Structure and biological properties of first row d-transition metal complexes with N-substituted sulfonamides

Cobalt (II), copper (II), nickel (II) and zinc (II) complexes with 2-hydroxy-1-naphthaldehyde derived N-substituted sulfonamides have been synthesized and the nature of bonding and structure of compounds have been deduced from physical, analytical and spectral (IR, ¹H NMR, ¹³C NMR, Mass and electronic) data. An octahedral geometry has been suggested for the complexes. Complexes along with the ligands were assessed for their antibacterial and antifungal activities on different species of pathogenic bacteria and fungi. The results revealed the ligands to possess moderate to significant antibacterial activity which was, in many cases, enhanced on chelation. Similar results were observed for antifungal activity. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina.     

Structural elucidation and biological significance of 2-hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates

2-Hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates [cobalt (II), copper (II), nickel (II) and zinc (II)] have been synthesized and characterized. The nature of bonding and structure of all the compounds have been deduced from elemental analyses, infrared, ¹H NMR, ¹³C NMR, mass spectrometry, electronic spectra, magnetic susceptibility and conductivity measurements. An octahedral geometry has been suggested for all the complexes. The metal complexes were screened for their antibacterial and antifungal activities on different species of pathogenic bacteria and fungi and their biopotency has been discussed. The results of these studies revealed that all compounds showed moderate to significant antibacterial activity against all bacterial strains and good antifungal activity against various fungal strains. In-vitro cytotoxic properties of all the compounds against Artemia salina was also studies by brine shrimp bioassay.     

Structural elucidation and biological significance of 2-hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates

2-Hydroxy-1-naphthaldehyde derived sulfonamides and their first row d-transition metal chelates [cobalt (II), copper (II), nickel (II) and zinc (II)] have been synthesized and characterized. The nature of bonding and structure of all the compounds have been deduced from elemental analyses, infrared, 1H NMR, 13C NMR, mass spectrometry, electronic spectra, magnetic susceptibility and conductivity measurements. An octahedral geometry has been suggested for all the complexes. The metal complexes were screened for their antibacterial and antifungal activities on different species of pathogenic bacteria and fungi and their biopotency has been discussed. The results of these studies revealed that all compounds showed moderate to significant antibacterial activity against all bacterial strains and good antifungal activity against various fungal strains. In-vitro cytotoxic properties of all the compounds against Artemia salina was also studies by brine shrimp bioassay.     

Adenosine adducts with first row transition metal perchlorates

Adducts of adenosine (ado) with 3d metal perchlorates were synthesized by refluxing mixtures of ligand and salt in ethanol-triethyl orthoformate. Metal(III) perchlorates formed adducts involving 2:3 metal to ado molar ratio (MCr, Fe), i.e., M2(ado)₃(ClO₄)₆·4H₂O, whereas 1:1 adducts were produced by metal(II) perchlorates, as follows: M(ado)(ClO₄)₂·2H₂0 (MMn, Co, Ni, Cu); and M(ado)(Cl0₄)₂ (MFe, Zn). All the new complexes seem to be polymeric, involving a linear chainlike backbone with single ado bridges between adjacent metal ions in most cases, i.e., −(-M-ado-)-_n. The coordination sphere of each metal ion is completed by terminal aqua, ado and, with the exception of the Cu²⁺ complex, −OClO₃ ligands, in the case of the hydrated new complexes. Ado would be binding through the N(1) and N(7) ring nitrogens, when functioning as bridging, bidentate. As regards the two water-free M(II) complexes (MFe, Zn), which are apparently distorted tetrahedral, the evidence available is interpreted in terms of the presence of tridentate bridging ado, binding through N(1), N(7) in the same fashion as above, and through one of the ribose hydroxyl oxygens, which form weaker bonds to M²⁺ ions located in a neighboring linear polymeric −(-M-ado-)-n unit; the coordination sphere in these complexes is completed by one −OClO₃ ligand.     

