Extent of the Acidification by N7-Coordinated cis-Diammine-Platinum(II) on the Acidic Sites of Guanine Derivatives

Coordination of two monoprotonated 2'-deoxyguanosine 5'-monophosphate species, H(dGMP)(-), via N7 to cis-(NH(2))(2)Pt(2+) gives the complex cis-(NH(2))(2)Pt(H.dGMP)(2) which is a four-protonic acid. The corresponding acidity constants were measured by potentiometric pH titrations (25; I = 0.1 M, NaNO(3)). The first two protons are released from the two -P(O)(2)(OH)(-) groups (PK(a/1)= 5.57; PK(a/2) = 6.29) and the next two protons are from the H(N1) sites of the guanine residues (PK(a/3) = 8.73; PK(a/4) = 9.48). The micro acidity constants of the various sites are also evaluated. Comparison of these data with those determined for the three-protonic H(2)(dGMP)(+/-) (PK(a/1) = 2.69 for the H(+)(N7) site; PK(a/2) = 6.29 for -P(O)(2)(OH)(-) ;PK(a/3) = 9.56 for H(N1)) shows that on average the N-7-coordinated Pt(2+) acidifies the phosphate protons by Delta pK(a) = 0.36 and the H(N1) sites by Delta pK(a) = 0.46. These results are further compared with those obtained previously for cis-(NH(2))(2)Pt(L)(2), where L = 9-ethylguanine or monoprotonated 2'-deoxycytidine 5'-monophosphate. Conclusions regarding platinated DNA are also presented.     

Interaction of [Rh(2)(O(2)CCH(3))(4)(H(2)O)(2)] and [Rh(2)(O(2)CCH(OH)Ph)(2)(phen)(2)(H(2)O)(2)](O(2)C-CH(OH)Ph)(2) With Sulfhydryl Compounds and Ceruloplasmin

The interaction of binuclear rhodium(II) complexes [Rh(2)(OOCCH(3))(4)(H(2)O)(2)], [Rh(2){OOCCH(OH)Ph}(2)(phen)(2)(H(2)O)(2)] {OOCCH(OH)Ph}(2), [Rh(2)(OOCCH(3))(2)(bpy)(2)(H(2)O)(2)](OOCCH(3))(2) and [Rh(2)Cl(2)(OOCMe)(2)(bpy)(2)](3H(2)O) with ceruloplasmin, cysteine, glutathione and coenzyme A have been investigated using. UV-Vis and CD spectroscopies. The complexes containing phen or bpy at pH = 7.4 and 4.0 are readily reduced with sulfhydryl compounds, while rhodium(II) acetate is relatively stable in these conditions. Complex [Rh(2){OOCCH(OH)Ph}(2)(phen)(2)(H(2)O)(2)] strongly changes structure of ceruloplasmin leading to the decrease of of alpha-helix content and loss of oxidase activity.     

二茂二氯化钛或锆与二茂基氯化钐复合催化乙烯聚合

分别以二茂二氯化钛(Cp2TiCl2)和二茂二氯化锫(Cp2ZrCl2)与钐茂金属催化剂复合组成催化体系，并以甲基铝氧烷为助催化剂，进行宽分子量分布聚乙烯合成研究。研究发现与使用Cp2TiCl2和二(甲基茂基)氯化钐复合体系相比，使用其与二(特丁基茂基)氯化钐[(t—BuCp)2SmCl]复合体系能得到具有较高粘均分子量的聚乙烯。同样，使用Cp2ZrCl2与(t—BuCp)2SmCl复合体系也能得到具有较高粘均分子量的聚乙烯。且使用含(t-BuCp)2SmCl复合体系得到分子量分布指数达3．5以上的聚乙烯。     

Analysis of platinum adducts with DNA nucleotides and nucleosides by capillary electrophoresis coupled to ESI-MS: indications of guanosine 5'-monophosphate O6-N7 chelation

