Metal-chelating polymers by anionic ring-opening polymerization and their use in quantitative mass cytometry

Metal-chelating polymers (MCPs) are important reagents for multiplexed immunoassays based on mass cytometry. The role of the polymer is to carry multiple copies of individual metal isotopes, typically as lanthanide ions, and to provide a reactive functionality for convenient attachment to a monoclonal antibody (mAb). For this application, the optimum combination of chain length, backbone structure, end group, pendant groups, and synthesis strategy has yet to be determined. Here we describe the synthesis of a new type of MCP based on anionic ring-opening polymerization of an activated cyclopropane (the diallyl ester of 1,1-cyclopropane dicarboxylic acid) using a combination of 2-furanmethanethiol and a phosphazene base as the initiator. This reaction takes place with rigorous control over molecular weight, yielding a polymer with a narrow molecular weight distribution, reactive pendant groups for introducing a metal chelator, and a functional end group with orthogonal reactivity for attaching the polymer to the mAbs. Following the ring-opening polymerization, a two-step transformation introduced diethylenetriaminepentaacetic acid (DTPA) chelating groups on each pendant group. The polymers were characterized by NMR, size exclusion chromatography (SEC), and thermogravimetric analysis (TGA). The binding properties toward Gd(3+) as a prototypical lanthanide (Ln) ion were also studied by isothermal titration calorimetry (ITC). Attachment to a mAb involves a Diels-Alder reaction of the terminal furan with a bismaleimide, followed by a Michael addition of a thiol on the mAb, generated by mild reduction of a disulfide bond in the hinge region. Polymer samples with a number average degree of polymerization of 35, with a binding capacity of 49.5 ± 6 Ln(3+) ions per chain, were loaded with 10 different types of Ln ions and conjugated to 10 different mAbs. A suite of metal-tagged Abs was tested by mass cytometry in a 10-plex single cell analysis of human adult peripheral blood, allowing us to quantify the antibody binding capacity of 10 different cell surface antigens associated with specific cell types.     

From bio-mineralisation to fuel cells: biomanufacture of Pt and Pd nanocrystals for fuel cell electrode catalyst

Biosynthesis of nano-scale platinum and palladium was achieved via enzymatically-mediated deposition of metal ions from solution. The bio-accumulated Pt(0) and Pd(0) crystals were dried, applied onto carbon paper and tested as anodes in a polymer electrolyte membrane (PEM) fuel cell for power production. Up to 100% and 81% of the maximum power generation was achieved by the bio-Pt and bio-Pd catalysts, respectively, compared to commercial fuel cell grade Pt catalyst. Hence, biomineralisation could pave the way for economical production of fuel cell catalysts since previous studies have shown that precious metals can be biorecovered from wastes into catalytically active bionanomaterials.     

Anticancer activity of new imidazole derivative of 1R,2R-diaminocyclohexane palladium and platinum complexes as DNA fluorescent probes

The aim of this study was synthesis of two new water-soluble fluorescent palladium and platinum complexes with formulas of [Pt(DACH)(FIP)](NO₃)₂ and [Pd(DACH)(FIP)](NO₃)₂, respectively, where FIP is 2-(furan-2-yl)-1H-imidazo[4,5-f][1,10] phenanthroline and DACH is 1R,2R-diaminocyclohexane. Fluorescence spectroscopy, circular dichroism (CD), thermal denaturation measurement, ionic strength, and kinetic study displayed groove binding of Pt complex on DNA, while due to binding of Pd complex, B form of DNA convert to Z form. Due to electrostatic interaction of Pd complex with DNA, the DNA form is converted and it provides enough space for Pd complex to insert between base stacking of DNA. UV–vis study shows two complexes could denature the DNA at low concentrations in exothermic process and Pt complex is more active than Pd complex. Finally, the anticancer and growth inhibitory activities of synthesized complexes were investigated against human colon cancer cell line HCT116 after incubation time of 24 h using MTT assay and higher activity was observed for the platinum complex. Interaction of the two metal derivative complexes was studied by molecular docking and molecular dynamics simulation. The results showed that Pt complexes have higher negative docking energy and higher tendency for interaction with DNA, and exert more structural change on DNA.     

