In vitro anti-proliferative,and in silico ribonucleotide reductase and pharmacokinetics studies of heteroleptic silver(I), nickel(II) and copper(II) complexes of 4-methyl-3-thiosemicarbazones and ibuprofen

ObjectivesThe present research focuses on the in vitro anti-proliferative, and in silico ribonucleotide reductase and pharmacokinetics studies of twelve heteroleptic metal complexes of the general formulae [Ag(L¹⁻⁴)(ibu)] (1–4) and [M(L¹⁻⁴)(ibu)₂] (5–12), where L¹⁻⁴ = 2-(1-(4-substitutedphenyl)ethylidene)-N-methylhydrazinecarbothioamide, ibu = non-steroidal anti-inflammatory drug (ibuprofen), and M = Cu(II) and Ni(II).MethodsVarious spectroscopic techniques were used to authenticate the structure of the synthesized complexes. UV-Vis and cyclic voltammetry techniques were used to analyse the stability and the reducing ability of the complexes. In vitro anti-proliferative studies by MTT assay, apoptotic behaviour and cellular uptake studies were investigated followed by the in silico interaction with ribonucleotide reductase (RNR) enzyme.ResultsThe spectral studies predicted distorted tetrahedral geometry around silver(I) ion and distorted octahedral geometry around nickel(II) and copper(II) ions. The reducing ability of the copper(II) complexes was analysed using ascorbic acid by UV-Vis and cyclic voltammetry techniques, which authenticate the reducing ability of the complexes and the possible interactions within the cells. The in vitro anti-proliferative activity of the synthesized complexes against three cancerous (estrogen positive (MCF-7), estrogen negative (MDA-MB-231) and pancreatic (PANC-1)) and one normal (MCF-10a) cell lines by MTT assay showed enhanced activity for copper(II) complexes 11 and 12 containing the hydrophobic substituents. The apoptotic and cellular uptake studies showed that the complex 12 is readily taken up by PANC-1 cell lines and induces ROS-mediated mitochondrial and caspase-dependent apoptosis. The in silico studies indicated hydrogen bonding, hydrophobic and π-pair (π–π, π–σ and π–cation) interactions between the complexes and the ribonucleotide reductase (RNR) enzyme. The in silico pharmacokinetics studies of the complexes predicted the drug-likeness characteristics of the complexes.ConclusionThe synthesized complexes are found to be less toxic to normal cells and inhibit the growth of cancerous cells by inducing mitochondrial-mediated and caspase dependent apoptotic pathway in PANC-1 cells.     

Copper(II) complexes of new pentadentate bis(benzimidazolyl)-dithioether ligands: synthesis, structure, spectra and redox properties

Copper(II) complexes of a series of linear pentadentate ligands containing two benzimidazoles, two thioether sulfurs and a amine nitrogen, viz. N,N^′-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}amine(L¹), N,N^′-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}N-methylamine (L²), 2,6-bis{4^′-(2″-benzimidazolyl)(methyl)-3^′-thiabutyl}pyridine(L³), N,N^′-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}amine (L⁴), N,N^′-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}N-methylamine (L⁵) and 2,6-bis{4^′-(2″-benzimidazolyl)-2^′-thiabutyl}-3pyridine (L⁶) have been isolated and characterized by electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes, [Cu(L¹)](BF₄)₂ (1) and [Cu(L²)](BF₄)₂ (4) have been structurally characterized by X-ray crystallography. The coordination geometries around copper(II) in 1 and 4 are described as trigonal bipyramidal distorted square based pyramidal geometry (TBDSBP). The distorted CuN₃S basal plane in them is comprised of amine nitrogen, one thioether sulphur and two benzimidazole nitrogens and the other thioether sulfur is axially coordinated. The ligand field spectra of all the complexes are consistent with a mostly square-based geometry in solution. The EPR spectra of complexes [Cu(L¹)](BF₄)₂ (1), [Cu(L¹)](NO₃)₂ (2), [Cu(L²)](BF₄)₂ (4) and [Cu(L³)](ClO₄)₂ (6) are consistent with two species indicating the dissociation/disproportionation of the complex species in solution. All the complexes exhibit an intense CT band in the range 305-395 nm and show a quasireversible to irreversible Cu^II/Cu^I redox process with relatively positive E_1/2 values, which are consistent with the presence of two-coordinated thioether groups. The addition of N-methylimidazole (mim) replaces the coordinated thioether ligands in solution, as revealed from the negative shift (222-403 mV) in the Cu^II/Cu^I redox potential. The present study reveals that the effect of incorporating an amine nitrogen donor into CuN₂S₂ complexes is to generate an axial copper(II)-thioether coordination and also to enforce lesser trigonality on the copper(II) coordination geometry.     

