Platinum compounds dinuclear

Figure 11 Dinuclear platinum compounds based on heterocycle bridges.

Figure 14. Schematic structures of isomeric dinuclear platinum compounds, [ (PtCI(NH3)2 2 p-H2N(CH2)nNH2)]2+ (n= 2-6).

Structure-Activity Relationships for Dinuclear Platinum Compounds... 

Both pyridine (pyr) and quinoline (quin) compounds are efficient cross-linking agents but not potent cytotoxic agents. Interstrand cross-linking is thus not by itself a sufficient requirement for cytotoxicity. These results were also of considerable interest because the mononuclear precursors were found to be similar in cytotoxicity to cisplatin itself, violating the classical structure-activity relationship of platinum compounds. Yet incorporation into the dinuclear structure did not produce active compounds ... 

This review summarized our systematic studies on dinuclear platinum compounds leading to identification of a novel clinical agent BBR 3464. The profile of antitumor activity is shared by the general structure with po-... 

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. 

A complementary structural and kinetics characterisation study regarding the halogen cleavage reaction (by pyridines) in dimethylaminomethylphenyl-C N pallada-and platina-cycles has been reported (see Scheme 15).269 This work followed by 30 years a pioneering study of the kinetics of monomerisation of a dinuclear bromine-bridged platinum compound using pyridine.270... 

Four chiral homologous complexes were also prepared. None of the palladium complexes showed mesomorphic properties, whereas a monotropic chiral discotic nematic phase was observed for the platinum complex (Table 18). The absence of mesomorphism for the dinuclear palladium complexes may be due to the type of chiral chain used, which differed from that used for the platinum system. All of the complexes form charge-transfer complexes with TNF. A Colh phase was induced for the two halo-bridged palladium complexes and for the platinum complex, as was observed for their non-chiral analogs. Flowever, the chiral nematic phase of the platinum compound was suppressed. At low TNF content, a chiral Nq phase was stabilized for the thiocyanato-bridged compound along with a non-chiral No phase at higher concentration. 

Figure 2 Synthetic scheme for formation of dinuclear compounds with spermidine as bridging ligand. Structures and abbreviations for active dinuclear platinum compounds with polyamine compounds which are discussed in text...

Dinuclear platinum and tetraplatinum compounds have also been studied, 58 (M=Pt). Synthesis and lyotropic-crystalline behavior (nematic), are discussed for this platinum compound, disc-shape in... 

Rather more dinuclear platinum(III) compounds are known [158] formally the Pt2+ unit is isoelectronic with Rh2+. The first species to be characterized was Pt2(S04)4(H20)2 (Figure 3.97a) ... 

Alternatively, arene displacement can also be photo- rather than thermally-induced. In this respect, we studied the photoactivation of the dinuclear ruthenium-arene complex [ RuCl (rj6-indane) 2(p-2,3-dpp)]2+ (2,3-dpp, 2,3-bis(2-pyridyl)pyrazine) (21). The thermal reactivity of this compound is limited to the stepwise double aquation (which shows biexponential kinetics), but irradiation of the sample results in photoinduced loss of the arene. This photoactivation pathway produces ruthenium species that are more active than their ruthenium-arene precursors (Fig. 18). At the same time, free indane fluoresces 40 times more strongly than bound indane, opening up possibilities to use the arene as a fluorescent marker for imaging purposes. The photoactivation pathway is different from those previously discussed for photoactivated Pt(IV) diazido complexes, as it involves photosubstitution rather than photoreduction. Importantly, the photoactivation mechanism is independent of oxygen (see Section II on photoactivatable platinum drugs) (83). 

---