Synthesis of a pH-independent bifurcated amphiphile

Abstract

An efficient synthetic method for preparing bifurcated amphiphiles has been developed such that the functionality for attachment is located at the interface between the lipophilic and hydrophilic side chains. Attachment of the amphiphile to the repeat units of polymeric substrates enables the rapid preparation of amphiphilic homopolymers. Keywordsamphiphile; amphiphilic monomer; amphiphilic polymer; amphiphilic homopolymerThe human production and use of amphiphilic compounds dates to prehistory, when triacylglycerides were hydrolyzed in alkaline solution affording soaps to enable the aqueous dispersion of lipids. Since that time amphiphiles have seen widespread use owing to their unique ability to modulate the surface properties of molecules, particles, or solid surfaces with respect to their environment. Amphiphilic materials also can be used to enhance medical technologies, from their encapsulation of potent but insoluble drugs in micellar carriers, to their disruption of fungal cell walls. Much effort has focused on the synthesis and applications of amphiphilic block copolymers; however, an equally promising but relatively under-explored architectures include amphiphilic homopolymers 1 and dendrimers, 2 in which each repeat unit bears both lipophilic and hydrophilic sidechains. If amphiphilic homopolymers can organize into discrete nanoscale reverse micelles, they offer promise as carriers to transport polar therapeutics through the lipophilic stratum corneum, thereby enhancing transdermal drug delivery.The traditional oral route for delivering drugs is incompatible with many therapeutics due to the harshly acidic and enzymatically active gastric environment, therefore efforts have shifted to investigate technologies that would allow the transdermal administration of these materials. While the lipids within the skin are permeable to small, lipophilic molecules, most therapeutics are required to be hydrophilic to permit their distribution throughout the body via the bloodstream. However, only a handful of therapeutics exhibits the amphiphilic character that affords both permeability through the skin and systemic delivery through the bloodstream. Amphiphilic carriers can be designed to compatibilize polar drugs with the skin lipids to enable their transdermal transport, while allowing their release once they reach the bloodstream.In order to probe the efficacy of amphiphilic homopolymers for improving transdermal drug delivery, a broad range of polymer sizes and architectures should be explored. The first step towards this goal is the development of an efficient synthetic method for preparing bifurcated * Corresponding author. Tel.: +1-504-862-8135; fax: +1-504-865-5596; e-mail: sgrayson@tulane.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in i...

Synthesis of cyclic amphiphilic homopolymers and their potential application as polymeric micelles

“…Bifurcated amphiphile precursors 10-12 has also been previously described by our labs. 31 General procedure for encapsulation studies Amphiphilic homopolymer was dissolved into a non-polar solvent (toluene) at a range of concentrations with a final volume of 2 mL. Excess dye/guest ($0.010 g) was added and the vial sealed with parafilm.…”

“…Towards this end, our labs have reported a modular synthetic route towards the preparation of bifurcated amphiphilic units which are both neutral and independent of pH. 31 The synthesis involves the successive attachment of a long alkane chain (in this case dodecane) and an oligoethylene glycol chain (in this case tetra(ethylene glycol)) to a tris-alcohol core to provide amphiphilic unit 1. This novel bifurcated amphiphile can be easily synthesized in five steps with an overall 76% yield.…”

Investigation on RAFT Polymerization of a Y‐Shaped Amphiphilic Fluorinated Monomer and Anti‐Fog and Oil‐Repellent Properties of the Polymers

“…Figure 3a illustrates the anti-fog behavior of the copolymer films and a video is presented in the Supporting Information (Movie S1). It can be clearly observed that no fog forms on the surfaces of PDMAEMA 50 -b-FA 5 , PDMAEMA 50 -b-FA 11 , and P(DMAEMA 197 -co-FA 10 ), but for P(DMAEMA 150 -co-FA 24 ), a thick fog develops on the surface. The results indicate that the surface of the block copolymers has excellent anti-fog properties, but the surface of the random copolymer can prevent fogging only when it has a low FA content.…”

“…[10] 1,1,1-tris(hydroxymethyl)ethane, [11] 1,3,5-trisubstituted benzenes, [12] tertiary amines, [13] etc. Herein, we selected epichlorohydrin as the linking reagent for the preparation of the amphiphilic monomer because of its advantages such as simplifying the synthetic procedure, commercial availability, and low cost.…”