Platinum nucleosides

Prusoff, Synthesis and biological activity of several amino nucleoside-platinum(II) complexes, J. Med. Chem. 29 681 (1986). 

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... 

Catalytic hydrogenation of methanolic solutions of the 4-nitroimidazoles (72 R1 = D-glucopyranosyl, D-arabinopyranosyl, D-xylopyranosyl R2 = H) using platinum oxide as catalyst gave the corresponding 4-aminoimidazole nucleosides (71 R1 = D-glucopyranosyl, D-arabinopyra-nosyl, D-xylopyranosyl R2 = H) (yields 16, 33, and 25%, respectively), which were apparently isolated as the free bases but no mention of the stability of these compounds was made (72LA67). 

The process is operated at a platinum electrode and a reduced efficiency due to side reactions is observed. A maximum yield of 55% is reported. The use of in situ generated NBS and bromine for the synthesis of nucleosides from silylated pyrimidines has been studied. Nokami etal. [125] suggest the use of only catalytic amounts of NBS or bromine and regeneration of the catalyst by anodic electrolysis in an undivided cell system. 

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>. 

A number of papers have examined the interaction between platinum complexes and nucleosides. Mono-nucleoside complexes K[Pt(nucleoside)Cl3] (nucleoside = guanosine, inosine, or xanthosine), which are 1 1 electrolytes, have been characterized by chemical analyses and n.m.r. spectroscopy. K2[(PtCl3)2(adenosine)] was also prepared. Various halogenoplatinum nucleoside complexes have been obtained from acidic, neutral, and basic solutions, and the bonding modes of the nucleoside examined using n.m.r. and i.r. spectroscopy.In neutral or weakly acid media adenosine and... 

I4122 Z = 8 Dx = 1.859 R = 0.059 for 1,146 reflections. The platinum atom is on a crystallographic, two-fold axis. It is coordinated to the N-7 sites of two diad-related, guanosine moieties and the nitrogen atoms of an ethylenediamine molecule. The Pt-N-7 distance is 1.967 A (196.7 pm). The nucleoside exhibits the anti conformation for the base, the C-3 endo pucker for the D-ribosyl group, and the g orientation around the exocyclic C-4 -C-5 bond. 

The dechlorination of chlorine-substituted pyrimido[5,4-rf]pyrimidine nucleosides succeeds with palladium on charcoal and anhydrous triethylamine in anhydrous ethanol (yield 71-75%).171,191 Tetraamino-substituted derivatives of type 3 can be reduced to triamino-substi-tuted pyrimido[5,4-e/ pyrimidincs using zinc powder or hydrogen over a platinum catalyst. The reoxidation of the 1,2,3,4-tetrahydro intermediate is performed with potassium iodide/iodine solution.215... 

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). 

There are cases when heavy metals are used in chemotherapy, for example cytostatic chemotherapy with as-platinum (Rosenberg 1969 [cited by Lippert 1999], Garban etal. 1989, Haiduc and Silvestru 1989, Johnsson et al. 1995). Numerous research studies into the interaction of DNA with metal ions also dealt with ds-platinum (Lippert 1999, Garban 2000). Cis-platinum interacts with nucleosides preferentially through the Ny site of guanine, but may also form bidentate chelates as a result of interaction both with Ny and sites. Modifications induced to ds-platinum by the interaction with guanine have been studied using quantum chemistry (Lippert 1999, Chojnacki et al. 2001). 

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