Aggregation Behavior of Pegylated Bile Acid Derivatives

Bile acids are amphiphilic endogenous steroids that act as anionic surfactants in the digestive tract and aggregate in aqueous solutions. Nonionic surfactants were synthesized by grafting poly­(ethylene glycol) chains of various lengths (pegylation) to three bile acids (lithocholic, deoxycholic, and cholic acid) using anionic polymerization. The aggregation properties of the derivatives were studied with viscosity measurements and light scattering as well as with steady-state and time-resolved fluorescence techniques, and the aggregates were visualized by transmission electron microscopy to elucidate the effect of pegylation on the aggregation process. The fluorescence results showed a good correlation with the capacity of the bile acid derivatives to solubilize a hydrophobic drug molecule. The solubilization of ibuprofen depends on the length and the number of grafted PEG chains, and the solubilization efficiency increases with fewer PEG chains on the bile acid. The results indicate their potential for use in the design of new bile acid-based drug-delivery systems

Guest Binding Dynamics with Cucurbit[7]uril in the Presence of Cations

The binding dynamics of <i>R</i>-(+)-2-naphthyl-1-ethylammonium cation (NpH⁺) with cucurbit[7]uril (CB[7]) was investigated. Competitive binding with Na⁺ or H₃O⁺ cations enabled the reaction to be slowed down sufficiently for the kinetics to be studied by fluorescence stopped-flow experiments. The binding of two Na⁺ cations to CB[7], i.e., CB[7]·Na⁺ (<i>K</i>₀₁ = 130 ± 10 M^–1) and Na⁺·CB[7]·Na⁺ (<i>K</i>₀₂ = 21 ± 2 M^–1), was derived from the analysis of binding isotherms and the kinetic studies. NpH⁺ binds only to free CB[7] ((1.06 ± 0.05) × 10⁷ M^–1), and the association rate constant of (6.3 ± 0.3) × 10⁸ M^–1 s^–1 is 1 order of magnitude lower than that for a diffusion-controlled process and much higher than the association rate constant previously determined for other CB[<i>n</i>] systems. The high equilibrium constant for the NpH⁺@CB[7] complex is a consequence of the slow dissociation rate constant of 55 s^–1. The kinetics results showed that formation of a complex between a positively charged guest with CB[<i>n</i>] can occur at a rate close to the diffusion-controlled limit with no detection of a stable exclusion complex

Explaining the Highly Enantiomeric Photocyclodimerization of 2‑Anthracenecarboxylate Bound to Human Serum Albumin Using Time-Resolved Anisotropy Studies

The mechanism for the high enantiomeric excess (ee) (80–90%) observed in the photocyclodimerization of 2-anthracenecarboxylate (AC) in the chiral binding sites of human serum albumin (HSA) was studied using fluorescence anisotropy. A long rotational correlation time of 36 ns was observed for the excited states of the ACs bound to the HSA site responsible for the high ee, suggesting that the ACs have restricted rotational mobility in this site. The ACs in this site have the same prochiral face protected by the protein, and this protection is responsible for the high ee observed. These insights provide a strategy for the rational design of supramolecular photochirogenic systems

Supramolecular Reversible On–Off Switch for Singlet Oxygen Using Cucurbit[<i>n</i>]uril Inclusion Complexes

A novel strategy to control the generation of singlet oxygen by a photosensitizer using cucurbit­[<i>n</i>]­urils inclusion complexes is shown herein, and the strategy has great potential for therapeutic applications. We show the basic requirements of the photosensitizer complexes in order to develop an <i>on</i>–<i>off</i> switch for singlet oxygen that is reversible using competitive binding. The supramolecular strategy proposed in this paper avoids complex synthetic schemes in order to activate or deactivate the photosensitizer as previous work has shown and supports the use of biocompatible materials. Mechanistic insights into the control over the generation of singlet oxygen are provided, which strongly emphasize the key role of the cucurbit­[<i>n</i>]­uril macrocycles in the stabilization or deactivation of the triplet excited state