A Versatile Method for Preparing Polysaccharide Conjugates via Thiol-Michael Addition

Abstract

Polysaccharide conjugates are important renewable materials. If properly designed, they may for example be able to carry drugs, be proactive (e.g., with amino acid substituents) and can carry a charge. These aspects can be particularly useful for biomedical applications. Herein, we report a simple approach to preparing polysaccharide conjugates. Thiol-Michael additions can be mild, modular, and efficient, making them useful tools for post-modification and the tailoring of polysaccharide architecture. In this study, hydroxypropyl cellulose (HPC) and dextran (Dex) were modified by methacrylation. The resulting polysaccharide, bearing α,β-unsaturated esters with tunable DS (methacrylate), was reacted with various thiols, including 2-thioethylamine, cysteine, and thiol functional quaternary ammonium salt through thiol-Michael addition, affording functionalized conjugates. This click-like synthetic approach provided several advantages including a fast reaction rate, high conversion, and the use of water as a solvent. Among these polysaccharide conjugates, the ones bearing quaternary ammonium salts exhibited competitive antimicrobial performance, as supported by a minimum inhibitory concentration (MIC) study and tracked by SEM characterization. Overall, this methodology provides a versatile route to polysaccharide conjugates with diverse functionalities, enabling applications such as antimicrobial activity, gene or drug delivery, and biomimicry.

Revisiting the Synthesis of Cellulose Acrylate and Its Modification via Michael Addition Reactions

“…Very recently, modification of cellulose acetate acrylate having only partial acryloyl group by thiol-ene reactions was reported . However, these methods using methacrylated and acrylated cellulose derivatives are not applicable to the synthesis of highly functionalized cellulose derivatives with high values of degree of substitution (DS) because the DS values of Michael acceptors are typically low (DS < 0.2). ,, …”

“…18 However, these methods using methacrylated and acrylated cellulose derivatives are not applicable to the synthesis of highly functionalized cellulose derivatives with high values of degree of substitution (DS) because the DS values of Michael acceptors are typically low (DS < 0.2). 15,16,18 We envisioned that simple cellulose acrylate 1 could be used as a good precursor to directly synthesize highly modified cellulose 2 by Michael addition with easily available function- alized nucleophiles such as amines if 1 with a high DS value could be synthesized from cellulose by acylation with acryloyl chloride (Scheme 1a). 19,20 Although there are few reports of the application of 1 to the precursor for versatile modification of cellulose, cellulose acrylate 1 is known as a precursor of radical polymerization.…”

“…In 2016, Edgar and co-workers reported a method for the synthesis of multifunctional cellulose esters using cross-metathesis followed by thiol-Michael addition . Later, some groups reported the synthesis of functional cellulose materials by thiol-Michael addition of methacrylated cellulose derivatives. , In this regard, Liu and co-workers reported surface functionalization of methacrylate-modified cellulose fibers using aza-Michael addition . Very recently, modification of cellulose acetate acrylate having only partial acryloyl group by thiol-ene reactions was reported .…”

Bio-Based Polymer Developments from Tall Oil Fatty Acids by Exploiting Michael Addition

“…The Michael reaction is a versatile synthesis type for linking electron-poor olefins to a wide range of nucleophiles [ 18 ]. Enolates [ 19 , 20 ], nitrogen-containing [ 21 , 22 , 23 , 24 , 25 , 26 ] reagents, and thiols [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ] are typical Michael donors, while alkyl acrylates are mainly used as Michael acceptors [ 33 ]. Adding an enolate anion to the α,β-unsaturated carbonyl compound to form a carbon–carbon bond is a Michael reaction [ 19 , 20 , 34 ].…”

“…A type of polymerization for the addition of hydroxyl monomers with electrophilic double or triple bonds is called the oxa-Michael reaction [ 35 , 36 ]. In the case of nitrogen and sulphur-containing donors, the reaction is called aza-Michael [ 21 , 22 , 23 , 24 , 25 , 26 , 37 ] and thio-Michael [ 26 , 27 , 28 , 29 , 30 , 31 , 32 ] addition reactions, respectively. In recent years, aza- and thio-Michael reactions have gained attention for polymerization [ 35 , 38 ].…”