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1.  Template Synthesis of Co(II), Ni(II) and Cu(II) Complexes Derived From Oxamide Ligand and the Reactivity of Cu(II) Complex Towards Human Serum Albumin 
A new oxamide ligand 2,2'-(oxalydimino)bis(diacetic acid)[C10H11O10N2],[L] has been synthesized by the condensation reaction of Iminodiacetic acid and Diethyloxalate. This ligand [L] was further allowed to interact with triethylene-tetraamine metal complexes [C16H26N6O8M]Cl2 (where M=Co11, Ni11 and Cu11) to yield the new N4 macrocyclic complexes 3, 3', 6, 6' tetraazadodeca 1-1' diimino N N tetraacetic acid M) chloride ([C16H26N6O8Co]Cl2, [C16H26N6O8Ni]Cl2 and [C16H26N6O8Cu]Cl2). These complexes were characterized by elemental analyses, i.r., n.m.r., e.p.r, and u.v.-vis spectroscopy. All the complexes show square planar geometry and are ionic in nature. The kinetic studies of the Cu(lI) complex were ascertained spectrophotometrically by observing the absorbance changes in presence of protein Human Serum Albumin (HSA) in phosphate buffer at different pH's at 300C. The absorbance changes were monitored at 278 nm (λmax of HSA) with respect to time and pseudo-first-order rate constants, kobs, were obtained from the slope of the straight line using the least squares regression method. The electrochemical behaviour of the Cu(ll) complex was monitored by cyclic voltammetry in a phosphate buffer. The Ep values-0.730 and-0.560 V respectively, were obtained at the scan rate of 0.1 Vs-1. The interaction of the Cu(II) complex with the HSA was studied at the same scan rate, which reveals weak binding as the E0 values do not shift considerably. The cyclic voltammogram of the Cu(II) complex bound to HSA was recorded at different pH's also (6.5 to 7.4). The pH-rate profile data reveals that the reactions are pH dependent.
PMCID: PMC2267083  PMID: 18365078
2.  Biological Activity of Some Cobalt(II) and Molybdenum(VI) Complexes: in vitro Cytotoxicity 
Cytotoxicity and cell growth inhibition studies were performed for five distinct cobalt(ll) [Co2(acac)tpmc](ClO4)3, [Co2(dibzac)tpmc](ClO4)3, [Co2(hfac)tpmc](CIO4)2, [Co2(tmhd)tpmc](CIO4)3 and [Co2(ox)tpmc](CIO4)2.3H20 and five molybdenum(Vl) complexes, [MoO2(pipdtc)2], [MoO2(morphdtc)], [MoO2(timdtc)2], [MoO2(pzdtc)2] and [MoO2(N-Mepzdtc)2]. The former were tested in two leukemia cell lines: chronic myelogenic leukemia (K562) and human promyelocytic cell line (U937). They showed to have relatively high toxicity in K562 cells and a relatively low cytotoxicity in U937 cells, as assessed by both MTT and Trypan Blue assays. The five molybdenum complexes were tested in human promyelotic U937 cell line and they showed to have high toxicity.
PMCID: PMC2267082  PMID: 18365076
3.  Biotransformation of Chloroaromatics: the Impact of Bioavailability and Substrate Specificity 
The effect of surfactants on the biodegradation of mono-aromatic hydrocarbons such as benzene, chlorobenzene and 1,2-dichlorobenzene by an Escherichia coli JMI09(MI) recombinant strain, carrying a gene cluster containing the genes for benzene dioxygenase, cis-benzene dihydrodiol dehydrogenase, and catechol 2,3-dioxygenase from Pseudomonas putida ML2, has been investigated. We observed that the efficiency of the benzene dioxygenase catalyzed conversions to cis-dihydrodiols depends on the balance among real substrate specificity, bioavailability, and toxicity effects of highly concentrated aromatic hydrocarbons. The utilization of non ionic surfactants makes it possible to partly overcome the limiting step of biodegradation processes for scarcely water soluble hydrocarbons hindered by their limited bioavailability.
