Binding of iodomercurates to sulfhydryl-blocked beta-lactoglobulin-A, -B, and -C

Sulfhydryl-blocked beta-lactoglobulins (beta-LG-S-SCH2CH2OH)-A, -B, and -C bind only one iodomercurate species, HgI3-, at only one site, with a dissociation constant of 4.0 X 10(-5) M at 25 degrees, pH 5.0, 0.10 ionic strength. (Binding to native beta-LG-SH-A, -B, and -C is more complex, involving the sulfhydryl and two other sites and several iodomercurates.) The red shift of the HgI3- spectrum on binding would ordinarily suggest a hydrophobic site, but the HgI3- site is distinct from, and independent of, the alkane-binding site of native and blocked beta-LG; HgI3- may bind a group that shifts its trigonal planar structure toward the tetrahedron of HgI4(2-). Binding of HgI3- to blocked beta-LG interferes with the well-known association of beta-LG-A to octamers at pH 4.6 and low temperature. The relation of the HgI3- site to the crystallographic iodomercurate-binding sites of beta-LG-SH is examined. To facilitate these and future studies of iodomercurate binding, the 200-400 nm spectra of HgI2, HgI3-, and HgI4(2-) in aqueous solutions and the thermodynamic formation constants at 25 degrees for the equilibria HgI2 + I- = HgI3- (4.9 X 10(3) M-1) and HgI3- + I- = HgI4(2-) (0.118 X 10(3) M-1) were obtained.     

Complexes of d(+)-biotin with Pd(II) and Pt(II)

The reactions of d(+)-biotin with K₂MX₄, where M = Pd(II) or Pt(II) and X = Cl or Br have been studied in acidic, neutral or alkaline aqueous solutions. Complexes of the type trans-M(Bio)₂X₂ have been isolated for both metals and characterized with elemental analyses, conductivity measurments, ir spectra, ¹Hnmr and ¹³Cnmr spectra. The complex of the type [Pd(Bio)Cl₂]₂ has also been isolated from DMF solutions. The results indicate that d(+)-biotin coordinates exclusively through its sulfur atom with these metals in all the complexes in the present study, in the solid state or in solution.     

Adriamycin Complexes of Pd(II) and Pt(II)

Perturbations of the ¹H NMR spectrum of the free base of Adriamycin in DMF solution were found when MCl₂(DMF)₂ (M = Pd or Pt) was added to the Adriamycin solutions. These perturbations were greatest for the 3' proton on the sugar ring and the effect decreased as the distance from this site increased. No changes were observed in the NMR spectrum of the rest of the molecule nor was there any color change when the metal solutions were added. This is interpreted as evidence that Adriamycin binds to these metals at the 3 ' amino group in DMF solution and that there is no reaction at the chromophore. The complexes were found to be in the fast exchange regime on the NMR time scale. As well, some products were isolated from reactions of Adriamycin with MCl₂(DMF)₂ in 20% MeOH/CH₂Cl₂ and MCl₂ in DMF solution. They were characterized by their elemental analyses, as well as by ¹H NMR and infrared spectroscopies.     

Metal anthracycline complexes as a new class of anthracycline derivatives. Pd(II)-adriamycin and Pd(II)-daunorubicin complexes: physicochemical characteristics and antitumor activity

Pd(II) complexes of two anthracyclines, adriamycin and daunorubicin, have been studied. Using potentiometric absorption, fluorescence, and circular dichroism measurements, we have shown that adriamycin can form two complexes with Pd(II). The first complex (I) involves two molecules of drug per Pd(II) ion; one of the molecules is chelated to Pd(II) through the carbonyl oxygen on C12 and the phenolate oxygen on C11, and the other one is bound to Pd(II) through the nitrogen of the amino sugar. This complexation induces a stacking of the two molecules of drug. In the second complex (II), two Pd(II) ions are bound to two molecules of drug (A1 and A2). One Pd(II) is bound to the oxygen on the carbons C11 and C12 of molecule A1 and the amino sugar of molecule A2 whereas the second Pd(II) ion is bound to the oxygen on C11 and C12 of molecule A2 and the amino sugar of molecule A1. The same complexes are formed between Pd(II) and daunorubicin. The stability constant for complex II is beta = (1.3 +/- 0.5) X 10(22). Interaction with DNA has been studied, showing that almost no modification of the complex occurred. This complex displays antitumor activity against P-388 leukemia that compares with that of the free drug. Complex II, unlike adriamycin, does not catalyze the flow of electrons from NADH to molecular oxygen through NADH dehydrogenase.     

