Thione Sulfur Atoms Research Articles

Theoretical, in Vitro Antiproliferative, and in Silico Molecular Docking and Pharmacokinetics Studies of Heteroleptic Nickel(II) and Copper(II) Complexes of Thiosemicarbazone-Based Ligands and Pefloxacin.

Twelve new heteroleptic nickel(II) and copper(II) complexes of the type [M(L1-6 )(Pfx)2 ] (1-12), where L1-6 =2-benzylidenehydrazinecarbothioamide (L1 ), 2-benzylidene-N-methylhydrazinecarbothioamide (L2 ), 2-benzylidene-N-phenylhydrazinecarbothioamide (L3 ), 2-(4-methylbenzylidene)hydrazinecarbothioamide (L4 ), 2-(4-methylbenzylidene)-N-methylhydrazinecarbothioamide (L5 ) and 2-(4-methylbenzylidene)-N-phenylhydrazinecarbothioamide (L6 ), Pfx=pefloxacin and M=Ni(II) or Cu(II) have been synthesised, and their structures were confirmed by different spectral techniques. The spectral data and density functional theory (DFT) calculations supported the bonding of pefloxacin drug molecule via one of the carboxylate oxygen atoms and the pyridone oxygen atom, and the thiosemicarbazone ligand via the imine nitrogen and the thione sulfur atoms with the metal(II) ion, forming distorted octahedral geometry. In vitro antiproliferative activity of the synthesized complexes was evaluated against three human breast cancer (T47D, estrogen negative (MDA-MB-231) and estrogen positive (MCF-7)) as well as non-tumorigenic human breast epithelial (MCF-10a) cell lines, which showed the higher activity for the copper(II) complexes. The interaction of the synthesized complexes with an oncogenic protein H-ras (121 p) was explored by in silico molecular docking studies. Further, in silico pharmacokinetics and ADMET parameters were also analysed to predict the drug-likeness as well as non-toxic and non-carcinogenic behavior, and safe oral administration of the complexes.

Theoretical, antioxidant, antidiabetic and in silico molecular docking and pharmacokinetics studies of heteroleptic oxovanadium(IV) complexes of thiosemicarbazone-based ligands and diclofenac

A series of new heteroleptic oxovanadium(IV) complexes with the general formula [VOL1–6(Dcf)] (1–6), where L1−6 = thiosemicarbazone (TSC)-based ligands and Dcf = diclofenac have been synthesized and characterized. The spectral studies along with the density functional theory calculations evidenced the distorted square-pyramidal geometry around oxovanadium(IV) ion through imine nitrogen and thione sulfur atoms of TSC moiety, and two asymmetric carboxylate oxygen atoms of diclofenac drug. The complexes were evaluated for in vitro antioxidant activity using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2'-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2) and superoxide radical scavenging assays with respect to the standard antioxidant drugs butylated hydroxyanisole (BHA) and rutin. The in vitro antidiabetic activity of the complexes was tested with enzymes such as α-amylase, α-glucosidase and glucose-6-phosphatase. The complexes containing methyl substituent showed higher activity than that containing the nitro substituent due to the electron-donating effect of methyl group. The in silico molecular docking studies of the oxovanadium(IV) complexes with α-amylase and α-glucosidase enzymes showed strong interaction via hydrogen bonding and hydrophobic interactions. The dynamic behavior of the proposed complexes was analyzed by molecular dynamics (MDs) simulations, which revealed the stability of docked structures with α-amylase and α-glucosidase enzymes. The in silico physicochemical and pharmacokinetics parameters, such as Lipinski’s ‘rule of five’, Veber’s rule and absorption, distribution, metabolism and excretion (ADME) properties predicted non-toxic, non-carcinogenic and safe oral administration of the synthesized complexes. Communicated by Ramaswamy H. Sarma

Pyridine‐2(1H)‐thione as a Bifunctional Nucleophile in Reaction with PdII and PtII Aryl Isocyanide Complexes