DNA is the ultimate target of platinum-based anticancer therapy. Since the N7 of guanine is known to be the major binding site of cisplatin and its analogues, adduct formation with model nucleotides, especially 2'-deoxyguanosine 5'-monophosphate (dGMP), has been studied in detail. During the last few years a coupled capillary eletrophoresis/electrospray-ionization mass spectrometry (CE/ESI-MS) method has been advantageously used in order to separate and identify platinum adducts with nucleotides in submillimolar concentrations in aqueous solutions. Beside the bisadduct, [Pt(NH(3))(2)(dNMP)(2)](2-) (NMP=2'-deoxynucleoside 5'-monophosphate), and the well-known monochloro and monohydroxo adducts, [Pt(NH(3))(2)Cl(dNMP)](-) and [Pt(NH(3))(2)(dNMP)OH](-), respectively, a third kind of monoadduct species with a composition of [Pt(NH(3))(2)(dNMP)](-) can be separated by CE and detected through the m/z values measured with ESI-MS. Different experimental setups indicate the existence of an O(6)-N7 chelate, whereas the formation of N7-alphaPO(4) macrochelates or dinuclear species is unlikely. Additionally, offline MS experiments with 2'-deoxyguanosine (dG) and stabilization of the controversially discussed O(6)-N7 chelate by oxidation with hydrogen peroxide support the assumption of the existence of O(6)-N7 chelation.     

Chiral platinum(II) metallointercalators with potent in vitro cytotoxic activity

Four platinum(II) metallointercalating complexes of 1,10-phenanthroline (phen) with the chiral ancillary ligands trans-R,R- and trans-S,S-1,2-diaminocyclohexane (R,R- and S,S-dach, respectively), and N,N'-dimethyl-R,R- and N,N'-dimethyl-S,S-1,2-diaminocyclohexane (Me(2)-R,R-dach and Me(2)-S,S-dach, respectively) have been synthesised and characterised. The crystal structure of [Pt(Me(2)-S,S-dach)(phen)](ClO(4))(2)1.5 H(2)O (C(20)H(26)Cl(2)N(4)O(9.5)Pt) has been determined; orthorhombic, space group P2(1)2(1)2(1)(No. 19), a=23.194(8), b=25.131(9), c=8.522(3) A. In vitro cytotoxic assays (IC(50)) in the human bladder cancer cell line 5637 and in the murine leukemia L1210 cell line revealed that [Pt(S,S-dach)(phen)](ClO(4))(2) (0.091 and 0.13 microM, respectively) and [Pt(R,R-dach)(phen)](ClO(4))(2) (0.54 and 1.50 microM, respectively) were more cytotoxic than cisplatin (0.31 and 0.50 microM, respectively) and considerably more cytotoxic than their methylated counterparts, [Pt(Me(2)-R,R-dach)(phen)](ClO(4))(2) and [Pt(Me(2)-S,S-dach)(phen)](ClO(4))(2) (both>23 microM). Chiral discrimination for [Pt(S,S-dach)(phen)](ClO(4))(2) over its R,R-enantiomer was observed in all 13 cancer cell lines investigated. Moreover, [Pt(S,S-dach)(phen)](ClO(4))(2) was more active than cisplatin in all cell lines tested and shows only partial cross-resistance to cisplatin in two cisplatin resistant cell lines.     

Properties of Binuclear Rhodium(II) Complexes and Their Antibacterial Activity

Binuclear rhodium(II) complexes [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)], [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) and [Rh(2)Cl(2)(mu-OOCCH(3))(terpy)(2)](H(3)O)Cl(2).9H(2)O (R = H, Me, Bu(n), ph, PhCHOH; N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (dmp) and 6,7-dimethyl-2,3- di(2-pyridyl)quinoxaline (dmpq); terpy 2,2':6',2'-terpyridine) have been synthesized and their structure and properties have been studied by electronic, IR and (1)H NMR spectroscopy. Antibacterial activity of these complexes against Staphylococcus aureus and Escherichia coli has been investigated. The most active antibacterial agents against S. aureus were [Rh(2)(OOCPh)(2)(phen)(2)(H(2)O)(2)](2+), [Rh(2)(OOCPh)(2)(dmpq)(2)(H(2)O)(2)](2+), [Rh(2)(OOCBu)(2)(phen)(2)(H(2)O)(2)](2+) and [Rh(2)-(OOCBu)(2)(bpy)(2)(H(2)O)(2)](2+) which were considerably more active than the appropriate nitrogen ligands. The complexes show rather low activity against E. coli.     

