Interactions of praseodymium and neodymium with nucleosides and nucleotides: absorption difference and comparative absorption spectral study.

The interactions of praseodymium(III) and neodymium(III) with nucleosides and nucleotides have been studied in different stoichiometry in water and water-DMF mixtures by employing absorption difference and comparative absorption spectrophotometry. The 4f-4f bands were analysed by linear curve analysis followed by gaussian curve analysis, and various spectral parameters were computed, using partial and multiple regression method. The magnitude of changes in both energy interaction and intensity were used to explore the degree of outer and inner sphere coordination, incidence of covalency and the extent of metal 4f-orbital involvement in chemical bonding. Crystalline complexes of the type [Ln(nucleotide)2(H2O)2]- (where nucleotide--GMP or IMP) were characterized by IR, 1H NMR, 31P NMR data. These studies indicated that the binding of the nucleotide is through phosphate oxygen in a bidentate manner and the complexes undergo substantial ionisation in aqueous medium, thereby supporting the observed weak 4f-4f bands and lower values for nephelauxetic effect (1-beta), bonding (b) and covalency (delta) parameters derived from coulombic and spin orbit interaction parameters.     

Antibacterial activity and spectral studies of trivalent chromium, manganese, iron macrocyclic complexes derived from oxalyldihydrazide and glyoxal

A new series of complexes is synthesized by template condensation of oxalyldihydrazide and glyoxal in methanolic medium in the presence of trivalent chromium, manganese and iron salts forming complexes of the type: [M(C(8)H(8)N(8)O(4))X]X(2) where M = Cr(III), Mn(III), Fe(III) and X = Cl(-1), NO(-1)(3), CH(3)COO(-1). The complexes have been characterized with the help of elemental analyses, conductance measurements, magnetic susceptibility measurements, electronic, NMR, infrared and far infrared spectral studies. On the basis of these studies, a five coordinate square pyramidal geometry for these complexes has been proposed. The biological activities of the metal complexes were tested in vitro against a number of pathogenic bacteria and some of the complexes exhibited remarkable antibacterial activities.     

Synthesis, spectroscopic, and antitumor activity of metal chelates of S-methyl-N-(l-isoquinolyl)-methylendithiocarbazate

Complexes of Mn(III), Fe(III), Fe(II), Co(III), Ni(II), Cu(II), Zn(II), and Pt(II) with S-methyl-N-(l-isoquinolyl) methylendithiocarbazate (N-N-SH) were isolated and characterized by elemental analysis, conductance measurement, magnetic susceptibilities, and spectroscopic studies. On the basis of these studies, a highly distorted, high-spin, chloro-bridged, polymeric octahedral structure for [Mn(N-N-S)Cl2]; a distorted, low-spin, monomeric octahedral structure for [Fe(N-N-S)2]; a distorted, high-spin, octahedral structure for [Ni(N-N-S)2]; and a square-planar structure for [M(N-N-S)X] (M = Ni, Cu, Pt or Zn and X = Cl- or -OAc) are suggested. With Fe(III), the complex [Fe(N-N-S)2][FeCl4] was isolated while the Co(II) was oxidized to yield the Co(III) ion as [Co(N-N-S)2]2[CoCl4]. All these complexes were screened for their antitumor activity against P 388 lymphocytic leukemia test system in mice. Except for Mn(III), Fe(III), and Co(III) complexes, all were found to possess significant activity; the Cu(II) and Zn(II) complexes showed a T/C% value of 160 and 195, respectively, at their optimum dosages.     

Synthesis, characterization, and antitumor activity of iron(II) and iron(III) complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones

Complexes of iron(II) and iron(III) with 1-formylisoquinoline thiosemicarbazone (1-iqtsc-H), 4-methyl-5-amino-1-formylisoquinoline thiosemicarbazone (4-Me-5-NH2-1-iqtsc-H) and 4-(m-aminophenyl)-2-formylpyridine thiosemicarbazone (4-m-NH2ph-2-pytsc-H) were synthesized and characterized by elemental analysis, conductance measurements, magnetic susceptibilities (from room temperature down to liquid N2 temperature), and M?ssbauer, electronic, and infrared spectral studies. On the basis of these studies, a highly distorted, high-spin, five-coordinate structure for Fe(HL)SO4 (HL = 1-iqtsc-H, 4-Me-5-NH2-1-iqtsc-H or 4-m-NH2ph-2-pytsc-H) and a distorted, low-spin, octahedral structure for Fe(HL)Cl2 are suggested. The EPR spectra of iron(III) complexes show that all have dxy low-spin ground state. All these complexes have been screened for their antitumor activity against the P 388 lymphocytic leukemia test system in mice and have been found to possess significant activity at the dosages employed.     