Palladium and platinum famotidine complexes

The molecule of the well-known ulceration inhibitor, famotidine, is an excellent coordinator of transition metal ions. The guanidine, amine group and thiazole nitrogen, and the thioether sulphur are preferential sites to bind metal ions. Pd(II) and Pt(II) derivatives of famotidine have been synthesized and studied structurally. There is evidence that the palladium complex is a monomer while the platinum complex forms a dimer. Due to the interesting structure of the platinum complex several assays have examined the possible antitumour activity. Changes in DNA conformation induced by both complexes have been detected by CD, interstrand crosslinking interactions and electrophoretic mobility, but studies of the cytotoxicity of the platinum compound with U937 human leukemia cells and HeLA human womb carcinoma cells show only a small antiproliferative potential.     

Biotinylated polyacrylamide-based metal-chelating polymers and their influence on antigen recognition following conjugation to a trastuzumab fab fragment

We report the synthesis and characterization of metal-chelating polymers (MCPs) with a terminal biotin and a polyacrylamide backbone harboring multiple diethylenetriaminepentaacetic acid (DTPA) chelating sites. These polymers are conjugated to a streptavidin (SAv)-modified Fab fragment of trastuzumab (tmFab) and subsequently complexed with (111)In through DTPA. Trastuzumab has specific targeting ability toward human epidermal growth factor receptor-2 (HER2), which is overexpressed on some types of breast cancer cells and ovarian cancer cells. (111)In can generate Auger electrons which cause lethal DNA double strand breaks. The radioimmunoconjugates (RICs) were designed to target HER2 overexpressing cancer cells and carry multiple copies of (111)In to these cells. The mole maximum specific activities of these polymers were investigated by loading the polymers with (111)In at an increasing (111)In to polymer ratio. The polymers show 55-fold to 138-fold higher maximum specific activity than DTPA modified tmFab-SAv. Moreover, the HER2 immunoreactivities of these RICs were evaluated by measuring their specific binding ability toward HER2 overexpressing SKOV-3 ovarian cancer cells. The results demonstrate that although in the presence of polymer there is increased nonspecific binding, HER2 targeting ability was retained, ensuring the radionuclide delivery ability of these RICs.     

Terminal-modified polylysine-based chelating polymers: highly efficient coupling to antibody with minimal loss in immunoreactivity.

A method is suggested for the preparation of chelating polymers containing a single terminal reactive group capable of interaction with proteins. These polymers were synthesized from N-CBZ-polylysine and DTPA and contain a terminal SH or pyridyldisulfide group. A polymer molecule with MW 13,500 is able to carry up to 40 DTPA residues. Polymers easily and quantitatively bind with antibodies (Fab fragments of antimyosin antibodies R11D10) with minimal effect on antibody immunoreactivity as revealed in ELISA assay and in direct immunoanalysis. Conjugates prepared can chelate radioactive metal ions reaching very high specific radioactivity (greater than 1 mCi 111In/10 micrograms of protein). Perspectives for their application are discussed.     

Platinum(II) complexes with 2-acetyl pyridine thiosemicarbazone. Synthesis, crystal structure, spectral properties, antimicrobial and antitumour activity

An interesting series of new platinum complexes has been synthesized by the reaction of Na(2)PtCl(4) with 2-acetyl pyridine thiosemicarbazone, HAcTsc. The new complexes, [Pt(AcTsc)Cl], [Pt(HAcTsc)(2)]Cl(2) and [Pt(AcTsc)(2)], have been characterized by elemental analyses and spectroscopic studies. The crystal structure of the complex [Pt(AcTsc)Cl] has been solved by single-crystal X-ray diffraction. The anion of HAcTsc coordinates in a planar conformation to the central platinum(II) through the pyridyl N, azomethine N and thiolato S atoms. Double intermolecular hydrogen bonds (NH-Cl), pi-pi and weak Pt-Pt and Pt-pi contacts lead to aggregation and to a two-dimensional supramolecular assembly. The antibacterial and antifungal effect of the novel platinum(II) complexes and the related palladium(II) complexes, [Pd(AcTsc)Cl], [Pd(HAcTsc)(2)]Cl(2) and [Pd(AcTsc)(2)], were studied in vitro. The complexes were found to have a completely lethal effect on Gram+ bacteria, while the same complexes showed no bactericidal effect on Gram- bacteria. Additionally, the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] showed effective antifungal activity towards yeast. Among these compounds [33], the most effective in inducing antitumour and cytogenetic effects are the complexes [Pt(AcTsc)(2)] and [Pd(AcTsc)(2)] while the rest, display marginal cytogenetic and antitumour effects.     

