Polyamines, platinum compounds

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...

There are two main aspects of study for the degradation of the platinum polyamines. First, the rate of degradation is important since this should be indicative of the mobility, location, and half life of the polymer in the body. Monomeric platinum compounds typically have more mobility, are less limited to location, and have shorter half lives (less than 24 hours) than their polymeric counterparts. Second, determining the... 

Complexes of other metals are used to sensitize emulsions, and some are used to sensitize even further (supersensitize) gold-sensitized emulsions. " Among these are (NH4)2[PtCl4], (NH4)2[PdCl4], (NH4)2[PdCy, K2[IrCl6] and similar compounds with ruthenium and the other halides. Sensitization by iridium salts and complex ions has been reviewed recently. Mechanisms of action of palladium(II) salts and complex ions on gold-sensitized emulsions have been studied. Several phosphine complexes of palladium and platinum, for example (2), are reported to be effective sensitizers, as are many macrocyclic polyamine compounds and their metal complexes,for example the Cu", Ni", Fe " and Rh " chelates of the cyclen ligand, 1,4,7,10-tetraazacyclododecane (3). 

Polymers should be eliminated more slowly, reducing the exposure of the kidneys, increasing the concentration of the compound that is retained by the body, and permitting lower effective doses of the drug to be used. Second, platinum polyamines should show... 

Platinum polyamines can be synthesized using a wide variety of diamines, including pyridine derivatives, pyrimidines, amino acids, and more complicated compounds such as methotrexate. 

Results of the ultraviolet and visible spectra studies appear in Table 2. Trans platinate compounds, including the diaminodihaloplatinum II compounds, typically exhibit three bands in the 150 to 450 nm region whereas the analogous cis products show four bands in this region. The cis-platinum II polyamines also exhibit four bands in this region (43, 44). 

A second difference is the poorer, more limited solubility of the palladium compounds compared to the analogous platinum polyamines. Most of the platinum polyamines thus far synthesized are soluble in a number of dipolar aprotic solvents with some even soluble in chloroform. Only the palladium polyamines derived from dissymmetrical diamines exhibit solubility in any attempted solvent and here solubility is limited to only dipolar aprotic solvents to an extent of 3% and less. Solubilization in dipolar aprotic liquids is dependent on a number of factors - the major one being the ability of the dipolar aprotic liquid molecules to polarize the solute molecules. The smaller size and corresponding poorer polarizability of the palladium atom is probably responsible for this trend. A further, but related factor, is the possible greater tendency for the palladium polymers to form crystalline regions. 

The cytopathic effect of platinum(n) polyamines on normal and transformed 3T3 cells was studied. Some of the compounds were more toxic to normal cells, while others were more effective at destroying the transformed cells. A cell differential ratio, which was simply the ratio of the percentage of cell death for the transformed cells compared to the normal cells, was established to rate the relative effect of cell inhibition. A value greater than one indicated that the polymer was more effective against the transformed cells. Examples of polymers with low cell differential ratios were products derived from tetraiodoplatinate, PtLt, and 1,8-diamino-/ -methane and the product from tetraiodoplatinate and pyrimethamine. The product with the largest cell differential ratio, a ratio of 14, was derived from tetrachloro-platinate and 2-chloro-p-phenylenediamine. 

Figure 3. A dinuclear platinum-polyamine compound as analog of BBR3464.

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