Synthesis,Characterization, Antimicrobial and Antimalarial Activities of Azines Based Schiff Bases and their Pd(II) Complexes

Herein, we report synthesis, characterization, antimicrobial and antimalarial activities of azines Schiff base ligands (L¹−L⁴) and their palladium (II) complexes ( C¹−C⁴ ) of [Pd(L)(OAc)₂] type. The azine ligands (L¹−L⁴) were prepared by condensation of carbonyl compounds with hydrazine hydrate and their complexes by the reaction of palladium acetate with L¹−L⁴ ligands in 1 : 1 molar ratio. The prepared ligands and their complexes were characterized by spectral characterization using ¹H &¹³C-NMR, FT-IR and mass spectral studies, which revealed that the ligands coordinates via azomethine nitrogen and heteroatom or aryl carbon with palladium. Moreover, Schiff bases and their palladium (II) complexes have been screened for their antibacterial (S. aureus, B. subtillis, and S. typhi, P. aeruginosa), antifungal (C. albicans, A. niger, and A. clavatus) and antimalarial (P. falciparum) activities. The Schiff base L⁴ showed good results for antibacterial against S. aureus (MIC, 50 μg/mL) and antimalarial against P. falciparum (IC₅₀, 0.83 μg/mL). The complex C¹ showed best antibacterial activity (MIC, 62.5 μg/mL) against S. typhi and the complex C⁴ exhibited remarkable antimalarial activity (IC₅₀, 0.42 μg/mL) among the tested compounds. Thus, azines based ligands and their Pd complexes can be good antimicrobial and antimalarial agents if explored further.     

Mercaptoethanesulfonic acid (CoM imitator) interaction studies with nickel(II) complexes of pyridyl groups containing tetradentate ligands: Synthesis, structure, spectra and redox properties

Nickel(II) complexes of N,N′-dimethyl-N,N′-bis(pyridyl-2yl-methyl)ethylene-diamine (L¹), N,N′-dimethyl-N,N′-bis(pyridyl-2-ylmethyl)-1,2-diaminopropane (L²) and N,N′-dimethyl-N,N′-bis(pyridyl-2-ylmethyl)-1,3-diaminopropane (L³) were prepared and their spectroscopic and redox properties studied. The distorted octahedral structure was determined for [NiL³ClCH₃OH](ClO₄) by using X-ray crystallography. The electronic spectral behavior of the complexes at different pHs was analyzed; it is shown that a new band grew at the expense of the other band intensity in acid media. The redox properties of ligands and their complexes show the peaks of Ni(II) → Ni(III) and Ni(II) → Ni(0) as these were detected at low concentration while Ni(II) → Ni(I) process was detectable clearly at high concentration. Furthermore, the interaction studies of 2-mercaptoethanesulfonic acid as a simulator of coenzyme M reductase (CoM) with NiN₄ chromophores are discussed.     

