Fertility Inhibitor Heterobimetallic Complexes of Platinum(II) and Palladium(II): Synthetic, Spectroscopic and Antimicrobial Aspects

Synthetic, spectroscopic and antimicrobial aspects of some fertility inhibitor heterobimetallic complexes have been carried out. These heterobimetallic chelates [M(C(5)H(5)N(3))(2)M(2)'(R)(4)]Cl(2) (M = Pd or Pt and M' = Si, Sn, Ti and Zr) have been successfully synthesinzed via the reaction of M(C(5)H(7)N(3))(2)Cl(2) with group four or fourteen dichlorides in 1:2 stoichiometric proportions. The products were characterized by elemental analyses, molecular weight determinations, magnetic susceptibility measurements, conductance, and IR multinuclear NMR and electronic spectral studies. A square planar geometry has been suggested for all the complexes with the help of spectral data. Conductivity data strongly suggest that chlorine atoms are ionic in nature due to which complexes behave as electrolytes. All the complexes have been evaluated for their antmicrobial effects on different species of pathogenic fungi and bacteria. The testicular sperm density, testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trails and biochemical parameters of reproductive organs have been examined and discussed.     

Synthesis and Properties of Hydrazino Amino Acyclic Carbenes of Gold(I), Platinum(II), Palladium(II) and Rhodium(III)

The nucleophilic addition of protected and substituted hydrazine derivatives to isonitrile complexes of gold(I), platinum(II), palladium(II) and rhodium(III) provides the corresponding hydrazino amino acyclic carbene complexes. These are characterized by their spectroscopic data, four different X‐ray single crystal structure analyses and their catalytic activity in the gold(I)‐catalyzed cycloisomerization of N‐propargylcarboxamides to alkylideneoxazolines is investigated.

     

Solvent-Extraction Behavior of Cobalt(II), Nickel(II), Copper(II), and Palladium(II) with Tri-n-butylphosphate

Abstract

A systematic study of the extraction behavior of cobalt(II), nickel(II), copper(II), and palladium(II) with TBP from thiocyanate system in various ranges of acid concentrations has been performed. The thiocyanate medium leads to enhanced extractions in all these cases compared to those in the previously used chloride medium. For palladium, the chloride and nitrate systems have been critically examined. Sixty-two per cent extraction occurs from 4 M hydrochloric acid using 100% TBP in a single run and the extraction becomes quantitative (>99%) after four successive equilibrations. A simpler method has been proposed for rapid extraction of palladium(II) as the thiocyanate complex. Quantitative extraction occurs in the presence of 1.2% thiocyanate solution from 0.5 to 2 M hydrochloric acid (initial) up to pH 8.0. The extractable species of cobalt(II), nickel(II), copper(II), and palladium(II) from thiocyanate medium are probably similar and of the type [M(CNS)₄]^2? [K·TBP·3H₂O]₂ ⁺ (buffer solution) and [M(CNS)₄]^2? [H·TBP·3H₂O]⁺ ₂ (acid solution). A simple extraction scheme has been worked out for the separation of palladium(II) from iron(III), cobalt(II), nickel, manganese(II), copper(II), and platinum.     

Highly Efficient Alkyne Hydroarylation with Chelating Dicarbene Palladium(II) and Platinum(II) Complexes

1 We report on a novel reaction protocol for the coupling of arenes with alkynes (the Fujiwara reaction), yielding products of formal trans‐hydroarylation of the triple bond. The protocol makes use of a chelating N‐heterocyclic dicarbene palladium(II) complex as catalyst and allows us to perform the reaction in a few hours with only 0.1 mol % catalyst yielding the trans‐hydroarylation product in high yields and with excellent selectivity. We discuss the applicability of this reaction protocol, which appears at present quite general with respect to the alkyne, albeit limited to electron‐rich arenes. We also present the results of catalyst optimisation with respect to the nature of the nitrogen substituents in the carbene units, of the bridging group between the carbene units and of the coordinated anionic ligands. Finally, we also discuss the catalytic performance of a related chelating dicarbene complex of platinum(II).     

