One-Step Synthesis of Azlactone-Functionalized SG1-Based Alkoxyamine for Nitroxide-Mediated Polymerization and Bioconjugation

Abstract

International audienceThe one-step synthesis of azlactone-functionalized SG1-based alkoxyamine (AzSG1) for the design of functional polymers by nitroxide-mediated polymerization (NMP) is reported. At 347.7 K, its dissociation rate constant, kd, was determined to be 2.72 x 10(-4) s(-1), leading to an activation energy, E-a, of 119.5 kJ mol(-1), which represents the lowest value ever reported for a secondary SG1-based alkoxyamine without any activation by an external stimulus. This was ascribed to enhanced stabilization of the released radical compared to other secondary alkyl radicals. The AzSG1 alkoxyamine was successfully used for the NMP for styrene, n-butyl acrylate, and methyl methacrylate with the addition of a small amount of acrylonitrile as a comonomer, without the need for free SG1. In all cases, first-order kinetics, good control with low dispersities (D = 1.2-1.4), and high living chain fractions (LF similar to 90%) were obtained. As a proof of concept, the conjugation of azlactone-functionalized polymers to benzylamine and lysozyme was successfully demonstrated. This work may be of high interest for conjugation as the azlactone functionality is also known to react with other nucleophiles such as alcohols or thiols

Thiolactone-Functional Reversible Deactivation Radical Polymerization Agents for Advanced Macromolecular Engineering

“…Alkoxyamines based on the SG1 nitroxide are well-established control agents for NMP polymerization. , Thus, a new thiolactone-functionalized alkoxyamine TL-SG1 was synthesized and evaluated in bulk NMP of St at 120 °C (Scheme ) for targeted DP n of 100 and 200.…”

“…Since the development of copper-assisted azide–alkyne cycloaddition (CuAAC) by Sharpless in 2001, new classes of “click” reactions have emerged and used for PPM. , Among them, thiol–ene chemistry appeared as a highly efficient, metal-free alternative “click” reaction, involving a thiol and an electron-deficient double bond under stoichiometric conditions at mild temperatures. , A second option is the thiol–thiosulfonate reaction, which allowed the functionalization of thiol-terminated polymers through the formation of a disulfide linkage. − Azlactones were also involved in a metal-free “click” reaction in the presence of amine. Azlactone-containing initiator, CTA, or monomers were developed to produce azlactone-functionalized polymers which could further react in PPM using amines. − …”

Synthesis and Applications of Protein/Peptide-Polymer Conjugates

“…The modification of proteins/peptides with polymers prepared by RDRP is perhaps the most well studied and understood approach. Futhermore the precision conferred by RDRP enables the composition of synthetic (co)polymers to be manipulated to ellicit additional properties to bestow on target biomolecules such as stimulated responsivity, usually via phase transition in response to fluctuations in temperature, pH and redox, all of which are associated with the microenvironment of stressed, diseased or malignant tissues and cells.…”

Radical ring-opening polymerization of novel azlactone-functionalized vinyl cyclopropanes

“…Owing to its high reactivity toward amines even in the absence of catalyst and without producing by-product, azlactone functionality has found wide use in organic, bioconjugation and (bio)macromolecular synthesis. [15][16][17][18][19][20] Furthermore, the amine-azlactone reaction satisfied the requirements to be classified as a "click" reaction. [21][22][23][24] Despite this potential, the synthesis and used of azlactone-functionalized polymers are limited by the availability of the corresponding monomers.…”