Synthesis, characterization, interaction with DNA and cytotoxicity in vitro of dinuclear Pd(II) and Pt(II) complexes dibridged by 2,2'-azanediyldibenzoic acid

The dinuclear complexes [Pd₂(L)₂(bipy)₂] (1), [Pd₂(L)₂(phen)₂] (2), [Pt₂(L)₂(bipy)₂] (3) and [Pt₂(L)₂(phen)₂] (4), where bipy = 2,2′-bipyridine, phen = 1,10-phenanthroline and L = 2,2′-azanediyldibenzoic dianion) dibridged by H₂L ligands have been synthesized and characterized. The binding of the complexes with fish sperm DNA (FS-DNA) were investigated by fluorescence spectroscopy. The results indicate that the four complexes bound to DNA with different binding affinity, in the order complex 4 > complex 3 > complex 2 > complex 1, and the complex 3 binds to DNA in both coordination and intercalative mode. Gel electrophoresis assay demonstrates the ability of the complexes to cleave the pBR 322 plasmid DNA. The cytotoxic activity of the complexes was tested against four different cancer cell lines. The four complexes exhibited cytotoxic specificity and significant cancer cell inhibitory rate.     

Binding of Cu(II) to non-prosthetic sites in ceruloplasmin and bovine serum albumin

The binding of Cu(II) to native human, porcine, bovine and ovine ceruloplasmin (Cp) and to bovine serum albumin (bSA) has been studied at pH 7.4, 30 mM barbital buffer. The results were analyzed for the strength and the number of binding sites using Scatchard plots. Evidence for additional copper binding sites in Cp and bSA was obtained suggesting a role for copper ion in the homeostatic regulation of Cu(II) and other metal ions in the serum. In the binding studies the Cp was freed of exogenous Cu(II) by passing it over a Chelex-100 column. Two flow rates were used, 4 ml/hr and 40 ml/hr, which removed Cu(II) of different affinities. Cp passed at the slower flow rate (Cp4) only contained the prosthetic copper atoms. Cp passed at the faster flow rate (Cp40) contained one additional copper atom with a Ka approximately 10(7) M-1. Another 2-6 Cu(II) ion could be added to the Cp40 with an average affinity of about Ka approximately 10(5) M-1. The Cu(II) ions found in Cp provide two distinguishable classes: (1) the prosthetic copper atoms and (2) the exogenous copper atoms that can be removed by Chelex-100. For bSA one copper atom was bound strongly with a Ka value approaching 10(12) - 10(13) M-1 and was not removed by Chelex-100 at any flow rate. A second copper atom was found with a Ka = 5.2 x 10(6) M-1 and was removed by Chelex-100 at 4 ml/hr. Three additional copper atoms were bound with a Ka = 1.6 x 10(5) M-1; they were readily removed by Chelex-100 at 40 ml/hr but were nondialysable.     