Recent developments in ruthenium anticancer drugs

Interest in Ru anticancer drugs has been growing rapidly since NAMI-A ((ImH(+))[Ru(III)Cl(4)(Im)(S-dmso)], where Im = imidazole and S-dmso = S-bound dimethylsulfoxide) or KP1019 ((IndH(+))[Ru(III)Cl(4)(Ind)(2)], where Ind = indazole) have successfully completed phase I clinical trials and an array of other Ru complexes have shown promise for future development. Herein, the recent literature is reviewed critically to ascertain likely mechanisms of action of Ru-based anticancer drugs, with the emphasis on their reactions with biological media. The most likely interactions of Ru complexes are with: (i) albumin and transferrin in blood plasma, the former serving as a Ru depot, and the latter possibly providing active transport of Ru into cells; (ii) collagens of the extracellular matrix and actins on the cell surface, which are likely to be involved in the specific anti-metastatic action of Ru complexes; (iii) regulatory enzymes within the cell membrane and/or in the cytoplasm; and (iv) DNA in the cell nucleus. Some types of Ru complexes can also promote the intracellular formation of free radical species, either through irradiation (photodynamic therapy), or through reactions with cellular reductants. The metabolic pathways involve competition among reduction, aquation, and hydrolysis in the extracellular medium; binding to transport proteins, the extracellular matrix, and cell-surface biomolecules; and diffusion into cells; with the extent to which individual drugs participate in various steps along these pathways being crucial factors in determining whether they are mainly anti-metastatic or cytotoxic. This diversity of modes of action of Ru anticancer drugs is also likely to enhance their anticancer activities and to reduce the potential for them to develop tumour resistance. New approaches to metabolic studies, such as X-ray absorption spectroscopy and X-ray fluorescence microscopy, are required to provide further mechanistic insights, which could lead to the rational design of improved Ru anticancer drugs.     

Synthesis and physicochemical studies of polymeric coordination complexes of some lanthanides with 1,4-dihydroxyanthraquinone

Coordination polymers of lanthanum(III), praseodymium(III), neodymium(III), samarium(III), dysprosium(III) and holmium(III) with 1,4-dihydroxyanthraquinone have been synthesized and characterised. Their magnetic moments, infrared spectra and electronic spectra have been studied to establish their structure. All the polychelates are amorphous, dark coloured powders, insoluble in common organic solvents and sparingly soluble in dimethylformamide. Nephelauxetic ratio (β), covalency factor (b^1/2), etc. have been evaluated wherever possible. Thermogravimetric studies (TGA) indicate a higher decomposition temperature of polychelates than the parent ligand. A.c.-conductivity, dielectric constant (ϵ′), dielectric loss (ϵ″), all at various frequencies, as well as d.c.-conductivity of the prepared polychelates, are reported. The analytical data are suggestive of a 2:3 metal-ligand stoichiometry in the polychelates.     

Cobalt complexes of terpyridine ligand: crystal structure and photocleavage of DNA