AbstractA method for obtaining C,S‐cyclometalated deprotonated diaminocarbene complexes via the addition of a bifunctional N,S‐nucleophile's endocyclic nitrogen atom to a coordinated isocyanide has been extended to the reactions with pyridine‐2(1H)‐thione. The coupling of PdII‐ and PtII‐bis(arylisocyanide) complexes with pyridine‐2(1H)‐thione leads to the formation of mononuclear C,S‐cyclometalated deprotonated diaminocarbene complexes in 90–96 % yield. The reaction proceeds via the initial coordination of the thione sulfur atom to the metal center followed by the intramolecular nucleophilic addition of the heterocyclic nitrogen atom to the metal‐ligated isocyanide carbon. Using an excess of pyridine‐2(1H)‐thione in this reaction leads to the formation of a mono‐C,S‐cyclometalated complex with a pendant mercaptopyridine ligand which is involved in the reversible intramolecular nucleophilic addition of the pyridine nitrogen to the isocyano carbon. The obtained complexes were characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopies, and single‐crystal X‐ray diffraction.

A novel manganese(II) bisthiocarbohydrazone complex: Crystal structures, Hirshfeld surface analysis, DFT and molecular docking study with SARS-CoV-2

A novel Mn(II) complex [Mn(H2L)Cl2]•H2O (1) of a ditopic ligand 1,5-bis(2-benzoylpyridine) thiocarbohydrazone (H2L) was synthesized and characterised physico-chemically. A part of the mother solution of the complex 1 and THF yielded single crystals in a triclinic space group and are found same from the crystals obtained from another mixture of the mother solution and ethyl acetate. Single crystal XRD studies have confirmed the mononuclear complex formation and absence of any interactions between the Mn(II) centers. A solution of the complex 1 in chloroform, conversely, yielded a crystallographically different complex [Mn(H2L)Cl2]•CHCl3 (1a) in monoclinic and is also characterised with single crystal XRD. The ligand is coordinated through thione sulfur atom to form a square pyramidal geometry around Mn(II) center in both the complexes. The molecular packing of the complexes is found influenced by the nature of solvent inclusion, and are stabilized by different non-covalent interactions in the lattice. The intermolecular interactions are quantified by Hirshfeld surface analyses, which reveal that H•••Cl interactions has maximum contribution to the total Hirshfeld surface in the complex 1a. This is the first crystal structure study of a manganese(II) complex of a bisthiocarbohydrazone ligand. The molecular and electronic structures of the complexes are studied by DFT quantum chemical calculations. The band gap (Eg) of the complex 1 was estimated as 2.45 eV using Kubelka-Munk model and is in agreement with the electronic spectral calculations of the complex at TD-DFT level. Molecular docking studies of both the ligand and the complex reveal their greater propensity towards SARS-CoV-2 main protease compared to B-DNA dodecamer. Also, the binding potential of the ligand and the complex with SARS-CoV-2 main protease is found higher than that with chloroquine and hydroxychloroquine.

Organoruthenium (II) complexes featuring pyrazole‐linked thiosemicarbazone ligands: Synthesis, DNA/BSA interactions, molecular docking, and cytotoxicity studies

AbstractA series of pyrazol‐derived thiosemicarbazone ligands (L1–L4) were synthesized and reacted with [Ru(p‐cymene)(μ‐Cl)Cl]2 to yield a series of “piano‐stool”‐type binuclear ruthenium (II)–arene‐thiosemicarbazone complexes (C1–C8) of the general type [(Ru(η6‐p‐cym)L)2(μ‐im/azpy)] Cl1–2 (L = diphenylpyrazole thiosemicarbazone; cym = p‐cymene; im = imidazole; azpy = 4,4′‐azopyridine). The thiosemicarbazone ligands act as N and S donors binding to the Ru(II) center via the imine nitrogen and the thione sulfur atoms. The complexes were characterized by NMR, FTIR, UV–Vis spectroscopy, and ESI+ mass spectrometry. The binding of the complexes to calf thymus deoxyribonucleic acid (CT‐DNA) and bovine serum albumin (BSA) was evaluated, and it has been established that the binuclear complexes have good binding efficacies with DNA (Kb = 104–105 M−1) and BSA (Ka = 105–106 M−1). This is attributed to the arene moieties present in the ligands of the complexes that can have hydrophobic interactions with DNA/BSA. Ethidium bromide (EB) displacement studies and DNA viscosity measurements revealed intercalative interaction of the complexes with DNA. Static interaction of the complexes with BSA was revealed by fluorescence quenching studies. Molecular docking studies confirmed base stacking, H‐bonding, and hydrophobic interactions with the biomolecules. In vitro antiproliferative studies of the complexes affirmed that the complexes are cytotoxic towards the HeLa (human cervical cancer) cell line with IC50 values in range of 17.3–41.3 μM.