Binding of Hg(II) to poly(dA): poly(dT) and its component single strands

Mercuric binding studies at pH 10 revealed that poly(dA): poly(dT) exhibits a more dramatic absorption spectral alteration than the alternating polymer poly(dA-dT):poly(dA-dT) and induces a unique intense positive CD band at 296 nm during the spectral titrations. Comparative studies with its component single strands suggest that the spectral alterations exhibited by poly(dA): poly(dT) are consistent with a binding model in which the mercuric ions initially bind to thymines and cause the eventual strand separation of the duplex, with subsequent high cooperative binding to the poly(dA) strands. This interpretation is supported by the binding isotherms indicating much stronger mercuric binding to poly(dT) than to poly(dA), with saturation binding densities of 1 Hg(II) per 2 bases and 1 Hg(II) per base, respectively, and very high binding cooperativity for poly(dA). Striking spectral alterations are exhibited by the mercuric binding to poly(dA), likely the consequence of binding to the amino group of dA in an alkaline solution. The mononucleoside dA exhibits minor spectral alterations upon similar mercuric chloride additions whereas the dinucleoside monophosphate d(AA) exhibits significant spectral changes, albeit less pronounced than those of poly(dA). Some sequence effects on the mercuric binding are observed in the dinucleotide studies. Our CD results on the mercuric binding to polynucleotides do not support the contention of (psi)-type condensed complex formation.     

DNA Interaction and photonicking properties of DNA-targeted acridine (2,2'-Bipyridine)platinum(II) complexes

Synthesis of two (2,2'-bipyridine)platinum(II) complexes tethered to one or two acridine chromophores is reported. These acridine complexes efficiently unwind and photocleave supercoiled plasmid DNA under physiological conditions of temperature and pH.     

Pyrrolidine dithiocarbamates of Pd(II)

The dithioester (CH₂)₄NCS₂CH₃ (PyDTM, 1-pyrrolidinecarbodithioate methyl ester) has been prepared by reaction of the parent ammonium salt with methyl iodide in water/ethanol. The reaction of PyDTM with PdCl₂ allowed to synthesize either [PdCl₂(PyDTM)], in which the ligand is chelated by both sulfur atoms, or [PdCl₂(PyDTM)₂], in which the ligand acts as monodentate through the thiocarbonyl sulfur. Thermal degradation of [PdCl₂(PyDTM)] yielded the [PdCl(PyDT)]_n species as an intermediate, which, in the presence of donors as chloride ions or dimethyl sulfoxide (DMSO), gave the complexes [PdCl(PyDT)(DMSO)] and NR₄[PdCl₂(PyDT)]. Moreover, PyDTM was found to react with various [PdCl(dithiocarbamato)]_n intermediates to form the mixed species [PdCl(dithiocarbamato)(PyDTM)], whose thermal degradation yielded the [Pd(dithiocarbamato)(PyDT)] complexes. The behaviour of the prepared compounds in either solution or solid phase has been described on the basis of IR and proton NMR spectra and thermogravimetric analysis (TG and DTA).     

Antiproliferative activity of Pt(II) and Pd(II) phosphine complexes with thymine and thymidine

Oxidative addition reactions between [M(PPh(3))(4)] (M=Pt and Pd) and N1-methylthymine (t)/3',5'-di-O-acetylthymidine (T) were carried out to give [M(II)(PPh(3))(2)Cl t (or T)] complexes, in which the metal is coordinated to the N3 of the base. All complexes were characterized by spectroscopic analyses (IR, NMR) and Fast Atom Bombardment mass spectrometry (FAB-MS); X-ray data for the thymine complexes and elemental analysis for the thymidine complexes are reported. The antiproliferative activity of the complexes was tested on human chronic myelogenous leukaemia K562 cells. Arrested polymerase-chain reaction analysis was carried on to correlate antiproliferative activity and inhibition of DNA replication. All Pd and Pt complexes exhibit antiproliferative activity, Pd complexes resulting always more active than Pt complexes. Arrested PCR data are strongly in agreement with the effects on cell growth, suggesting that inhibition of the DNA replication by the synthesized compounds is the major basis for their in vitro antiproliferative activity.     