Synthesis, characterization and X-ray crystal structures of copper(II) and nickel(II) complexes with potentially hexadentate Schiff base ligands

Copper(II) and nickel(II) complexes of potentially N₂O₄ Schiff base ligands 2-({[2-(2-{2-[(1-{2-hydroxy-5-[2-phenyl-1-diazenyl]phenyl}methylidene)amino] phenoxy}ethoxy) phenyl]imino}methyl)4-[2-phenyl-1-diazenyl]phenol (H₂L¹) and 2-({[2-(4-{2-[(1-{2-hydroxy-5-[2-phenyl-1-diazenyl]phenyl}methylidene)amino] phenoxy}butoxy) phenyl]imino}methyl)4-[2-phenyl-1-diazenyl]phenol (H₂L²) prepared of 5-phenylazo salicylaldehyde (1) and two various diamines 2-[2-(2-aminophenoxy)ethoxy]aniline (2) and 2-[4-(2-aminophenoxy)butoxy]aniline (3) were synthesized and characterized by a variety of physico-chemical techniques. The single-crystal X-ray diffractions are reported for CuL¹ and NiL². The CuL¹ complex contains copper(II) in a near square-planar environment of N₂O₂ donors. The NiL² complex contains nickel(II) in a distorted octahedral geometry coordination of N₂O₄ donors. In all complexes, H₂L¹ behaves as a tetradentate and H₂L² acts as a hexadentate ligand. Cyclic voltammetry of copper(II) complexes indicate a quasi-reversible redox wave in the negative potential range.     

Examining the impact of steric and electronic variation in N2S scorpionate ligands on the properties of zinc(II) and cadmium(II) complexes

A series of LZn(II)Br (1-4) and LCd(II)Cl complexes (9-11) has been prepared by the reaction of metal halide precursors with the lithium salts of the N₂S⁻ ligands bis(3,5-diisopropylpyrazol-1-yl)dithioacetate (L¹), bis(3,5-di-tert-butylpyrazol-1-yl)dithioacetate (L²), N-phenyl-2,2-bis(3,5-diisopropylpyrazol-1-yl)thioacetamide (L³) and N-phenyl-2,2-bis(3,5-di-tert-butylpyrazol-1-yl)thioacetamide (L⁴). Characterization by X-ray crystallography and DOSY NMR studies indicate that LZnBr complexes 1-4 are mononuclear both in the solid state and in solution. Steric differences between ligands L¹-L⁴ result in distortion from an ideal tetrahedral geometry for each complex, with the degree of distortion depending on the bulk of the ligand substituents. In contrast, the related complex L³CdCl was shown by X-ray crystallography to dimerize in the solid state to form the chloride-bridged five-coordinate complex [L³CdCl]₂ (10). Despite 10 having a dinuclear structure in the solid state, DOSY NMR studies indicate 9-11 exist as mononuclear LCdCl species in solution. In addition, Zn(II) cyanide complexes of the form LZnCN [L = L¹ (5), L³ (7), L⁴ (8)] have been characterized and the X-ray structure of 8 determined. Moreover, density functional theory calculations have been conducted which yield important insight into the bonding in 1-4 and 5-8 and the electronic impact of ligands L¹-L⁴ on the zinc(II) ion and its ability to function as a Lewis acid catalyst.     

The influence of inductive ligand electronics on the metrical parameters and redox potentials of a series of manganese(II) compounds

In order to assess the changes in the redox activity of a metal ion that result from inductive effects, three electronically modified derivatives of the ligand, N-benzyl-N,N′-bis(2-pyridylmethyl)-1,2-ethanediamine (L^H), have been prepared: N-(4-nitro)benzyl-N,N′-bis(2-pyridylmethyl)-1,2-ethanediamine (L^NO2), N-(4-chloro)benzyl-N,N′-bis(2-pyridylmethyl)-1,2-ethanediamine (L^Cl), and N-(4-methoxy)benzyl-N,N′-bis(2-pyridylmethyl)-1,2-ethanediamine (L^OMe). Due to the lack of a fully conjugated π-system between the 4-benzyl substituent and the N-donors, the electronic perturbation should influence a bound metal ion’s redox properties through primarily inductive pathways. The organic ligands react with MnCl₂ to form mononuclear complexes with the general formula [Mn(L^R)Cl₂]. The parent ligand, L^H, and its three derivatives each coordinate Mn(II) ions in a cis-α conformation, with the amine N-donors installed trans to the Mn-Cl bonds. Despite its distance from the metal ion, the electron-donating or - withdrawing group has a notable impact on both the metrical parameters of the Mn(II) compounds and the Mn(III/II) reduction potential. A single inductive perturbation can vary the reduction potential by as much as 50 mV.     

