Platinum, dichloro trans

An ion of nominal m/z 442 was produced from cis-dichloro-trans-dihydroxo-bis-2-propanamine/platinum (IV) (CHIP) by ion/molecule reactions (IMR) of the major electron impact (El) fragment ion with the neutral molecule. As shown in Figure 3, this ion dissociated when irradiated by the cw laser for ca. 500 ms to produce two daughter photofragment ions, m/z 366 and m/z 311, by loss of various ligands (Equation 1). 

Figure 3. Top. Ion/molecule reaction product formed by reaction of cis-dichloro-trans-dihydroxo-bis-2-propanamine platinum (IV) with its 50 eV electron impact fragments. Bottom. Dissociation pattern produced upon irradiation with cw CO2 laser, same experimental conditions and delay times as in the top spectrum. (Reproduced from ref. 18. Copyright 1987 American Chemical Society.)...

Figure 3.116 Platinum compounds studied for possible anti-tumour activity. I, cw-Dichlorodi-ammineplatinum(II) cisplatin, platinol NSC 119875 neoplatin platinex. II, s-Diammine(l,l-cyclobutanedicarboxylato)platinum(II) JM-8 paraplatin NSC 241240. Ill, Oxiplatin. IV, Tetraplatin. V, Amminediacetatodichloro(cyclohexylamine)platinum(IV). VI, cis-Dichloro-trans-dihydroxy-cu-bis(isopropylamine)platinum(IV) iproplatin JM-19 CHIP NSC 256927.

Iproplatin [CHIP, cis-dichloro-trans-dihydroxo-bis(isopropylamine) plati-num(iv) see Figure 1 for structure], like carboplatin, was selected for clinical evaluation because of its favourable efficacy profile in preclinical studies, i.e. less nephrotoxicity but antitumour activity comparable to that of cisplatin. Iproplatin was the first quadrivalent platinum(iv) complex possessing an octahedral configuration, rather than the square-planar configuration of cisplatin and... 

Cl2H28Cl2NPPt, t rans-Dichloro(trans-2,5-dimethylpyrrolidine)(trieth-ylphosphine)platinum(II), 46B, 1058 Cl2H28Cl2N4Ni08 r Bis(2,4,4-trimethyl 1,5-diazapent-1-ene)nickel(II) perchlorate, 41B, 1065... 

Molecules having only a sulfoxide function and no other acidic or basic site have been resolved through the intermediacy of metal complex formation. In 1934 Backer and Keuning resolved the cobalt complex of sulfoxide 5 using d-camphorsulfonic acid. More recently Cope and Caress applied the same technique to the resolution of ethyl p-tolyl sulfoxide (6). Sulfoxide 6 and optically active 1-phenylethylamine were used to form diastereomeric complexes i.e., (-1-)- and ( —)-trans-dichloro(ethyl p-tolyl sulfoxide) (1-phenylethylamine) platinum(II). Both enantiomers of 6 were obtained in optically pure form. Diastereomeric platinum complexes formed from racemic methyl phenyl (and three para-substituted phenyl) sulfoxides and d-N, N-dimethyl phenylglycine have been separated chromatographically on an analytical column L A nonaromatic example, cyclohexyl methyl sulfoxide, did not resolve. 

Gis-dichloro-diammino-platinum, [Pt(NH3)2Cl2], was first prepared by Peyronne.2 It is easily formed by adding ammonia to a cold solution of platinous chloride in hydrochloric acid, when a greenish-yellow voluminous precipitate separates. This is boiled with water and filtered hot, when, on cooling the filtrate, the substance crystallises in yellow microscopic needles. It is sparingly soluble in water, and is more pure yellow than the isomeric trans-compound. Both cis- and fraws-dichloro-diammino-platinum are obtained on heating tetrammino-platinous chloride with hydrochloric acid. 

Dichloro(diethylene)platinum(II), cis and trans forms( ), formation of, from tetrachloro(di-ethylene)diplatinum(II), 5 215 Dichloro (di-2-pyridylamine)cobalt-(II), 5 184... 

