A simple circular dichroism (CD) method has been developed for describing qualitative and quantitative complexation of achiral or racemate, chromophore containing drug molecules with different cyclodextrins. The method is based on the inherent selectivity of the induced circular dichroism (ICD) signal; it appears as a result of the chromophoric guest molecule’s interaction with a chiral host molecule: the absorption transition of the guest molecule becomes chirally perturbed because of the proximity of the chiral host molecule. The outcome of the interaction will be the appearance of the ICD sign.
Since neither cyclodextrins (no chromophore), nor achiral chromophore containing drugs (achiral, or used as racemic compounds) in themselves exhibit a CD signal, while the complex produces an ICD signal. The acquired ICD signal has inherent selectivity for the complex, its sign and intensity gives information about the approximate structure as well as the stability relative to each other in case of different cyclodextrins.
If altering the host concentration, the change in the measured signal intensity is applicable for quantification of the stability constants. It was achieved by using the law of mass action for 1:1 drug complex.
Using nonlinear parameter fitting, the equilibrium constants could be obtained and compared with each other for the complexes of different cyclodextrins.
With this technique 27 different antifungal azole-cyclodextrin stability constants were determined of which 16 have not been available in the literature previously.
The most important advantage of the method is its inherent selectivity along with its sensitivity which is similar to UV/VIS spectroscopy. If supported by theoretical calculations it can provide detailed structural information about the complex, for example the inner or outer localization of the guest molecule.
Drawback is the need for a chromophore on the guest molecule which has to have the ability to interact with cyclodextrin for the appearance of the ICD signal. In addition, low stability values (logK<2) cannot be determined, as a result of the low intensity ICD signal’s disadvantageous signal-noise ratios. In case of racemates the calculated stability constant is the average of the value of the enantiomers.
Along with investigation of cyclodextrin complexes, CD is also used for describing drug interactions with other macromolecules, such as DNA and proteins and might be a possible technique to explore complexation with different oligo- or polysaccharide type drug delivery systems.
Full text available (open access): https://link.springer.com/article/10.1007/s10847-019-00938-2
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