Poly(4‐acryloylmorpholine) oligomers carrying a β‐cyclodextrin residue at one terminus

Abstract

A straightforward synthesis of amphiphilic β‐cyclodextrin‐poly(4‐acryloylmorpholine) (β‐CD‐PACM) polymers of controlled molecular weight, consisting of the radical polymerization of 4‐acryloylmorpholine in the presence of 6‐deoxy‐6‐mercapto‐β‐cyclodextrin (β‐CD‐SH) as chain‐transfer agent, has been established. These derivatives carry a single β‐cyclodextrin (β‐CD) moiety at one terminus and their average molecular weight is in the order of 104. Thus, their β‐CD content is ∼ 10% by weight. No evidence of un‐functionalized PACM was found in the final products. The chain‐transfer constant (CT) of β‐CD‐SH was found to be 1.30 by independently determining the reaction constants of both chain‐transfer and propagation reactions. This ensures that the molecular weight, hence the β‐CD content of the polymers, does not significantly vary with conversion. These β‐CD‐PACM polymers are highly soluble in water as well as in several organic solvents such as chloroform and lower alcohols. They proved capable of solubilizing in water poorly soluble drugs such as 9‐[(2‐hydroxyethoxy)methyl]guanine (Acyclovir) and of gradually releasing them in aqueous systems. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1607–1617, 2008

Stimuli-responsive 4-acryloylmorpholine/4-acryloylpiperidine copolymers via nitroxide mediated polymerization

“…4AM homopolymer is completely water‐soluble and it does not exhibit any thermoresponsive behaviour in aqueous solution in a reasonable temperature range. 4AP homopolymer, conversely, was shown to exhibit an LCST‐type transition at around 4–6 °C .…”

“…The reasons for this are not entirely clear at this point but it is possible that the second batch was polymerized strictly thermally at high temperatures, which has been observed in acrylate polymerizations. 46,47 Thermoresponsive Behavior of 4AM/4AP Statistical Copolymers in Aqueous Solution 4AM homopolymer is completely water-soluble 48 and it does not exhibit any thermoresponsive behaviour in aqueous solution in a reasonable temperature range. 4AP homopolymer, conversely, was shown to exhibit an LCST-type transition at around 4-6 8C.…”

Cyclodextrins and Polymer Nanoparticles

“…A group with Cavalli, Trotta, Ferruti, Ranucci, et al used a well-known amphiphilic biocompatible polymer, poly(4acryloylmorpholine) (PACM), to prepare a water-soluble tadpole-like b-CD conjugate (b-CD-PACM) capable of forming nanoparticles for the delivery of acyclovir [56,57]. The b-CD-PACM polymer was prepared by radical polymerization of 4-acrylmorpholine in the presence of 6-deoxy-6-mercapto-b-CD (b-CD-SH) as chain transfer agent.…”

Amphiphilic Poly(4‐acryloylmorpholine)/Poly[2‐(N‐carbazolyl)ethyl acrylate] Random and Block Copolymers Synthesized by NMP

“…It is only recently that Schubert and coworkers were capable of successfully homopolymerizing 4AM in a controlled manner using an SG1‐based unimolecular initiator, 2‐({ tert‐ butyl[1‐(diethoxyphosphoryl)‐2,2‐dimethylpropyl]amino}oxy)‐2‐methylpropanoic acid (BlocBuilder, Scheme ) 24. Poly(4AM) is water‐soluble and biocompatible,25 and poly(4AM)‐containing materials have subsequently been applied for next‐generation drug delivery vehicles,25 biochemical sensors,26 and polychelatogens for waste water purification 27. The incorporation of an additional functional segment or the incorporation of a secondary functional comonomer via random copolymerization can impart additional functionality to the final copolymer.…”