Platinum compounds trinuclear

Dinuclear and trinuclear compounds represent a new class of platinum anticancer complexes and are among the most studied platinum compounds in antitumor chemistry. Many of these complexes circumvent cisplatin-resistance mechanisms. In contrast to cisplatin, the polynuclear complexes predominantly form interstrand cross-links. The dinuclear complex [ tranx-PtCl(NH3)2 2 /u.-(H2N(CH2) NH2) ]2+ (l,l/t,t) (17, Figure 9) is antitumor-active and shows no cross-resistance in cisplatin-resistant cell fines. Binding studies sfiowed tfiat DNA binding for this compound is different from that for cisplatin, as illustrated by the increased interstrand cross-linking. However, clinical testing was abandoned because of severe neurotoxicity. 

There are many carbonyl complexes of nickel, palladium, and platinum containing phosphines (L). Nickel compounds of the type [Ni(CO)4 j,Lj,] are readily formed in substitution reactions of [Ni(CO)4]. Palladium and platinum phosphine carbonyls are prepared by reactions of compounds of these metals with carbon monoxide in the presence of phosphines. The following complexes are known [M(CO)L3], [M3(C0)3L3], [M3(C0)3L4], [Pt(CO)2L2] and [M4(CO)5L4] (M = Pd, Pt). Trinuclear platinum compounds resist oxidation. 

The demethylation of methylcobalamin by various platinum compounds requires the presence of species in the II and IV oxidation states. The initial step involves the platinum(II) complex, for example, [PtCU] , which gives a binuclear intermediate, equation (39), that in turn reacts with platinum(IV) to give methylplatinum(IV) species such as [CH3PtCl5f either directly or via a trinuclear intermediate, as in equations (40) and (42), respectively ... 

Fig. 1. Structures of dinuclear and trinuclear compounds containing the cisplatin synthon (2,2lc,c and 2,2,2tc,c,c) and the principal bifunctional DNA-binding agents studied. Abbreviations refer to the number of chloride leaving groups on each platinum and their geometry relative to the diamine bridge [22],...

An extension to work on platinum(i) isocyanides discussed above has been undertaken, showing that it is possible to coordinate metals other than platinum. In the first instance, platinum and palladium compounds were added to the dinuclear Pt(i) compound 103 to give either the linear trinuclear complex 105 (when a -M(0) source was used), or a combined dimer-monomer complex 124 (when a -M(ii) source was added) (Scheme 28). An A-frame complex 125 results when the -source is added to 102. 

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