Effect of pendant group structure on the hydrolytic stability of polyaspartamide polymers under physiological conditions

We describe the synthesis of metal chelating polymers based on polyaspartamide and polyglutamide backbones as carriers for (111)In in radioimmunoconjugates. These polymers [PAsp(DTPA), PGlu(DTPA)] have a biotin end group and diethylenetriaminepentaacetic acid (DTPA) chelators attached to the primary amines of the diethylenetriamine (DET) pendant groups of biotin-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} [PAsp(DET)] and of biotin-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]glutamide} [PGlu(DET)]. Like Asn-containing proteins and polypeptides, polyaspartamides undergo uncatalyzed degradation under model physiological conditions (10 mM phosphate buffer, pH 7.4, 150 mM NaCl). We studied the uncatalyzed degradation of the polyaspartamide polymers by size exclusion chromatography and found that the degradation rate was sensitive to the nature of the pendant groups. The metal-free polymer underwent somewhat slower degradation than the corresponding polymers in which the DTPA groups were saturated with Eu(3+) or In(3+), but even after 14 days, substantial fractions of the polymers survived. We conclude that these polymers undergo negligible degradation on the time scale (24-48 h) of radioimmunotherapy treatment of tumors with (111)In. From a mechanistic perspective, we note that these degradation rates are on the order of the deamidation rates reported [J. Peptide Res. 2004, 63, 426] for Asn-containing pentapeptides, with half-times on the order of 10 days, but much slower than the rapid decay (hours) reported recently [Biomaterials 2010, 31, 3707] for poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} itself. This variation in degradation rate can be explained in terms of the influence of positive charges on the pendant group enhancing the acidity of the side-chain amide nitrogen of the aspartamide repeat unit. The DET pendant group is positively charged at pH 7, but in indium-loaded PAsp(DTPA) this charge is offset by the net negative charge of the DTPA-In complex.     

Biological activity of palladium(II) and platinum(II) complexes of the acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate and the X-ray crystal structure of the [Pd(asme)2] (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) complex

Palladium(II) and platinum(II) complexes of general empirical formula, [M(NS)(2)] (NS=uninegatively charged acetone Schiff bases of S-methyl- and S-benzyldithiocarbazate; M=Pt(II) and Pd(II)) have been prepared and characterized by a variety of physicochemical techniques. Based on conductance, IR and electronic spectral evidence, a square-planar structure is assigned to these complexes. The crystal and molecular structure of the [Pd(asme)(2)] complex (asme=anionic form of the acetone Schiff base of S-methyldithiocarbazate) has been determined by X-ray diffraction. The complex has a distorted cis-square planar structure with the ligands coordinated to the palladium(II) ions as uninegatively charged bidentate NS chelating agents via the azomethine nitrogen and the mercaptide sulfur atoms. The distortion from a regular square-planar geometry is attributed to the restricted bite angles of the ligands. Antimicrobial tests indicate that the Schiff bases exhibit strong activities against the pathogenic bacteria, Bacillus subtilis (mutant defective DNA repair), methicillin-resistant Staphylococcus aureus, B. subtilis (wild type) and Pseudomonas aeruginosa and the fungi, Candida albicans (CA), Candida lypotica (2075), Saccharomyces cerevisiae (20341) and Aspergillus ochraceous (398)-the activities exhibited by these compounds being greater than that of the standard antibacterial and antifungal drugs, streptomycin and nystatin, respectively. The palladium(II) and platinum(II) complexes are inactive against most of these organisms but, the microbe, Pseudomonas aeruginosa shows strong sensitivity to the platinum(II) complexes. Screening of the compounds for their cytotoxicities against T-lymphoblastic leukemia cancer cells has shown that the acetone Schiff base of S-methyldithiocarbazate (Hasme) exhibits a very weak activity, whereas the S-benzyl derivative (Hasbz) is inactive. However, the palladium(II) complexes exhibit strong cytotoxicities against this cancer; their activities being more than that of the standard anticancer drug, tamoxifen. The [Pt(asme)(2)] complex exhibits a very weak cytotoxicity, whereas [Pt(asbz)(2)] is inactive against leukemic cells.     