Behaviour of the Antitumor Agent Vanadocene Dichloride in Physiological and Therapeutic Media, Blood Plasma and Human Blood - An EPR Study

By means of EPR spectroscopy the behaviour of the vanadocene dichloride (I), Cp(2)VCl(2) (Cp=eta(5)-C(5)H(5)), in various deoxygenated and non-deoxygenated physiological media and therapeutic solution as well as in blood plasma and stabilized human blood was studied. On the basis of measured values of isotropic spectroscopic splitting factor g(iso) and isotropic hyperfine coupling constant A(iso), the vanadocene species, [Cp(2)V(H(2)O)Cl](+) (II; g(iso)= 1.985, |A(iso)| = 7.68 mT), [Cp(2)V(H(2)O)(2)](2+) (III; g(iso)= 1.983, |A(iso)| = 7.92 mT), [Cp(2)V(OH(2) (IV; g(iso)= 1.991, |A(iso)| = 6.285 mT), [Cp(2)VCl(DMSO)](+) (V; g(iso)= 1.985, |A(iso)| = 7.69 mT), the vanadyl species [VO(DMSO)(5)](2+) (VI; g(iso)= 1.964, |A(iso)| = 10.78mT) and [VO(H(2)O)(5)](2+) (VII; g(iso)= 1.955, |A(iso)| = 11.56 mT) have been identified. From the measurements it follows that I does not react in its first coordination sphere with any component of a system used other than water and DMSO, resp. As to water-containing media, its behaviour is fully consistent with that of I in pure aqueous media. It was found the only vanadocene species present after application of the therapeutic solution of I into human blood to be IV not interacting in its first coordination sphere with any blood component.     

Effects of hypoxia and transferrin on toxicity and DNA binding of ruthenium antitumor agents in hela cells

Nuclear DNA binding and inhibition of growth of HeLa cells in culture were determined after 24 h incubation with the ruthenium anticancer agents cis-[Cl(2)(NH(3))(4)Ru]Cl (CCR) and (ImH)trans-[(Im)(2)Cl(4)Ru] (ICR) as a function of [Ru], Po(2), and added transferrin. Consistent with the "activation-by-reduction" hypothesis, cytotoxicity and DNA binding for both complexes increased under reduced oxygen conditions. Consistent with the "transferrin- transport" hypothesis, inhibition of cell growth also increased with added transferrin for both complexes. Despite their differences in charge, reduction potentials and substitution rates, both complexes behaved remarkably similarly indicating a common mechanism of action for both. Under atmospheric Conditions (Po(2) = 159 torr), CCR inhibited HeLa cell growth with IC(50) = 3.5 muM, while that for ICR was 2.0 muM. The binding of both complexes to DNA (Ru(DNA)/P(DNA)) correlated with toxicity and was approximately linear in the concentration of the ruthenium complex in the culture medium, [Ru]. For both complexes, IC(50) values decrease and DNA binding increases with decreasing log(Po(2)). In general, DNA binding at all oxygen pressures for both complexes is in the range of one Ru per 1000-2000 DNA base pairs at [Ru] = IC(50).     

Synthesis and Anti-Candida Activity of Cobalt(II) Complexes of Benzene-1,2-Dioxyacetic Acid (bdoaH(2)). X-Ray Crystal Structures of [Co(bdoa)(H(2)O)(3)] 3.5H(2)O and {[CO(phen)(3)](bdoa)}(2)24H(2)O (phen = 1,10-Phenanthroline)

Co(CH(3)CO(2))(2)4H(2)O reacts with benzene-1,2-dioxyacetic acid (bdoaH(2)) to give the Co(2+) complexes [Co(bdoa)(H(2)O)(3)]H(2)O (1a) and [Co(bdoa)(H(2)O)(3)] 3.5H(2)O (1b). Subsequent reaction of 1a with 1,10- phenanthroline produces [CO(phen)(3)] bdoa10H(2)O (2a) and {[CO(phen)(3)](bdoa)}(2)24H(2)O (2b). Molecular structures of 1b and 2b were determined crystallographically. In 1b the bdoa(2-)- ligates the metal by two carboxylate oxygens and two ethereal oxygens, whereas in 2b the bdoa(2-) is uncoordinated. The Mn(2+) and Cu(2+) complexes [Mn(bdoa)(phen)(2)]H(2)O (3) and [Cu(pdoa)(imid)(2)] (4) were also synthesised, 1a-4 and other metal complexes of bdoa H(2) (metal = Mn(2+), Co(2+) ,Cu(2+), Cu(+) ) were screened for their ability to inhibit the growth ofhe yeast Candida albicans. Complexes incorporating the 1,10-phenanthroline ligand were the most active.     

