SUBSTITUTION OF INOSINE FOR CHLORIDE IN [PT-2(HDTA)CL-2](2-) (HDTA(4-) = 1,6-HEXANEDIAMINE-N,N,N',N'-TETRAACETATE)

The substitution reaction of inosine (ino) with the displacement of Cl - from [Pt-2(II)(hdta)Cl-2](2-), (hdta(4-) = 1,6-hexanediamine-N,N,N', N'-tetraacetate) has been studied in D2O at 35.0 degrees C. Each Pt-II center has initially the coordination comparable to mer-[Pt(mida)Cl]( -), (mida(2-) = N-methyliminodiacetate), as shown by the Pt-195 NMR si gnal at -1330 ppm for mer,mer-[Pt-2(hdta)Cl-2](2-) and -1317 ppm for m er-[Pt(mida)Cl](-). By operating under conditions wherein the ratio of [inosine]:available Pt-II binding sites = 0.25, (excess Pt-II), the f irst ligand addition of inosine was followed by monitoring with time t he changes in the 500 MHz NMR spectrum of [Pt-2(hdta)Cl](2-). The H-8 proton resonance of inosine (site of Pr-II-coordination) appears at 8. 82 ppm for the coordinated [Pt-2(hdta) (ino)Cl](-) complex, replacing the 8.32 ppm H-8 resonance of free inosine, A substitution rate of 3.4 8 x 10(-4) s(-1), controlled by the loss of Cl- was determined. For co mparison, the guanosine bases of DNA displace Cl- from cis-[Pt(NH3)(2) Cl-2] about 3.4 times more slowly. Time-dependent spectra of the tethe r CH2 protons of the hdta(4-)backbone also exhibit characteristic down field shifts as Cl- is displaced by ino, sith the second CH2 outward f rom the Pt-II-N bond experiencing the largest influence (Delta delta= -0.21 ppm). The C-13 NMR spectrum of the product mixture of [Pt-2(hdta )-(ino)Cl](-):[Pt-2(hdta)Cl-2](2-) showed 27% of the ino-substituted c omplex (25% theoretical). Also no free carboxylate resonances appear n ear 175 ppm, but rather only the new resonance at 188.6 ppm for the in osine complex and the 188.4 ppm resonance of the [ Pt-2(hdta)Cl](2-) e xcess reagent sire detected. This identifies the first inosine additio n step as occurring only with Cl- displacement. a second addition step further displaces a coordinated glycinato group at a slower rate. (C) 1998 Elsevier Science S.A.