Dicopper(II) and dinickel(II) complexes of Schiff-base macrocycles derived from 5,5-dimethyl-1,9-diformyldipyrromethane

The synthesis and characterisation of two dicopper(II) and two dinickel(II) macrocyclic complexes, [Cu^II₂L^Pr] (10), [Cu^II₂L^Bu] (11), [Ni^II₂L^Pr] (12) and [Ni^II₂L^Bu] (13), are reported. The two new Schiff-base macrocycles (L^Pr)⁴⁻ and (L^Bu)⁴⁻ are isolated as dimetallic complexes 10-13 by the [2+2] condensation of 5,5-dimethyl-1,9-diformyldipyrromethane (9) and 1,3-diaminopropane or 1,4-diaminobutane, respectively, using Cu²⁺ or Ni²⁺ template ions. Single crystal X-ray structure determinations carried out on 10-13 show that each metal atom is in a square planar N₄ geometry, being bound to two deprotonated pyrrole nitrogen atoms of one dipyrromethane unit and to the two adjacent imine nitrogen atoms. NMR spectra obtained for the two dinickel(II) complexes 12 and 13 show that in CDCl₃ solution they are highly symmetrical and diamagnetic.     

Synthesis, structure, and properties of monomeric Fe(II), Co(II), and Ni(II) complexes of neutral N-(aryl)-2-pyridinecarboxamides

We have prepared and structurally characterized six-coordinate Fe(II), Co(II), and Ni(II) complexes of types [M^II(HL¹)₂(H₂O)₂][ClO₄]₂ (M = Fe, 1; Co, 3; and Ni, 5) and [M^II(HL²)₃][ClO₄]₂ · MeCN (M = Fe, 2 and Co, 4) of bidentate pyridine amide ligands, N-(phenyl)-2-pyridinecarboxamide (HL¹) and N-(4-methylphenyl)-2-pyridinecarboxamide (HL²). The metal centers in bis(ligand)-diaqua complexes 1, 3 and 5 are coordinated by two pyridyl N and two amide O atoms from two HL¹ ligands and six-coordination is completed by coordination of two water molecules. The complexes are isomorphous and possess trans-octahedral geometry. The metal centers in isomorphous tris(ligand) complexes 2 and 4 are coordinated by three pyridyl N and three amide O atoms from three HL² ligands. The relative dispositions of the pyridine N and amide O atoms reveal that the pseudo-octahedral geometry have the meridional stereochemistry. To the best of our knowledge, this work provides the first examples of structurally characterized six-coordinate iron(II) complexes in which the coordination is solely by neutral pyridine amide ligands providing pyridine N and amide O donor atoms, with or without water coordination. Careful analyses of structural parameters of 1-5 along with that reported in the literature [M^II(HL¹)₂(H₂O)₂][ClO₄]₂ (M = Cu and Zn) and [Co^III(L²)₃] have allowed us to arrive at a number of structural correlations/generalizations. The complexes are uniformly high-spin. Spectroscopic (IR and UV/Vis) and redox properties of the complexes have also been investigated.     