Anti-cancer and anti-fungal evaluation of novel palladium(II) 1-phenyl-1H-tetrazol-5-thiol complexes

The binuclear [Pd2(κ2-ptt)4] (1) and mixed ligand complexes of the type [Pd(κ1-S-ptt)2(κ2-diamine)] (2–4) (Hptt is 1-phenyl-1H-tetrazole-5-thiol), diamine; ethylene diamine (en), 1,10-phenanthroline (Phen) or 2,2′-bipyridyl (Bipy) as co-ligands have been synthesized. The obtained complexes were characterized by elemental analysis, 1H-, 13C-{1H} NMR, molar conductivity, UV–Vis and IR spectroscopy. In complex 1 the ptt anion coordinated as a bridging bidentate via the thione sulfur atom and deprotonated nitrogen atom of the heterocyclic ring to afford a dimeric complex. Whereas in 2–4 the ptt bonded as a monodentate through the thiolato sulfur atom, while the diamine ligands are coordinated as bidentate chelates to afford a square planner arrangement around the Pd(II) center. The anti-fungal activity of the prepared complexes (1–4) was tested against two fungi types (Candida albicans, and Aspergillus niger). All the complexes showed moderate activity compared to standard Fluconazole. Moreover, the anti-cancer activity of complexes (2–4) were examined against ovarian and breast cancer cells. Cell viability assays show that complexes (2–4) are promising anti-tumor in vitro.

Binuclear Ni(II) complexes containing ONS donor Schiff base ligands: Preparation, spectral characterization, X-ray crystallography and biological exploration

Four binuclear Ni(II) complexes [[Ni2(H-DEAsal-tsc)2(μ-dppm)]·2Cl (1), [Ni2(DEAsal-mtsc)2(μ-dppm)] (2), [Ni2(DEAsal-etsc)2(μ-dppm)] (3) and [Ni2(DEAsal-ptsc)2(μ-dppm)] (4)] were synthesized from the ligands namely 4(N,N)-diethylaminosalicylaldehyde-4(N)-thiosemicarbazone [H2-DEAsal-tsc] H2L1/4(N,N)-diethylaminosalicylaldehyde-4(N)-methyl thiosemicarbazone [H2-DEAsal-mtsc] H2L2/4(N,N)-diethylaminosalicylaldehyde-4(N)-ethyl thiosemicarbazone [H2-DEAsal-etsc] H2L3/4(N,N)diethylaminosalicylaldehyde-4(N)-phenyl thiosemicarbazone [H2-DEAsal-ptsc] H2L4 and 1,1′-bis(diphenylphosphino)methane (dppm) and characterized by a number of spectro analytical techniques. The molecular structure of complexes [Ni2(H-DEAsal-tsc)2(μ-dppm)]·2Cl (1) and [Ni2(DEAsal-ptsc)2(μ-dppm)] (4) have been confirmed by single crystal X-ray diffraction studies. The analysis indicated that in complex 1, the ligand [H2-DEAsal-tsc] coordinated as monobasic tridentate donor through phenolic oxygen, azomethine nitrogen and thione sulfur atoms. However, in complex 4, the ligand [H2-DEAsal-ptsc] behaved as dibasic tridentate donor with thiolate sulfur coordination. Their ability to bind with Calf Thymus Deoxyribonucleic acid (CT-DNA) and Bovine Serum Albumin (BSA) were analysed spectrometrically. Intercalative interaction of the complexes with DNA was confirmed by ethidium bromide (EB) displacement studies and DNA viscosity measurements. The interaction mechanism of the complexes with BSA was found as static. In vitro antiproliferative studies of the ligands and complexes in A549 (human lung carcinoma cancer), MCF-7 (human breast cancer) and HeLa (human cervical cancer) cell lines witnessed significant cytotoxic nature of the complexes with low IC50 values (in μM) than the standard metallo-drug cisplatin. Further, the results of Lactate Dehydrogenase (LDH) and Nitric oxide (NO) release assays supported the effectiveness of the complexes on the above said cancer cells.