Furthermore the cis-benzene dihydrodiol dehydrogenase and the extradiol catechol 2,3-dioxygenase, which in the presently analyzed biodegradative pathway should further degrade the pollutants, are known, the first to be selectively specific for the (lR,2R)-dihydrodiol derivative which is not produced by the benzene dioxygenase, the second, to be dead-end inhibited by the corresponding chlorinated catechois. In the present example this results in the accumulation of the corresponding chlorinated cis-dihydrodiols which can be useful for asymmetric synthesis.
On the other hand the practical utilization of the system for bioremediation purposes requires the efficient conversion of the chlorinated catechols by specific intradiol ring-cleaving dioxygenases, the crystal structures of some of these last enzymes are currently under analysis in our laboratory to understand the structuralfunctional correlations. Preliminary data show overall structures similar to the catechol 1,2-dioxygenase from Acinetobacter sp. ADP1 thus suggesting that the substrate specificity differences are mainly related to subtle differences in the catalytic site.
PMCID: PMC2267078  PMID: 18365077
4.  Biological and Clinical Aspects of Lanthanide Coordination Compounds 
The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems.
PMCID: PMC2267075  PMID: 18365075
5.  Interactions of Zn(II) Ions with Three His-Containing Peptide Models of Histone H2A 
The interactions of Zn(ll) ions with the blocked hexapeptide models -TESHHK-, -TASHHK- and -TEAHHK- of the -ESHH- motif of the C-terminal of historic H2A were studied by using potentiometric and IH-NMR techniques. The first step of these studies was to compare the pKa values of the two His residues inside each hexapeptide calculated by potentiometric or H-NMR titrations. Hereafter, the potentiometric titrations in the pH range 5 11 suggest the formation of several monomeric Zn(ll) complexes. It was found that all hexapeptides bind to Zn(ll) ions initially through both imidazole nitrogens in weakly acidic and neutral solutions forming slightly distorted octahedral complexes. At higher pH values, the combination of potentiometric titrations and one and two dimensional NMR suggested no amide coordination in the coordination sphere of Zn(II) ions. Obviously, these studies support that the -ESHH- sequence of histone H2A is a potential binding site for Zn(II) ions similarly with the Cu(II) and Ni(ll) ions, presented in previous papers.
PMCID: PMC2267071  PMID: 18365073
6.  Comparative Analysis of Metal Binding Characteristics of Copper Chaperone Proteins, Atx1 and ATOX1 
The metal binding properties of the human copper chaperone ATOXI and its yeast homologue Atxl have been characterized. Complexes of these proteins with Cu(I), Ag (1), Cd(II) and Hg(II) were studied by native gel electrophoresis, chemical cross-linking followed by SDS-PAGE, as well as by size exclusion chromatography, mutagenesis and UV-visible absorption spectroscopy. Results indicate that binding of different metals to either ATOXI or Atxl altered conformation of subunit structure and the oligomerization state of the proteins. Furthermore, it has been demonstrated that freshly reduced apoprotein is capable to convert Cu(ll) to Cu(l) stoichiometrically to the amount of protein present, while oxidized protein is only twenty per cent as active. Titration of Cu(ll) with either oxidized or reduced protein resulted in similar increase in absorbance at 254 nm, implicating Cu-thiolate formation in both forms of the protein, but titration with Ag(i) caused the increase in absorbance at 254 nm with the reduced protein only. These data indicate that Cu(1), Ag(1), Hg(ll) and Cd(ll) are all capable of binding to ATOXI and Atxl, but the characteristics of the binding to these copper chaperones differ for different metals.
PMCID: PMC2267068  PMID: 18365072
7.  Cytotoxicity Profiles for a Series of Triorganophosphinegold(I) Dithiocarbamates and Triorganophosphinegold(I) Xanthates 
A series of triorganophosphinegold(1) dithiocarbamate (R3PAuS2CNR'2) and xanthate (R3PAuS2COR') complexes have been prepared and characterised spectroscopically. Based on crystallographic evidence, the molecules feature linear gold(1) geometries defined by sulphur and phosphorus donors. The complexes, along with a series of known anti-cancer agents, have been screened against a panel of seven human cancer cell lines. Uniformly, the dithiocarbamate derivatives are more active than their xanthate counterparts, with the most active complex being Et3PAu(S2CNEt2), and are more active than cisplatin in all cell lines screened but, not as potent as taxol.
