Karen A. Crouse

Coordination chemistry and bioactivity of Ni2+, Cu2+, Cd2+ and Zn2+ complexes containing bidentate Schiff bases derived from S-benzyldithiocarbazate and the X-ray crystal structure of bis[S-benzyl-β-N-(5-methyl-2-furylmethylene)dithiocarbazato]cadmium(II)

New bidentate isomeric NS and NS′ Schiff bases were derived from the condensation of S-benzyldithiocarbazate (SBDTC) with 5-methyl-2-furyldehyde and 2-furyl-methylketone. Reaction of NS ligand with Ni(II), Cu(II), Cd(II) and Zn(II) salts gave solid complexes. Only the Ni(II) complex of the NS′ ligand was isolated. All complexes were characterized by a variety of physico-chemical techniques, viz. elemental analyses, molar conductivity, i.r. and electronic spectral studies. The Schiff bases behaved as uninegatively charged bidentate ligands. Square-planar structures have been proposed for the Cu(II) complex containing the NS Schiff base ligand and the Ni(II) complexes of the bidentate NS and NS′ Schiff base ligands. Single crystal X-ray diffraction study of [Cd(NS)2] showed that the complex was bis chelated with a distorted tetrahedral structure. The antimicrobial properties of the Schiff bases and their metal complexes indicate that the organic compounds are stronger antifungal agents than their complexes with the metals studied. However, the zinc complex of the Schiff base, S-benzyl-β-N-(5-methyl-2-furyl)methylenedithiocarbazate, (NS), was found to be highly active against CEM-SS (Human cell T-lymphoblastic leukemia) with a CD50 value of 2.0 μg cm−3, while [Cd(NS)2] was moderately active with a CD50 value of 4.95 μg cm−3. None of the compounds were found to be active against HT-29 (Human colon adenocarcinoma cells). The bioactivity of a previously reported tridentate NNS Schiff base (SBD1) and its metal complexes with nickel(II) and copper(II) are also discussed.

S-methyldithiocarbazate and its Schiff bases: evaluation of bondings and biological properties.

Eight selective nitrogen-sulfur donor ligands have been synthesized from the condensation of S-methyldithiocarbazate (SMDTC) with aldehydes and ketones with a view to evaluating their antimicrobial and cytotoxic activities, and also to correlate the biological properties with the structure of the ligands. The compounds were all characterized by elemental analyses and other physicochemical techniques. SMDTC and the Schiff bases were screened for antimicrobial and cytotoxic activities. SMDTC showed very large inhibition zones (24-44 mm) against bacteria and fungi with a minimum inhibitory concentration (MIC) of 390-25,000 and 1562-6250 microg ml(-1), against different bacteria and fungi, respectively. Streptomycin and nystatin were used as the internal standards against bacteria and fungi, respectively. SMDTC along with its Schiff bases with pyridine-2-carboxaldehyde, acetylacetone and 2,3-butanedione were strongly antifungal and the MIC values were comparable to nystatin. Most of the Schiff bases were strongly cytotoxic. In particular, those with pyridine-2-carboxaldehyde and 2,3-butanedione have CD(50) values of 5.5, 1.9-2.0 microg ml(-1), respectively, against leukemic cells, while against colon cancer cells, the values were 3.7 and 2.0 microg ml(-1), respectively. The glyoxal Schiff base was strongly active only against leukemic cell with CD(50) value of 4.0 microg ml(-1). The present findings have been compared with standard drugs.

Coordination chemistry and bioactivity of some metal complexes containing two isomeric bidentate NS schiff bases derived from S-benzyldithiocarbazate and the x-ray crystal structures of S-benzyl-β-N-(5-methyl-2-furylmethylene)dithiocarbazate and bis[S-benzyl-β-N-(2-furylmethylketone)dithiocarbazato]cadmium(II)

Abstract Isomeric bidentate ligands having nitrogen–sulfur donor sequence were prepared by condensing S-benzyldithiocarbazate (SBDTC) with 5-methyl-2-furyladehyde (NS) and 2-furylmethylketone (NS′). Complexes of these ligands with lead, tin, iron, cobalt and cadmium gave complexes of [M(L)2] (M=Pb, Fe and Cd) and [M(L)2]Cln (M=Sn, n=2 and Co, n=1) (L=NS and NS′). The compounds have been characterized by spectroscopic studies (infrared, 1H NMR and electronic spectra). X-ray crystallographic analysis of S-benzyl-β-N-(5-methyl-2-furylmethylene)dithiocarbazate shows the presence of two independent molecules in the asymmetric unit. The molecule adopts a trans–cis configuration, as was observed in other analogues, such as SBDTC where the furylmethylene and benzyl groups are trans and cis about the NC and CS bonds, respectively. The molecular structure of bis[S-benzyl-β-N-(2-furylmethylketone)dithiocarbazato]cadmium(II) shows a tetrahedral geometry about the central cadmium atom with the bidentate ligand coordinating through the thioketo sulfur and the azomethine nitrogen atoms. The lead(II) complex of the NS ligand was highly cytotoxic against leukemic cells (CEM-SS) with a CD50 of 3.25 μg cm−3 while antimicrobial screening showed that the [Fe(NS)2]Cl2·H2O complex was effective against Aspergillus achraceous.