Synthesis, Spectral, Modeling, Docking and Cytotoxicity Studies on 2‐(2‐aminobenzoyl)‐N‐ethylhydrazine‐1‐carbothioamide and its divalent metal complexes

2‐(2‐aminobenzoyl)‐N‐ethylhydrazine‐1‐carbothioamide (H3L) and its Cu (II), Co (II), Ni (II) and Zn (II) complexes have been synthesized. The structures of the isolated compounds were suggested based on elemental analyses, spectral analyses (FTIR,1H and13CNMR, MS, ESR and UV–Visible) and magnetic moments measurements. The free ligand exists in the keto‐thione form, while in the metal complexes; it exists in the enol form and coordinates as mononegative bidentateviadeprotonated enolic oxygen and N2H nitrogen. Both Co (II) and Ni (II) complexes have an octahedral, while Cu (II) complex has a square planar geometry. The compounds have direct electronic transitions with optical band gap (Eg) values in the range 3.14–3.40 eV. The ligand and its complexes were optimized using DFT/B3LYP methodology. The ligand optimization results supported the involvement of the carbonyl oxygen, thione sulfur and N2H hydrogen atoms in hydrogen bonding formation. Furthermore, the obtained structures of the ligand and its complexes were subjected to molecular docking study to predict interactions cause their cytotoxicity. Finally, thein vitrocytotoxicity activities of the ligand and its complexes were investigated against Hela and WISH cell lines where the Zn (II) complex exhibited higher activity than the other compounds against the two cell lines in accordance with molecular docking suggestion.

Simultaneous cyclisation and coordination of dithizone to the fac-[Re(CO)3]+ core

The reaction of dithizone (H2dtz) with an organometallic rhenium(I) precursor; [Re(CO)5Cl] in ethanol led to the isolation of the octahedral organometallic fac-[Re(CO)3]+ core complex fac-[Re(CO)3(Hdtz)(dttz)] (1). The chelating ligand 1,2-diphenyltetrazolethione-5 zwitterion (dttz) in 1 was formed from the double deprotonation and cyclisation of dithizone in ethanol. The cyclisation of H2dtz to dttz zwitterion is a good example of the conversion of N,S-donor dithizone to S-donor ligand. Both dithizone anion Hdtz− and neutral zwitterion dttz coordinated to the fac-[Re(CO)3]+ core in which Hdtz− is coordinated as bidentate chelate via thiolate sulfur and azoic nitrogen atoms while dttz coordinated as monodentate ligand via thione sulfur atom. In addition to the synthesis, infra-red, 1H NMR, electronic properties and X-ray crystal structure of the complex 1 are reported.

Structural architectures and biological properties of main group bismuth(III) iodide complexes with heterocyclic thioamides

A series of mononuclear, dinuclear and polynuclear bismuth(III) iodide complexes (1–5) bearing heterocyclic thioamide ligands, 2-mercapto-3,4,5,6-tetrahydro-pyrimidine (tHPMT), 2-mercapto-benzimidazole (MBZIM), 2-mercapto-1-methylimidazole (MMI), 2-mercaptobenzothiazole (MBZT) and 2-mercaptopyridine (PYT), have been synthesized and characterized by melting point, elemental analysis, FT-IR spectroscopy, Raman spectroscopy, 1H, 13C NMR spectroscopy, UV–Vis spectroscopy and Thermal Gravimetry-Differential Thermal Analysis (TG-DTA). Moreover, the crystal structures of 1–5 have been also determined with single crystal X-ray diffraction analysis. The use of the above mentioned heterocyclic thioamide ligands have allowed synthesis of the first examples of bismuth(III) iodide thioamide complexes. {[BiI3(tHPMT)3]} (1) is the first structural example of a neutral mononuclear bismuth(III) iodide complex with octahedral geometry around the bismuth(III) ion with meridional conformation. {[BiI2(µ2-I)(MBZIM)2]2} (2) is the first example of a dinuclear bismuth(III) iodide complex with octahedral geometry around the bismuth(III) ion with trans-S/cis-I arrangement. {[BiI(µ2-I)2(MMI)]n} (3) and {[BiI(µ2-I)2(MBZT)]n·CH3OH} (4) are the first examples of the polynuclear bismuth(III) iodide complexes with octahedral geometry around the bismuth(III) ions. The ligand molecules are coordinated via the thione sulfur atoms in both complexes but in complex 3, ligand molecules are trans to each other in polymeric chain while, in complex 4, ligand molecules are cis to each other in polymeric chain. {[BiI(µ2-S,N-PYT)2]n} (5) is the first example of a polynuclear bismuth(III) iodide complex with pentagonal bipyramidal geometry around the bismuth(III) ions. The seven coordinate bismuth(III) atom has a N2S4I-donor set consisting of one iodine atom and two chelating and bridging μ2-S,N (η2-S:η1-N) pyridine-2-thionate anions.Complexes 1–5 were evaluated for their in vitro cytotoxic activity against human adenocarcinoma cervix (HeLa) and breast (MCF-7) cancer cells. The toxicity of the complexes was studied against human fetal lung fibroblast cells (MRC-5). The influence of 1–5, upon the catalytic peroxidation of the linoleic acid by the enzyme lipoxygenase (LOX), was evaluated experimentally.

