 times higher than in HepG2 cells.

Synthesis and Biological Evaluation of Novel Zn(II) and Cd(II) Schiff Base Complexes as Antimicrobial, Antifungal, and Antioxidant Agents

(E)-N,N-Dimethyl-2-((E-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (DMPTHP) and their Zn(II) and Cd(II) complexes have been synthesized and characterized. Different tools of analysis such as elemental analyses, IR, mass spectra, and 1H-NMR measurements were used to elucidate the structure of the synthesized compounds. According to these spectral results, the DMPTHP ligand behaved as a mononegatively charged tridentate anion. Modeling and docking studies were investigated and discussed. Novel Schiff base (DMPTHP) ligand protonation constants and their formation constants with Cd(II) and Zn(II) ions were measured in 50% DMSO solution at 15°C, 25°C, and 35°C at I = 0.1 mol·dm−3 NaNO3. The solution speciation of different species was measured in accordance with pH. Calculation and discussion of the thermodynamic parameters were achieved. Both log K1 and –ΔH1, for M(II)-thiosemicarbazone complexes were found to be somewhat larger than log K2 and –ΔH2, demonstrating a shift in the dentate character of DMPTHP from tridentate in 1 : 1 chelates to bidentate in 1 : 2; M : L chelates and steric hindrance were generated by addition of the 2nd molecule. The compounds prepared have significant activity as antioxidants, similar to ascorbic acid. It is hoped that the results will be beneficial to antimicrobial agent chemistry. The formed compounds acted as a potent antibacterial agent. Molecular docking studies were investigated and have proved that DMPTHP as antibacterial agents act on highly resistant strains of E. coli and also as an anticancer agent.

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.

Structural and spectral characterization of Cu(II) complexes of N(4)-substituted thiosemicarbazones derived from 2-hydroxyacetophenone: Crystal structure of a dinuclear Cu(II) complex

Copper(II) complexes of 2-hydroxyacetophenone-N(4)-cyclohexylthiosemicarbazone (H2L1) and 2-hydroxyacetophenone-N(4)-phenylthiosemicarbazone (H2L2) have been synthesized and characterized by different physicochemical techniques like magnetic studies and electronic, infrared and EPR spectral studies. [(CuL1)2] (1) is a dinuclear complex having four coordination around copper(II) with distorted square planar geometry. The two individual dinuclear complexes are interconnected through two bifurcated classical hydrogen bond interactions producing a sheet-like structure along b axis. [(CuL2)2]·1/2H2O (2) also has a dimeric structure. The thiosemicarbazones bind to the metal as dianionic ONS donor ligand in all the complexes, except in the complexes [Cu(HL1)Cl]·2H2O (3), [Cu(HL1)Br]·4H2O (4) and [Cu(HL1)NO3]·C2H5OH(H2O) (5), where the ligand moieties are coordinated as monoanionic (HL¯) ones. Complexes [CuL1dmbipy] (6), [CuL2dmbipy]·3H2O (7), [CuL2bipy]·H2O (8) and [CuL2phen]·2C2H5OH (9) are heterocyclic base adducts. The synthesis and characterization of monomeric and dimeric Cu(II) complexes with 2-hydroxyacetophenone-N(4)-cyclohexyl/phenyl substituted ONS donor ligands is described. It also reports the crystal structure of a novel binuclear Cu(II) complex with oxygen bridging and its interesting coordination. This compound [CuL1]2 is a rare example of copper(II)-thiosemicarbazone complex with oxygen bridging structure.

Comparable investigation of binding interactions between three arene ruthenium(II) thiosemicarbazone complexes and calf thymus DNA

Arene ruthenium(II) thiosemicarbazone complexes with different structures have received considerable attention in biomedical research. In order to reveal deeper structural influences on their biological functions, the binding interactions between three arene ruthenium(II) thiosemicarbazone complexes and calf thymus DNA (ctDNA) were comparably investigated by viscosity measurements and multi-spectroscopic techniques. Weak hypochromic effects were determined from the absorption spectra of the three ctDNA–compound systems. The raised melting temperature and the decreased relative viscosity of ctDNA were ascribed to the presence of these compounds. These compounds intercalated into the double helical structure of ctDNA through hydrogen bonding and van der Waals interactions. The right-handed B-form helicity of ctDNA remained unchanged after the addition of these compounds. The number of arene ruthenium(II) groups and the space steric hindrance of these compounds were responsible for the differences in the fluorescence quenching and the intercalative binding interactions. Compound C, with two arene ruthenium(II) groups and less steric hindrance, exhibited the strongest binding ability with ctDNA. These results provide a molecular understanding of the intercalative binding interactions between DNA and arene ruthenium(II) thiosemicarbazone complexes, which gives a new insight for the biological applications of arene ruthenium(II) complexes in the future.

Cytotoxic effects, microbiological analysis and inhibitory properties on carbonic anhydrase isozyme activities of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone and its Cu(II), Co(II), Zn(II) and Mn(II) complexes

Metal complexes of thiosemicarbazones have been receiving considerable attention in biological applications such as antimicrobial and anticancer therapies. In this work, Co(II), Zn(II) and Mn(II) complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) were synthesized for the first time and characterized by EPR, FT-IR, NMR, UV–Vis spectroscopies, TG/DSC and elemental analysis. X-ray powder diffraction analysis was carried out for Zn(II) complex. HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were tested as enzyme inhibitory agents. All compounds are effective inhibitor of cytosolic carbonic anhydrase I and II isoforms (hCA I and II) enzymes. IC50 values of HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were determined as 93.35, 324.46, 25.67, 1.06 and 22.36 μM for CA I isozyme and 99.02, 86.64, 57.76, 10.34 and 36.48 μM for CA II isozyme, respectively. The evaluation of potential cytotoxic effects of the compounds was performed against normal epithelial breast mammary gland CRL-4010, estrogen-positive low metastatic MCF-7 and triple negative highly metastatic MDA-MB-231 breast adenocarcinoma cell lines by MTT assay. The results showed that the tested metal complexes have high cytotoxic effects than their ligand molecule. In particular, the Cu(II) complex displayed preciously high cytotoxic properties different from the others. Given these facts, the Cu(II) complex could be debated as potential chemotherapeutic molecule against drug-resistant breast cancer cells. Minimum inhibitory concentrations of the compounds against the test organisms were also detected for the microbiological analysis.