Synthesis of Lead(II) Minoxidil Coordination Polymer: A New Precursor for Lead(II) Oxide and Lead(II) Hydroxyl Bromide

A new lead(II) coordination polymer, [PbBr₂(C₉H₁₅N₅O)]_n (1), where C₉H₁₅N₅O is (2,4-diamino-6-piperidine-1-yl) pyrimidine N-oxide (minoxidil) is synthesized and characterized. Polymer 1 is synthesized in methanol by sonochemical and hydrothermal methods from lead(II) acetate, KBr and the minoxidil ligand. The crystal structure of [PbBr₂(C₉H₁₅N₅O)]_n indicates a syndiotactic coordination polymer. The Pb(II) atom lies on a mirror plane; the mirror plane is perpendicular to the pyrimidine ring bisecting the piperidine ring. N–H···O intramolecular and C–H···Br, N–H···N strong intermolecular interactions were observed. Micro-rods of PbO and nano-plates of PbOHBr were prepared by thermal decomposition of the nano-structured [PbBr₂(C₉H₁₅N₅O)]_n as a precursor. Characterization of the products was carried out using X-ray crystallography, elemental analysis, FTIR spectroscopy, scanning electron microscopy, energy dispersive X-ray analysis and thermal analysis. The sonochemical method resulted in a significant reduction of reaction time, reaction temperature and particle sizes of the products.     

Structural and Dynamic Aspects of Palladium(II)‐Based Self‐Assembled Binuclear Coordination Complexes

Self‐assembled binuclear complexes of Pd₂L′₂L₂ and Pd₂L₄ type formulations have been achieved by combining the cis‐protected palladium(II) component i. e., [PdL′]²⁺ (where L′ stands for tmeda) and naked palladium(II) separately with a 3‐pyridyl appended non‐chelating bidentate ligand, L under suitable conditions. Supramolecular fusion of the Pd₂L₄ and PdL′₂ type complexes have been demonstrated that provided the corresponding Pd₂L′₂L₂ type complex. One pot synthesis of the binuclear Pd₂L′₂L₂ type complex is achieved by combining palladium(II), L′ and L at equimolar ratio, however, along with an unidentified trap. The crystal structure of a Pd₂L₄ type complex confirmed the binuclear architecture of the cage. Intermolecular H‐bonding and π‐π stacking interactions are analyzed from the crystal structure and the extended intermolecular interactions apparently generated a grid pattern.     

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with O,S Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues

(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug development. Over the last few years, classical structure–activity relationships (SAR) have been broken by some promising new compounds based on platinum or other metals. We focus on the synthesis and characterization of 17 different complexes with β-hydroxydithiocinnamic acid esters as O,S bidendate ligands for nickel(II), palladium(II), and platinum(II) complexes. (2) Methods: The bidendate compounds were synthesized and characterized using classical methods including NMR spectroscopy, MS spectrometry, elemental analysis, and X-ray crystallography, and their cytotoxic potential was assessed using in vitro cell culture assays. Data were compared with other recently reported platinum(II), ruthenium(II), and osmium(II) complexes based on the same main ligand system. (3) Results: SAR analyses regarding the metal ion (M), and the alkyl-chain position (P) and length (L), revealed the following order of the effect strength for in vitro activity: M > P > L. The highest activities have Pd complexes and ortho-substituted compounds. Specific palladium(II) complexes show lower IC₅₀ values compared to cisplatin, are able to elude cisplatin resistance mechanisms, and show a higher cancer cell specificity. (4) Conclusion: A promising new palladium(II) candidate (Pd3) should be evaluated in further studies using in vivo model systems, and the identified SARs may help to target platinum-resistant tumors.     