Stabilities and 1H NMR studies of (diethylenetriamine)Pd(II) and (1,1,4,7,7-pentamethyldien)Pd(II) with nucleosides and related ligands

Plots of stability constant logarithms versus pK_a for dienPd²⁺ binding to a variety of nitrogen heterocycles yield straight lines, all of 0.67 slope. Points for binding at pyridine like purine N1 and pyrimidine N3 nitrogens in nucleosides and 5′-mononucleotides fall on a single straight line. The base line for binding at imidazole like purine N7 nitrogens is 0.8 log units stronger than for N1 binding. N7 binding to purine bases with a 6-oxo group is enhanced by 1.6 log units above the N7 base line. The presence of a 5′-phosphate group enhances N7 binding (but not N1 binding) by 0.5–0.7 log units. Weaker binding occurs with pmdienPd²⁺ and the straight line slopes are 0.79. The N7 base line rises 1.2 log units above the N1 line. Presence of the 6-oxo group enhances pmdien binding by 2.3 units ruling out a significant coordinated dien hydrogen bond to the 6-oxo group. There is no enhancement of pmdienPd²⁺ binding to N7 due to the 5′-phosphate of nucleotides. This result suggests that the 0.5–0.7 log unit enhancement for dienPd²⁺ is due to a hydrogen bond from coordinated dien to the phosphate. Due to the terminal methyl groups, rotation of pyrimidines, benzimidazole, and purines is restricted in pmdienPd²⁺ complexes and two rotamers are evident in proton magnetic resonance spectra. With benzimidazole and purine nucleosides and 5′-nucleotides there is an approximately 2:1 mole ratio of the two rotamers. Nuclear Overhauser effect experiments and chemical shift analysis permit identification of all peaks for pmdien methyl groups and aromatic ring protons.     

Rapid synthesis of bis (2,2′-bipyridine) nitratocopper(II) nitrate using a hydrothermal method and its application to dye-sensitized solar cells

In this study we synthesized bis (2,2′-bipyridine) nitratocopper(II) nitrate in order to examine its the crystal structure, optical property and application to dye-sensitized solar cells (DSSCs). Single X-ray analysis results revealed that the acquired complex exhibited five-coordination with four nitrogen atoms of bipyridine and the oxygen bond of the ion. The reflectance UV-Vis absorptions showed three absorptions that were assigned to ligand-to-ligand at around 230-350 nm, metal-to-ligand charge transfer at around 350-600 nm, and d-d transfer at around ∼650 nm. Cyclic voltammetry in acetonitrile revealed a reversible Cu(I) → Cu(II) oxidation process at a highest occupied molecular orbital (HOMO) and a lowest unoccupied molecular orbital (LUMO) levels of −4.692 and −4.071 eV, respectively. The photoelectric efficiency in DSSCs was approximately 0.032% with the nanometer-sized TiO₂ in the condition of an open-circuit voltage (V_oc) of 0.346 V, a short-circuit current density (J_sc) of 0.166 mA/cm² at an incident light intensity of 100 mW/cm².     

Pd(II) and Pt(II) complexes with aromatic diamines: study of their interaction with DNA

Pd(II) and Pt(II) new complexes with simple aromatic diamines were synthesised and characterised with the aim of studying their possible antitumour activity. The aromatic diamines chosen were 2,3-diaminotoluene (2,3 dat), 3,4-diaminotoluene (3,4 dat), 4,5-diaminoxylene (4,5 dax) and 2,3-diaminophenol (2,3 dap). The complexes, of formulae cis-[MCl(2)(diamine)], were characterised by elemental analysis, conductivity measurements, 1H, 13C(1H) and 195Pt NMR spectroscopy. The X-ray crystal structure was also resolved for the palladium complexes with 2,3-diaminotoluene and 4,5-diaminoxylene. The DNA adduct formation of the eight new complexes synthesised was followed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the modifications caused by the complexes on plasmid DNA pBR322 were also obtained. Values of IC50 were also calculated for the four platinum complexes against the cisplatin resistant tumour cell line A2780cisR.     

Complex compounds of Pd(II), Pt(II), Cu(I) and Hg(II) with tertiary thioamides

Synthesis and chemical and physical characterization of four new complex compounds of thiobenzpyrolidide [1-(pyrolidine)-thiobenzoyl] with Pd(II), Pt(II), Cu(I) and Hg(II) are presented. The purposed chemical structure for these complexes is suggested by the elemental chemical analysis, molecular mass measurements, electric conductivities as well as by UV-VIS and IR spectra. The obtained compounds may in principle be used as enzyme inhibitors having a pronounced insecticidal action.     