Design,synthesis, MTT assay,DNA interaction studies of platinum(II) complexes

The square planar Pt(II) complexes of the type [Pt(Lⁿ)(Cl₂)] (where Lⁿ = L^1?3 = thiophene-2-carboxamide derivatives and L^4?6 = thiophene-2-carbothioamide derivatives) have been synthesized and characterized by physicochemical and various spectroscopic studies. MIC method was employed to inference the antibacterial potency of complexes in reference to free ligands and metal salt. Characteristic binding constant (K_b) and binding mode of complexes with calf thymus DNA (CT-DNA) were determined using absorption titration (0.76–1.61 × 10⁵ M^?1), hydrodynamic chain length assay and fluorescence quenching analysis, deducing the partial intercalative mode of binding. Molecular docking calculation displayed free energy of binding in the range of –260.06 to –219.63 kJmol^?1. The nuclease profile of complexes towards pUC19 DNA shows that the complexes cleave DNA more efficiently compared to their respective metal salt. Cytotoxicity profile of the complexes on the brine shrimp shows that all the complex exhibit noteworthy cytotoxic activity with LC₅₀ values ranging from 7.87 to 15.94 μg/mL. The complexes have been evaluated for cell proliferation potential in human colon carcinoma cells (HCT 116) and IC₅₀ value of complexes by MTT assay (IC₅₀ = 125–1000 μg/mL).     

In-vitro antibacterial,antifungal activity of some transition metal complexes of thiosemicarbazone Schiff base (HL) derived from N4-(7′-chloroquinolin-4′-ylamino) thiosemicarbazide

The synthetic, spectroscopic, and biological studies of Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Fe(III) and Cr(III) complexes of N⁴-(7′-chloroquinoline-4′-ylamino)-N¹-(2-hydroxy-benzylidene)thiosemicarbazone (HL) obtained by the reaction of N⁴-(7′-chloroquinolin-4′-ylamino)thiosemicarbazide with 2-hydroxybenzaldehyde. The structures of the complexes were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic, ¹H and ¹³C NMR and Mass spectra) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed the non-electrolytic nature of the complexes. The resulting colored products are mononuclear in nature. On the basis of the above studies, only one ligand was suggested to be coordinated to each metal atom by thione sulfur, azomethine nitrogen and phenolic oxygen to form mononuclear complexes in which the thiosemicarbazone behaves as a monobasic tridendate ligand. The ligand and its metal complexes were tested against Gram + ve bacteria (Staphylococcus aureus), Gram ? ve bacteria (Escherichia coli), fungi (Candida albicans) and (Fusarium solani). The tested compounds exhibited significant activity.     

Copper(II) complexes of N2-alkyl-(S)-amino acid amides as chiral selectors for dynamically coated chiral stationary phases in RP-HPLC

Copper(II) complexes of N²-octyl-(S)-phenylalaninamide (Noc-Phe-NH₂), N²-dodecyl-(S)-phenylalaninamide (Ndo-Phe-NH₂), and N²-octyl-(S)-norleucinamide (Noc-NLeu-NH₂), dynamically adsorbed on a reversed-phase C₁₈ column, were able to perform the direct enantiomeric separation of unmodified amino acids, amino acid amides and esters, hydroxy acids, and dipeptides by elution with aqueous or mixed aqueous-organic solutions containing copper(II) sulphate or acetate. The role played by several parameters in the separation procedure was examined with the copper(II) complex of Noc-Phe-NH₂ [concentration of the copper(II) ion in the eluent, pH and eluent polarity, amount of adsorbed selector]. The separation was shown to occur entirely on the stationary phase. The mechanism of chiral discrimination is discussed in terms of the chromatographic parameters and of the structure of the copper(II) complexes in solution and in the solid state. The chiral stationary phase maintained its separation ability for about 3 months. However, the column could be easily restored by recovering the selector with methanol and repeating the loading procedure. © 1996 Wiley-Liss, Inc.     

Copper (II) and zinc (ii) metal-based salicyl-, furanyl-, thienyl- and pyrrolyl-derived ONNO,NNNO, ONNS & NNNS donor asymmetrically mixed schiff-bases with antibacterial and antifungal potentials