Complexes of a tridentate ONS Schiff base. Synthesis and biological properties

Several new complexes of a tridentate ONS Schiff base derived from the condensation of S-benzyldithiocarbazate with salicylaldehyde have been characterised by elemental analyses, molar conductivity measurements and by i.r. and electronic spectra. The Schiff base (HONSH) behaves as a dinegatively charged ligand coordinating through the thiolo sulphur, the azomethine nitrogen and the hydroxyl oxygen. It forms mono-ligand complexes: [M(ONS)X], [M=NiII, CuII, CrIII, SbIII, ZnII, ZrIV or UVI with X = H2O, Cl]. The ligand produced a bis-chelated complex of composition [Th(ONS)2] with ThIV. Square-planar structures are proposed for the NiII and CuII complexes. Antimicrobial tests indicate that the Schiff base and five of the metal complexes of CuII, NiII, UVI, ZnII and SbIII are strongly active against bacteria. NiII and SbIII complexes were the most effective against Pseudomonas aeruginosa (gram negative), while the CuII complex proved to be best against Bacillus cereus (gram positive bacteria). Antifungal activities were also noted with the Schiff base and the UVI complex. These compounds showed positive results against Candida albicans fungi, however, none of them were effective against Aspergillus ochraceous fungi. The Schiff base and its zinc and antimony complexes are strongly active against leukemic cells (CD50 = 2.3–4.3 μg cm−3) while the copper, uranium and thorium complexes are moderately active (CD50 = 6.9–9.5 μg cm−3). The nickel, zirconium and chromium complexes were found to be inactive.

Coordination chemistry and biological activity of two tridentate ONS and NNS Schiff bases derived from S-benzyldithiocarbazate

Two tridentate Schiff bases having ONS and NNS donor sequences were prepared by condensing S-benzyldithiocarbazate (NH2NHCSSCH2Ph) (SBDTC) with pyridine-2-carboxaldehyde and salicylaldehyde, respectively. Complexes of these ligands with NiII, ZnII, CrIII, CoII, CuII, and SnII were studied and characterized by elemental analyses and various physico-chemical techniques. NiII, CuII, ZnII and SnII complexes were four-coordinate while the CrIII, SrIII and CoIII complexes were six-coordinate. The ONS Schiff base was moderately active against leukemia, while its zinc, antimony and cobalt complexes were strongly active against leukemic cells with DC50 = 0.35–5.00.

Coordination chemistry and biological activity of nickel(II) and copper(II) ion complexes with nitrogen–sulphur donor ligands derived from S-benzyldithiocarbazate (SBDTC)

A bidentate and a quadridentate Schiff base having NS and NNSS donor sequences were prepared by condensing S-benzyldithiocarbazate (NH2NHCSSCH2Ph) with 2,3-butanedione (1:1 and 1:2 mole ratio). NiII and CuII complexes of these ligands were studied and characterised by elemental analyses and various physico-chemical techniques. The nickel complexes, [Ni(NS)2] and [Ni(SNNS)], were diamagnetic with square-planar and five-coordinate structures, respectively. The copper complex was, however, pentacoordinated. The ligands and the complexes were screened for anticancer activity against T-lymphoblastic leukemic cells (CEM-SS) and colon cancer cells (HT-29). The NS Schiff base was strongly active against leukemic cells with a CD50 value of 2.05 μg cm−3. The nickel and copper complexes were found to be stronger antioxidants than Vitamin E.

Conjugation of a new series of dithiocarbazate Schiff base Copper(II) complexes with vectors selected to enhance antibacterial activity.

A new series of six Schiff bases derived from S-methyldithiocarbazate (SMDTC) and S-benzyldithiocarbazate (SBDTC) with methyl levulinate (SMML, SBML), levulinic acid (SMLA, SBLA), and 4-carboxybenzaldehyde (SM4CB, SB4CB) were reacted with copper(II), producing complexes of general formula ML2 (M = Cu(II), L = ligand). All compounds were characterized using established physicochemical and spectroscopic methods. Crystal structures were determined for three Schiff bases (SMML, SBML, SBLA) and two Cu(II) complexes (Cu(SMML)2 and Cu(SMLA)2). In order to provide more insight into the behavior of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. The parent ligands and their respective copper(II) complexes exhibited moderate antibacterial activity against both Gram-negative and Gram-positive bacteria. The most active ligand (SB4CB) and its analogous S-methyl derivative (SM4CB) were conjugated with various vector moieties: polyarginines (R1, R4, R9, and RW9), oligoethylene glycol (OEG), and an efflux pump blocker, phenylalanine-arginine-β-naphthylamide (PAβN). Nonaarginine (R9) derivatives showed the most encouraging synergistic effects upon conjugation and complexation with copper ion including enhanced water solubility, bacteria cell membrane permeability, and bioactivity. These Cu(II)-R9 derivatives display remarkable antibacterial activity against a wide spectrum of bacteria and, in particular, are highly efficacious against Staphylococcus aureus with minimum inhibitory concentration (MIC) values of 0.5-1 μM. This pioneer study clearly indicates that the conjugation of cell-penetrating peptides (CPPs) to dithiocarbazate compounds greatly enhances their therapeutic potential.

