Second-sphere co-ordination of carboplatin and rhodium complexes by cyclodextrins (cyclomalto-oligosaccharides)

The cyclomalto-oligosaccharides [cyclodextrins, αCD (1), βCD (2), and γCD (3)] and the pure methylated derivatives, hexakis(2,6-di-O-methyl)-αCD (DM- αCD, 4) and heptakis(2,6-di-O-methyl)-βCD (DM-βCD, 5), function as second-sphere ligands towards diammine(η⁴-cycloocta-1,5-diene)rhodium(I) hexafluorophosphate (8), ethylenediammine(η⁴-cycloocta-1,5-diene)rhodium(I) hexafluorophosphate (9), and diammine(1,1-cyclobutanedicarboxylato)platinum(II) (11, carboplatin). The transition metal complexes are included inside the cavities of the CDs both in aqueous solution (¹H-m.m.r. data) and in the solid state (X-ray data). In the crystals of the 1:1 adducts 8-αCD and 11-αCD, the transition metal complexes have their organic ligands inserted into the cavity of 1 and their ammine ligands hydrogen-bonded to secondary hydroxyl groups on the rim. The ammine ligands of 8 are displaced in the presence of either αCD or DM-αCD, but 9 is stable. Although 8 and 9 also form adducts with βCD, 11 is specific in forming a 1:1 adduct with αCD in aqueous solution. The standard enthalpy (-25.3 kJ.mol^-1) and entropy (-42 J.K^-1.mol^-1) changes for the "reaction" between 11 and αCD indicate that adduct formation is an enthalpy driven process. The greatly increased solubility (from 50 to 240mm) of 11 in aqueous solutions of αCD, and its encapsulation by αCD in the solid state, could find applications in the use of carboplatin in cancer chemotherapy.