Two new cobalt complexes, [Co(pytpy)(2)](ClO(4))(2), 1, and [Co(pytpy)(2)](ClO(4))(3), 2 where pytpy=pyridine terpyridine, have been synthesized and characterized. Single-crystal X-ray structure of both the complexes has been resolved. The structure shows the complexes to be a monomeric cobalt(II) and cobalt(III) species with two pytpy ligands coordinated to the metal ion to give a six coordinate complex. Both cobalt(II) and cobalt(III) complexes crystallize in meridional configuration. The interaction of these complexes with calf thymus DNA has been explored by using absorption, emission spectral, electrochemical studies and viscosity measurements. From the experimental results the DNA binding constants of 1 and 2 are found to be (1.97+/-0.15)x10(4)M(-1) and (2.7+/-0.20)x10(4)M(-1) respectively. The ratio of DNA binding constants of 1 and 2 have been estimated to be 0.82 from electrochemical studies, which is in close agreement with the value of 0.73 obtained from spectral studies. The observed changes in viscosity of DNA in the presence of increasing amount of complexes 1 and 2 suggest intercalating binding of these complexes to DNA. Results of DNA cleaving experiments reveal that complex 2 efficiently cleaves DNA under photolytic conditions while complex 1 does not cleave DNA under similar conditions.     

Antibacterial activity and spectral studies of trivalent chromium,manganese, iron macrocyclic complexes derived from oxalyldihydrazide and glyoxal

A new series of complexes is synthesized by template condensation of oxalyldihydrazide and glyoxal in methanolic medium in the presence of trivalent chromium, manganese and iron salts forming complexes of the type: [M(C₈H₈N₈O₄)X]X₂ where M = Cr(III), Mn(III), Fe(III) and X = Cl^{? 1}, , CH₃COO^{? 1}. The complexes have been characterized with the help of elemental analyses, conductance measurements, magnetic susceptibility measurements, electronic, NMR, infrared and far infrared spectral studies. On the basis of these studies, a five coordinate square pyramidal geometry for these complexes has been proposed. The biological activities of the metal complexes were tested in vitro against a number of pathogenic bacteria and some of the complexes exhibited remarkable antibacterial activities.     

Altered expression of HES-1, BETA2/NeuroD, and PDX-1 is involved in impaired insulin synthesis induced by glucocorticoids in HIT-T15 cells

Rat tail tendon (RTT) collagen has been reacted with a homologous series of chromium(III) complexes viz., (H2O)(4)Cr(OH)(2)Cr(H2O)(4+)(4) 1 (dimer), Cr(3)(OH)(4)(H2O)(5+)(9) 2 (trimer), and Cr(4)(OH)(4)(O2)(H2O)(4+)(12) 3 (tetramer), and the structural alterations brought about by these complexes have been investigated through atomic force microscopy (AFM) and circular dichroism (CD) studies. Examination of Cr(III)-treated tendons using AFM revealed changes in the D-periodicity of collagen, which may arise due to differences in the topological distribution of various Cr(III) complexes. Evidence for organisation of monomeric collagen into quarter staggered fibrils in the presence of Cr(III) dimer, 1, has been obtained. The quaternary structural changes induced by chromium in the protein have been correlated to the conformational changes of collagen in the absence of denaturation.     

Evaluating hydrogen bond interactions in enzymes containing Mn(III)-histidine complexation using manganese-imidazole complexes

It is often difficult to control hydrogen bond interactions in small molecule compounds that model metalloenzyme active sites. The imidazole-containing ligands 4,5-dicarboxyimidazole (H(3)DCBI) and 4,5-dicarboxy- N-methylimidazole (H(2)MeDCBI) allow examination of the effects of internal hydrogen bonding between carboxylate and imidazole nitrogen atoms. A new series of mononuclear manganese imidazole complexes have been prepared using these ligands: Mn(III)(salpn)(H(2)DCBI)(DMF) (1), Mn(III)(salpn)(HMeDCBI) (2), Mn(III)(dtsalpn)(HMeDCBI) (3), [Mn(IV)(dtsalpn)(HMeDCBI)]PF(6) (4), Mn(III)(salpn)(H(2)DCBI) (5), Mn(III)(dtsalpn)(H(2)DCBI) (6), and Mn(IV)(dtsalpn)(H(2)DCBI)PF(6) (8). Complexes 1, 2, 3, 5, and 6 have been prepared by direct reaction of salpn [salpn=(salicylideneaminato)-1,3-diaminopropane)] or dtsalpn [dtsalpn=(3,5-di- t-butylsalicylideneaminato)-1,3-diaminopropane)] and H(3)DCBI and H(2)MeDCBI with Mn(III) acetate, while complexes 4 and 8 were made by bulk electrolysis of complex 3 or 6 in dichloromethane. Complexes 1, 2, and 6 were characterized by X-ray diffraction. The impact of hydrogen bonding interactions of the complexes has been demonstrated by X-ray diffraction, cyclic voltammetry, and EPR spectroscopy. In all complexes the central metal ion is present in a six-coordinate geometry. Magnetic susceptibility measurements confirm the spin and oxidation states of the complexes. The cyclic voltammograms of 3 and 6 in dichloromethane reveal single, reversible redox waves with E(1/2)=600 mV and 690 mV, respectively. The X-band EPR spectrum of 4 shows a broad signal around g=4.4, and the corresponding complex 8 possesses a broad signal at slightly lower field ( g=5.5) than 4. These studies demonstrate that even small changes in the effective charge of the imidazole ligand can have a profound impact on the structure, spectroscopy, and magnetism of manganese(IV) complexes. We use these observations to present a model that may explain the origin of the g=4.1 signal in the S(2) state of photosystem II.     

