Synthesis and interfacial properties of glyco-lipophosphoramidates

Abstract

Lipophosphoramidates are a class of amphiphilic molecules that are tunable; and are heavily explored for a variety of industrial and medicinal applications. Self-assembled structures derived from such molecules enhance the bioavailability, selectivity and pharmacokinetic properties of drug molecules. Herein we report the synthesis of novel glyco-lipophosphoramidates (GLP-3, GLP-4, GLP-5, GLP-6) with varying linear and branched hydrocarbon tails via the Staudinger-phosphite reaction. The incorporation of the carbohydrate moiety as the head group region of the amphiphile promotes biocompatibility and biodegradability. Surface activity, adsorption, and aggregation behavior in aqueous solution were examined using surface tension, Langmuir monolayers, and atomic force microscopy (AFM). The critical aggregation concentrations (CAC) and Langmuir isotherms showed the typical dependence on acyl chain structure. Gibbs adsorption profiles provided limiting molecular areas in the range 55–85 Å2. AFM imaging revealed the formation of large spherical aggregates in aqueous solution above the CAC. Dye encapsulation studies support the self-assembly into vesicles by GLP-3, GLP-4 and GLP-5; demonstrating the potential for drug delivery or nanocarrier applications.