Cyclodextrin complex stoichiometry

Armstrong et al. developed a chromatographic technique which could be used to evaluate the stoichiometry and all relevant binding constants for most substrate-CD systems (8). This method was not dependent on a solute s spectroscopic properties, conductivity, electrochemical behavior, or solubility. This work presented theory and chromatographic evidence for multiple cyclodextrin complex formation. Previous theoretical work considered only 1 1 complex formation (9-12). A two to one complexation equation was derived by expanding on the equation first used in 1981 to describe the 1 1 complexation behavior of a solute in a pseudophase system (13.14). Using this method, it was demonstrated that closely related compounds such as structural isomers of nitroaniline could exhibit different binding behaviors (8). 

Utsuki, T. Hirayama, F. Uekama, K. Different photodimerization behavior of tranilast in a-, P- and y-cyclodextrin complexes cavity-size and stoichiometry dependence. J. Chem. Soc., Perkin Trans 1993, 2 (1), 109-114. 

D Anna F, Riela S, Meo PL, Noto R. Stability and stoichiometry of some binary fluorophore-cyclodextrin complexes. Tetrahedron 2004 60 5309-14. 

Although Freudenberg s hypothesis that complex-formation occurred by inclusion within the cavity was generally accepted, there was no direct evidence for this, either in solution or in the solid state. Broser and Lautsch had found by spectrophotometric titration that the complexes of a series of dyes with the cyclodextrins in solution obeyed the mass action law with a stoichiometry of 1 1. They suggested that association on the outside of the ring might not have a defined stoichiometric composition, and they thus interpreted their results as being consistent with inclusion by cyclodextrin. Their results were not conclusive, however. 

As already mentioned, it is difficult to obtain information on the stoichiometry of cyclodextrin-analyte complexes based on CE separations. Nuclear magnetic resonance and other spectrometric techniques (UV, circular... 

Mechanisms of interactions between cyclodextrins and enantiomers were reported by Parker and Kataky [15,16]. The complexes have a 1 1 stoichiometry and they all have a host-guest structure. 

Cyclodextrins have been covalently modified for catalytic oxidation, such as compounds 57, 62-65 (Schemes 3.14 to 3.16) [44, 45]. Enantioselective epoxidation of styrene derivatives, and carene using 20-100 mol% of the CD-ketoester 57 has been achieved. The inclusion-complex formation was confirmed by aH NMR titration experiments, confirming the 1 1 substrate catalyst stoichiometry under the reaction conditions. In the oxidation of carene, NOE and ROESY experiments showed different behavior according to the size of the R group (Scheme 13.14). Evidence was found for the formation of inclusion complexes with compounds 58 and 59. On the other hand, compounds 60 and 61 proved to interact with the catalyst via a tail inclusion vide infra). The increased diastereoselectivity observed with compounds 58 and 59 might be explained by a closer proximity to the covalently linked dioxirane. 

The emulsions of P-cyclodextrins grafted on silicone could encapsulate the antifungal substance griseofulvin inside the P-cyclodextrin cavity by formation of inclusion complex. The encapsulation rate was limited to the 1 1 stoichiometry of the complex. Supplementary amount of griseofulvin slowly precipitated as crystalline particles in the aqueous phase. 

An alternative is the solubilization with the help of cyclodextrins because these are soluble in water and can incorporate organic molecules inside their hydrophobic cavity [11-13]. P-cyclodextrin is the most useful regarding the typical size of molecules to be solubilized. Griseofulvin forms inclusion complexes of 1 1 stoichiometry with P-cyclodextrin [14, 15]. One possible problem is the moderate solubility of P-cyclodextrin in water (18.5 g/L) and the even lower solubility of most inclusion complexes. A more dramatic problem is the preparation of inclusion complexes of water-soluble cyclodextrins and organic molecules that are not soluble in water. The complexation takes place by means of hydrophobic interactions inside the cavity, which require the presence of water as a solvent. 

Utsuki, T., Imamura, K., Hirayama, R, Uekama, K. Stoichiometry-dependent changes of solubihty and photo reactivity of an antiulcer agent, 2 -carboxymedioxy-4,4 -bis(3-mediyl-2-butenyloxy) chalcone, in cyclodextrin inclusion complexes. Eur. J. Phamu Sci. 1993, i, 81—87. 

Cyclodextrins (hosts) form inclusion complexes with many kinds of molecules and ions (guests), either in the solid phase or in solution. The stoichiometry of guest compounds to host compounds in inclusion complexes is usually 1 1 in aqueous solution. 

The supramolecular (host) system is viewed as a confined space in which the probes and/or quenchers are located. Assumptions have to be made regarding the availability of complexation sites in each system. For host-guest complexes, such as cyclodextrins, stoichiometries of complexation are assumed or determined experimentally [50,51]. In the case of self-assembled systems, such as micelles or vesicles, the most common assumption is that at low probe/mi-celle ratios the distribution of probes follows a Poisson distribution [30]. This means that the probability of encountering a molecule in a particular micelle is independent of how many molecules are already in that micelle. 

The association and dissociation rate constants for hydronium ions to cyclodextrin cavities has been studied by measuring the fluorescence of 2-naph-thol [178]. The pKa of the excited single state of this molecule is much lower than for the ground state and the deprotonated species has different absorption and emission spectra. This spectroscopic signature was explored to characterize the mobility of H". Upon complexation to the cyclodextrin, the acidity of the naphthol decreased. In addition, excited state deprotonation was decreased in the presence of a-cyclodextrin due to the formation of a complex with 1 2 naphthol cyclodextrin stoichiometry. Thus, the cyclodextrin environment precluded the exit of the hydronium ion from the cavity. 

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