A new series of asymmetric salicyl-, furanyl-, thienyl- and pyrrolyl-derived ONNO, NNNO, ONNS & NNNS donor antibacterial and antifungal Schiff-bases and their copper(II) and zinc(II) metal complexes have been synthesized and characterized. IR spectra indicated the ligands to act as quartdentate towards divalent metal ions via two azomethine-N, deprotonated-O of salicyl, furanyl-O, thienyl-S and/or pyrrolyl-N. The magnetic moments and electronic spectral data suggest octahedral geometry for Cu(II) and Zn(II) complexes. NMR spectral data of the ligands and their diamagnetic zinc(II) complexes well-define their proposed structures/geometries. Elemental analyses data of the ligands and metal complexes agree with their proposed structures/geometries. The synthesized ligands, along with their metal complexes were screened for their antibacterial activity against B. cereus, C. diphtheriae, E. coli, K. pneumoniae, P. mirabilis, P. aeruginosa, S. typhi, S. dysenteriae and S. aureus strains and for in-vitro antifungal activity against T. schoenleinii, C. glabrata, P. boydii, C. albicans, A. niger, M. canis and T. mentagrophytes. The results of these studies show the metal complexes to be more antibacterial/antifungal against one or more species as compared to the uncomplexed ligands. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties. Eight compounds, L₄, (1), (7), (8), (11), (17), (19) and (23) displayed potent cytotoxic activity with LD₅₀ = 1.445 × 10^{? 3}, 1.021 × 10^{? 3}, 7.478 × 10^{? 4}, 8.566 × 10^{? 4}, 1.028 × 10^{? 3}, 9.943 × 10^{? 4}, 8.730 × 10^{? 4} and 1.124 × 10^{? 3} M respectively, against Artemia salina.     

Reaction of [MCl2(CH3CN)2] (M = Pd(II), Pt(II)) compounds with N1-alkylpyridylpyrazole-derived ligands

Palladium(II) and platinum(II) complexes with N-alkylpyridylpyrazole-derived ligands, 2-(1-ethyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L¹) and 2-(1-octyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L²), cis-[MCl₂(L)] (M = Pd(II), Pt(II)), have been synthesised. Treatment of [PdCl₂(L)] (L = L¹, L²) with excess of ligand (L¹, L²), pyridine (py) or triphenylphosphine (PPh₃) in the presence of AgBF₄ and NaBPh₄ produced the following complexes: [Pd(L)₂](BPh₄)₂, [Pd(L)(py)₂](BPh₄)₂ and [Pd(L)(PPh₃)₂](BPh₄)₂. All complexes have been characterised by elemental analyses, conductivity, IR and NMR spectroscopies. The crystal structures of cis-[PdCl₂(L²)] (2) and cis-[PtCl₂(L¹)] (3) were determined by a single crystal X-ray diffraction method. In both complexes, the metal atom is coordinated by one pyrazole nitrogen, one pyridine nitrogen and two chlorine atoms in a distorted square-planar geometry. In complex 3, π-π stacking between pairs of molecules is observed.     

Metal complexes of a new class of polydentate Mannich bases: Synthesis and spectroscopic characterisation

A new class of polydentate Mannich bases featuring an N₂S₂ donor system, bis((2-mercapto-N-phenylacetamido)methyl)phosphinic acid H₃L¹ and bis((2-mercapto-N-propylacetamido)methyl)phosphinic acid H₃L², has been synthesised from condensation of phosphinic acid and paraformaldehyde with 2-mercaptophenylacetamide W1 and 2-mercaptopropylacetamide W2, respectively. Monomeric complexes of these ligands, of general formula K₂[Cr^III(Lⁿ)Cl₂], K₃[M′^II(Lⁿ)Cl₂] and K[M(Lⁿ)] (M′ = Mn(II) or Fe(II); M = Co(II), Ni(II), Cu(II), Zn(II), Cd(II) or Hg(II); n = 1, 2) are reported. The structures of new ligands, mode of bonding and overall geometry of the complexes were determined through IR, UV–Vis, NMR, and mass spectral studies, magnetic moment measurements, elemental analysis, metal content, and conductance. These studies revealed octahedral geometries for the Cr(III), Mn(II) and Fe(II) complexes, square planar for Ni(II) and Cu(II) complexes and tetrahedral for the Co(II), Zn(II), Cd(II) and Hg(II) complexes. Complex formation studies via molar ratio in DMF solution were consistent to those found in the solid complexes with a ratio of (M:L) as (1:1).     