PMCID: PMC2267067  PMID: 18365074
8.  Role of Metal Ions and Hydrogen Bond Acceptors in the Tautomeric Equilibrium of Nitro-9[(Alkylamino)Amino]-Acridine Drugs 
3-nitro-9-[2-(dialkylamino)ethyl)]aminoacridines (alkyl = methyl or ethyl) have been used as ligands towards platinum(If). The end product is a complex in which the acridine acts as a tridentate ligand contributing the two exocyclic nitrogen atoms and one of the two peri carbons. The metallation takes place predominantly at the peri position of the unsubstituted ring. The coordinated acridine is in the imino tautomeric form although, in the free state, it occurs exclusively in the amino form (both in the solid state and in solution). The imino tautomer is considered to be the biologically active form. In the platinated species the N(10)H of the acridine can be involved in strong hydrogen bonding with a chloride ion leading to formation of an association complex, the formation constant has been found to be 1.4±103 M−1. The N(10)H┄CI interaction can influence the tautomeric equilibrium of the acridine dye also in the uncoordinated species, however, the shift in favor of the imino tautomer is not complete.
PMCID: PMC2269723  PMID: 18365071
9.  Organotin(IV) Derivatives of L-Cysteine and their in vitro Anti-Tumor Properties 
The synthesis and characterization of the organotin compounds [(n-C4H9)2Sn(cys)] (1), [(C6H5)2Sn(cys)] (2), [(C6H5)3Sn(Hcys).(H2o)] (3), {[(CH3)2Sn(Kcys)2].2(H20)} (4), {[(n-C4H9)2Sn(Kcys)2].2(H20)} (5) and {[(C6H5)2Sn(Kcys)2].2(H20)} (6) (where H2cys = L-cysteine) are reported. The compounds have been characterized by elemental analysis and 1H-NMR, Uv-Vis, FT-IR and MOssbauer spectroscopic techniques. Attempted recrystallization of (2) in DMSO/methanol 2:1 solution yielded after several days unexpectedly the dimeric compound bis(tri-phenyltin)sulphide {[(C6H5)3Sn]2S} (7) which has been characterized by x-ray analysis. The structure of the parent complex (2) as well as the mechanism of the decomposition of cysteine are being further investigated. The in vitro anticancer activity of complexes (I)- (6), against human leukemia (HL60), human liver (Bel7402), human stomach (BGC823) and human cervix epithelial human carcinoma (Hela), nasopharyngeal carcinoma (KB) and lung cancer (PG) tumor cells, were evaluated.
PMCID: PMC2267074  PMID: 18365068
10.  Organic Derivatives of Mercury and Tin as Promoters of Membrane Lipid Peroxidation 
The toxicity mechanisms of mercury and tin organic derivatives are still under debate. Generally the presence of organic moieties in their molecules makes these compounds lipophilic and membrane active species. The recent results suggest that Hg and Sn compounds deplete HS-groups in proteins, glutathione and glutathione-dependent enzymatic systems; this process also results in the production of reactive oxygen species (ROS), the enhancement of membrane lipids peroxidation and damage of the antioxidative defence system. The goal of this review is to present recent results in the studies oriented towards the role of organomercury and organotin compounds in the xenobiotic-mediated enhancement of radical production and hence in the promotion of cell damage as a result of enhanced lipids peroxidation. Moreover the conception of the carbon to metal bond cleavage that leads to the generation of reactive organic radicals is discussed as one of the mechanisms of mercury and tin organic derivatives toxicity. The possible use of natural and synthetic antioxidants as detoxification agents is described. The data collected recently and presented here are fundamentally important to recognizing the difference between the role of metal center and of organic fragments in the biochemical behavior of organomercury and organotin compounds in their interaction with primary biological targets when entering a living organism.