Synthesis, characterization, DNA binding, and cytotoxic studies of some mixed-ligand palladium(II) and platinum(II) complexes of alpha-diimine and amino acids

The syntheses of nine palladium(II) complexes of type [Pd(phen)(AA)]+ (where AA is an anion of glycine, L-alanine, L-leucine, L-phenylalanine, L-tyrosine, L-tryptophan, L-valine, L-proline, or L-serine) have been achieved. These palladium(II) complexes have been characterized by ultraviolet-visible, infrared, and 1H NMR spectroscopy. The binding studies of several complexes [M(NN)(AA)]+ (where M is Pd(II) as Pt(II), NN is 2,2'-bipyridine or 1,10-phenanthrodine, and AA is an anion of amino acid) with calf thymus DNA have been carried out using UV difference absorption and fluorescence spectroscopy. The mode of binding of the above complexes to DNA suggests the involvement of the hydrogen bonding between them. Several complexes [M(phen)(AA)]+ (where M is Pd(II) or Pt(II) and AA is an anion of amino acid) have also been screened for cytotoxicity in P388 lymphocytic cells. Of them, only two complexes, [Pd(Phen)(Gly)]+ and [Pd(phen)(Val)]+, show comparable cytotoxicity, as cisplatin does.     

Syntheses, Characterization, and Antitumor Activities of Platinum(II) and Palladium(II) Complexes with Sugar-Conjugated Triazole Ligands

Four platinum(II) and palladium(II) complexes with sugar-conjugated bipyridine-type triazole ligands, [Pt(II) Cl(2) (AcGlc-pyta)] (3), [Pd(II) Cl(2) (AcGlc-pyta)] (4), [Pt(II) Cl(2) (Glc-pyta)] (5), and [Pd(II) Cl(2) (Glc-pyta)] (6), were prepared and characterized by mass spectrometry, elemental analysis, (1) H- and (13) C-NMR, IR as well as UV/VIS spectroscopy, where AcGlc-pyta and Glc-pyta denote 2-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside (1) and 2-[4-(pyridin-2-yl)-1H-1,2,3-triazol-1-yl]ethyl β-D-glucopyranoside (2), respectively. The solid-state structure of complex 6 was determined by single-crystal X-ray-diffraction analysis. These complexes exhibited in vitro cytotoxicity against human cervix tumor cells (HeLa) though weaker than that of cisplatin.     

Taniaphos and Walphos ligands: Oxidative electrochemistry and complexation. Synthesis, characterization, oxidative electrochemistry and X-ray structures of [(Taniaphos/Walphos)MCl2] (M = Pd or Pt)

The oxidative electrochemistry of chiral, bidentate ferrocenylphosphines, five Taniaphos and seven Walphos ligands, was studied in methylene chloride. In general, two waves of varying reversibility were observed. Complexes of the general type [(phosphine)MCl₂] (phosphine = Taniaphos or Walphos; M = Pd or Pt) were prepared and characterized by NMR. Upon coordination, the oxidative electrochemistry of the ligands was greatly simplified. The X-ray structures of a Taniaphos platinum complex as well as a palladium and a platinum complex with a Walphos ligand were determined.     

DNA as molecular target of analogous palladium and platinum anti-Trypanosoma cruzi compounds: a comparative study

In the search for drugs with anti-trypanosome activity, we had previously synthesized two series of platinum and palladium analogous compounds of the formula [M^IICl₂(HL)], where HL were bioactive 5-nitrofuryl or 5-nitroacroleine thiosemicarbazone derivatives. In this work, we thoroughly characterized [M^IICl₂(HL)] complexes interaction with DNA by using different techniques: gel electrophoresis, DNA viscosity measurements, circular dichroism (CD) and atomic force microscopy (AFM). Electrophoresis results showed that all complexes induced a withdrawal of DNA superhelicity demonstrated by a decrease in electrophoretic mobility of supercoiled DNA form. This effect on migration was dependent on dose but also on the nature of both the metal and the ligand. In general, the effect produced by palladium complexes was significantly more intense than that observed for the corresponding platinum analogs. Differences between palladium and platinum complexes were also observed in CD experiments. While palladium complexes induce evident calf thymus (CT)-DNA profile changes compatible with B-DNA to Z-DNA conformational transition, no clear effect was observed for platinum ones. Additionally, AFM studies showed that changes in the shape of plasmid DNA, like supercoiling, kinks and thickness increase resulted more intense for the former. In addition, either Pd or Pt complexes increased the viscosity of CT DNA solutions in a concentration dependent manner. Although the nature of DNA interaction of both series of analogous palladium and platinum complexes seemed to be similar, an explanation for the observed differential intensity of the effect could be related to the known kinetic stability differences between palladium and platinum compounds.     