Separation of Palladium(II) and Platinum(IV) by Bulk Liquid Membranes during Electrodialysis

Abstract

The process of PdCl₄ ^2? and PtCl₆ ^2? separation extracting from binary hydrochloric mixtures as well as palladium(II) extraction from individual solutions by bulk liquid membranes containing diphenylthiourea and di‐o‐tolylthiourea in 1,2‐dichloroethane is studied at galvanostatic electrodialysis. The effects of the current density, the composition of the liquid membrane and of aqueous solutions on the rate of the metal transport are determined. It is shown that an effective separation of Pt(IV) from Pd(II) is achieved in the presence of an excess of the carrier. Maximum separation factor β_Pt/Pd of 380 is obtained in 1 hour of electrodialysis under optimal conditions. The transport of platinum(IV) is supposed to occur in the form of ionic associates (PdL₄Cl)₂PtCl₆. Platinum(IV) concentration and composition of the strip solution do not exert a considerable influence on the separation factor.     

Adsorptive Recovery of Palladium(II) and Platinum(IV) on the Chemically Modified-Microalgal Residue

A biomass waste of microalgae was chemically modified by immobilizing the functional group of polyethyleneimine to prepare a new type of adsorbent. The adsorption test revealed that this adsorbent exhibited remarkably high selectivity for Pd(II) and Pt(IV) over base metal ions in HCl solution. From the adsorption isotherm, its maximum adsorption capacity for Pd(II) and Pt(IV) was evaluated as 2.0 and 0.8 mmol/g, respectively. This adsorbent also exhibited high affinity and selectivity for Pd(II) and Pt(IV) even in the presence of high concentrations of base metals in actual leach liquor.     

Zn-Enhanced Asp-Rich Antimicrobial Peptides: N-Terminal Coordination by Zn(II) and Cu(II), Which Distinguishes Cu(II) Binding to Different Peptides

The antimicrobial activity of surfactant-associated anionic peptides (SAAPs), which are isolated from the ovine pulmonary surfactant and are selective against the ovine pathogen Mannheimia haemolytica, is strongly enhanced in the presence of Zn(II) ions. Both calorimetry and ITC measurements show that the unique Asp-only peptide SAAP3 (DDDDDDD) and its analogs SAAP2 (GDDDDDD) and SAAP6 (GADDDDD) have a similar micromolar affinity for Zn(II), which binds to the N-terminal amine and Asp carboxylates in a net entropically-driven process. All three peptides also bind Cu(II) with a net entropically-driven process but with higher affinity than they bind Zn(II) and coordination that involves the N-terminal amine and deprotonated amides as the pH increases. The parent SAAP3 binds Cu(II) with the highest affinity; however, as shown with potentiometry and absorption, CD and EPR spectroscopy, Asp residues in the first and/or second positions distinguish Cu(II) binding to SAAP3 and SAAP2 from their binding to SAAP6, decreasing the Cu(II) Lewis acidity and suppressing its square planar amide coordination by two pH units. We also show that these metal ions do not stabilize a membrane disrupting ability nor do they induce the antimicrobial activity of these peptides against a panel of human pathogens.     

Platinum (II) Compounds With Antitumor Activity Studied by Molecular Mechanics

A SERIES OF PT(LL) COMPLEXES WITH ANTITUMOR PROPERTIES: [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]PtL(2) (meso-1-PtL(2)) and [erythro-1-(2,6-dichloro-4-hydroxyphenyl)-2-(2-halo-4-hydroxyphenyl)ethylenediamine]PtL(2), [2L=2Cl-,2I-,SO(4) (2)-; halo = F (erythro-8-PtL(2)),halo = Cl (erythro-9-PtL(2))] has been modelled by molecular mechanics (MM). The MM calculations were carried out for different isomers and ligand conformations meso-delta, meso-lambda, d,l-delta, d,I-lambda. The compounds with the lowest MM energies have the same geometries as those obtained by X-ray analysis. The calculated MMX energy orders: meso-1-PtL(2) < erythro-9-PtL(2) < erythro-8-PtL(2) for L=I-, Cl- and SO(4) (2-) are reverse to the known antitumor activity order - the lowest energy complex (the most stable one)is the one with the highest estrogen activity (meso-1-PtL(2)). The type of the leaving group (L) does not alter the energy order, which is in agreement with the biological experiments that show a slight dependence of the estrogen properties on the leaving group type.     

