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DOI: 10.1039/A904898G (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 2, 1999, 2533-2538

Complexation of antiretroviral nucleosides 2′,3′-dideoxyinosine, 2′,3′-dideoxyadenosine and 2′,3′-dideoxyguanosine with β-cyclodextrin. A 1H NMR study

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Bozenna Golankiewicz, G. Perlovich, J. Poznański, J. Sitkowski, the late L. Stefaniak, J. Zeidler and Wojciech Zielenkiewicz

Abstract

A number of successful applications have been found that use cyclodextrin complexation ability. In the present work we analyse β-cyclodextrin (β-CD) complexes with 2′,3′-dideoxynucleosides (ddA, ddG, ddI) exhibiting high antiviral activity against HIV strains. The formation of the complexes has been analysed by 1H NMR-monitored titration. On the basis of concentration dependencies of proton chemical shifts, the nucleosides in this study form complexes of 1∶1 stoichiometry with β-CD. The bonding constants depend on ligand type and could be estimated as 35 ± 10 M–1 for ddA; 55 ± 10 M–1 for ddI and 85 ± 20 M–1 for ddG–β-CD complexes. ROESY spectra demonstrate that ligands penetrate the hydrophobic cavity of the β-CD. Finally, on the basis of ROESY data, the “low resolution” ddG–β-CD complex structure has been determined by multistep restrained molecular dynamics calculations. Calculated ddG–β-CD complex structure fully agrees with experimental data obtained for other β-CD complexes.

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