NMR Study of Complexation of Metallacarboranes with Cyclodextrins

Page: 209

J. Rak a, M. Tkadlecováa, P. Cíglera,b, and V. Krála,c

a Department of Analytical Chemistry, Institute of Chemical Technology, Prague; b Gilead Sciences Research Center, Institute of Organic Chemistry and Biochemistry, Academy o Sciences of the Czech Republic, c Zentiva Co. Prague

 

Metallacarboranes and their derivatives are the recently discovered inhibitors of HIV protease. The main goal of this work was to study the interaction of parent metallacarborane derivatives with cyclodextrins (CD) differing in the inner cavity size. This interaction can improve the drug solubility and its transport to the cells. For α, β- and γ-CD, NMR titrations with sodium cobalt(III) bis(1,2-dicarbollide) were performed at various CD concentrations. It was found that the greatest change in the 1H NMR chemical shift is observed at position 3 of CD on the inner broader rim of the cone-shaped molecule of CD. For α-CD, the NMR titration curves correspond to the 1:1 stoichiometry and to the stability constant ca. 900. For β-CD, simultaneous formation of 1:1 and 2:1 complexes and higher stability constants at least by two orders of magnitude follow from the titration curves. For γ-CD, more than two types of complexes are present. It was shown for β-CD that the increased temperature does not significantly influence the titration curves. The model, consisting of a high number of adjustable parameters, for the determination of stability constants of the complexes must be confirmed by independent analytical methods such as isothermal calorimetry and X-ray structure determination.

 

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