Dichloroplatinum

Another rather extensive series of similar data, obtained using CS2 solutions and nujol mulls, has been published by Shindo (Fig. 4). His series include considerable data for jS-substituted compounds, for which the question of a choice of substituent constants does not arise. His data also show considerable scatter but seem to suggest strongly that <7+-values are indicated for + M substituents and normal <7-values for —M substituents. The conclusion is confirmed by the short series of similar data reported by Costa and Blasina and by Shupack and Orchin. The data of the latter authors for the NO frequencies in mws-ethylene pyridine N-oxide dichloroplatinum(II) complexes are also moderately well correlated with <7+-values. 

Pyridine 1-oxide, like pyridine, can act as a ligand in transition metal complexes, but unfortunately good stability constants are not known. However, Shupack and Orchin have found that the C===C stretching frequency of the ethylene ligand in trans-ethylene pyridine 1-oxide dichloroplatinum(II) varies linearly with the pA and hence with the C7-value (ct+ or a, respectively) of substituents in the pyridine oxide. The data for the above reaction series are included in Table V. 

Attempts have been made to catalyze the arrangement of 3-oxaquadricyclane to oxepins with transition-metal complexes.1 32 1 35 When dimethyl 2,4-dimethyl-3-oxaquadricyclane-l,5-dicarboxylate is treated with bis(benzonitrile)dichloroplatinum(II) or dicarbonylrhodium chloride dimer, an oxepin with a substitution pattern different from that following thermolysis is obtained as the main product. Instead of dimethyl 2,7-dimethyloxepin-4,5-dicarboxylate, the product of the thermal isomerization, dimethyl 2,5-dimethyloxepin-3,4-dicarboxylate (12), is formed due to the cleavage of a C O bond. This transition metal catalyzed cleavage accounts also for the formation of a 6-hydroxyfulvene [(cyclopentadienylidene)methanol] derivative (10-15%) and a substituted phenol (2-6%) as minor products.135 The proportion of reaction products is dependent on solvent, catalyst, and temperature. 

CnHuClgNaOePtS trans-Dichloroplatinum(II)(dimethyl sulfoxide)cytidine 38 517... 

The coordination chemistry of tertiary phosphine-functionalized calix[4]arenes have been described.279 Treatment of a bis(diphenylphosphino) or bis(dimethylphosphino) derivative of calix[4]arene with [PtCl2(COD)] leads to the formation of the corresponding dichloroplatinum(II) complex. The related diplatinum(II) species has also been reported with the tetrafunctionalized calix[4]arene.280 The mononuclear derivative is susceptible to oligomerization if the two free phosphine ligands are not oxidized or complexed to another metal center such as gold(I).279 The platinum(II) coordination chemistry of a mono-281 and diphosphite282 derived calix[ ]arene (n = 4 and 6, respectively) has also been described. 

The first examples of platinum(II) complexes of the steroid 5-cholestene have been reported.283 Treatment of two equivalents of 5-cholestene-3 -diphenylphosphine (n = a) or -dimethylphos-phine (n = (3) with [PtCl2(PhCN)2] or [PtCl2(SEt2)2], respectively, affords the corresponding trara-dichloroplatinum(II) derivatives (103) in high yield. 

New reproducible syntheses of platinum(II) carbonato complexes of the type [Pt(C03)L2] (L mono- or bidentate tertiary phosphine) involve the reaction of Ag2C03 with [PtCl2L2] in water-saturated CH2C12 solution.3 Other methods of preparation include the conversion of the dichloroplatinum(II) complexes to the corresponding bis(alkoxo)- or bis(phenoxo)-platinum(II) species, followed by hydrolysis in the presence of C02. 

Kelland LR, Mistry P, Abel G, et al. Mechanism-related circumvention of acquired cis-diammine-dichloroplatinum(II) resistance using two pairs of human ovarian carcinoma cell lines by ammine/ amine platinum(IV) dicarboxylates. Cancer Res 1992 52 3857-3864. 

Keizer HJ, Karim ABMF, Njo KH, et al. Feasibility study on daily administration of cis-diammine-dichloroplatinum(II) in combination with radiotherapy. Radiotherap Oncol 1984 1 227-234. 

Stewart DJ, Wallace S, Feun L, et al. A phase I study of intracarotid artery infusion of cis-diammine dichloroplatinum(II) in patients with recurrent malignant intracerebral tumors. Cancer Res 1982 42 2059-2062. 

Dichloro(l,5-cyclooctadiene)platinum(II) may be prepared from hexachloro-platinic acid,3 by heating bis(benzonitrile)dichloroplatinum(II)4 in 1,5-cyclo-... 

