Fluorescent and chemico-fluorescent responsive polymers from dithiomaleimide and dibromomaleimide functional monomers

Abstract

A new class of brightly fluorescent and profluorescent methacrylate and acrylate monomers is reported. The fluorescent monomers contain the dithiomaleimide (DTM) fluorophore, which imparts a large Stokes shift (up to 250 nm) and bright emission. Furthermore, the simple and efficient chemistry of the DTM group, as well as its excellent processability (highly soluble, neutral functional group) makes monomer preparation straightforward. Copolymerisation at 10 mol% loading with a range of hydrophobic and hydrophilic monomers is demonstrated by RAFT polymerisation. Reactions proceed to high monomer conversion with excellent control over molecular weight (Đ M < 1.3) under standard polymerisation conditions. Incorporation of these fluorescent DTM-functional monomers has little effect on polymer properties, with PEG (meth)acrylate copolymers retaining their water solubility and thermoresponsive behaviour. A thiol-exchange reaction is also possible, whereby the thiol ligands of the pendent DTM groups can be exchanged by conjugate addition-elimination with an alternative thiol. Monomers containing the dibromomaleimide (DBM) group gave profluorescent copolymers. Reaction of the DBM group with thiols (to form the DTM group) corresponds to a chemico-fluorescent response, leading to an OFF-to-ON switching of fluorescence. This post-polymerisation functionalisation is shown to be fast and highly efficient (>95% conversion in 3 h), and by using thiols of different polarities can be used to progressively tune the LCST cloud point of a thermoresponsive polymer over a range of 11 C. Therefore, both DTM and DBM functional monomers provide a simple and effective tool for fluorescent labelling of (meth)acrylate polymers.

One-pot synthesis of super-bright fluorescent nanogel contrast agents containing a dithiomaleimide fluorophore

“…510 nm. This is in accordance with the uorescence prole of the small molecule DTM dyes and the DTM labelled polymers and micelles previously reported, [24][25][26] indicating that covalent attachment of the DTM unit into a nanogel particle has not signicantly affected the wavelengths of excitation and emission. The quantum yield (Q) for the aqueous solution of NG1 (which has the highest DTM DoF) was calculated relative to the reference 5-(6)-carboxyuorescein (5(6)-FAM) at 445 nm and found to be 54% (see ESI for details †).…”

“…21,22 We have recently reported that the dithiomaleimide (DTM) group is a highly versatile uorophore which can be simply incorporated into polymers and polymer nanoparticles using functional monomers and initiators for both controlled free radical and ring-opening polymerisation. [23][24][25][26] We demonstrated that nanoparticles containing the DTM uorophore could be prepared by amphiphilic block copolymer synthesis using a DTM functional initiator, followed by block copolymer selfassembly in water to produce spherical micelles. 25 While the small molecule DTM exhibited all of the typical effects expected of a small dye molecule (quenching, short emission lifetime), when incorporated into the micellar state the DTM does not self-quench.…”

Dimeric Drug Polymeric Micelles with Acid‐Active Tumor Targeting and FRET‐Traceable Drug Release

“…[20] Furthermore, the strong green fluorescence of dithiomaleimides can be taken advantage of for tracking the ndds. [21,22] …”

Utilizing functionalized bromomaleimides for fluorogenic conjugation and PEGylation of enzymes

“…dithiophenolmaleimide) . The dye has found applications in polymer research after the supramolecular assembly of DTM‐functionalized polymers was shown to dictate emissivity, emission polarization and fluorescence lifetime . This has been attributed to the polymeric scaffold preventing both solvent and collisional quenching effects.…”