Reaction of Benzylidene Chlorides with О-Methyl Diethylphosphinothioate

О-Methyl diethylphosphinothioate reacts with benzylidene chlorides to form arenecarbthioaldehyde trimers and diethylphosphinoyl chloride. This result suggests that the reaction involves initial attack of the thione sulfur atom of the phosphinothioyl group on the methine carbon atom of the gem-dichloride.

Monodentate Coordination of N, N′‐Disubstituted Thiocarbamide Ligands: Syntheses, Structural Analyses, In Vitro Cytotoxicity and DNA Damage Studies of Cu(I) Complexes

AbstractStructural analysis of three novel substituted thiocarbamide ligands N‐(naphthyl)‐N′‐(isobutoxycarbonyl) thiocarbamide (H2L1), N‐(4‐methoxyphenyl)‐N′‐(isobutoxycarbonyl) thiocarbamide (H2L2) & N‐(2‐methoxy‐4‐nitrophenyl)‐N′‐(isobutoxycarbonyl) thiocarbamide (H2L3) and their copper(I) complexes [(H2L1)2CuCl] (1), [(H2L2)2CuCl] (2) and [(H2L3)2CuCl] (3) was performed using various spectroscopic techniques (FT−IR, 1H and 13C NMR, UV‐Visible),TG analysis and single crystal X‐ray studies of (H2L1) and [(H2L1)2CuCl] (1). The copper(I) complexes possess trigonal planar geometry coordinating through two thione sulfur atoms from two ligand molecules and one chloride ion. Two intramolecular hydrogen bonding interactions present between (−N1H) and carbonyl oxygen (−N2H) and coordinated chlorine stabilize the trigonal planar structure of the complexes. Cyclic voltammogram of complexes 1–3 displayed quasireversible redox behaviour corresponding to CuI/CuII couple. Determination of in vitro cytotoxicity of ligands and their complexes using five human carcinoma cell lines 2008, C13* (cervical carcinoma), A2780, A2780/CP and IGROV‐1 (ovarian carcinoma) revealed that copper(I) complexes were more potent inhibitors than the ligands against all the cell lines. The most effective were complexes 2 and 3. The comet assay test of complexes 2 and 3 against 2008, C13* and IGROV‐1 cell lines indicated significant damage to the DNA structure.

Molecular modeling, spectral investigation and thermal studies of the new asymmetric Schiff base ligand; (E)‐N'‐(1‐(4‐((E)‐2‐hydroxybenzylideneamino)phenyl)ethylidene)morpholine‐4‐carbothiohydrazide and its metal complexes: Evaluation of their antibacterial and anti‐molluscicidal activity