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

Studies directed at establishing the structural features that control Pt/DNA interactions and the anticancer activity of Pt drugs are described. [(1)H, (15)N]-HSQC 2D NMR spectroscopic studies of the reactions of cisplatin with oligonucleotides containing ApG and GpA binding sites reveal dramatic differences in the rates of formation of monofunctional adducts at the two sites. When the reactant is cis-[Pt(NH(3))(2)(OH(2))(2)](2+) no such differences are observed suggesting that outer-sphere interactions between the reactant and the oligonucleotide may play a substantial role in determining the rates. Rates of closure to the bifunctional adducts are similar to those observed for cisplatin. Studies of the adduct profiles formed by sterically bulky and/or optically active complexes reveal that steric interactions play a major role in mediating the binding of Pt(ll) to DNA but that hydrogen bonds play less of a role. In vitro cytotoxic activities for these complexes do not always follow the trends that would be expected on the basis of the adduct profiles.     

Synthesis and Biological Activity of Manganese (II) Complexes of Phthalic and Isophthalic Acid: X-Ray Crystal Structures of [Mn(ph)(Phen)(2)(H(2)O)]. 4H(2)O, [Mn(Phen)(2)(H(2)O)(2)](2)(Isoph)(2)(Phen). 12H(2)O and {[Mn(Isoph)(bipy)](4). 2.75biby}(n)(phH(2) = Phthalic Acid; isoph = Isophthalic Acid; phen = 1,10-Phenanthroline; bipy = 2,2-Bipyridine)

Manganese(II) acetate reacts with phthalic acid (phH(2)) to give [Mn(ph)].0.5H(2)O (1). Reaction of 1 with 1,10-phenanthroline produces [Mn(ph)(phen)].2H(2)O (2) and [Mn(ph)(phen)(2)(H(2)O)].4H(2)O (3). Reaction of isophthalic acid (isophH(2)) with manganese(II) acetate results in the formation of [Mn(isoph)].2H(2)O (4). The addition of the N,N-donor ligands 1,10-phenanthroline or 2,2'-bipyridine to 4 leads to the formation of [Mn(2) (isoph)(2)(phen)(3))].4H(2)O (5), [(Mn(phen)(2)(H(2)O)(2)](2)(isoph)(2)(phen).12H(2)O (6) and {[Mn(isoph)(bipy)](4).2.75 biby}(n) (7), respectively. Molecular structures of 3, 6 and 7 were determined crystallographically. In 3 the phthalate ligand is bound to the manganese via just one of its carboxylate groups in a monodentate mode with the remaining coordination sites filled by four phenanthroline nitrogen and one water oxygen atoms. In 6 the isophthalates are uncoordinated with the octahedral manganese center ligated by two phenanthrolines and two waters. In 7 the Isophthalate ligands act as bridges resulting in a polymeric structure. One of the carboxylate groups is chelating a single manganese with the other binding two metal centres in a bridging bidentate mode. The phthalate and isophthalate complexes, the metal free ligands and a number of simple manganes salts were each tested for their ability, to inhibit the growth of Candida albicans. Only the "metal free" 1,10-phenanthroline and its manganese complexes were found to be active.     

Synthesis, Characterisation and Antifungal Activities of Some New Copper(II) Complexes of Isomeric 3,5,7,7,10,12,14,14-Octamethyl-1,4,8,11-Tetraazacyclotetradecanes

Three isomeric Me(8)[14]anes, L(A), L(B) and L(C), undergo complexation with copper(II) salts to form a series of [CuLX(n)(H(2)O)(x)]X(y).(H(2)O)(z) complexes where L = L(A), L(B) and L(C); X = Cl, Br, NO(3); n, x, y and z may have values of 0, 1 or 2. The complexes have been characterised on the basis of analytical, spectroscopic, magnetic and conductance data. Further, the X-ray crystal structure of one complex, [CuL(B)(OH(2))(2)](NO(3))(2), has been determined. The antifungal activity of all three isomeric ligands and their complexes has been investigated against a range of phytopathogenic fungi.     