PMCID: PMC2267073  PMID: 18365070
11.  Alkali-Ion-Crown Ether in Art and Conservation: The Applied Bioinorganic Chemistry Approach 
Dried varnish is rich in many ester moieties, which may be broken down into small, soluble compounds by esterase activity or alkaline hydrolysis. Two methods for varnish removal have been developed, including the treatment of either lipase or RbOH / PEG-400 crown ether which allow aged oil varnishes or paint coverings to be removed or thinned. These techniques are designed to proceed in a controlled manner without damaging lower paint or base layers. Unfortunately, lipase did not react with the aged ester groups of dried linseed oil varnish. Surprisingly, the varnish came off in the presence of Tris buffer alone which, in addition, formed reactive metal complexes. A better choice was the use of high Mr alkali ion polyethylene glycol–400 (PEG-400) crown ether type chelates. PEG-400 complexes alkali ions including rubidium and other alkaliions impeding the diffusion of their basic counter ions into lower varnish or paint layers. Possible migration of alkali metal ions into the paint layer during alkaline varnish removal was determined by labelling the cleansing solutions with 86Rb. Fortunately, varnish is degraded on the surface only. Lower paint or varnish layers are not attacked even if chemically similar to the varnish or over painting to be removed as virtually no 86Rb was detected on the paint surface.
PMCID: PMC2267072  PMID: 18365066
12.  Oxidative Activity of Copper(II) Complexes with Aminoglycoside Antibiotics as Implication to the Toxicity of These Drugs 
The majority of aminoglycosidic antibiotics anchor Cu(ll) ions by {NH2, O} chelates of the A and C rings of its molecule as distinct from amikacin, which belongs to the class of substituted ones. The results indicate that all these antibiotics effectively bind copper(ll) at physiological pH. Cyclic voltammetry investigations and kinetic studies of H2o2 disproportionation and hydroxyl radicals detection made it possible to support the mechanism of oxidative reactivity of cupric complexes of aminoglycosides, which involves Cu(1) and Cu(lll) redox states and metal-bound, rather than free radical species. The mechanism of this process appears to be complicated, and may have deleterious side-effects by leaking radical intermediates. The presence of these reactive oxygen species may be responsible for modulating the biological activity of these drugs.
The interactions of copper(ll) complexes of aminoglycosides with oxidation-susceptible biomolecules: 2’-deoxyguanosine, plasmid DNA and yeast tRNAphe in both the presence and absence of hydrogen peroxide showed that the complexes with H2o2 are the most efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNAphe. Some of these reactions may play a role in aminoglycoside-induced ototoxicity and nephrotoxicity; moreover, they may suggest that Cu(ll)-aminoglycosides are potentially dangerous genotoxic agents. These complexes were also screened for their antibacterial activity and bioassays were engaged to find out the possibility of Cu(ll)-kanamycin A complexes to induce tumor necrosis factor (TNF), interferon (IFN) and interleukin-10 (IL-10) in human peripheral blood leukocytes. The aim of these studies was to compare the biological action of antibiotic alone and complexed with copper(ll) ions in both neutral and oxidative environment.
PMCID: PMC2267070  PMID: 18365069
13.  Novel Carboranyl Derivatives of Nucleoside Mono- and Diphosphites and Phosphonates: A Synthetic Investigation 
A number of nucleoside mono- and diphosphites and phosphonates containing 1,2-dicarbadodecaborane (12) (la-6b) at 5'-position of the sugar moiety have been synthesized in good yields. Experimental details along with the spectroscopic and analytical data, supporting the formation of the title compounds, are presented. These constitute a new generation of boron compounds that are envisioned to be useful in cancer treatment via Boron Neutron Capture Therapy (BNCT).
PMCID: PMC2267069  PMID: 18365067
14.  Biosorption of Chromium (VI) from Aqueous Solutions onto Fungal Biomass 
The biosorption of chromium (VI) on eighteen different natural biosorbents: Natural sediment, chitosan, chitin, Aspergillus flavus I-V, Aspergillus fumigatus I-ll, Helmintosporium sp, Cladosporium sp, Mucor rouxii mutant, M. rouxii IM-80, Mucor sp-I and 2, Candida albicans and Cryptococcus neoformans was studied in this work. It was found that the biomass of C. neoformans, natural sediment, Helmintosporium sp and chitosan was more efficient to remove chromium (VI) (determined spectrophotometrically at 540 nm using diphenylcarbazide as the complexing agent) achieving the. following percentage of removals: 98%, 98% and 63%, respectively. The highest adsorption was obtained with C. neoformans and Helmintosporium sp at pH 2.0 and 4.0 + 0.2, respectively, at 28∘C after 24 hours of incubation, with 0.2 mg/L of cellular biomass.