Cytotoxic palladium(II) complexes of 8-aminoquinoline derivatives and the interaction with human serum albumin

Palladium(II) complexes are potential antitumor metallodrugs for their chemical resemblance to platinum(II) complexes. Two palladium(II) complexes (1 and 2) in the formula of [PdLⁿCl] [L¹ = N-(tert-butoxycarbonyl)-l-methionine-N′-8-quinolylamide, L² = L-alanine-N′-8-quinolylamide] have been synthesized accordingly. The structures of the complexes were fully characterized by X-ray crystallography. The palladium(II) center in 1 is coordinated by two N atoms and an S atom from L¹ with one chloride anion as the leaving group; while that in 2 is coordinated by three N atoms from L² with one chloride anion as the leaving group. The interaction between complex 1 and human serum albumin (HSA) has been investigated using fluorescence and circular dichroism spectroscopies. The complex seems to react with HSA chiefly through hydrophobic and electrostatic interactions, and it does not alter the α-helical nature of HSA. The cytotoxicity of these complexes has been tested against the human cervical cancer (HeLa), human mammary cancer (MCF-7), and human lung cancer (A-549) cell lines. Complex 1 displays a cytotoxic activity comparable to that of cisplatin, but complex 2 is less active than cisplatin.     

Interaction of free functional group with platinum(II) center in cyclometalated complexes: A structural and photophysical property investigation

A series of flexible multidentate ligands containing N,P-donor, 2-[N-(diphenylphosphino)methyl]amino-pyridine (L¹), 2-[N-bi-(diphenylphosphino) methyl]amino-pyridine (L²), 2-[N-(diphenylphosphino)methyl]amino-7-methyl-1,8-naphthyridine (L³) and 4-[(N-diphenylphosphino)methyl]amino-pyridine) (L⁴) have been synthesized. The mono- and dinuclear cyclometalated platinum(II) complexes [Pt(C^N^N)L¹]ClO₄ (HC^N^N = 6-phenyl-2,2′-bipyridine), [Pt₂(C^N^N)₂L¹](ClO₄)₂, [Pt₂(C^N^N)₂L²](ClO₄)₂, [Pt(C^N^N)L³]ClO₄ and [Pt₂(C^N^N)₂L⁴](ClO₄)₂ were prepared and their structures determined by X-ray crystal analysis. These complexes exhibit long-lived bright orange emissions ranging from 560 to 610 nm in the solid state at room temperature. In solution, dinuclear complexes have emissions with higher quantum yields than mononuclear complexes. This can be attributed to intramolecular interaction of free functional group with Pt(II) at axial position, resulting in the quenching of phosphorescence for platinum(II) complexes in the ³MLCT excited state.     

Seven-coordinate Mn(II) and Co(II) complexes of the pentadentate ligand 2,6-diacetyl-4-carboxymethyl-pyridine bis(benzoylhydrazone): Synthesis, crystal structure and magnetic properties

The metal complexation properties of a functionalized N₃O₂ donor ligand H₂L², where H₂L² stands for 2,6-diacetyl-4-carboxymethyl-pyridine bis(benzoylhydrazone), are investigated by structural and spectroscopic (IR, ESI-MS and EPR) characterization of its Mn(II) and Co(II) complexes. The ligand H₂L² is observed to react essentially in the same fashion as its unmodified parent H₂L¹ producing mixed-ligand [M(H₂L²)(Cl₂)] complexes (M = Mn^II (1), Co^II (3)) upon treatment with MCl₂. Complexes [M(HL²)(H₂O)(EtOH)]BPh₄ (M = Mn 2, M = Co 4), incorporating the supporting ligand in the partially deprotonated form (HL²)⁻, are formed by salt elimination of the [M(H₂L²)(Cl₂)] compounds with NaBPh₄. Compounds 2 and 4 are isostructural featuring distorted pentagonal-bipyramidal coordinated Mn^II and Co^II ions, with the H₂O and EtOH ligands bound in axial positions. Intermolecular hydrogen bonding interactions of the type M-OH₂?O-M involving the H₂O ligands and the carbonyl functions of the supporting ligand assembles the complexes into dimers. Temperature-dependent magnetic susceptibility measurements (2-300 K) show a substantially paramagnetic Curie behavior for the Mn²⁺ compound (2) influenced by zero-field splitting and significant orbital angular momentum contribution for 4 (high-spin Co^II). The exchange coupling across the Mn^II-OH₂?O-Mn^II bridges in 2 was found to be less than 0.1 cm⁻¹, suggesting that no significant intradimer exchange coupling occurs via this path.     

