Conformationally Controlled Oligocholate Membrane Transporters: Learning through Water Play

Abstract

Controlled translocation of molecules and ions across lipid membranes is the basis of numerous biological functions. Because synthetic systems can help researchers understand the more complex biological ones, many chemists have developed synthetic mimics of biological transporters. Both systems need to deal with similar fundamental challenges. In addition to providing mechanistic insights into transport mechanisms, synthetic transporters are useful in a number of applications including separation, sensing, drug delivery, and catalysis. Disciplines Chemistry CommentsReprinted (adapted) C O N S P E C T U S C ontrolled translocation of molecules and ions across lipid membranes is the basis of numerous biological functions. Because synthetic systems can help researchers understand the more complex biological ones, many chemists have developed synthetic mimics of biological transporters. Both systems need to deal with similar fundamental challenges. In addition to providing mechanistic insights into transport mechanisms, synthetic transporters are useful in a number of applications including separation, sensing, drug delivery, and catalysis.In this Account, we present several classes of membrane transporters constructed in our laboratory from a facially amphiphilic building block, cholic acid. Our "molecular baskets" can selectively shuttle glucose across lipid membranes without transporting smaller sodium ions. We have also built oligocholate foldamers that transiently fold into helices with internal hydrophilic binding pockets to transport polar guests. Lastly, we describe amphiphilic macrocycles, which form transmembrane nanopores in lipid bilayers through the strong associative interactions of encapsulated water molecules.In addition to presenting the different transport properties of these oligocholate transporters, we illustrate how fundamental studies of molecular behavior in solution facilitate the creation of new and useful membrane transporters, despite the large difference between the two environments. We highlight the strong conformational effect of transporters. Because the conformation of a molecule often alters its size and shape, and the distribution of functional groups, conformational control can be used rationally to tune the property of a transporter. Finally, we emphasize that, whenever water is the solvent, its unique properties;small size, strong solvation for ionic functionalities, and an extraordinary cohesive energy density (i.e., total intermolecular interactions per unit volume);tend to become critical factors to be considered. Purposeful exploitation of these solvent properties may be essential to the success of the supramolecular process involved;this is also the reason for the "learning through water play" in the title of this Account.

A Standard Structure for Bile Acids and Derivatives

“…Consequently, the hydrophobic-hydrophilic balance of the compound is either increased or reduced, thus modifying its self-aggregation in aqueous solution. Several papers dealing with the physicochemical properties and applications in fields such as supramolecular chemistry, biomedicine, and pharmaceutics have been reported [18,[22][23][24][25][26][27][28].…”

Water‐Soluble Molecularly Imprinted Nanoparticles (MINPs) with Tailored, Functionalized, Modifiable Binding Pockets

“…[21] Charged functional groups (e.g., ammonium, guanidinium, or carboxylate) often have a strong tendency to stay within or at least close to water to satisfy their solvation needs. [22] Binding selectivity of MINP-COOH An important property of molecularly imprinted materials is their binding selectivity. The above study demonstrated binding selectivity for acid-and base-functionalized template analogues in a pH-dependent manner.…”

Surface-Cross-Linked Micelles as Multifunctionalized Organic Nanoparticles for Controlled Release, Light Harvesting, and Catalysis

“…16−20 This Feature Article summarizes our recent efforts in polymerizing/cross-linking surfactant micelles and converting them into multifunctional nanoparticles. Our surface-cross-linked micelles (SCMs) can be tuned in multiple ways including surface functionality, internal content, and water or oil solubility.…”