PMCID: PMC2267066  PMID: 18365065
15.  Nickel(II), Copper(II) and Zinc(II) Complexes of 9-[2- (Phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA), the 8-Aza Derivative of the Antiviral Nucleotide Analogue 9-[2-(Phosphonomethoxy)ethyl] adenine (PMEA). Quantification of Four Isomeric Species in Aqueous Solution 
The acidity constants of the twofold protonated acyclic nucleotide analogue 9-[2-(phosphonomethoxy)- ethyl]-8-azaadenine, H2(9,8aPMEA)±, as well as the stability constants of the M(H;9,8aPMEA)+ and M(9,8aPMEA) complexes with the metal ions M2+ =Ni2+, Cu2+ or Zn2+, have been determined by potentiometric pH titrations in aqueous solution at I=0.1 M (NaNO3) and 25℃. The result for the release of the first proton from H2(9,8aPMEA)+ (pKa= 2.73), which originates from the (N1)H+ site, was confirmed by UV-spectrophotometric measurements. Application of previously determined straight-line plots of log KMM(R-PO3) versus PKH3(R-HPO3)' for simple phosph(on)ate ligands, R- PO-, where R represents a residue without an affinity for metal ions, proves that the primary binding site of 9,8aPMEA2- is the phosphonate group for all three metal ions studied. By stability constant comparisons with related ligands it is shown, in agreement with conclusions reached earlier for the Cu(PMEA) system [PMEA2-=dianion of 9-[2- (phosphonomethoxy)ethyl]adenine], that in total four different isomers are in equilibrium with each other, i.e. (i) an open isomer with a sole phosphonate coordination, M(PA)op, where PA2-=PMEA2-or 9,8aPMEA2-, (ii) an isomer with a 5-membered chelate involving the ether oxygen, M(PA)cl/o, (iii) an isomer which contains 5- and 7-membered chelates formed by coordination of the phosphonate group, the ether oxygen and the N3 site of the adenine residue, M(PA)cl/O/N3, and finally (iv) a macrochelated isomer involving N7, M(PA)cl/]N7. The Cu2+ systems of PMEA2- and 9,8aPMEA2- behave quite alike; the formation degrees for Cu(PA)op, CuM(PA)cl/O, Cu(PA)cl/O/N3 and Cu(PA)cl/N3 are approximately 16, 32, 45 and 7%, respectively, which shows that Cu(PA)cl/N7 is a minority species. In the Ni2+ and Zn2+ systems the open isomer is the dominating one followed by M(PA)cl/O, but there are indications that the other two isomers also occur to some extent.
PMCID: PMC2267076  PMID: 18365084
16.  Studies of Zinc(II) and Nickel(II) Complexes of GSH, GSSG and Their Analogs Shed More Light on Their Biological Relevance 
Glutathione, Υ-Glu-Cys-Gly, is one of the most abundant small molecules in biosphere. Its main form is the reduced monomer (GSH), serving to detoxicate xenobiotics and heavy metals, reduce protein thiols, maintain cellular membranes and deactivate free radicals. Its oxidized dimer (GSSG) controls metal content of metallothionein. The results presented provided a quantitative and structural description of Zn(II)- glutathione complexes, including a novel ternary Zn(II)-GSH-His complex. A solution structure for this complex was obtained using 2D-NMR. The Complexes studied may contribute to both zinc and glutathione physiology. In the case of Ni(ll) complexes an interesting dependence of coordination modes on the ratios of reactants was found. At high GSH excess a Ni(GSH)2 complex is formed, with Ni(ll) bonded through S and N and/or O donor atoms. This complex may exist as a high- or low-spin species. Another goal of the studies presented was to describe the catalytic properties of Ni(II) ions towards GSH oxidation, which appeared to be an important step in nickel carcinogenesis. The pH dependence of oxidation rates allowed to determine the Ni(GSH)2 complex as the most active among the toxicologically relevant species. Protonation and oxidation of metal-free GSH and its analogues were also studied in detail. The monoprotonated form HL2- of GSH is the one most susceptible to oxidation, due to a salt bridge between S- and NH3+ groups, which activates the thiol.