Chelates of tetracycline with first row transition metal perchlorates

2:1 adducts of tetracycline (tc) with 3d metal perchlorates (M = Cr ³⁺, Mn ²⁺, Fe ²+, ^Fe3+, ^Co2+, Ni ²⁺, Cu ²⁺, Zn ²⁺) are synthesized by boiling under reflux mixtures of tc free base and metal salt in ethanol— triethyl orthoformate. Characterization studies suggest that the new complexes are monomeric chelates involving bidentate tetracycline ligands, chelating via the amide group oxygen and the C3O oxygen of the ring A tricarbonylmethane. The complexes also contain unidentate coordinated −OClO ₃ ligands, as weil as ionic ClO ₄^-. The M ³⁺ (Cr, Fe) complexes are hexacoordinated of the [M(tc) ₂(OClO ₃)2 ₃]ClO ₄ type (MO ₆ chromophores), with two bidentate chelating tc and two unidentate perchlorato ligands in the first coordination sphere of the central metal ion. In the M2+ (Mn, Fe, Co, Ni, Cu, Zn) complexes, the inner coordination sphere of the metal ion is occupied by two bidentate chelating tc and only one −OClO ₃ ligand, and the coordination number is five, i.e. [M(tc) ₂OClO ₃]ClO ₄ (MO ₅absorbing species).     

Antibacterial, antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin

A new series of 4-({[2, 4-dioxo-2H-chromen-3 (4H)-ylidene] methyl} amino) sulfonamides have been obtained by the condensation reaction of 4-hydroxycoumarin with various sulfonamides (sulfanilamide, sulfaguanidine, p-aminomethyl-sufanilamide, p-aminoethylsufanilamide, sulfathiazole, sulfamethoxazole, sulfamethazine and 4-[(2-amino-4-pyrimidinyl) amino] benzenesulfonamide) in the presence of an excess of ethylorthoformate. These compounds were screened for their in-vitro antibacterial activity against four Gram-negative (E. coli, S. flexneri, P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) bacterial strains and for in-vitro antifungal activity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani and C. glaberata. Results revealed that a significant antibacterial activity was observed by compounds (4) and (5), (6) and (8) against two Gram-negative, (P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) species, respectively. Of these (4) was found to be the most active. Similarly, for antifungal activity compounds (3) and (8) showed significant activity against M. canis and, (6) and (8) against F. solani. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and only two compounds, (4) and (8) possessing LD50 = 2.9072 x 10(-4) and 3.2844 x 10(-4) M, respectively, displayed potent cytotoxic activity against Artemia salina     

Antibacterial,antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin

A new series of 4-({[2, 4-dioxo-2H-chromen-3 (4H)-ylidene] methyl} amino) sulfonamides have been obtained by the condensation reaction of 4-hydroxycoumarin with various sulfonamides (sulfanilamide, sulfaguanidine, p-aminomethylsufanilamide, p-aminoethylsufanilamide, sulfathiazole, sulfamethoxazole, sulfamethazine and 4-[(2-amino-4-pyrimidinyl) amino] benzenesulfonamide) in the presence of an excess of ethylorthoformate. These compounds were screened for their in-vitro antibacterial activity against four Gram-negative (E. coli, S. flexneri, P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) bacterial strains and for in-vitro antifungal activity against T. longifusus, C. albicans, A. flavus, M. canis, F. solani and C. glaberata. Results revealed that a significant antibacterial activity was observed by compounds (4) and (5), (6) and (8) against two Gram-negative, (P. aeruginosa and S. typhi) and two Gram-positive (B. subtilis and S. aureus) species, respectively. Of these (4) was found to be the most active. Similarly, for antifungal activity compounds (3) and (8) showed significant activity against M. canis and, (6) and (8) against F. solani. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties and only two compounds, (4) and (8) possessing LD₅₀ = 2.9072 × 10^{? 4} and 3.2844 × 10^{? 4} M, respectively, displayed potent cytotoxic activity against Artemia salina     

DNA cleavage reaction induced by dimeric copper(II) complexes of N-substituted thiazole sulfonamides

A new dinuclear copper(II) complex has been synthesised and structurally characterised: [Cu2(tz-ben)4] (Htz-ben = N-thiazol-2-yl-benzenesulfonamide). Its crystal structure, magnetic properties and electronic paramagnetic resonance (EPR) spectra were studied in detail. In the compound the metal centres are bridged by four non-linear triatomic NCN groups. The coordination geometry of the copper ions in the dinuclear entity is distorted square pyramidal (4+1). Two thiazole N and two sulfonamido N atoms occupy the equatorial positions and one sulfonamido O atom is in the axial position. Magnetic susceptibility data show a strong antiferromagnetic coupling, -2J = 114.1 cm(-1). The EPR spectra of a polycrystalline sample of compound has been obtained at the X- and Q-band frequencies at different temperatures. Above 20K the spectra are characteristic of S = 1 species with a zero field splitting parameter D = 0.4 cm(-1). The EPR parameters are discussed in terms of the known binuclear structures. The chemical nuclease ability of the title complex and that of the related [Cu2(tz-tol)4] compound (Htz-tol = N-thiazol-2-yl-toluenesulfonamide) is reported. The participation of hydroxyl radicals and a singlet oxygen-like entity in the DNA cleavage reaction has been deduced from the assays with radical oxygen scavengers.     