Preparation of Rh[16aneS4-diol](211)At and Ir[16aneS4-diol](211)At complexes as potential precursors for astatine radiopharmaceuticals. Part I: Synthesis

The goal of this study was to evaluate a new approach that can be applied for labeling biomolecules with (211)At. Many astatine compounds that have been synthesized are unstable in vivo, providing motivation for seeking different (211)At labeling strategies. The approach evaluated in this study was to attach astatide anions to soft metal cations, which are also complexed by a bifunctional ligand. Ultimately, this complex could in principle be subsequently conjugated to a biomolecule with the proper selection of ligand functionality. We report here the attachment of (211)At(-) and *I(-) (*I = (131)I or (125)I) anions to the soft metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13-tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I(-) anions were used for preliminary studies directed at the optimization of reaction conditions and to provide a baseline for comparison of results with (211)At. Four complexes Rh[16aneS4-diol]*I/(211)At and Ir[16aneS4-diol]*I/(211)At were synthesized in high yield in a one-step procedure, and the products were characterized mainly by paper electrophoresis and reversed-phase HPLC. The influences of time and temperature of heating and concentrations of metal cations and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were determined. Yields of about 80% were obtained when the quantities of Rh(III) or Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250 nmol, respectively, and the pH ranged 3.0-4.0. Syntheses required heating for 1-1.5 h at 75-80 degrees C. The influence of microwave heating on the time and completeness of the complexation reaction was evaluated and compared with the conventional method of heating in an oil bath. Microwave synthesis accelerates reactions significantly. With microwave heating, yields of about 75% for Rh[16aneS4-diol](131)I and Ir[16aneS4-diol](131)I complexes were obtained after only 20 min exposure of the reaction mixtures to microwave radiation. In conclusion, this study has shown that it is possible to attach an astatide anion to soft metal cations in a simple and fast one-step procedure, with high yields. These complexes will be evaluated as reagents for labeling biomolecules.     

Multidimensional NMR methods for protein structure determination

Structural studies of proteins are critical for understanding biological processes at the molecular level. Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for obtaining structural and dynamic information on proteins and protein-ligand complexes. In the present review, methodologies for NMR structure determination of proteins and macromolecular complexes are described. In addition, a number of recent advances that reduce the molecular weight limitations previously imposed on NMR studies of biomolecules are discussed, highlighting applications of these technologies to protein systems studied in our laboratories.     

Rare earth metal complexes of cytidine

The interactions of La(III), Pr(III), Nd(III), Sm(III), Gd(III), Dy(III) and Er(III) and cytidine with glycine, histidine and oxalic acid for the formation of binary (1:1) and ternary complexes (1:1:1) have been investigated by potentiometric equilibrium measurements at 35 °C and 0.10 mol dm⁻³ (KNO₃) ionic strength. These investigations were undertaken to assess the influences of charge on the structure and stability of metal nucleoside complexes in solution. Cytidine forms more stable complexes with trivalent lanthanones compared to bivalent transition metal ions. This is explained on the basis of the differences in the charge of the metal ions concerned. The ternary complexes of these systems are more stable than the corresponding binary complexes. This enhanced stability is measured in terms of ΔlogK (difference between the stability of overall (1:1:1) and binary (1:1)). Based on the trends in ΔlogK values, various factors that affect the stability of these complexes have been explained.     

