Encapsulation of platinum(II)-based DNA intercalators within cucurbit[6,7,8]urils

The partial encapsulation of platinum(II)-based DNA intercalators of the type Pt(5-Cl-phen)(ancillary ligand)](2+), where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbitn]uril (CBn], where n is 6, 7 or 8) has been examined by (1)H and (195)Pt NMR and mass spectrometry. For CB7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low Pt(5-Cl-phen)(S,S-dach)](2+) (5CLSS) to CB8] ratios (i.e. 0.25:1) but over the ancillary ligand at higher ratios (i.e. 2:1). For CB6] binding, 5CLSS exhibits both portal and cavity binding, with the ancillary ligand displaying chemical shifts consistent with fast exchange kinetics on the NMR timescale for portal binding and slow exchange kinetics for cavity binding. Binding constants could not be determined using UV-vis, circular dichroism or fluorescence spectrophotometry, but a binding constant for binding of 5CLSS to CB6] of approximately 10(5) M(-1) was determined using (1)H NMR. Finally, the effect of CBn] encapsulation on the cytotoxicity of the metal complexes was examined using L1210 murine leukaemia cells in vitro growth inhibition assays. The cytotoxicity is highly dependent on both the metal complex and the CBn] size, and whilst CB7] and CB8] generally decreased cytotoxicity, it was found that CB6] increased the cyotoxicity of 5CLSS up to 2.5-fold.