Binding properties and stoichiometries of a palladium(II) complex to metallothioneins in vivo and in vitro

This paper will be the first to discuss the in vivo and in vitro properties of a Pd(II) complex, K2PdCl4, interacting with metallothioneins (MTs). In vivo experiments revealed that intraperitoneal injections of K2PdCl4 into rabbits led to the simultaneous synthesis of Pd-MT in the kidney and Zn7MT in the liver. The renal Pd-MT complex contains 3.6 +/- 0.3 Pd, 2.1 +/- 0.2 Zn, and 1.0 +/- 0.1 Cu per mole protein. It was found that pre-treatment with Zn(NO3)2 before K2PdCl4 injections significantly enhanced renal Pd-MT level. The same pre-treatment also increases hepatic Zn-MT levels. These results strongly suggest that Pd(II) ions can be bound in vivo by MT existing in the rabbit kidneys to form Pd-MT. Gel-filtration chromatographic studies after the incubation of either native Cd5Zn2MT2 or Zn7MT2 with K2PdCl4 in vitro demonstrate that Pd(II) ions promote the non-oxidative oligomerization of native MTs. Increasing the level of Pd(II) relative to MT led to a concomitant increase in the apparent yield of MT oligomers. At relatively low Pd-MT ratio, Pd(II) is found predominantly in the oligomers while the monomeric products are chiefly composed of the reactants, Cd5Zn2MT2 or Zn7MT2. Based on our experimental data, the mechanisms of the reactions between Pd(II) and MTs in vivo and in vitro are discussed.     

Synthesis and characterisation of new N1-alkyl-3,5-dipyridylpyrazole derived ligands. Study of their reactivity with Pd(II) and Pt(II)

Two new pyrazole-derived ligands, 1-ethyl-3,5-bis(2-pyridyl)pyrazole (L¹) and 1-octyl-3,5-bis(2-pyridyl)pyrazole (L²), both containing alkyl groups at position 1 were prepared by reaction between 3,5-bis(2-pyridyl) pyrazole and the appropriate bromoalkane in toluene using sodium ethoxide as base.The reaction between L¹, L² and [MCl₂(CH₃CN)₂] (M = Pd(II), Pt(II)) resulted in the formation complexes of formula [MCl₂(L)] (M = Pd(II), L = L¹ (1); M = Pd(II), L = L² (2); M = Pt(II), L = L¹ (3); M = Pt(II), L = L² (4)). These complexes were characterised by elemental analyses, conductivity measurements, infrared, ¹H, ¹³C{¹H} NMR and HMQC spectroscopies. The X-ray structure of the complex [PtCl₂(L²)] (4) was determined. In this complex, Npyridine and Npyrazole donor atoms coordinate the ligand to the metal, which complete its coordination with two chloro ligands in a cis disposition.     

Complexation of Pd(II) with nucleosides. Evidence for a strong interaction Pd⋯HN by NMR

Bis-derivatives of phenylantimony(III) with some monothio-β-diketones have been synthesized and characterized as five coordination species by elemental analyses, molecular weight and spectral data. The stereochemistry of the complexes having asymmetrical ligands is discussed.     

Facile synthesis and reactivity study of mixed phosphane-isocyanide Pd(II) and Pd(0) complexes