The cis isomer of dichloro-bis(triethylphosphine)platinum(II) is a white crystalline solid with low solubility in benzene, ethanol, and acetone. It may be isomerized to an equilibrium mixture with the yellow trans isomer by heating to 180°C. or by exposure to sunlight in benzene solution.6 The trans isomer (m.p. 140-142°C.) is readily soluble in nonpolar organic solvents and can easily be separated from the equilibrium mixture by extraction with ether. 

Platinum complexes incorporating an optically active amine have been employed for resolution of racemic mixtures of optically active olefins by reaction of the olefin with dichloro-platinum(II). The differing solubility of the diastereoisomers permits separation by fractional crystallization and the olefin can be recovered by reaction of the complex with aqueous alkali cyanide. Using either (-f)-l-phenyl-2-aminopropane (Dexedrine) or (-f)- or (—)-a-phenyl-ethylamine. Cope and co-workers have resolved the optical isomers of trans double bond coordinated and, with (—)-phenylethyl-amine)dichloroplatinum(II), a bridged complex with each double bond coordinated to a different platinum atom. 

Bis(4-imino-2-pentanonato)nickel(II), synthesis 60 Tetraamminepalladium(II) tetrachloropalladate(II) and trans-dichlorodiamminepalladium(II), synthesis 61 Tris(ethylenediamine)platinum(IV) chloride, synthesis 62 ct8-Dichloro(ethylenediamine)platinum(II), synthesis 63... 

In these syntheses, Peppard had to rely on the very weak trans effect in the cobalt complex [Co(NH3) i (SO3) 2 ]-. The cis-dichloro-cis-diammineethylenediaminecobalt(III) ion is asymmetric, and Peppard partially resolved it into its enantiomeric forms by adsorption on quartz ground to 100 mesh. This method of resolution is frequently, but not always, effective. Before it can be fully utilized, we will need to learn a great deal more about the principles of adsorption. The preparation of Peppard s isomer s is particularly interesting because cobalt(III) complexes rearrange easily, whereas the platinum compounds do not. 

Spectroscopic and crystallographic studies of platinum-base complexes give some insight into the reactivity of the platinum compounds and their possible binding sites on DNA. The reactions of the different nucleosides or nucleotides with the chloro and aquo derivatives of O Cs- and trans-DDP have been studied by UV spectroscopy (36), raman difference spectrophotometry (37) and high pressure liquid chromatography (38). For both chloro isomers, the rates of the reactions with various nucleic acid monomers show the following trend GMP > AMP > CMP and dG > dA > dC T, The dichloro and diaquo derivatives react slowly with thymidine and UMP (37) or not at all (38, 39). 

The stoichiometry of the platinum-base complex depends on the Pt base ratio and also on the pH. For instance, it has been shown that the aia-diaquo species reacts with adenine, adenosine and AMP to give 1 1, 1 2 and 2 1 (Pt base) complexes. Similar results have been observed for the trans isomer except that the 1 2 complexes with adenosine and AMP were not formed (40). The diaquo and dichloro species of cis- and trans-DDP bind to GMP and dGMP to give 1 1 and 1 2 complexes as shown by raman spectroscopy (41) and NMR (42). Cis-[Pt(NH3)2(H20)2] forms a 1 2 complex with cytidine or uridine at acid pH whereas under neutral conditions the 1 1 complex is formed (43). It also reacts with GpG and GpC forming a bidentate complex with the two bases (44). 

Figure 4-11 depicts a possible sequence whereby cisplatin, forming a reactive aquo intermediate, reacts with the N-7 nitrogen of two guanine bases on two different DNA chains, thus cross-linking them in a manner analogous to the nitrogen mustards. This mechanism, of course, offers no explanation for the lesser bioactivity of the trans-diammin-dichloro-platinum stereoisomer since there seems no apparent reason for a similar reaction sequence not to occur. 

Table 2. Formation of trans-Dichloro(diamnexpropane-1,3-diyl)platinum(IV) plexes from the bis-Pyridine Complexes and Diamines...

Cl4N4PtC4H,8, Platinum(II), dichloro-bis(l,2-ethanediamine monohydro-chlorideK trans-, 27 315 Cl4NgW2C2gH25, Tungsten(VI), tetrachloro-bis(l,l-dimethylethanamine)bis[(l,l-dimethylethyl)imido]bis()i-phenyl-imido)di-, 27 301... 

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