锆氢试剂与含硫有机化合物脱硫反应的研究

锆氢试剂Ｃｐ２Ｚｒ（Ｈ）Ｃｌ，Ｃｐ２ＺｒＨ２可在温和条件下使直链或支链硫醇发生脱硫反应，生成相应的烷烃，使硫脲发生脱硫反应，生成氨和氢氰酸，并分别得到两种锆的硫桥络合物（Ｃｐ２ＺｒＣｌ）２Ｓ１和（Ｃｐ２ＺｒＳ）２ ２。而锆氢试剂与硫醚不能发生此类脱硫反应。     

Binuclear Rhodium(II) Complexes With Selective Antibacterial Activity

Binuclear rhodium(II) complexes [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] {R = H, Me; N-N = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen)} and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) (R = Me, Et;) have been synthesized and their structure and properties have been studied by electronic, IR and (1)H NMR spectroscopy. Antibacterial activity of these complexes against Escherichia coli and Staphylococcus aureus has been investigated. The most active antibacterial agents against E. coli were [Rh(2)Cl(2)(mu-OOCR)(2)(N-N)(2)] and [Rh(2)(mu-OOCR)(2)(N-N)(2)(H(2)O)(2)](RCOO)(2) {R = H and Me} which were considerably more active than the appropriate nitrogen ligands. The complexes show low activity against S. aureus. The activity of the complexes [Rh(2)(OOCR)(2)(N-N)(2)(H(2)O)(2)](OOCR)(2) against E. coli decreases in the series: R=H congruent withCH(3)>C(2)H(5)>C(3)H(7) congruent withC(4)H(9). The reverse order was found in the case of S. aureus.     

锌（Ⅱ）-色氨酸-邻菲咯啉配合物的合成及其与DNA的作用和生物毒性研究

合成了一种新的锌（Ⅱ）-色氨酸-邻菲咯啉配合物[Zn（Trp）（phen）2]Cl·7H2O（Ⅰ）（Trp为L-色氨酸离子,phen为邻菲咯啉）。通过元素分析、红外光谱及热重一差热分析对其进行了结构表征。采用电子吸收光谱法、荧光光谱法及琼脂糖凝胶电泳法考察了其与DNA的作用,研究了配合物对斑马鱼胚胎的生物毒性,并与2种已知结构的锌-邻菲咯啉配合物[zn（phen）2]Cl2·5H2O（Ⅱ）和[zn（phen）]Cl2（Ⅲ）进行了比较。结果表明,配合物与鲑鱼精DNA作用大小顺序为配合物Ⅰ〉配合物Ⅱ〉配合物Ⅲ．但作用方式不同;在抗坏血酸存在下,配合物Ⅰ对pBR322DNA的切割作用最强;配合物对斑马鱼胚胎毒性作用大小顺序为配合物Ⅱ〉配合物I〉配合物Ⅲ。     

Effect of Copper Acyclovir Complexes on Herpes Simplex Virus Type 1 and Type 2 (HSV-1, HSV-2) Infection in Cultured Cells

We have found that when copper, zinc or cobalt is bound to a suitable ligand, the appropriate complex exhibited a significant anti-HSV effect (Varadinova et al., 1993; 1996). Recently published data by Sagripanti et al. (1997) also show that the inhibition of HSV by copper was enhanced by reducing agents and that mechanism of the inactivation is similar as for copper-mediated DNA damage (Aruoma, et al. 1991; Dizdaroglu, et al., 1991; Toyokuni and Sagripanti, 1994). Therefore it was interesting to study the efect of Cu(ll) coordination compounds with acyclovir (ACV) on the replication of HSV in cultured cells. The experiments on cytotoxicity as well as on the activity of three different Cu-ACV complexes [Cu(ACV)(2)Cl(2)(H(2)O)(2)] = (A); [Cu(ACV)(2)(H(2)O)(3)](NO(3))(2).H(2)O = (B) and [Cu(ACV)(2)(H(2)O)(2)](NO(3))(2)] = (C) towards virus replication, with special attention on the growth of ACV-resistant strain R-100 were performed on MDBK cells. ACV was used as a reference compound. The following results were obtained: 1) Increased cell's viability in the presence of 20-40(g/ml ACV and decreased one in the presence of Cu-ACV complexes with relative level (A) > (B) > (C); 2) Cu-ACV complexes are more cytotoxic than the ligand - ACV and the relative level is (C)>(B)>(A); 3) The anti-HSV effect of ACV can be modulated by copper at levels depending on the specificity of the particular virus strain: (i) for the ACV sensitive strain DA (HSV-1) - ACV ((A) > (C) > (B); (ii) for the ACV sensitive strain Bja (HSV-2) (A) > ACV > (C) > (B); (iii) for strain R-100 (ACV(R), TK(a)) - (A) > ACV > (C) > (B). This findings are consistent with previously published data and undoubtedly show that Cu-ACV complexes could be useful in the treatment of HSV infections, especially when the causative agent is a resistant to ACV mutant.     