Respiratory chain supercomplexes in plant mitochondria

Supercomplexes are defined associations of protein complexes, which are important for several cellular functions. This "quintenary" organization level of protein structure recently was also described for the respiratory chain of plant mitochondria. Except succinate dehydrogenase (complex II), all complexes of the oxidative phosphorylation (OXPOS) system (complexes I, III, IV and V) were found to form part of supercomplexes. Compositions of these supramolecular structures were systematically investigated using digitonin solubilizations of mitochondrial fractions and two-dimensional Blue-native (BN) polyacrylamide gel electrophoresis. The most abundant supercomplex of plant mitochondria includes complexes I and III at a 1:2 ratio (I1 + III2 supercomplex). Furthermore, some supercomplexes of lower abundance could be described, which have I2 + III4, V2, III2 + IV(1-2), and I1 + III2 + IV(1-4) compositions. Supercomplexes consisting of complexes I plus III plus IV were proposed to be called "respirasome", because they autonomously can carry out respiration in the presence of ubiquinone and cytochrome c. Plant specific alternative oxidoreductases of the respiratory chain were not associated with supercomplexes under all experimental conditions tested. However, formation of supercomplexes possibly indirectly regulates alternative respiratory pathways in plant mitochondria on the basis of electron channeling. In this review, procedures to characterize the supermolecular organization of the plant respiratory chain and results concerning supercomplex structure and function are summarized and discussed.     

Biological activity of complexes derived from pyridine-2-carbaldehyde thiosemicarbazone. Structure of

Biological studies on [Fe(L)2](NO3).0.5H2O (1), [Fe(L)2][PF6] (2), [Co(L)2](NCS) (3), [Ni(HL)2]Cl2.3H2O (4) and Cu(L)(NO3) (5), where HL=C7H8N4S, pyridine-2-carbaldehyde thiosemicarbazone, have been carried out. The crystal structure of compound 3 has been solved. It consists of discrete monomeric cationic entities containing cobalt(III) ions in a distorted octahedral environment. The metal ion is bonded to one sulfur and two nitrogen atoms of each thiosemicarbazone molecule. The thiocyanate molecules act as counterions. The copper(II) and iron(III) complexes react with reduced glutathione and 2-mercaptoethanol. The reaction of compound 1 with the above thiols causes the reduction of the metal ion and bis(thiosemicarbazonato)iron(II) species are obtained. The redox activity, and in particular the reaction with cell thiols, seems to be related to the cytotoxicity of these complexes against Friend erithroleukemia cells and melanoma B16F10 cells.     

Synthesis,spectroscopic, and antibacterial activity of tetraazamacrocyclic complexes of trivalent chromium,manganese, and iron

A new series of macrocyclic complexes of type [M(TML)X]X₂, where M = Cr(III), Mn(III), or Fe(III), TML is tetradentate macrocyclic ligand, and X = Cl^?, NO₃^?, CH₃COO^? for Cr(III), Fe(III) and X = CH₃COO^? for Mn (III), has been synthesized by condensation of benzil and succinyldihydrazide in the presence of metal salt. The complexes have been so formulated due to the 1:2 electrolytic nature of these complexes as shown by conductivity measurements. The complexes have been characterized with the help of various physicochemical techniques such as elemental analysis, molar conductance, electronic and infrared spectral studies, and magnetic susceptibility. On the basis of these studies, a five-coordinate distorted square pyramidal geometry, in which two nitrogens and two carbonyl oxygen atoms are suitably placed for coordination toward the metal ion, has been proposed for all the complexes. The complexes have been tested for their in vitro antibacterial activity. Some of the complexes show remarkable antibacterial activities against some selected bacterial strains. The minimum inhibitory concentrations shown by these complexes have been compared with those shown by some standard antibiotics such as linezolid and cefaclor.     

New complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin

New solid complex compounds of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin were synthesized. The molecular formula of the complexes is Ln(C₁₅H₉O₇)₃ · nH₂O, where Ln is the cation of lanthanide and n = 6 for La(III), Sm(III), Gd(III) or n = 8 for Ce(III), Pr(III), Nd(III) and Eu(III). Thermogravimetric studies and the values of dehydration enthalpy indicate that water occurring in the compounds is not present in the inner coordination sphere of the complex. The structure of the complexes was determined on the basis of UV-visible, IR, MS, ¹H NMR and ¹³C NMR analyses. It was found that in binding the lanthanide ions the following groups of morin take part: 3OH and 4CO in the case of complexes of La, Pr, Nd, Sm and Eu, or 5OH and 4CO in the case of complexes of Ce and Gd. The complexes are five- and six-membered chelate compounds.     

A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast

Whereas the majority of disease-related mitochondrial DNA mutations exhibit significant biochemical and clinical heterogeneity, mutations within the mitochondrially encoded human cytochrome b gene (MTCYB) are almost exclusively associated with isolated complex III deficiency in muscle and a clinical presentation involving exercise intolerance. Recent studies have shown that a small number of MTCYB mutations are associated with a combined enzyme complex defect involving both complexes I and III, on account of the fact that an absence of assembled complex III results in a dramatic loss of complex I, confirming a structural dependence between these two complexes. We present the biochemical and molecular genetic studies of a patient with both muscle and brain involvement and a severe reduction in the activities of both complexes I and III in skeletal muscle due to a novel mutation in the MTCYB gene that predicts the substitution (Arg318Pro) of a highly conserved amino acid. Consistent with the dramatic biochemical defect, Western blotting and BN-PAGE experiments demonstrated loss of assembled complex I and III subunits. Biochemical studies of the equivalent amino-acid substitution (Lys319Pro) in the yeast enzyme showed a loss of enzyme activity and decrease in the steady-state level of bc1 complex in the mutant confirming pathogenicity.     

Template synthesis,spectroscopic, antibacterial,and antifungal studies of trivalent transition metal ion macrocyclic complexes

A novel series of complexes of the type [M(C₃₆H₂₂N₆)X]X₂, where M = Cr(III), Mn(III), Fe(III); X = Cl^?, NO₃^?, CH₃COO^?; and (C₃₆H₂₂N₆) corresponds to the tetradentate macrocyclic ligand, have been synthesized by condensation of 1,8-diaminonaphthalene and isatin in the presence of trivalent metal salts in methanolic medium. The complexes have been characterized by elemental analysis, conductance and magnetic measurements, and UV/Vis, IR, and mass spectroscopy. On the basis of these studies, a five coordinate square pyramidal geometry for all of these complexes is proposed. All synthesized macrocyclic complexes have been tested for in vitro antimicrobial activities against some pathogenic bacterial strains, viz. Staphylococcus aureus, Bacillus subtilis (Gram-positive), Escherichia coli, Pseudomonas aeruginosa (Gram-negative), and two fungal strains, viz. Aspergillus niger, Aspergillus flavus. The MICs shown by the complexes against these microbial strains have been compared with MICs shown by standard antibiotic ciprofloxacin and the antifungal drug amphotericin-B.     

Complexation of iron(III) and iron(II) by citrate. Implications for iron speciation in blood plasma

Estimates of the concentrations and identity of the predominant complexes of iron with the low-molecular-mass ligands in vivo are important to improve current understanding of the metabolism of this trace element. These estimates require a knowledge of the stability of the iron-citrate complexes. Previous studies on the equilibrium properties of the Fe(III)-citrate and Fe(II)-citrate are in disagreement. Accordingly, in this work, glass electrode potentiometric titrations have been used to re-determine the formation constants of both the Fe(III)- and Fe(II)-citrate systems at 25 degrees C in 1.00 M (Na)Cl and the reliability of these constants has been evaluated by comparing the measured and predicted redox potentials of the ternary Fe(III)-Fe(II)-citrate system. The formation constants obtained in this way were used in computer simulation models of the low-molecular-mass iron fraction in blood plasma. Redox equilibria of iron are thus included in large models of blood plasma for the first time. The results of these calculations show the predominance of Fe(II)-carbonate complexes and a significant amount of aquated Fe(II) in human blood plasma.