A new tetradentate asymmetric Schiff base ligand; (E)‐N'‐(1‐(4‐((E)‐2‐hydroxybenzylideneamino)phenyl)ethylidene)morpholine‐4‐carbothiohydrazide (H2L) was prepared by consecutive condensation reactions between p‐aminoacetophenone, salicylaldehyde and 4‐morpholinethiosemicarbazide. The structures of the obtained ligand along with its Co(II), Ni(II), Cu(II), Zn(II), Cd(II), Cr(III), Fe(III) and Ru(III) complexes were authenticated by different analytical and spectral techniques. The ligand behaves as a monobasic tetradentate one and chelates with metal ions through the deprotonated phenolic oxygen, imine nitrogen, thione sulfur and azomethine nitrogen atoms (ONNS chromophore). All nonelectrolyte metal complexes possess octahedral geometry, except Ni(II) and Cu(II) complexes (2, 3) which have tetra‐coordinate structures. The thermal stability of metal complexes is higher than that of the free ligand and the general thermal degradation pathways were discussed based on thermogravimetric technique. The activation thermodynamic parameters as well as the order of reaction (n) were estimated from DTG curves by using Piloyan method. Thermogravimetric analyses and mass spectra of metal complexes confirm the number of solvents in their inner and outer spheres. Molecular modeling data were used to demonstrate the thermal decomposition pathways of the ligand and its metal complexes, confirming their chemical structures. The ESR spectra of Cu(II) complexes indicate that the unpaired electron is localized mainly in the d(x2‐y2) orbital with axial symmetry. Powder X‐ray diffraction analyses for Co(II), Cu(II) and Ru(III) complexes (1, 3, 7) show that copper complex has a crystalline nature, whereas, cobalt and ruthenium complexes are amorphous. The ligand and its metal complexes were tested in vitro for their anti‐molluscicidal activity against Eobania vermiculata. The results reveal that the investigated compounds have remarkable anti‐molluscicidal activities against the tested land snail with various sensitivity levels. The synthesized compounds were also screened in vitro for their antibacterial activity against Gram‐positive bacteria; Staphylococcus aureus and Gram‐negative bacteria; Escherichia coli and the results were compared with the activity of ceftriaxone. The data show that all investigated compounds display a high antibacterial activity against the tested bacterial strains with different inhibition degrees and the activity is significantly higher against Staphylococcus aureus than Escherichia coli.

P-Cymene Based Organometallic Ruthenium(II)-Arene Complexes with Benzaldehyde Derived Thiosemicarbazones: Synthesis, Characterization and Antimicrobial Activity

Objective: Thiosemicarbazone (TSC) containing three new mononuclear ruthenium(II)-arene complexes were synthesized so as to contribute to the development of ruthenium complexes with pharmacologically attracted properties. Methods: Reactions of the ruthenium(II)-arene dimer [{RuCl(μ-Cl)(η6-p-cymene)}2] (1) with the respective TSC1-3 (1:2 molar ratio) in methanol resulted in p-cymene containing new conformationally rigid half-sandwich organometallic ruthenium(II)-arene complexes; [(η6-p-cymene)Ru(TSC1-κ3O,N,S)]Cl (I), [(η6-p-cymene)Ru(Cl)(TSC2-κ2N,S)]Cl (II), and [(η6-p-cymene)Ru(Cl)(TSC3-κ2N,S)]Cl (III). The molecular structures of complexes I, II and III were elucidated on the spectroscopic data obtained by the application of 1H NMR, Fourier transform infrared (FT-IR), UV-vis and elemental analysis techniques. In vitro antimicrobial activities of the synthesized three ruthenium(II)-arene complexes were evaluated using the disc diffusion method. Results: The spectroscopic data indicated that TSC1 was bounded to the metal as a tridentate ligand with its thione sulfur atom, phenolic oxygen atom and azomethine nitrogen atom in the complex I, while TSC2 and TSC3 were bounded to metal center as bidentate manner through their thione sulfur atom and imine nitrogen (C=N) atom in the complexes II and III, respectively. The obtained antimicrobial activity results showed that these complexes efficiently inhibit the growth of Gram-positive bacterial strains. Conclusion: The TSC1-3 containing ruthenium(II)-arene complexes were successfully synthesized and their molecular structures were also determined by the spectroscopic methods. All ruthenium(II)-arene complexes showed higher antibacterial activities against Gram-positive bacterial strains than the Gram-negative ones. Keywords:

Synthesis and crystal structures of bis(imidazolidine-2-thione-κS)bis(thiocyanato-κS)mercury(II) and bis(cyanido)bis(μ2 -imidazolidine-2-thione-κS)mercury(II).Hg(CN)2