Syntheses and characterization of new nickel coordination polymers with 4,4'-dipyridylsulfide. Dynamic rearrangements of one-dimensional chains responding to external stimuli: temperature variation and guest releases/re-inclusions

Crystal structures and dynamic rearrangements of one-dimensional coordination polymers with 4,4'-dipyridylsulfide (dps) have been studied. Reaction of Ni(NO(3))(2)·6H(2)O with dps in EtOH yielded [Ni(dps)(2)(NO(3))(2)] ·EtOH (1), which had channels filled with guest EtOH molecules among the four Ni(dps)(2) chains. This coordination polymer reversibly transformed the channel structure responding to temperature variations. Immersion of 1 in m-xylene released guest EtOH molecules to yield a guest-free coordination polymer [Ni(dps)(2)(NO(3))(2)] (2a), which was also obtained by treatment of Ni(NO(3))(2)·6H(2)O with dps in MeOH. On the other hand, removal of the guest molecules from 1 upon heating at 130 °C under reduced pressure produced a guest-free coordination polymer [Ni(dps)(2)(NO(3))(2)] (2b). Although the 2a and 2b guest-free coordination polymers have the same formula, they showed differences in the assembled structures of the one-dimensional chains. Exposure of 2b to EtOH vapor reproduced 1, while 2a did not convert to 1 in a similar reaction. Reaction of Ni(NO(3))(2)·6H(2)O with dps in acetone provided [Ni(dps)(NO(3))(2)(H(2)O)] ·Me(2)CO (4) with no channel structure. When MeOH or acetone was used as a reaction solvent, the [Ni(dps)(2)(NO(3))(2)] · (guest molecule) type coordination polymer, which was observed in 1, was not formed. Nevertheless, the reaction of Ni(NO(3))(2)·6H(2)O with dps in MeOH/acetone mixed solution produced [Ni(dps)(2)(NO(3))(2)]·0.5(MeOH·acetone) (5), which has an isostructural Ni-dps framework to 1.     

Determination of biotransformation products of platinum drugs in rat and human urine

Cisplatin is an extremely effective cancer chemotherapeutic agent, but its use is often accompanied by toxicity. Second generation drugs such as carboplatin are becoming more widely used because of reduced toxicity. Since biotransformation products have been implicated in the toxic responses, we have begun to investigate the reactions of cisplatin and carboplatin with potential biological ligands. Reaction products were characterized using HPLC with inductively coupled plasma - mass spectrometry (HPLC-ICP-MS), (1)H and (13)C NMR and fast atom bombardment - mass spectrometry (FAB-MS). Three Pt-creatinine complexes, cis-[Pt(NH(3))(2)Cl(Creat)](+), cis-[Pt(NH(3))(2)(H(2)O)(Creat)](2+) and cis-[Pt(NH(3))(2)(Creat)(2)](2+), were synthesized and the platinum was shown to coordinate to the ring nitrogen, N(3). Human urine samples from patients on cisplatin chemotherapy were shown to contain cisplatin, its hydrolysis product and biotransformation products containing Pt-creatinine, Pt-urea and Pt-uric acid complexes. Urine from carboplatin patients shows fewer biotransformation products. Studies with control and diabetic (protected against cisplatin toxicity) rats showed systematic differences in the biotransformation products formed on administration of cisplatin.     

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.