PMCID: PMC2267084  PMID: 18365081
17.  Synthesis and Characterization of a New Cobalt(II) Complex with 2-(2-Pyridyl)Imino-N-(2-Thiazolin-2-yl)Thiazolidine (PyTT) 
The compound aquanitrate-кObis[2-(2-pyridy)-imin-кN-N-(2-thiazin-кN-2-y)thiazidine]cbat() nitrate has been isolated and characterized by single crystal X-ray diffraction, IR spectroscopy, UV-Vis-NIR diffuse reflectance and magnetic susceptibility measurements. The environment around the cobalt atom may be described as a distorted octahedral geometry with the ligand-metal-ligand bite angles varying between 84.07(8)° and 98.66(8)°.The metallic atom is coordinated to two thiazoline nitrogens [av. Co-N =2.067 Å], two imino nitrogens [av. Co-N =2.122 Å], one oxygen atom of the nitrate group monodentate [Co-O(1)= 2.249(2) Å] and the oxygen atom of the water molecule [Co-O(IW)= 2.105(2) Å]. Electronic UV-Vis-NIR spectral data and the calculated magnetic moment are indicative of octahedral Co(ll) complexes. In the same way as other PyTT complexes, the organic moiety preserves the imino-thiazolidine form detected in the structure of PyTT.
PMCID: PMC2267081  PMID: 18365082
18.  Calixarenes and Their Biomimetic Applications 
The synthetic models for the structures, spectroscopic properties and catalytic activities of metalloprotein active sites have been reviewed. Calixarenes were used as new biomimetic catalysts because of their advantage of providing preorganiiation of the catalytic group, which can bind the substrate dynamically that results in fast turnover and fast release of the products. Functional and structural models based on calixarenes are presented and in addition importance of molecular recognition and non-covalent interactions e.g. hydrogen bonding and their role in biological systems are discussed with the help of synthetic systems.
PMCID: PMC2267080  PMID: 18365079
19.  Synthesis, Structure, Properties And Biological Behaviour Of The Complex [RuIV (H2L) Cl2].2H2O (H4L= 1,2-Cyclohexanediamminetetraacetic Acid) 
The highly water-soluble ruthenium complex [Ru(H2L)Cl2]2H2o, in which H4L is the sequestering ligand trans-l, 2-cyclohexanediamminetetraacetic acid (cdta) has been synthesized, structurally characterized and its properties studied. The X-ray crystallographic study shows that the chelating coordinated ligand is tetradentate while the ruthenium environment is octahedral and slightly distorted, with two chloride anions coordinated in cis positions. Potentiometric, conductimetric and infrared studies confirm the presence of two free carboxylic groups, while electronic and voltammetric studies show that the central ion is Ru(IV). The testing of the cytotoxic activity of this complex against three different human cancer cell lines indicates that [Ru(H2L)Cl2].2H2O shows a remarkable and selective antiproliferative effect against the human uterine neck carcinoma HeLa and the malign adenocarcinoma ADLD, showing only a discrete turnout cell inhibition activity against colon adenocarcinoma HT-29. The important antiprotiferative behaviour of complex 1 against the human adenocarcinoma ADLD, indicates that [Ru(H2L)Cl2].2H2O might be considered as potential antineoplastic compound.
PMCID: PMC2267079  PMID: 18365080
20.  Metals, Health and the Environment – Emergence of Correlations Between Speciation and Effects 
Over the last half-century both the identification of the causes of diseases and the use of inorganic compounds to treat such conditions have been considerably enlightened through our emerging capabilities to identify the pivotal chemical species involved. The ‘duty of care’ placed upon scientists to protect the environment from manufactured chemicals and to limit their effects upon humans therefrom is best realised from a speciation knowledge database. This paper discusses categorising chemicals in terms of their persistence, bioaccumulation, and toxicities and uses speciation information to optimise desirable effects of chemicals in several applications such as the manufacture of pulp for paper and in the foliar nutrition of crops. Simultaneously, the chemical wasting side effects of industrial overdosing is easily avoided if speciation approaches are used. The move towards new environmentally friendly ligand agents is described and methods of finding substitute agents (often combinations of two or more chemicals) to replace nonbiodegradable EDTA. The geosphere migration of metals through the environment is discussed in terms of speciation. Future objectives discussed include improved means of communicating speciation-based recommendations to decision makers.
PMCID: PMC2267077  PMID: 18365083

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