Structural, magnetic, electrochemical, catalytic, DNA binding and cleavage studies of new macrocyclic binuclear copper(II) complexes

The macrocyclic symmetrical and a series of unsymmetrical binuclear copper(II) complexes have been synthesized by using mononuclear complex [CuL] [3,3′-((1E,7E)-3,6-dioxa-2,7-diazaocta-1,7-diene-1,8-diyl)bis(3-formyl-5-methyl-2-diolato)copper(II)]. Another compartment of the [CuL] have been condensed with various diamines like 1,2-bis(aminooxy)ethane (L¹), 1,2-diamino ethane(L^2a), 1,3-diamino propane(L^2b), 1,4-diamino butane(L^2c), 1,2-diamino benzene(L^2d), 1,8-diamino naphthalene(L^2e) and characterized by elemental, spectroscopic, and X-ray crystallographic methods. The influence of the coordination geometry and the ring size of the binucleating ligands on the electronic, redox, magnetic, catecholase activity, DNA binding and cleavage properties have been studied. The molecular structures of the symmetrical binuclear complex [Cu₂L¹(H₂O)₂](ClO₄)₂ (1) and unsymmetrical binuclear complex [Cu₂L^2b(ClO₄)(H₂O)]ClO₄ (2b) were determined by X-ray crystallography. Both of them were discrete binuclear species in which each Cu(II) ions are in distorted square pyramid. The Cu?Cu distances vary from 3.0308 (2b) to 3.0361 Å (1). Electrochemical studies evidenced that two quasi-reversible one electron-transfer reduction waves −0.91 to −1.01 V, −1.26 to −1.55 V) for binuclear complexes are obtained in the cathodic region. Cryomagnetic investigation of the binuclear complexes reveals a weak antiferromagnetic spin exchange interaction between the Cu(II) ions within the complexes (−2J = 104.4-127.5 cm⁻¹). The initial rate (V_in) for the oxidation of 3,5-di-tert-butylcatechol to o-quinone by the binuclear Cu(II)complexes are in the range 3.6 × 10⁻⁵ to 7.3 × 10⁻⁵ Ms⁻¹. The binuclear Cu(II) complexes are avid binders to calf thymus DNA. The complexes display significant oxidative cleavage of circular plasmid pBR322 DNA in the presence of mercaptoethanol using the singlet oxygen as a reactive species. The aromatic diamine condensed macrocyclic ligands of copper(II) complexes display better DNA interaction and significant chemical nuclease activity than the aliphatic diamine condensed macrocyclic Cu(II) complexes.     

Synthesis,structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases

A series of new cobalt(III) complexes were prepared. They are [CoL¹(py)₃]·NO₃ (1), [CoL²(bipy)(N₃)]·CH₃OH (2), [CoL³(HL³)(N₃)]·NO₃ (3), and [CoL⁴(MeOH)(N₃)] (4), where L¹, L², L³ and L⁴ are the deprotonated form of N′-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N′-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N′-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2′-bipyridine. The complexes were characterized by infrared and UV–Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC₅₀ values of 4.27 and 0.35 μmol L⁻¹, respectively. Complex 2 has medium activity against urease, with IC₅₀ value of 68.7 μmol L⁻¹. While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed.