Renaturation effects of cis and trans platinum II and IV compounds on calf thymus deoxyribonucleic acid.

The effects of cis dichlorodiammine platinum [cis Pt(II)], trans dichlorodiammine platinum (trans Pt(II)], cis tetrachlorodiammine platinum [cis Pt(IV)], trans tetrachlorodiammine platinum [trans Pt(IV)], and ethylenediaminedichloride platinum [Pt(II)en] on the absorption spectra, and thermal hyper- and hypochromicity of calf thymus DNA were investigated. Platinum-induced renaturation was studied as one parameter of interstrand cross-linking. Based on a DNA cross-linking hypothesis, the tumor-inhibitory platinum compounds cis Pt(II), cis Pt(IV) and Pt(II)en would be expected to induce renaturation following thermal denaturation, whereas the ineffective drugs, trans Pt(II) and trans Pt(IV) would not. All five bind to DNA in such a way as to induce renaturation. However, cis Pt(IV) requires at least a 3- to 4-fold longer incubation time than is required by the other compounds to form the coordination bonds necessary for renaturation. Maximum renaturation with all compounds was observed at a molar Pt/base ratio of 0.05 except cis Pt(IV), with which it was 0.25. The rate of the formation of the platinum-coordinated cross-links by fresh cis Pt(II) suggests two reactions or types of reactions occur. The first is rapid and destabilizes the DNA helix, whereas the second is slow and responsible for renaturation following thermal denaturation. These results suggest that cis Pt(IV) may be activated cellularly and that cross-linking is not the primary mechanism of action of the tumor-inhibitory platinum compounds.     

Following spread of fire blight in Western, Central and Southern Europe by molecular differentiation of Erwinia amylovora strains with PFGE analysis

Fire blight has been detected recently in several areas of northern Spain and north-eastern Italy. To follow spread of the disease within Europe, more than 120 Erwinia amylovora strains isolated from 1957-1900 in England, France, Germany, The Netherlands, Belgium, Poland, Italy and Spain were assayed using pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA after XbaI digestion. Pattern types Pt1 and Pt4 were found for strains from England. Pt1 was also found in central Europe and eastern France, Pt4 in western France. Pt2 appeared first in Egypt, from where strains with this pattern disseminated northwards as far as into the Balkans. Pt3 was typical for northern France and Belgium. Strains from Spain displayed the pattern types Pt3 and Pt4. In Italy, Pt2 was found in the south-eastern areas, Pt3 in the north-eastern areas, and Pt1 was found very recently in orchards adjacent to the Austrian border, together with Pt3. Despite barely controlled trade with fire blight host plants and associated plant products within Europe, the PFGE patterns of the E. amylovora isolates were ordered indicating sequential spread. On the other hand, the appearance of Pt3 in northern Italy and central Spain can be explained by the import of contaminated plants by nurseries.     

Rapid detection of hypoxanthine-guanine phosphoribosyltransferase on cellogel

Zusammenfassung 541 Serumproben von nichtverwandten Deutschen aus dem Kölner Raum wurden auf ihre Pt- und C3-Typen untersucht. Bei 537 Seren fand sich eine Überein-stimmung der Pt A-Typen mit den C3 F-Typen, der Pt AB-Typen mit den C3 FS-Typen und der Pt B-Typen mit C3 S-Typen. Die C3-Varianten F0.65S, F0.6S, F0.5S wurden als Pt AB bestimmt, die C3-Variante F0.55S wurde als Pt B bestimmt. Die Frage der Vergleichbarkeit der Systeme sowie die Untersuchungsmethoden werden diskutiert.

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Comparative studies on posttransferrin (Pt) and C3 in the polymorphism of the third component of human complement

Summary Sera of 541 unrelated Germans from the Cologne area were examined for their Pt and C3 types. There was correspondence between Pt A and C3 F, Pt AB and C3 FS, and Pt B and C3 S in 537 sera. C3 variants F0.65S, F0.6S, F0.5S were determined as Pt AB, C3 F0.55S was determined as Pt B. The question of possible identity and the methods used are discussed.

     

Bioreduction of Pt (IV) from aqueous solution using sulphate-reducing bacteria

The aims of this study were to investigate the role of sulphate-reducing bacteria in facilitating Pt removal from aqueous solutions and to investigate the role of a hydrogenase enzyme in Pt reduction in vitro. To avoid precipitation of Pt as Pt sulphide, a resting (non-growing) mixed culture was used. A pH-dependent rate of Pt removal from aqueous solution was observed, indicating that metal speciation was the main factor for its removal from solution. The maximum initial concentration of Pt(IV) that the cells can effectively remove from solution was 50 mg/l, while the maximum capacity was only 4 mg of Pt per gram of resting biomass. Transmission electron microscopy and energy dispersive X-ray analyses indicated that Pt was being precipitated in the periplasm, a major area of hydrogenase activity in the cells. In vitro investigation of Pt reduction with hydrogen as the electron donor showed that 49% was removed within 1 h when a relatively pure hydrogenase extract was used, 31% was removed with a cell-free soluble extract and 70% removed by live cells.     

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.     

High-performance liquid chromatographic separation of the biotransformation products of oxaliplatin

A novel single reversed-phase HPLC system was developed for separating oxaliplatin and its biotransformation products formed in rat plasma. The major stable biotransformation products of oxaliplatin formed in rat plasma were identified as Pt(dach)(Cys)₂, Pt(dach)(Met) and free dach. The minor biotransformation products Pt(dach)Cl₂, Pt(dach)(GSH) and Pt(dach)(GSH)₂ could also be resolved from other Pt-dach complexes. Among these biotransformation products, the identification of Pt(dach)(Met) was further confirmed by LC–ESI-MS, and the identification of Pt(dach)(Cys)₂, Pt(dach)(GSH), Pt(dach)(GSH)₂ and free dach was confirmed by atomic absorption and double isotope labeling. This HPLC technique should prove useful for separating and identifying the biotransformation products of Pt-dach drugs such as oxaliplatin, ormaplatin and Pt(dach)(mal) in biological fluids. This will allow a more complete characterization of the pharmacokinetics and biotransformations of these Pt-dach drugs, which should in turn lead to a better understanding of the mechanisms leading to their toxicity and efficacy.     

Cytotoxicity, radiosensitization, and DNA interaction of platinum complexes of thiazin and xanthene dyes

Complexes of the platinum(II) tetrachlorodianion with positively charged nuclear dyes have been prepared in an effort to produce neutral molecules which could gain ready access to the nuclear DNA where the platinum(II) tetrachlorodianion could function as a radiosensitizing and a bifunctional alkylating agent. The thiazin dyes Thionin, Azure B, and Methylene Blue, the aminoxanthene dye Pyronin Y, and the thiazole dye Thioflavin have each been complexed to the platinum(II) tetrachlorodianion(PtCl4) in a ratio of 2:1(dye:PtCl4). Studies of the interaction of these complexes and of the dyes with the pBR322 plasmid superhelical DNA demonstrated that while each complex and dye readily associated with the DNA in a dose-dependent manner, only Pt(Thioflavin)2 and Thioflavin produced irreversible DNA changes (single-strand breaks). In exponentially growing EMT6 cells the cytotoxicity of these drugs was assessed in normally oxygenated and hypoxic cells at both pH 7.4 and 6.45. At concentrations ranging from 1 to 500 microM, Pt(Methylene Blue)2 was significantly more cytotoxic than the other thiazin dye complexes Pt(Thionin)2 and Pt(Azure B)2. The cytotoxicity of Pt(Thionin)2 and Pt(Methylene Blue)2 was increased in normally oxygenated and hypoxic cells at low pH. Both Pt(Pyronin Y)2 and Pt(Thioflavin)2 were more toxic than the thiazin complexes. Pt(Pyronin Y)2 was most cytotoxic to normally oxygenated cells at normal pH and hypoxic cells at low pH, while Pt(Thioflavin)2 was most cytotoxic to cells at low pH under both oxygenation conditions. In vitro studies of the radiosensitizing properties of these agents in EMT6 cells demonstrated that exposure to 100 microM for 1 h before and during irradiation (except for Pt[Thioflavin]2, which was assayed at 25 microM) resulted in enhancement rations of 2.5, 1.9, 1.5, and 1.5 for Pt(Azure B)2, Pt(Thionin)2, Pt(Pyronin Y)2, and Pt(Thioflavin)2, respectively, in hypoxic cells. In contrast, Pt(Methylene Blue)2 (and Methylene Blue) proved to be a radioprotector of normally oxygenated cells and did not sensitize hypoxic cells to the cytotoxic effects of radiation. In the FSaIIC fibrosarcoma in vivo administration of each drug at 100 mg/kg intraperitoneally (ip) 15 min prior to irradiation (except for Pt[Thioflavin]2, which was given at 1 mg/kg ip) showed that, with single radiation fractions of 10 and 20 Gy, dose-modifying factors of 2.1, 1.8, 1.5, and 1.2 were produced by Pt(Azure B)2, Pt(Thionin)2, Pt(Pyronin Y), and Pt(Methylene Blue)2, respectively, after correcting for growth delays induced by the drug alone. In comparison, misonidazole at 1 g/kg ip produced a dose-modifying factor of 1.4.(ABSTRACT TRUNCATED AT 400 WORDS)     

Oxaliplatin and Its Enantiomer Induce Different Condensation Dynamics of Single DNA Molecules

The interactions of DNA with oxaliplatin (Pt(R,R-DACH)) or its enantiomer (Pt(S,S-DACH)) were investigated using magnetic tweezers and atomic force microscope. In the process of DNA condensation induced by Pt-DACH, only diadducts and micro-loops are formed at low Pt-DACH concentrations, while at high Pt-DACH concentrations, besides the diadducts and micro-loops, long-range cross-links are also formed. The diadduct formation rate of Pt(R,R-DACH) is higher than that of Pt(S,S-DACH). However, the proportions of micro-loops and long-range cross-links for Pt(S,S-DACH) are higher than those for Pt(R,R-DACH). We propose a model to explain these differences between the effect of Pt(R,R-DACH) and that of Pt(S,S-DACH) on DNA condensation. The study has strong implications for the understanding of the effect of chirality on the interaction between Pt-DACH and DNA and the kinetics of DNA condensation induced by platinum complexes.     

Highly Durable Platinum Single‐Atom Alloy Catalyst for Electrochemical Reactions

Single atomic Pt catalyst can offer efficient utilization of the expensive platinum and provide unique selectivity because it lacks ensemble sites. However, designing such a catalyst with high Pt loading and good durability is very challenging. Here, single atomic Pt catalyst supported on antimony‐doped tin oxide (Pt1/ATO) is synthesized by conventional incipient wetness impregnation, with up to 8 wt% Pt. The single atomic Pt structure is confirmed by high‐angle annular dark field scanning tunneling electron microscopy images and extended X‐ray absorption fine structure analysis results. Density functional theory calculations show that replacing Sb sites with Pt atoms in the bulk phase or at the surface of SbSn or ATO is energetically favorable. The Pt1/ATO shows superior activity and durability for formic acid oxidation reaction, compared to a commercial Pt/C catalyst. The single atomic Pt structure is retained even after a harsh durability test, which is performed by repeating cyclic voltammetry in the range of 0.05–1.4 V for 1800 cycles. A full cell is fabricated for direct formic acid fuel cell using the Pt1/ATO as an anode catalyst, and an order of magnitude higher cell power is obtained compared to the Pt/C.     

Synthesis and spectroscopic properties of reconstituted zinc-myoglobin appending a DNA-binding platinum(II) complex

A reconstituted zinc-myoglobin (ZnMb) dyad, ZnMb-[Pt(bpy)(en)]2+, has been prepared by incorporating chemically-modified zinc-porphyrin, being capable of DNA-binding of the Pt complex, [Pt(bpy)(en)]2+, where bpy and en are 2,2'-bipyridine and ethylenediamine, respectively. The steady-state fluorescence of the cofactor, [Pt(bpy)(mu-enPP)Zn]Cl2, in MeOH indicates that the excited singlet state of zinc--porphyrin was almost quenched, probably because of the strong hydrophobic and pi-pi stacking interactions between the [Pt(bpy)(mu-enPP)Zn]2+ ions. In the reconstituted ZnMb-[Pt(bpy)(en)]2+, the quenching reaction of 1(ZnMb)* with the [Pt(bpy)(en)]2+ moiety does not occur, indicating apo-Mb matrix is essential. On the other hand, when the [Pt(bpy)(en)]2+ moiety was excited, the enhancement of the fluorescence from ZnMb unit was observed. It is suggested that the energy transfer from (1)([Pt(bpy)(en)]2+)* to ZnMb occurs. The spectroscopic changes of ZnMb-[Pt(bpy)(en)]2+ in the presence of calf-thymus DNA were also provided. Soret band at 428 nm gradually decreased, and isosbestic points at 321, 414, and 432 nm were observed with increasing the DNA concentration. When the Pt(II) moiety was excited at lambda(ex) 321 nm, the fluorescence signal around 600 nm similarly decreased. The synthetic manipulation of ZnMb by using a DNA-binding Pt(II) complex demonstrates sensitive fluorescent signal for DNA and valuable information to study photoinduced electron transfer within a Mb-DNA complex.     

