Solubilization of substituted indole compounds by beta-cyclodextrin in water

Area of Science:

• Supramolecular Chemistry
• Physical Chemistry
• Pharmaceutical Sciences

Background:

• Cyclodextrins are widely used as host molecules for drug delivery and solubilization.
• Substituted indole compounds (SICs) represent a class of molecules with diverse biological activities.
• Understanding the interaction between cyclodextrins and guest molecules is crucial for optimizing formulation strategies.

Purpose of the Study:

• To investigate the solubilization behavior of eight substituted indole compounds (SICs) using beta-cyclodextrin (beta-CD) in aqueous solutions.
• To determine the stoichiometry of the inclusion complexes formed between SICs and beta-CD.
• To elucidate the factors influencing the differential solubilization of structurally similar SICs.

Main Methods:

• Solubility studies of SICs in beta-CD/water solutions.
• Spectroscopic techniques to characterize inclusion complex formation.
• Analysis of stoichiometry and binding interactions.

Main Results:

• 1,2,3,4-Tetrahydrocarbazole and N-methyl-1,2,3,4-tetrahydrocarbazole formed 1:1 inclusion complexes with beta-CD.
• The remaining six SICs formed 1:2 inclusion complexes with beta-CD.
• Solubilization differences among similar SIC pairs were explained by variations in contact area, molecular polarity, and hydrogen bonding.

Conclusions:

• Beta-cyclodextrin effectively solubilizes substituted indole compounds through inclusion complexation.
• The stoichiometry of complexation (1:1 or 1:2) depends on the specific SIC structure.
• Steric hindrance, polarity, and hydrogen bonding are key factors governing the extent of solubilization and complex stability.