Group-10 metal complexes of biological molecules and related ligands: structural and functional properties

The complexes of group-10 metals, Ni, Pd, and Pt, with biological molecules and related ligands have been attracting increasing attention in recent years due to their reactivities and functions, such as catalysts and drugs, and their biological relevance. The well-defined structures and kinetic inertness especially of Pt complexes have been used as the sites for weak interactions with other molecules. The Ni complexes have been reported as models not only for Ni enzymes but also for other metalloenzyme active sites for deeper understanding of the reactivities such as oxygen activations and detailed electronic structures. Pd Complexes are widely known for their catalytic activities in conversions of various organic molecules including useful biological molecules, such as Suzuki?Miyaura cross-coupling, while Pt complexes have been intensively studied for their antitumor activities. We focus in this review on our recent results on weak interactions and reactivities of the group-10 metal complexes with biological molecules and related compounds, and discuss their structural features and some new properties pointing to functional possibilities.     

Chemical and biological properties of pentaammineruthenium-bleomycin complexes

The reaction of [(H2O)(NH3)5RuII]2+ with bleomycin forms at least two stable products following oxidation to the Ru(III) analog. Spectroscopic and electrochemical measurements indicate monodentate binding of [(NH3)5RuIII] to the imidazole and pyrimidine moieties, with coordination to the latter involving the exocyclic amine nitrogen. DNA cleavage studies show the complexes to be ineffective in DNA strand scission. In vitro biological studies reveal these adducts to be cytotoxic.     

Design,synthesis, and biological properties of triazole derived compounds and their transition metal complexes

Triazole derived Schiff bases and their metal complexes (cobalt(II), copper(II), nickel(II), and zinc(II)) have been prepared and characterized using IR, ¹H and ¹³C NMR, mass spectrometry, magnetic susceptibility and conductivity measurements, and CHN analysis data. The structure of L², N-[(5-methylthiophen-2-yl)methylidene]-1H-1,2,4-triazol-3-amine, has also been determined by the X-ray diffraction method. All the metal(II) complexes showed octahedral geometry except the copper(II) complexes, which showed distorted octahedral geometry. The triazole ligands and their metal complexes have been screened for their in vitro antibacterial, antifungal, and cytotoxic activity. All the synthesized compounds showed moderate to significant antibacterial activity against one or more bacterial strains. It is revealed that all the synthesized complexes showed better activity than the ligands, due to coordination.     

Antioxidant properties of complexes of flavonoids with metal ions

The formation of complexes of metal ions with the flavonoids quercetin (L1), rutin (L2), galangin (L3) and catechin (L4) has been investigated by UV-visible spectroscopy. The antioxidant activities of the compounds were evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicalscavenging method. In this work, we have shown that the complexed flavonoids are much more effective free radical scavengers than the free flavonoids. We suggest that the higher antioxidant activity of the complexes is due to the acquisition of additional superoxide dismutating centers. Radical scavenging activities of the compounds were also investigated from an electrochemical point of view. There is a relationship between the logarithm of the antioxidant activity (represented by EC50) and the oxidation potential. The synergic effect of the complexes and ascorbic acid were studied by [13C]-NMR analyses. The results show that ascorbic acid can protect flavonoids from oxidative degradation, and reveal antioxidant synergies between ascorbic acid and the compounds.     

Carbonic anhydrase inhibitors: Schiff's bases of aromatic and heterocyclic sulfonamides and their metal complexes

Schiff's bases were obtained from aromatic/heterocyclic sulfonamides and amino-sulfonamide derivatives, such as sulfanilamide, homosulfanilamide, 4-aminoethyl-benzenesulfonamide and 5-amino-1,3,4-thiadiazole-2-sulfonamide. Metal complexes of some of these Schiff's bases, incorporating Zn(II), Co(lI), Ni(II) and Cu(II) ions, were also prepared and tested as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more specifically the red blood cell isozymes I and II. The Schiff's bases behaved as medium potency CA I and CA II inhibitors, whereas their metal complexes showed a highly enhanced potency, with several low nanomolar CA II inhibitors detected.     

