Chemoselective, Postpolymerization Modification of Bioactive, Degradable Polymers

Abstract

Degradable polymers promote sustainability, mitigate environmental impact, and facilitate biological applications. Tailoring degradable polymers is challenging because installing functional group-rich side chains is difficult when the backbone itself is susceptible to degradation. A convenient means of side chain installation is through post-polymerization modification (PPM). In functionalizing polyoxazinones, a class of degradable polymers generated by the ring-opening metathesis polymerization (ROMP), we predictably found PPM challenging. Even the versatile azide-alkyne cycloaddition click reaction was ineffective. To solve this problem, we screened PPM reactions whose efficiencies could be assessed using photochemistry (excimer formation). The mildest, pH-neutral process was functionalization of a ketone-containing polymer to yield either oxime (acid labile)-or alkyoxylamine (stable)-substituted polymers. Using this approach, we equipped polymers with fluorophores, reporter groups, and bioactive epitopes. These modifications imbued the polymers with distinctive spectral properties and biological activities. Thus, polyoxazinones are now tunable through a modular method to diversify a macromolecule's function

Modular Approach to Degradable Acetal Polymers Using Cascade Enyne Metathesis Polymerization

“…[8][9][10] Ac ellulose-derived levoglucosenol monomer recently described by Schlaad and co-workers produced high molecular weight polyacetal thermoplastics,t hough without control of molecular weight and dispersity. [12][13][14] While the dispersities reported were modest, targetable molecular weights were obtained in good agreement with theory.F urther,t he examples by Schlaad and Kiessling required significantly acidic (pH < 4) or basic conditions (pH > 9) to degrade,l eading to materials that would persist in abiological environment for long periods of time. [12][13][14] While the dispersities reported were modest, targetable molecular weights were obtained in good agreement with theory.F urther,t he examples by Schlaad and Kiessling required significantly acidic (pH < 4) or basic conditions (pH > 9) to degrade,l eading to materials that would persist in abiological environment for long periods of time.…”

“…[11] The most successful strained monomer to date is Kiesslings bicyclico xazinone system, which features an easily modified synthetic handle for introducing fluorophores and bioactive epitopes ( Figure 1B). [12][13][14] While the dispersities reported were modest, targetable molecular weights were obtained in good agreement with theory.F urther,t he examples by Schlaad and Kiessling required significantly acidic (pH < 4) or basic conditions (pH > 9) to degrade,l eading to materials that would persist in abiological environment for long periods of time.…”

“…Reduction of the substituent size in methyl acetal M4 Mes resulted in slightly higher dispersities relative to M1 Mes at M/I = 100 ( = 1.24, entry 11), consistent with the steric argument proposed. Theb ulkier isopropyl M5 Mes further improved polymerization characteristics and provided reduced dispersities at M/I = 500 ( = 1.44, entry 13). There appears to be al imit on the benefits of steric crowding,a st he tert-butyl dimethylsilyl (TBS) acetal M6 Mes polymerized at am uch slower rate than the other monomers examined and halted at low conversions (entry 14).…”

Supramolecular Behaviour and Fluorescence of Rhodamine-Functionalised ROMP Polymer

“…[8][9][10][11] The living nature of the ROMP reaction allows for the preparation of a vast array of copolymers with excellent control over chain length, functional density, and monomer variety, and has led to the preparation of a wide range of bio-related and therapeutic ROMP polymers. [12][13][14][15][16][17][18][19][20][21][22] In a wider context, ROMP also allows for the incorporation of dyes that are not suitable for free radical polymerisation processes, and the control ROMP affords can deliver polymer conjugates below 45 kDa, as require to allow renal clearance in eventual in vivo applications. 8 We here report the synthesis and analysis of a new fluorophore-rich block copolymer prepared by ROMP.…”

Controlled Release of Ibuprofen from Polymeric Nanoparticles

“…Having previously made a pure drug platform from salicylic acid 17 , we were interested in utilising the ring opening metathesis polymerisation (ROMP) process as a means of approaching a controlled drug release polymer system. The exquisite control that ROMP affords in preparing well-controlled functionally dense polymers and copolymers 18,19 and their resulting self-assembly has led to several examples of bio-related and therapeutic ROMP polymers [20][21][22][23][24][25][26] . Chemically degradable ROMP polymers, in other words when the mechanism of drug release is a chemical process such as ester hydrolysis and not a biological process, is an area that is gaining more attention [27][28][29] .…”