Intra-articular injections of orgotein proved effective in degenerative joint disease The side effects of radiation therapy in patients with bladder tumors were also reduced by the administration of SOD The nephrotoxicity of cw-diamine-dichloroplatinum in rats was similarly lowered by the subcutaneous administration of (Cu,Zn)-SOD... 

II(S)) and/or to a different reaction rate of the two diastereomeric 7r-olefin complexes to the corresponding diastereomeric alkyl-rhodium complexes (VI(s) and VI(R)). For diastereomeric cis- or trans-[a-methylbenzyl]-[vinyl olefin] -dichloroplatinum( II) complexes, the diastereomeric equilibrium is very rapidly achieved in the presence of an excess of olefin even at room temperature (40). Therefore, it seems probable that asymmetric induction in 7r-olefin complexes formation (I — II) cannot play a relevant role in determining the optical purity of the reaction products. On the other hand, both the free energy difference between the two 7r-olefin complexes (AG°II(S) — AG°n(R) = AG°) and the difference between the two free energies of activation for the isomerization of 7r-com-plexes II(S) and II(R) to the corresponding alkyl-rhodium complexes VI(s) and VI(R) (AG II(R) — AG n(S) = AAG ) can control the overall difference in activation energy for the formation of the diastereomeric rhodium-alkyl complexes and hence the sign and extent of asymmetric induction. 

Second, the asymmetric induction in hydroformylation at room temperature is in the range of that observed in the formation of cis-a- [methyl-benzylamine] - [olefin] -dichloroplatinum (II) complexes after reaching... 

The cr-dimethylacetal complex (40) is then hydrolyzed on passage through an alumina column, producing the cr-acetaldehyde complex (38) which is converted to the 7r-vinyl alcohol complex (39) by protonation. Wakatsuki, Nojakura, and Murahashi reported the synthesis of l,3-bis(7r-ethenol)2,4-dichloro- i-dichloroplatinum(II) (41) (42), however, Thyret, who recently reported the NMR evidence for the formation of tetracarbonyl(7r-ethenol)iron (42) at low temperature, could not reproduce the synthesis of (41) (43). 

A mixture of 1.34 g of 2,2-bis(aminomethyl)-l,3-propanediol, 4.15 g of potassium dichloroplatinate and 22 ml of water was stirred for 2 h, then cooled, the solid collected and washed three times with cold water. This solid was recrystallized from 60 ml of hot water, giving 890.0 mg of the desired [2,2-bis(aminomethyl)-l,3-propanediol-N,N ]dichloroplatinum as beige crystals, melting point 223°-225°C (dec.). 

The first recognized member of this species Co(CO)3[(C6H5)3P]2 + [Co(CO)4] was reported (219) as recently as 1958 though it seems likely that cationic metal carbonyls had been made, but unrecognized, at a much earlier date. Thus, for example, Schiitzenburger (222) reported in 1870 the interaction of ammonia and dichloroplatinum(II) dicarbonyl. 

The pioneering work of Rosenberg [1][2] on the effect of d.v-diammine-dichloroplatinum(II) (cisplatin) on bacteria and mice has led to the discov-... 

Another fascinating aspect of the Ptn complexes is that /ra/tv-diammine-dichloroplatinum(II) (transplatin), the geometrical isomer of cisplatin, has much lower cytotoxicity potency than cisplatin although it also binds to DNA [3][10][34], The nature of the adducts formed in the in vivo reaction between DNA and transplatin is not yet completely elucidated, and in vitro there were some controversies. Sterical constraints preclude formation of... 

Although animal models can provide important information regarding the bioavailability and pharmacology of potential anticancer drugs in mammals, they are not always accurate predictors of activity against human tumor cells. In one report [27], the activity of a series of isomeric [l,2-bis(di-fluorophenyl)ethylenediamine]dichloroplatinum(II) compounds was evaluated in MXT murine mammary carcinomas in vivo the same compounds were also tested against several human cell lines in culture. The in vivo screen revealed a 2,6-difluoro-substituted compound to be the most active, whereas the 2,4-difluoro-substituted compound was most active against the human breast-cancer cell lines. It was concluded that the mouse mammary carcinoma is not an appropriate model for human breast cancers. Extreme caution must be employed when animal tumor results are used to predict activity in human tumors. 

The landmark discovery of the antitumor activity of m-diamminc-dichloroplatinum(II) (m-CNFFFPtCh, cisplatin, d.v-DDP) by Barnett Rosenberg, first reported in 1969 in Nature, was an extremely fortunate one for a number of reasons. 

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