A volumetric and NMR study of cyclodextrin-inhalation anesthetic complexes in aqueous solutions

Abstract

The apparent molar volumes (Vϕ) of two anesthetics (halothane and forane) have been determined in water and in binary solvent (H2O + cyclodextrin) systems at 25 °C. The results show that the magnitudes of Vϕ are greater in ternary solutions than in the binary aqueous systems. The apparent molar volumes at infinite dilution (Vϕo) of halothane in ternary solutions are observed to depend on the following factors: (i) the magnitude of the binding constant (K1:1), (ii) the lipophilicity of the anesthetic, (iii) the mole ratio of the host/halothane system, and (iv) the topology (i.e., facial vs. inclusion) of the host/guest complex. The volumetric properties of the ternary systems have been analyzed in terms of the complexed and uncomplexed species by application of Young’s rule. The formation of 1:1 CD–halothane complexes was successfully modeled using a two-state model. The binding affinity of the various cyclodextrins toward halothane is listed in descending order as follows: DM-β-CD > HP-β-CD > β-CD > α-CD > TM-β-CD.