Comparison of the reactivity of oxaliplatin, pt(diaminocyclohexane)Cl2 and pt(diaminocyclohexane1)(OH2)2(2+) with guanosine and L-methionine

The initial rates of reactivity of oxaliplatin, its metabolites Pt(dach)Cl2 and Pt(dach)(OH2)2(2+) with guanosine and L-met in water, NaCl and phosphate were compared. Versus guanosine, the most reactive molecule was Pt(dach)(OH2)2(2+), about 40 fold that of oxaliplatin, the least reactive was Pt(dach)Cl2, Versus L-met, Pt(dach)(OH2)2(2+), was also the most reactive species but only about 2 fold more reactive than Pt(dach)Cl2 and oxaliplatin. Pt(dach)(OH2)2(2+) was approximately 3 fold less reactive versus methionine than guanosine whereas oxaliplatin and Pt(dach)Cl2 were about seven fold more reactive versus methionine than guanosine. Thus, the three platinum compounds oxaliplatin, Pt(dach)Cl2 and Pt(dach)(OH2)2(2+) react with L-met but only the Pt(dach)(OH2)2(2+) has a high reactivity with guanosine. Oxaliplatin, which is stable in water, has to be transformed in the presence of chloride in chloro-derivatives which are aquated to become active particularly versus guanosine. These data demonstrate that oxaliplatin has similarities with cisplatin in terms of chloride versus water coordination and in terms of dependence on chloride concentration for transformations.     

The role of copper transporters in the development of resistance to Pt drugs

Recent studies in yeast, mouse and human cells suggest that the conserved metal binding transporters of the Cu homeostasis pathway can mediate resistance to Pt drugs in cancer cells. This review summarizes the data available from these studies. The observation that cells selected for resistance to Cu or the Pt drugs display bidirectional cross-resistance, parallel defects in the transport of Cu and the Pt drugs and altered expression of Cu transporters is consistent with the concept that the Cu homeostasis proteins regulate sensitivity to the Pt drugs by influencing their uptake, efflux and intracellular distribution. This model is supported by the finding that when mammalian and yeast cells are genetically engineered to express altered levels of the Cu transporters they exhibit altered sensitivity to Pt drugs and are defective in intracellular Pt accumulation due to altered uptake and/or efflux rates. Negative associations between the expression of ATP7A and ATP7B and the outcome of Pt therapy further support the significance of the Cu homeostasis proteins as both markers of and contributors to Pt resistance.     

Structures of Au/Pt bimetallic clusters: homogeneous or segregated?

The question whether Au can alloy with Pt at the nano-scale size is still controversial. By performing density functional theory calculations for several small Au/Pt bimetallic clusters Au_mPt_n (m + n = 4–6, 13), we find that, in all the most stable geometries, Pt atoms prefer to assemble together to form the core while Au atoms like to surround the Pt atoms to form the shell, and that evenly mixed clusters are structurally unstable. The unique geometric characteristics can be explained by analyzing the different electronic properties of Pt–Pt, Au–Pt and Au–Au bonds, and is expected also to apply to larger Au/Pt bimetallic clusters.     

Electrochemical behavior of L-cysteine and its detection at carbon nanotube electrode modified with platinum

The electrochemical behavior of L-cysteine (CySH) on platinum (Pt)/carbon nanotube (CNT) electrode was investigated by cyclic voltammetry. CNTs used in this study were grown directly on graphite disk by chemical vapor deposition. Pt was electrochemically deposited on the activated CNT/graphite electrode by electroreduction of Pt(IV) complex ion on the surface of CNTs. Among graphite, CNT/graphite, and Pt/CNT electrodes, improved electrochemical behavior of CySH oxidation was found with Pt/CNT electrode. On the other hand, a sensitive CySH sensor was developed based on Pt/CNT/graphite electrode. A linear calibration curve can be observed in the range of 0.5 microM-0.1 mM. The detection limit of the Pt/CNT electrode is 0.3 microM (signal/nose=3). Effects of pH, scan rate, and interference of other oxidizable amino acids were also investigated and discussed. Additionally, the reproducibility, stability, and applicability of the Pt/CNT electrode were evaluated.     