Abstract Two mercury(II) complexes containing imidazolidine-2-thione (Imt) and thiocyanate or cyanide ligands, [Hg(Imt)2(SCN)2] (1) and [Hg(Imt)2(CN)2].Hg(CN)2 (2), have been prepared and characterized by IR and NMR spectroscopy and X-ray crystallography. In compound 1, the mercury atom is located on a two-fold rotation axis and is coordinated to two thione sulfur atoms of imidazolidine-2-thione (Imt) and to two sulfur atoms of thiocyanate in a distorted tetrahedral mode with the S-Hg-S bond angles in the range of 98.96(3)–148.65(6)°. In 2, the mercury atom is hexa-coordinated having a distorted octahedral geometry composed of two cyanide C atoms [Hg-C=2.055(5) Å] and four weakly bound thione S atoms of imidazolidine-2-thione (Imt) [Hg-S=3.1301(13) and 3.1280(13) Å]. One free Hg(CN)2 molecule is also present in the crystal. In both complexes, the molecular structure is stabilized by N-H…N and N-H…S hydrogen bonding interactions.

Synthesis, characterization, molecular modeling and biological activity of metal complexes derived from (E)-N'-(furan-2-ylmethylene)morpholine-4-carbothiohydrazide

A new series of some biologically active Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes was synthesized from the novel thiosemicarbazone ligand; (E)-N'-(furan-2-ylmethylene)morpholine-4-carbothiohydrazide (HL). Elemental, spectral, thermal analyses, magnetic susceptibility and molar conductivity measurements were used to elucidate the structure of separated compounds. The data prove that the ligand reacts with all metal ions in a neutral thione form. The electrolytic tetra-coordinate Cu(II); Zn(II) complexes (5, 6; 10) bind through the thione sulfur, furfural oxygen and azomethine nitrogen atoms of the ligand (NSO type) to construct fused five membered rings. However, the rest non-electrolyte octahedral complexes chelate via the furfural oxygen and azomethine nitrogen atoms of the ligand (NO type). Molecular modeling was conducted for the ligand and two representative complexes (1, 5) in order to substantiate their chemical structures. Thermal analyses are compatible with molecular modeling studies to support the proposed thermal decomposition pathways of metal complexes which start with the rupture of the long and weak N–NH bond. The thermal stability of metal complexes varies according to the number of solvents of crystallization, ionic radii and steric effect of anions. The ESR spectra of Cu(II) complexes are compatible with a primarily (dx2–y2)1 ground state with axial symmetry. The ligand and its Co(II); Cu(II); Cd(II) complexes (1; 5, 8; 11) along with their mixtures with metaldehyde were screened in vitro for their molluscicidal activity against Eobania vermiculata. Combination with metaldehyde enhances the toxicity effect of the tested compounds through reducing the period required for mortality and increasing the percentage of mortality after 24 h of treatments. The tested compounds gathered with metaldehyde are strongly affecting on the activity of ACP and ALP enzymes and TP content which are very important factors in the mucous secretion of Eobania vermiculata. These effects lead to excess mucous secretion, causing dryness and death for the snails.

Spectral studies, thermal investigation and biological activity of some metal complexes derived from (E)-N′-(1-(4-aminophenyl)ethylidene)morpholine-4-carbothiohydrazide

A new series of biologically active Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) complexes derived from the novel thiosemicarbazone ligand; (E)-N′-(1-(4-aminophenyl)ethylidene)morpholine-4-carbothiohydrazide (HL) were synthesized. The mode of bonding of the ligand and the geometrical structures of its metal complexes were achieved by different analytical and spectral methods. The ligand coordinated with metal ions in a neutral bidentate fashion through the thione sulfur and azomethine nitrogen atoms. All metal complexes adopted octahedral geometry, except Cu(II) complexes (3, 6, 7) which have a square planar structure. The general thermal decomposition pathways of the ligand along with its metal complexes were explained. The thermal stability of the complexes is controlled by the number of outer and inner sphere water molecules, ionic radii and the steric hindrance. The activation thermodynamic parameters; (activation energy (E*), enthalpy of activation (ΔH*), entropy of activation (ΔS*) and Gibbs free energy (ΔG*)) along with order of reaction (n) were estimated from DTG curves. The ESR spectra of Cu(II) complexes indicated that (dx2-y2)1 is the ground state with covalence character of metal–ligand bonds. The molluscicidal and biochemical effects of the ligand and its Ni(II); Cu(II) complexes (2; 3, 5, 7) along with their combinations with metaldehyde were screened in vitro on the mucous gland of Eobania vermiculata. The tested compounds exhibited a significant toxicity against the tested animals and have almost the same toxic effect of metaldehyde which increases the mucous secretion of the snails and leads to death.

