betadex and helvolic-acid

The host-guest interaction between the steroid antibiotics sodium fusidate and potassium helvolate as guests and the hosts beta- and gamma-cyclodextrin was studied by 13C and 1H NMR techniques. The analysis of chemical shifts of individual nuclei leads to inconsistent values of the association constants and fails generally in the case of mixtures of 1:1 and 1:2 stoichiometries. The problem of parameter correlation is identified and the global analysis of two or more nuclei is proposed as a very effective method for the detection of complexes of higher stoichiometries and for the precise determination of the involved association constants. A matrix formulation of global analysis and the determination of confidence intervals is described. An analytical solution of the cubic equation, necessary for the description of higher order complexes, is presented in detail and its use together with commercial fitting software is compared with dedicated implementations. gamma-Cyclodextrin forms with both studied steroids, sodium fusidate and potassium helvolate, 1:1 complexes with high values of the association constants, K(1)=(60+/-24)x10(3)lmol(-1), and K(2)=(22+/-9)x10(3)lmol(-1), respectively. To the contrary, beta-cyclodextrin forms 1:1 and 1:2 (guest:host) complexes with both steroids, with moderate K(1) and low K(2) values (K(1)=(0.74+/-0.13)x10(3)lmol(-1), K(2)=(0.210+/-0.075)x10(3)lmol(-1)), and (K(1)=(2.42+/-0.87)x10(3)lmol(-1), K(2)=(0.06+/-0.09)x10(3)lmol(-1)), respectively.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Carbon Isotopes; Cyclodextrins; Drug Delivery Systems; Fusidic Acid; gamma-Cyclodextrins; Models, Chemical; Models, Theoretical; Nuclear Magnetic Resonance, Biomolecular; Protons

The complexation of two steroid antibiotics of the fusidane family, sodium fusidate and potassium helvolate, by beta-CD and gamma-CD has been studied by using 1D and 2D-NMR techniques. Both guests form 1:1 complexes with gamma-CD and 1:2 (guest:cyclodextrin) complexes with beta-CD. Thus, both antibiotics behave as monotopic and ditopic guests when they are complexed by gamma-CD and beta-CD, respectively. Both steroids enter into the cavity of the gamma-CD by the side chain, reaching the central region of the steroid (rings C and D), whereas the A and B (partially) rings remain outside. For beta-CD complexes, ROESY spectra show a remarkable absence of interactions of the protons of the C and D rings, whereas clear interactions corresponding to the side chain, and A and B rings are observed. The obtained equilibrium constants (see previous paper) are discussed in terms of the structures proposed for the complexes. NMR spectra of sodium fusidate are revised, and a full assignment of the 1H and 13C NMR spectra is presented for potassium helvolate.

Topics: Anti-Bacterial Agents; beta-Cyclodextrins; Binding Sites; Cyclodextrins; Drug Delivery Systems; Fusidic Acid; gamma-Cyclodextrins; Models, Chemical; Models, Theoretical; Nuclear Magnetic Resonance, Biomolecular