Platinum uptake by horticultural crops

Summary The chance for exposure of man to Pt has increased because of the loss of Pt by the catalytic converter used to reduce levels of harmful auto emissions. Whether Pt can be taken up by plants and introduced into man's primary food chain was studied. Pt uptake was analyzed by plasma emission spectroscopy from a week's exposure to 0.057, 0.57, or 5.7 ppm Pt inHoaglands solution. Roots and shoots of nine horticulturally important crops were tested. Chlorosis of young tissue was usually evidenced and dry weights of five species were significantly reduced by 5.7 ppm Pt. Several species showed increases in dry weight at the lowest concentration of Pt. All species accumulated Pt in significantly high amounts in the roots at all concentrations of Pt (for cauliflower and tomato > 1000 ppm at 5.7 ppm Pt). Only pepper, cauliflower, and radish accumulated Pt in their tops. Water loss was increased at low Pt treatment levels and decreased at high levels. The results indicate that Pt can enter into man's food chain directly and probably in large amounts from root crops. Contribution from Southern Piedmont Conservation Research Center, Watkinsville, GA 30677, Athens, Georgia Area, Southern Region, Agricultural Research Service, USDA, in cooperation with the University of Georgia.     

Antibodies against (1R,2R)-cyclohexanediamineplatinum(II)-DNA adduct recognize the conformational differences of isomeric analogues of cyclohexanediamine

Antibodies reactive to (1R,2R)-cyclohexanediamineplatinum(II)-DNA ((1R,2R)-cyclohexanediamine: 1R,2R-dach) adducts were elicited by immunization of rabbit with calf thymus DNA modified by Pt(1R,2R-dach)Cl2 at a ratio of bound platinum per nucleotide ((D/N)b) of 0.0335. In an enzyme-linked immunosorbent assay (ELISA), the binding of specific antibodies to Pt(1R,2R-dach)-DNA adduct (60 microliters of 1.235 x 10(-7) M Pt in each wells) on the assay plate was competitively inhibited by Pt(1R,2R-dach)-DNA adduct ((D/N)b = 0.0653) in the solution. Almost equal inhibition was observed with Pt(1S,2S-dach)-DNA ((D/N)b = 0.0412), an optical isomer of 1R,2R-dach. Pt(1R,2S-dach)-DNA ((D/N)b = 0.0371) and Pt(1R,3S-dach)-DNA ((D/N)b = 0.0281) in which the cyclohexane ring is stereochemically perpendicular to the platinum chelate plane, also inhibited antibody binding, but these adducts gave only incomplete inhibition at higher Pt-DNA adduct concentrations. Although Pt(1R,2R-dach)-d(GpG) and Pt(1R,2R-dach)(NH3)2 inhibited antibody binding, the affinity of the antibody for Pt(1R,2R-dach)(NH3)2 was lower than with Pt(1R,2R-dach)-DNA, and the inhibition behavior of Pt(1R,2R-dach)-d(GpG) was biphasic, i.e., at the lower concentration the inhibition curve was consistent with that of Pt(1R,2R-dach)-DNA, but at the higher concentration it shifted to that of Pt(1R,2R-dach)(NH3)2. The affinity of the antibody for cis-DDP was markedly lower than with Pt(1R,2R-dach)(NH3)2. These facts suggest that the antibodies may bind to the substituents (the platinum and its surroundings) of the various Pt complexes rather than the DNA structure altered by platinum binding.     

用固定化弗劳地柠檬酸杆菌XP05从溶液中回收铂

比较了5种固定弗劳地柠檬酸杆菌XP05菌体的方法,其中明胶海藻酸钠包埋法为固定菌体的最佳方法。扫描电子显微镜观察表明,XP05菌体较均匀地分布于包埋基质中。固定化XP05菌体吸附Pt^4＋受吸附时间、固定化菌体浓度、溶液的pH值和Pt^4＋起始浓度的影响。吸附作用是一个快速的过程;吸附Pt^4＋的最适pH值为1.5;在50～250 mg P^4＋/L范围内,吸附量与Pt^4＋起始浓度成线性关系,吸附过程符合Langmuir和Freundlich吸附等温模型。在Pt^4＋起始浓度250 mg/L、固定化菌体2.0 g/L、pH 1.5和30℃条件下,振荡吸附60 min, 吸附量为35.3 mg/g。0.5 mol/L HCl能使吸附在固定化菌体上的Pt解吸98.7%。从废铂催化剂处理液回收铂的结果表明,在Pt^4＋起始浓度111.8 mg/L、固定化菌体4.0 g/L、pH 1.5和30℃条件下,振荡吸附60 min, 吸附量为20.9 mg/g。在填充床反应器中,在Pt^4＋起始浓度50 mg/L、流速1.2 ml/min、固定化菌体1.86 g的条件下,饱和吸附量达24.7 mg/g; 固定化XP05菌体经4次吸附解吸循环后吸附率仍达78％。     