Lewis Acid Behavior of Cationic Complexes of Palladium(II) and Platinum(II): Some Examples of Catalytic Applications

The behavior of a variety of cationic diphosphine complexes of Pd(II) and Pt(II) as Lewis acid catalysts is reviewed. The reactions considered are the Baeyer–Villiger oxidation of ketones, the acetalization of aldehydes and ketones and the Diels–Alder reaction in both their regular and enantioselective version.     

Adsorption Thermodynamics and Kinetics of Mercury (II), Cadmium (II) and Lead (II) on Lignite

This study examines the adsorption thermodynamics and kinetics of heavy metal ions [(Hg (II), Cd (II), Pb (II)] on a demineralized lignite coal. The study also investigates the effects of process parameters like contact time, pH, concentration of metal ion, temperature and adsorbent mass on the extent of metal-ion adsorption from solution.The results of the kinetic studies show that the adsorption reaction is first order with respect to the metal cation solution concentration, with activation energies of 4.9, 8.2 and 9.1 kJ mol^–1 for Hg (II), Cd (II) and Pb (II), respectively. These low activation energy values indicate that the adsorption reaction is diffusion-controlled. The results of the thermodynamic investigations indicate that the adsorption reactions are spontaneous (ΔG°< 0), slightly exothermic (ΔH°< 0) and irreversible (ΔS°> 0).The results of the study further show that the adsorption process is pH, adsorbent mass and metal-ion concentration dependent. Adsorption increases with increase in these variables. Temperature has only a marginal effect on adsorption. The reasons for these observations have been suggested.     

Cell Growth-Inhibiting Properties of Selected Carrier-Bound, Monoamine-Coordinated Platinum(II) Compounds

In contradistinction to the ligand arrangement in coordination compounds of the square-planar cis-diamminedichloroplatinum(II) type as represented by the prototype anticancer drug cisplatin, scant attention has been paid in cancer research to those platinum complexes in which only a single amino group (in addition to different ligands) is coordinated to the metal. In continuation of earlier research in this laboratory focused on macromolecular compounds containing monoamine-coordinated platinum, we have now synthesized a series of such polymeric platinum conjugates and assessed their antiproliferative activity in cell culture tests conducted against several human cancer cell lines. Conjugates containing hydroxylated side groups as hydrosolubilizing entities are found to exhibit poor, or no, activity up to the highest drug concentration tested (50 g Pt/mL). In contrast, those conjugates in which the solubilizing units are characterized by the presence of potentially cationic tert-amine side chain terminals show remarkably high cell-killing activity, with IC₅₀ in the range of 1–6 g Pt/mL against the HeLa cervical epitheloid carcinoma line. Two selected samples tested against the A-2780 human ovarian cancer line and its cisplatin-resistant A-2780-cis counterpart shows lack of cross-resistance with cisplatin (resistance factor 1). These findings augur well for the development of polymer-conjugated monoamine-coordinated platinum compounds with carcinostatic properties.     