Mononuclear metal complexes with piroxicam: synthesis, structure and biological activity

Piroxicam (=Hpir) is a non-steroidal anti-inflammatory and an anti-arthritic drug. VO(2+), Mn(2+), Fe(3+), MoO(2)(2+) and UO(2)(2+) complexes with deprotonated piroxicam have been prepared and characterized with the use of infrared, UV-Vis, nuclear magnetic resonance and electron paramagnetic resonance spectroscopies. The experimental data suggest that piroxicam acts as a deprotonated bidentate ligand in all complexes and is coordinated to the metal ion through the pyridine nitrogen and the amide oxygen. Molecular mechanics calculations in the gas state have been performed in order to propose a model for the Fe(3+), VO(2+) and MoO(2)(2+) complexes. Potential anticancer cytostatic and cytotoxic effects of piroxicam complexes with VO(2+), Mn(2+) and MoO(2)(2+) on human promyelocytic leukemia HL-60 cells have been investigated. Among all complexes, only VO(pir)(2)(H(2)O) clearly induces apoptosis after 24-h incubation, whereas piroxicam induces apoptosis after 57-h incubation.     

Self-assembly and cytotoxicity study of waterwheel-like dinuclear metal complexes: the first metal complexes appended with multiple free hydroxamic acid groups

Two waterwheel-like dinuclear complexes [M(2)(PHA)(4)(H(2)O)(2)] (M = Cu(II) (1), Zn(II) (2); HPHA = phthal-hydroxamic acid) appended with four free hydroxamic acid groups, namely, free hydroxamic acid metal complexes (FHAMCs) have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which adopts the paddlewheel motif with four bidentate carboxylate ligands joining two Cu(II) ions. The relative cytotoxicities of compounds 1 and 2 against SMMC-7721 and HO-8910 cell lines are similar and more predominant than HPHA (IC(50): Cu(II)>Zn(II)>HPHA). The synergic effect of the bound water molecules, multiple free hydroxamic acid groups and dimetal active sites with bridging carboxylate may have significant impacts on their pharmacological activity. As the prototype for a new class of hydroxamic acid derivatives, the self-assembly of FHAMCs presents a promising new strategy in designing multiple hydroxamic acids with remarkable bioactivities.     

Structure and electronic properties of heme complexes with various ligands

The electronic and atomic structures, and the molecular dynamics of the atomic structure at 310 K of a set of heme complexes with His and Gly amino acids in the 5th coordination position and some ligands (O2, NO) in the 6th position were studied by ab initio (3-21G basis set) and semiempirical (PM3) quantum chemistry methods and the method of molecular dynamics. It was shown that the type of coordination of the imidazole ring influences the constant of chemical bonding of molecular oxygen of the complexes. On the other hand, NO and O2 molecules have different transinfluence on the ligand in the 5th coordination position. It was shown that temperature affects profoundly the atomic and electronic structures of the complexes, the tightness of chemical bonding and their reactivity.     

Vibrational characterisation and biological activity of carnosine and its metal complexes

The spectroscopic characterisation of free carnosine and its coordination compounds with Cu(II), Zn(II) and Co(II) ions are discussed. Raman and IR studies on metal-carnosine systems have been performed, obtaining a relationship between the vibrational spectra and the structure of the predominant species formed. The biological activity of free carnosine and of its complexes is briefly considered.     

Mononuclear metal complexes with ciprofloxacin: Synthesis, characterization and DNA-binding properties

Five novel metal complexes of the quinolone antibacterial agent ciprofloxacin with Mn²⁺, Fe³⁺, Co²⁺, Ni²⁺ and have been prepared and characterized with physicochemical, spectroscopic and electrochemical techniques. In all these complexes, ciprofloxacin acts as a bidentate deprotonated ligand bound to the metal through the pyridone oxygen and one carboxylate oxygen. The central metal in each complex is six-coordinate and a slightly distorted octahedral geometry is proposed. The lowest energy model structures of the Mn²⁺, Fe³⁺ and complexes have been determined with molecular modeling calculations. The cyclic voltammograms of the complexes have been recorded in dmso solution and in 1/2 dmso/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution and the corresponding redox potentials have been estimated. The biological activity of the complexes has been evaluated by examining their ability to bind to calf-thymus DNA (CT DNA) with UV and fluorescence spectroscopies and cyclic voltammetry. UV studies of the interaction of the complexes with DNA have shown that these compounds can bind to CT DNA. The binding constants of the complexes with CT DNA have also been calculated. The cyclic voltammograms of the complexes in the presence of CT DNA have shown that the complexes can bind to CT DNA by both the intercalative and the electrostatic binding mode. Competitive studies with ethidium bromide (EB) have shown that the complexes exhibit the ability to displace the DNA-bound EB indicating that the complexes bind to DNA probably via intercalation in strong competition with EB for the intercalative binding site.