Synthesis, structural characterization, electrochemical studies and DFT calculations on nickel(II) complexes of N-picolinoyl-N′-benzothioylhydrazide and 5-(pyridine-4-yl)-2H-1,2,4-triazole-3-thione

Two Ni(II) complexes, [Ni(pbth)2] and [Ni(ptt)2(en)2] {Hpbth = N-picolinoyl-N′-benzothioylhydrazide, Hptt = 5-(pyridine-4-yl)-2H-1,2,4-triazole-3-thione} have been synthesized and characterized by physico-chemical and spectroscopic methods. [Ni(pbth)2] contains a pair of N-picolinoyl-N′-benzothioylhydrazide ligands coordinated via their thione sulfur, pyridyl nitrogen and hydrazinic nitrogen atoms, forming two C2N2Ni and two CSN2Ni five-membered chelate rings. The intermediate compound 1-isonicotinoyl-3-thiosemicarbazide is converted to 5-(pyridine-4-yl)-2H-1,2,4-triazole-3-thione in the presence of ethanolic NaOH, giving the complex [Ni(ptt)2(en)2] in which the ptt ligands coordinate through their triazole ring nitrogen atoms, while four more nitrogens from two ethylenediamine ligands complete the octahedral structure. The crystal structures of the complexes involve various types of intermolecular extended hydrogen bonds, forming supramolecular frameworks. Cyclic voltammetry studies of both complexes show quasi-reversible redox behavior. Density Functional Theory electronic structure calculations corroborate our experimental findings.

First 3,5-diacetyl-1,2,4-triazol derived mono(thiosemicarbazone) and its palladium and platinum complexes: Synthesis, structure and biological properties

Preparation and characterization of 3,5-diacetyl-1,2,4-triazol mono(4-phenylthiosemicarbazone) ligand, H3L, and its derived palladium(II) and platinum(II) complexes, [Pd(HL)(PPh3)] and [Pt(HL)(PPh3)], is described. The molecular structures of the two new metal complexes have been determined by single crystal X-ray diffraction. In both complexes the metal ion is four-coordinated with a [N2SP] donor environment, via one triazole nitrogen atom, the azomethine nitrogen and thione sulfur atoms of the thiosemicarbazone moiety and a phosphorous atom from the triphenylphosphine coligand. The cytotoxicity of the new compounds synthesized was investigated in vitro against T-47D, A2780 and A2780cisR human cancer cell lines, being H3L the species with the highest activity. In addition, the DNA binding ability of H3L with calf thymus DNA was explored by UV–Vis absorption spectroscopy.

Synthesis and characterization of a new bioactive mono(thiosemicarbazone) ligand based on 3,5-diacetyl-1,2,4-triazol diketone and its palladium and platinum complexes

Preparation and characterization of a new 4N-p-chlorophenyl substituted thiosemicarbazone ligand, H3L2, and its derived palladium(II) and platinum(II) complexes, [Pt(HL2)(PPh3)] and [Pd(HL2)(PPh3)], is described. The molecular structures of the two new metal complexes have been determined by single crystal X-ray diffraction. In both complexes the metal ion is four-coordinated with a [N2SP] donor environment, via one triazole nitrogen atom, the azomethine nitrogen and thione sulfur atoms of the thiosemicarbazone moiety and a phosphorous atom from the triphenylphosphine coligand. The biological activity of the new compounds synthesized was initially explored by determining their antiproliferative activity in vitro against T-47D, A2780 and A2780cisR human cancer cell lines. The cytotoxicity data suggest that these compounds may be endowed with important antitumor properties, especially H3L2 since is capable not only to circumvent cisplatin resistance in A2780cisR cells but also to exhibit high antiproliferative activity in breast cancer T-47D cells.