Preparation of platinum(II) complexes with L-serine using KI. X-ray crystal structure, HPLC and 195Pt NMR spectra

The preparation of platinum(II) complexes containing L-serine using K(2)[PtCl(4)] and KI as raw materials was undertaken. The cis-trans isomer ratio of the complexes in the reaction mixture differed significantly depending on whether KI was present or absent in the reaction mixture. One of the two [Pt(L-ser-N,O)(2)] complexes (L-ser=L-serinate anion) prepared using KI crystallizes in the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions a=8.710(2) A, b=9.773(3) A, c=11.355(3) A, Z=4. The crystal data revealed that this complex has a cis configuration. The other [Pt(L-ser-N,O)(2)] complex also crystallizes in the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions a=7.0190(9) A, b=7.7445(6) A, c=20.946(2) A, Z=4. The crystal data revealed that this complex has a trans configuration. The 195Pt NMR chemical shifts of trans-[Pt(L-ser-N,O)(2)] and cis-[Pt(L-ser-N,O)(2)] complexes are -1632 and -1832 ppm, respectively. 195Pt NMR and HPLC measurements were conducted to monitor the reactions of the two [Pt(L-ser-N,O)(2)] complexes with HCl. Both 195Pt NMR and HPLC showed that the reactivities of cis- and trans-[Pt(L-ser-N,O)(2)] toward HCl are different: coordinated carboxyl oxygen atoms of trans-[Pt(L-ser-N,O)(2)] were detached faster than those for cis-[Pt(L-ser-N,O)(2)].     

Preparation, 195Pt NMR spectra and biological activity of platinum (IV) complexes with dipeptides

Three dipeptide complexes of the form K[Pt(IV) (dipep) Cl(OH)2] and four dipeptide complexes of the form K[Pt(IV)-(Hdipep)Cl2(OH)2] were newly prepared. The 195 Pt NMR peak of the K[Pt(IV) (dipep)Cl(OH)2] complexes appeared at about 1200 ppm and these chemical shifts were about 3150 ppm downfield compared with those of the K[Pt(II) (dipep) Cl] complexes. The chemical shifts of the K[Pt(IV) (Hdipep) Cl2 (OH)2] complexes were at about 900 ppm, i.e., about 3050 ppm downfield compared with those of the K[Pt(II) (Hdipep)Cl] complexes. The H[Pt(IV) (Hdigly) Cl2(OH)2] and K[Pt(IV) (Hdigly) Cl2(OH)2] complexes inhibited the growth of C. albicans at a more diluted concentration than cisplatin at 1 microgram/ml, but the platinum complexes only weakly inhibited the growth of these cells compared with the cisplatin-inhibited growth of Meth-A and Hep-2 cells at 10 micrograms/ml. These results suggested that the platinum complexes selectively inhibited the growth of fungal cells.     

The preparation, characterisation, and DNA adduct profile of 2-amino-2-methyl-3-butanoneoximedichloroplatinum(II), a platinum(II) complex designed to bind to GpA sequences of DNA

The complex, 2-amino-2-methyl-3-butanoneoximedichloroplatinum(II), [Pt(ambo)Cl2], was chosen because of its potential to bind to GpA sequences of duplex DNA. Crystals of [Pt(ambo)Cl2] are monoclinic, space group, P2(1)/n, a = 6.799(4), b = 17.642(5), c = 8.193(2) A, beta = 102.10(3) degrees, Z = 4, R = 0.033 (1864 F). The binding of [Pt(ambo)Cl2] to salmon-sperm DNA was studied using enzymatic digestion and HPLC analysis. [Pt(ambo)Cl2] was found to form fewer GpG and ApG intrastrand adducts and more monofunctional adducts than [Pt(en)Cl2]. Binding to GpA sequences could not be established, but [Pt(ambo)Cl2] forms substantially more adducts with adenine than does [Pt(en)Cl2].