The reaction between an equimolecular mixture of isocyanide CNR (CNR = di-methylphenyl isocyanide (DIC), tert-butyl isocyanide (TIC), triphenyl phosphane (PPh₃) and a dechlorinated solution of the palladium allyl dimers [Pd(η³-allyl)Cl]₂ (allyl = 2-Meallyl, 1,1-Me₂allyl) in stoichiometric ratio yields the mixed derivative [Pd(η³-allyl)(CNR)(PPh₃)] only. Apparently, the mixed derivative represents the most stable species among all the possible ones that might be formed under those experimental conditions. Theoretical calculations are in agreement with the experimental observation and the energy stabilization of the mixed species with respect to the homoleptic derivatives is traced back to an overall push-pull effect exerted by the isocyanide and the phosphane acting synergically. Similar behavior is observed in the case of the synthesis of the palladacyclopentadienyl complexes [Pd(C₄(COOMe)₄)(CNR)(PPh₃)] and of the palladium(0) olefin complexes whose synthesis invariably yields the mixed [Pd(η²-olefin)(CNR)(PPh₃)] derivatives. The paper includes studies on the reactivity toward allylamination in the case of the palladium(II) allyl complexes. A diffractometric investigation on the solid state structures of four different palladium isocyanide-phosphane complexes is also included.     

Crystal structures of Pt(II) and Pd(II) complexes with the free radical 4-aminoTEMPO

Pt(II) and Pd(II) compounds containing the free radical 4-aminoTEMPO (4amTEMPO) were synthesized and characterised by X-ray diffraction methods. The disubstituted complexes cis- and trans-Pt(4amTEMPO)₂I₂ were studied. The trans isomer was prepared from the isomerisation of the cis analogue. The two Pd(II) compounds trans-Pd(4amTEMPO)₂X₂ (X = Cl and I) were also characterised by crystallographic methods. A mixed-ligand complex cis-Pt(DMSO)(4amTEMPO)Cl₂ was synthesized from the isomerisation of the trans isomer in hot water. Its crystal structure was also determined. In all the complexes, the 4amTEMPO ligand is bonded to the metal through the -NH₂ group, since the nitroxide O atom is not a good donor atom for the soft Pt(II) and Pd(II) metals. The conformation of the 4-aminoTEMPO ligand was compared to those of the few reported structures in the literature.     

Influence on reactivity of chloro ligand substitution in mononuclear cationic Pd(II) and Pt(II) triphos complexes: X-ray structure of the nitrate derivatives

The substitution of chloro ligand in [M(triphos)Cl]Cl complexes [M=Pd (1), Pt (2); triphos=Ph₂PC₂H₄P(Ph)C₂H₄PPh₂] by reaction with 1 equiv. of KX resulted in the formation of the ionic complexes [M(triphos)X]Cl [X=I, M=Pd (3), Pt (4); X=CN, M=Pd (5), Pt (6)]. Methanolic solutions of silver nitrate in excess displace the chloro ligand and counterion of 1 and 2, giving rise to the formation of the crystalline complexes [M(triphos)(ONO₂)](NO₃) [M=Pd (7), Pt (8)] suitable for X-ray diffraction studies. The complexes show a distorted square-planar environment around the metal, there being three coordination sites occupied by phosphorus atoms from the triphos and the fourth by the oxygen atom from a nitrate acting as monodentate ligand. A second NO₃ ⁻ is acting as counterion with D_3h symmetry. The use of a high excess of SnCl₂ in the presence of 1 equiv. of PPh₃ enabled the formation of complexes [M(triphos)(PPh₃)](SnCl₃)₂ [M=Pd (9), Pt (10)]. These complexes, in addition to [M(triphos)X]X [X=Br, M=Pd (1a), Pt (2a); X=I, M=Pd (1b), Pt (2b)], were synthesised and all Pt(II) complexes characterised by microanalysis. Mass spectrometry, IR spectroscopy, NMR spectroscopy and conductivity measurements were also used for characterisation. The structure and reactivity studies in solution were carried out by ³¹P{¹H} NMR. The trends in chemical shifts δ (P) and ¹J(¹⁹⁵Pt, ³¹P) coupling constants were used to establish a sequence in the X ligand exchange reactions. While [Pd(triphos)I]I (1b) undergoes a ring-opening reaction by titration with AuI, the analogous Pt(II) complex (2b) does not react. The formation of new five-coordinate Pd(II) and Pt(II) complexes was observed by titration of 5–8 with potassium cyanide.