Platinum complexes with nucleosides

Thymidine or 2 -deoxyuridine have been converted to corresponding 3 -amino, 5 -amino, and 3, 5 -diamino analogues by a previously reported methodology the resulting amino nucleosides were also complexed with platinum salts, and their biological activity studied. 

The synthesis and X-ray structure of a platinum(II) complex containing the well-known antiviral nucleoside acyclovir (9-(2-hydroxyethoxymethyl)guanine, acv) have been described.222 Treatment of acyclovir with [PtCl(DMSO)(en)]+ results in the formation of [Pt(en)(acv)2]2+ (74), whereby two acv molecules are coordinated to the platinum(II) center via their N-7 atoms. The related complex C7,y-[P tCl (NI13)2(acv)]+ (75) has also been reported.223... 

A comparative study of the tetrammine complex [Pt(NH3)4]+ has shown that for platinum, adenine is a better cr donor than ammonia but it has weak n capacity <93JCC45>. Mixed-ligand complexes of m-dichloroethionine-Pd(II) with purines and purine nucleosides have also been prepared. In the complexes of purines and their corresponding nucleosides, the ligand binding site is N-7 whereas in the case of pyrimidines and their nucleosides it is N-3 <90ICA129>. 

Spectroscopic and crystallographic studies of platinum-base complexes give some insight into the reactivity of the platinum compounds and their possible binding sites on DNA. The reactions of the different nucleosides or nucleotides with the chloro and aquo derivatives of O Cs- and trans-DDP have been studied by UV spectroscopy (36), raman difference spectrophotometry (37) and high pressure liquid chromatography (38). For both chloro isomers, the rates of the reactions with various nucleic acid monomers show the following trend GMP > AMP > CMP and dG > dA > dC T, The dichloro and diaquo derivatives react slowly with thymidine and UMP (37) or not at all (38, 39). 

Such sugar-metal complexes as (444) were formed in high yield by electrolysis of the appropriate ligand (see p. 133) in methanolic solution using anodes of the metal (Cu or Ni or Co) and a platinum cathode. The interaction between Cu cations and adenosine, guanosine, cytidine, and uridine in aqueous DMSO at various pH values has been studied by e.s.r. and n.m.r. spectroscopy. Since Cu cations were shown to complex specifically with 0-2 and 0-3 of these nucleosides at pH 8.5-10, complex formation can be used to distinguish 5 -ribonucleotides from 2 - and 3 -ribonucleotides and 2 -deoxyribonucleosides. Under certain conditions, Cu cations can form complexes having as many as four bases bound to the metal. 

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