Isomer formation in the binding of [PtCl2(cis-cyclohexane-1,3-diamine)] tooligonucleotides and the X-ray crystal structure of [PtCl2(cis-cyclohexane-1,3-diamine)]center dot dimethylformamide
St. Cham et al., Isomer formation in the binding of [PtCl2(cis-cyclohexane-1,3-diamine)] tooligonucleotides and the X-ray crystal structure of [PtCl2(cis-cyclohexane-1,3-diamine)]center dot dimethylformamide, J CHEM S DA, (19), 2001, pp. 2769-2774
Citations number
46
Categorie Soggetti
Inorganic & Nuclear Chemistry
Journal title
JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS
The crystal structure of [PtCl2(cis- 1,3-chxn)] (cis-1,3-chxn = (cis-cyclol
texane-1,3 -diamine)) as the dimethylformamide solvate is reported. When [P
tCl2(cis-1,3-chxn)] binds to d(GpG). two isomers are formed that are readil
y separated by HPLC. Both the HPLC and GFAAS studies of the products show t
hat the isomers form in a I : I ratio. Competition experiments involving d(
GpG) and the aquated and nonaquated forms of [PtCl2(cis-1,3-chxn)] and [PtC
l2(NH3)(2)] showed that the slower binding of the former complex was due to
slower aquation and not steric bulk. 1D and 2D NMR studies of the [Ptd(GpG
)(cis-1,3-chxn)] isomers showed that both the dinucleotide and the diamine
were highly fluxional, even at low temperatures, and this prevented formati
on of strong cross peaks in the NOESY and ROESY spectra and hence identific
ation of the isomers. [PtCl2(cis-1,3-chxn)] was reacted with a 52-mer oligo
nucleotide having six GpG binding sites and the products were enzymatically
digested and separated by HPLC. The two [Ptd(GpG)(cis-1,3-chxn)] stereoiso
mers were the only significant platinated products. again forming in a 1 :
1 ratio although it had been anticipated that stereoselectivity would be ob
served in the reaction with the 52-mer because of the potential for steric
interactions with the cis-1,3-chxn ligand. Molecular modelling revealed tha
t the observed lack of stereo selectivity was clue to the ability of the ci
s-1,3-chxn ligand to adopt a continuum of conformations that allow it to av
oid severe steric clashes with the DNA.