Coordination chemistry and biological activity of bidentate and quadridentate nitrogen–sulfur donor ligands and their complexes

The ligand S-benzyldithiocarbazate (SBDTC) acts as a bidentate sulfur–nitrogen chelating agent. The reaction of SnII or SbIII with SBDTC under alkaline conditions gives complexes of composition [Sn(SBDTCA)2] · 2H2O and [Sb(SBDTCA)Cl2 · 2H2O]. A quadridentate Schiff base of SBDTC with benzil, having a donor sequence SNNS, yields complexes, [Cd(SNNS)] and [Zr(O)(SNNS) · H2O]. The ligands and the complexes have been characterized by elemental analyses, i.r., u.v.–vis., molar conductance measurements and 1H-n.m.r. spectroscopy. SBDTC, SnII and SbIII complexes and the SNNS Schiff base together with its CdII and ZrIV complexes display significant antifungal, antibacterial and anti-cancer activity. The SnII complex and the SNNS free Schiff base were very effective against Melanoma (skin cancer cells). The SBDTC and its SnII complex were also very effective against Renal carcinoma (kidney cancer cells). The results have been compared with those of the uncomplexed metal salts and the free ligands. The minimum concentrations for the evaluation of the above activities for CD50 of the samples were in the 1.0–15 μg cm−3 range.

Synthesis, characterization and biological evaluation of transition metal complexes derived from N, S bidentate ligands.

Two bidentate NS ligands were synthesized by the condensation reaction of S-2-methylbenzyldithiocarbazate (S2MBDTC) with 2-methoxybenzaldehyde (2MB) and 3-methoxybenzaldehyde (3MB). The ligands were reacted separately with acetates of Cu(II), Ni(II) and Zn(II) yielding 1:2 (metal:ligand) complexes. The metal complexes formed were expected to have a general formula of [M(NS)2] where M = Cu2+, Ni2+, and Zn2+. These compounds were characterized by elemental analysis, molar conductivity, magnetic susceptibility and various spectroscopic techniques. The magnetic susceptibility measurements and spectral results supported the predicted coordination geometry in which the Schiff bases behaved as bidentate NS donor ligands coordinating via the azomethine nitrogen and thiolate sulfur. The molecular structures of the isomeric S2M2MBH (1) and S2M3MBH (2) were established by X-ray crystallography to have very similar l-shaped structures. The Schiff bases and their metal complexes were evaluated for their biological activities against estrogen receptor-positive (MCF-7) and estrogen receptor-negative (MDA-MB-231) breast cancer cell lines. Only the Cu(II) complexes showed marked cytotoxicity against the cancer cell lines. Both Schiff bases and other metal complexes were found to be inactive. In concordance with the cytotoxicity studies, the DNA binding studies indicated that Cu(II) complexes have a strong DNA binding affinity.

Studies on coordination chemistry of a nitrogen–sulfur donor ligand with lighter and heavier metal ions and biological activities of its complexes

Complexes of S-benzyldithiocarbazate (SBDTC) with lighter and heavier metals, viz., CrIII, FeIII, SbIII, ZrIV, ThIV and UVI have been prepared and characterized by elemental analyses, conductivity measurements, and spectral studies. The complexes: [Cr(SBDTCA)3],** [Fe(SBDTCA)3], [Sb(SBDTCA)3], [Sb(SBDTCA)2Cl · H2O], [Zr(O)(SBDTCA)2 · H2O], [Th(SBDTCA)(NO3)3 · H2O)], and [U(O)2(SBDTCA)2] were all prepared in alkaline media. They were all hexa-coordinated with bidentate, uninegative chelation of the ligand. [Fe(SBDTCA)3], [Sb(SBDTCA)3] and [Sb(SBDTCA)2Cl · H2O] were strongly effective against bacteria giving clear inhibition zones with Pseudomonas aeruginosa and Bacillus cereus. The compounds showed poor antifungal activity. The antimony complexes were strongly cytotoxic against leukemic cells with CD50 values of 3.2–6.7 μg cm−3 as compared to the CD50 value of 14.5 μg cm−3 of the free SbCl3 molecule.