Toxicity, Spectroscopic Characterization and Electrochemical Behaviour of New Macrocclic Complexes of Lead(II) and Palladium(II) Metals

Tetraazamacrocyclie complexes of lead and palladium have been synthesized by the template process using the bis(benzil)ethylenediamine precursor. The tetradentate macrocycle (maL) reacts with PbCl(2), PdCl(2) and different diamines in a 1:1:1 molar ratio in methanol to give several solid complexes of the types [Pb(maL)(R)Cl(2)] and [Pd(maL)(R)]Cl(2) (where R = 2,6-diaminopyridine or 1,2-phenylenediamine). The macrocycle and its metal complexes have been characterized by elemental analysis, molecular weight determinations, molar conductivity, IR, (1)H NMR, (13)C NMR, electronic, mass and electrochemical studies. The macrocyclic ligand coordinates through the four azomethine nitrogen atoms which are bridged by benzil moieties. IR spectra suggest that the pyridine nitrogen is not coordinating. The palladium complexes exhibit tetracoordinated square-planar geometry, whereas a hexacoordinated octahedral geometry is suggested for lead complexes. The macrocycle along with its complexes have been screened in vitro against a number of pathogenic fungi and bacteria to assess their growth inhibiting potential.     

Synthesis and Characterization of the New Nano Flowers Lead(II) Coordination Polymer with Hemidirected Coordination Sphere

Nano flowers of a new polymeric lead(II) complex containing the azide anions, [Pb(baea)(N₃)·(N₃)] _n (“baea” is the abbreviation of bis(2-aminoethyl)amine), has been synthesized by a sonochemical method. The new nano-structure was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, elemental analyses, and IR spectroscopy. Single crystalline material was obtained using a heat gradient applied to a solution of the reagents. Single-crystal X-ray diffraction analyses show that the coordination number for Pb^II ions is five, PbN5 and hold hemidirected coordination geometry. To the best of our knowledge, the 1D coordination polymer interact with each other via supramolecular and weak Pb···N interactions to create 2D supramolecular frameworks.     

Adsorption of Mercury(II), Lead(II), Cadmium(II) and Zinc(II) from Aqueous Solutions using Mercapto‐Modified Silica Particles

This article presents a novel systematic approach to the fabrication of highly functionalized, silica (SiO₂) nanoparticles used for the adsorption of heavy‐metal ions (Hg²⁺, Pb²⁺, Cd²⁺, Zn²⁺). Almost monodispersed silica (SiO₂) nanoparticles with narrow particle size distributions of around 85 ± 5 nm were formed using the Stöber process. The prepared SiO₂ nanoparticles were successfully surface‐treated during a one‐step procedure by the covalent attachment of mercaptopropyl groups onto the surfaces of the SiO₂ nanoparticles. A FTIR spectra analysis confirmed that the binding of the mercaptosilane molecules onto the surface of the silica nanoparticles mediated the Si–O–Si and –SH vibrations. TEM/EDXS micrographs indicated the almost monodispersed and spherical morphology of the prepared product with strong signals of Si and S, thus implying that the coating procedure involving the mercapto groups onto the silica surface had been successfully accomplished. The final results for the heavy‐metal (Hg²⁺, Pb²⁺, Cd²⁺, Zn²⁺) adsorption showed the strongest affinity within the following sequence Hg²⁺ (99.9%) > Pb²⁺ (55.9%) > Cd²⁺ (50.2%) > Zn²⁺ (4%). Adsorption equilibrium was achieved after 1 h for all the analyzed samples.     

Carbenes Made Easy: Formation of Unsymmetrically Substituted N‐Heterocyclic Carbene Complexes of Palladium(II), Platinum(II) and Gold(I) from Coordinated Isonitriles and their Catalytic Activity

From palladium(II) or platinum(II) bis(isonitrile) complexes and from gold(I) isonitrile complexes, both easily available from simple precursors, the corresponding mono‐N‐heterocyclic carbene (NHC) complexes could be obtained selectively in good yields under very mild conditions. The reagents are simple β‐chloroammonium salts in the presence of a weak base. Unsymmetric NHC complexes are accessible. Thus over only two steps from simple metal precursors a broad variety of NHC complexes is available, the method is ideal to quickly assemble catalyst libraries. The palladium complexes are active pre‐catalysts in Suzuki cross‐coupling even with the additional isonitrile ligand on palladium.