Synthesis,structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro

Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)₂(sac)₂]·H₂O (1), trans-[Pt(2-hmpy)₂(sac)₂]·3H₂O (2), trans-[Pd(2-hepy)₂(sac)₂] (3) and trans-[Pt(2-hepy)₂(sac)₂] (4), have been synthesized and characterized by elemental analysis, UV–vis, IR and NMR. Single crystal X-ray analysis reveals that the metal(II) ions in each complex are coordinated by two sac and two 2-hmpy or 2-hepy ligands with a trans arrangement. Anticancer effects of 1–4 were tested against four different cancer cell lines (A549 and PC3 for lung cancer, C6 for glioblastoma, and Hep3B for liver cancer). Cytotoxicity was first screened by the MTT assay and the results were further confirmed by the ATP assay. The mode of cell death was determined by both histological and biochemical methods. Among the metal complexes, complex 2 resulted in relatively stronger anti-growth effect in a dose-dependent manner (3.13–200 μM), compared to the others, by inducing apoptosis.     

Effects of platinum and palladium ions on the production and reactivity of neutrophil-derived reactive oxygen species

This study was designed to investigate the effects of platinum, as hydrogen hexachloroplatinate (Pt; 0.0025-25 microM), on the production of reactive oxygen species (ROS) by human neutrophils in vitro. ROS were measured by lucigenin-enhanced chemiluminescence (LECL). Addition of Pt to neutrophils was accompanied by a lag phase of about 1 min, followed by a linear dose-related increase in LECL, which peaked at around 4 min and achieved statistical significance at concentrations of 0.025 microM Pt and higher. Interestingly, Pt-mediated enhancement of LECL was not associated with meaningful alterations in neutrophil oxygen consumption, assembly of NADPH oxidase, or cytosolic Ca2+ and was completely attenuated by superoxide dismutase and inhibitors of NADPH oxidase, but not by catalase or scavengers of hydroxyl radical, and was undetectable with cells from individuals with chronic granulomatous disease. Exposure of alpha1-proteinase inhibitor to Pt-treated neutrophils resulted in inactivation of elastase-inhibitory capacity, underscoring the potential toxicity of neutrophil/Pt interactions. The pro-oxidative actions of Pt were mimicked by palladium (Pd), but not by cisplatin or rhodium. These observations demonstrate that Pt and Pd potentiate the reactivity, as opposed to the generation of neutrophil-derived oxidants, an activity that may contribute to airway inflammation in occupationally and possibly environmentally exposed individuals.     

Long term urinary platinum, palladium, and gold excretion of patients after insertion of noble metal dental alloys

The aim of this study was to investigate to which extent noble-metal dental alloys contribute to the total platinum (Pt), palladium (Pd), and gold (Au) body burden of the general population. The urinary Pt, Pd, and Au excretion was determined in three non-occupationally exposed volunteers before and up to 3 months after insertion of a highgold dentalalloy. The in-vitro release of Pt, Pd, and Au from four different types of dental alloys into either artificial saliva or 1% lactic acid solution was additionally investigated. The Pt, Pd, and Au concentrations were determined by sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). Before insertion of the high-gold dental alloy, the Pt excretion of the patients ranged between 1.0 and 7.4 ng l-1 (0.6-3.3 ng g-1 creatinine). In the immediate post-insertion phase the Pt excretion rose to 10.5-59.6 ng l-1 (14.5-33.2 ng g-1 creatinine). This is a mean increase by a factor of 12 compared with the average Pt excretion before insertion. Three months after insertion, the Pt excretion was still elevated by a factor of 7. Contrary to Pt, the Au and Pd excretion in urine was not significantly increased after insertion of this type of high-gold dental alloy. Our in-vitro investigations confirm the assumption that Pt, Pd, and Au are released from noble metal containing dental alloys by corrosion. Under the applied conditions, the release was in the lower ng cm-2 range. It can be concluded that the Pt release from dental alloys can predominantly contribute to the Pt exposure of non-occupationally exposed persons. It can exceed the exposure from all other environmental sources including the Pt release from automobile exhaust catalysts.     

