Platinum uracil blue

Platinum-acetamide-blue and platinum-uracil-blue compounds have been reported. The tetranuclear uracil blue [Pt4(l-MeU)4(NH3)g](N03)5-H20, where 1-MeU is the mono-anion of 1-methyluracil, has structure and properties resembling 2-pyridone-blues. Platinum blue compounds with uridine, isonicotinamide, malonamide, and biuret have been described. ... 

Platination of the N3 position in 1-substituted uracil and thymine derivatives requires proton abstraction and usually occurs only at high pH, but the Pt-N3 bond, once formed, is thermodynamically stable (log K 9.6) [7]. Platinum binding to N3 increases the basicity of 04, which becomes an additional binding site leading to di- and trinuclear complexes. A list of X-ray structurally characterized species is given by Lippert [7]. Pt complexes of uracil and thymine can form intensely colored adducts (e.g. platinum pyrimidine blues), which show anticar-cinogenic activity analogously to the monomeric species [7]. 

Several blue tetra- and octanuclear Pt complexes, prepared upon reaction of cis-[Pt(NH3)2(H20)2]2+ with open and cyclic amides, as well as cyclic imides and a uracil nu-cleobase, and comprised of binuclear building blocks interacting through Pt-Pt bond formation, have been isolated and structurally characterized in recent years. Without exception, the average Pt oxidation state in these compounds is 2.25. Nevertheless, the structure and mode of action as antitumor agents of the Platinum Pyrimidine Blues , as prepared by Rosenberg in the early 70 s, remain elusive. This account represents a summary of our present knowledge on cationic Platinum Blues , with a focus on those blues obtained from cis-[Pt(NH3)2(H20)2]2+ and pyrimidine nucleobases, and presents speculations on reasonable alternative structures. 

Since "aquo-complexes" of platinum(ll), prepared by treating the chloro-complexes with aqueous silver nitrate solution, did interact with both thymine and uracil to give the platinum-pyrimidine blues (25), it was evident that the interaction of the chloro-complexes with DNA bases could be different from that... 

The platinum—pyrimidine blues, derived from cisplatin, are an interesting class of complexes with antitumour activity. They were first discovered as a result of studies on the interaction of c/ [PtCl2(NH3)2] and its aquated products with pyrimidines. The identification of DNA as the target for platinum attack naturally led to a systematic study of the reactions of the complex with nucleic acid constituents. The observation that with polyuridine no immediate reaction took place but that a blue color slowly developed in solution, from which a blue solid could be isolated, led to the preparation of a series of complexes containing substituted uracils and thymines. 

It has recently been shown by Spikes150 that uracil and a number of substituted uracils are subject to dye-sensitized photooxidation under certain conditions. Methylene blue and Eosin Y were active photosensitizers in the pH range 8-11.5, but were inactive below pH 8. FMN was very active over the pH range of 2.4-11.5. Photooxidation was measured with a rotating platinum oxygen electrode. 

The work by Lippard and coworkers [2][24][25][88][95][98-100] derives its chief motivation from the understanding of the interaction between the anticancer drug cA-[PtCl2(NH3)2] and pyrimidine nucleobases. Unfortunately, the reaction of c7v-[PtCl2(NH3)2] with molecules such as uracil or thymine leads to non-crystalline dark blue materials ( platinum blues ) which are difficult to characterize. The use of a ligand with similar but more restricted number of donor sites, such as a-pyridone (hp), allowed isolation and full characterization of relevant platinum complexes. Related work has used 1-methyluracil (1-Me-urac) and 1-methylthymine (1-Me-thym) in which one of the pyrimidine nitrogens has been blocked [101]. 

MeT as one base, and neutral cytosine, guanine or adenine as second nucleobase proceeds without formation of undesired side products only if the anionic ligand is attached to Pt first. On the other hand, reaction of cis-Pt(II) with uracil or thymine in 1 1 ratio results in formation of the complicated platinum blues... 

Similar reactions in which the acetonitrile is replaced by amides or uracil derivatives produce analogous platinum blues. The ultimate product in the aquation of the [PtCl4] anion is the Ptaq cation, whose preparation and properties have been described, and whose anation kinetics can be now studied (c/. Pd q ). 

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