Synthesis, characterization, and cytotoxic studies of alpha-diimine/1,2-diamine platinum(II) and palladium(II) complexes of selenite and tellurite and binding of some of these complexes to DNA.

Eleven new complexes of formula [M(NN)(XO3)] (where M is Pd(II) or Pt(II); NN is 2,2'-bipyridine, 1,10-phenanthroline, 2,2'-dipyridylamine, ethylenediamine or (+-)trans-1,2-diaminocyclohexane, and XO3(2-) is SeO3(2-) or TeO3(2-)) have been synthesized. These water soluble complexes have been characterized by chemical analysis and conductivity measurements as well as ultraviolet-visible and infrared spectroscopy. In these complexes the selenite or tellurite ligand coordinates to platinum(II) or palladium(II) as bidentate with two oxygen atoms. These complexes inhibit the growth of P 388 lymphocytic leukemia cells, their targets are DNA. The selenite complexes invariably show I.D.50 values less than cisplatin. However, the I.D.50 values of the tellurite complexes are usually higher than cisplatin, except that of [Pd(dach)(TeO3)] which has comparable I.D.50 values, as compared to cisplatin. [Pt(bipy)(SeO3)] and [Pd(bipy)(SeO3)] have been interacted with calf thymus DNA and bind to DNA through a coordinate covalent bond.     

Palladium and platinum 3,5-diacetyl-1,2,4-triazol bis(thiosemicarbazones): chemistry, cytotoxic activity and structure-activity relationships

The preparation of platinum(II) complexes derived from 3,5-diacetyl-1,2,4-triazol bis(4-phenylthiosemicarbazone) (H(5)L(1)), 3,5-diacetyl-1,2,4-triazol bis(thiosemicarbazone) (H(7)L(2)), 3,5-diacetyl-1,2,4-triazol bis(4-methylthiosemicarbazone) (H(5)L(3)) and 3,5-diacetyl-1,2,4-triazol bis(4-ethylthiosemicarbazone) (H(5)L(3)) is described. The new complexes [Pt(mu-H(3)L(1))](2), [Pt(mu-H(5)L(2))](2), [Pt(mu-H(3)L(3))](2) and [Pt(mu-H(3)L(4))](2) have been characterized by elemental analyses, fast atom bombardment mass spectrometry (FAB(+)) and spectroscopic studies. The crystal and molecular structure of compounds [Pt(mu-H(3)L(1))](2), parent ligand H(5)L(1) and [Pt(mu-H(3)L(3))](2) have been determined by single crystal X-ray diffraction. The ligands coordinate, in a dideprotonate form to the platinum ions in a new tridentate fashion (NNS) and S-brigding bonding modes. Thus the molecular units of the platinum complexes are stacked as dimers. The testing of the cytotoxic activity of the synthesized compounds together with their palladium analogues against human A2780 and A2780cisR epithelial ovarian carcinoma cells lines suggests that the compounds may be endowed with important antitumor properties since they show IC(50) values in a micromolar range similar to those of cisplatin. The structure and antitumor activity relationships of platinum and palladium complexes are also discussed.     

Fate of platinum metals in the environment

For many years now automotive exhaust catalysts have been used to reduce the significant amounts of harmful chemical substances generated by car engines, such as carbon monoxide, nitrogen oxides, and aromatic hydrocarbons. Although they considerably decrease environmental contamination with the above-mentioned compounds, it is known that catalysts contribute to the environmental load of platinum metals (essential components of catalysts), which are released with exhaust fumes. Contamination with platinum metals stems mainly from automotive exhaust converters, but other major sources also exist. Since platinum group elements (PGEs): platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru) and iridium (Ir) seem to spread in the environment and accumulate in living organisms, they may pose a threat to animals and humans. This paper discusses the modes and forms of PGE emission as well as their impact on the environment and living organisms.