Modification of RAFT‐polymers via thiol‐ene reactions: A general route to functional polymers and new architectures

Abstract

An investigation into the aminolysis of x-end groups of RAFT-polymers and simultaneous thiol-ene reactions with ene-bearing compounds is described. Three different polymers, P(MMA), P(HPMA), and P(NIPAAm), with low PDIs were synthesized using dithiobenzoate and trithiocarbonate RAFT agents. P(NIPAAm) synthesized with trithiocarbonate RAFT agent and P(HPMA) synthesized with dithiobenzoate RAFT agent were both functionalized with a methacrylate-modified mannose and a maleimide-modified biotin via one-pot simultaneous aminolysis and thiol-ene reactions with product yields above 85%. The presence of ene-compounds during aminolysis was shown to prevent the formation of disulfide interchain crosslinking. Using the same approach, P(MMA), P(HPMA), and P(NIPAAm) were converted to (meth)acrylate macromonomers with high yields ([80%). In the case of P(MMA), the simultaneous aminolysis and thiol-ene addition prevented any intrachain side reactions, i.e., thiolactone formation. New architectures such as graft and block copolymers were successfully generated from the macromonomers.

Living Radical Polymerization by the RAFT Process – A Third Update

“…A [459] St [459] MA [459] tBA [459] TEGA [459] NIPAm [459] (Continued ) [460] (178/MA) [460] (178/tBA) [460] (178/MMA) [460] (178/St) [460] (178/MA-b-tBA) [460] (178/MA-b-St) [460] 179 S S S HO 2 C A* PEGA [461,462] PFPA [463] tBA [461] NIPAm [220,461,464] NIPAm/372 [464] NIPAm/391 [465] 180…”

“…[44] The first reports involved the use of N,N-dialkyl dithiocarbamate derivatives as ATRP initiators. Dithiocarbamates do not provide effective control over the polymerization [241] MMA, St 456 Propylamine Network cleavage [603] BA, St 441 Butylamine/TCEP/BA In situ thiol-ene multiblock cleavage [604] PEGA 47 Butylamine/TCEP/divinyl sulfone In situ thiol-ene [281] MA, DMAm, NIPAm, St, C 2 H 5 S (121) Hydrazine - [375] St, PEGMA Ph (54, 18) Hydrazine - [375] St Ph (18) Hydrazine Used in thiol-epoxide [193] St Ph (18) DEAm (18) Hydrazine In situ thiol-epoxide [193] St/AcS Ph (11) Hydrazine Au nanoparticles [176] EGDMA, 421, 420 Ph (18) Hexylamine Used in thiol-ene or other reaction [588] St PhCH 2 S 1) KOH, 2) Zn/AcOH Au nanoparticles [338] St PhCH 2 S (89) Ethylene diamine Initiator for ROP C [339] HPMAm Ph (11) NaBH 4 /PBu 3 In situ thiol-ene (AA) [161] HPMAm Ph (68) Butylamine MeOH/degassed used in thiol-ene [307] NIPAm Ph (18) NaBH 4 Used in thiol-ene [247] MMA Ph (18) Hexylamine In situ thiol-ene [220] HPMAm Ph (18) Hexylamine In situ thiol-ene [220] NIPAm CH 2 (CO 2 H)CH 2 S (179) Hexylamine In situ thiol-ene [220] NIPAm C 4 H 9 S (159) Hexylamine/DMPP Used in thiol-ene [446] NIPAm C 12 H 25 S (123) Hexylamine/Bu 3 Ph Used in thiol-ene [398] Am Ph (18) NaBH 4 Used in thiol ene [244] DEAm Ph ( StMe OEt Ozone --(C¼O)SOEt [606] BA OEt Ozone --(C¼O)SOEt [607] iBoA 2-pyridyl Air AIBN, THF/Ph 3 P -OH [605] MMA, acrylates Ph Air AIBN, THF/Ph 3 P -OH [182,605] St, acrylates P n S Air AIBN, THF/Ph 3 P -OH [182] MA, BA CH 2 Ph Air AIBN, THF/Ph 3 P -OH [182] St CH 2 Ph Air AIBN, THF/Ph 3 P -OH …”

Dicer-Labile PEG Conjugates for siRNA Delivery

“…To investigate this novel strategy, 3′-sense or 5′-antisense thiol-modified, we covalently conjugated blunt-ended DsiRNAs, targeting against enhanced green fluorescent protein (eGFP) expression were covalently conjugated to PEG with varying molecular weights via a stable thioether bond using a mild and efficient synthetic approach (via Michael addition reaction). 39 The release of siRNA from the DsiRNA-PEG conjugates was investigated in vitro using recombinant human Dicer. The gene silencing efficiency of the conjugates was investigated using in vitro cultured human neuroblastoma SH-EP cells stably expressing eGFP and immunogenic properties in human peripheral mononuclear cells (PBMCs).…”

RAFT polymerization mediated bioconjugation strategies

“…Alternatively, thiol-functional polymers can be used directly for bioconjugations without any further modification. 62,[67][68][69][70] The removal of thiocarbonylthio group from the bioconjugate structure may be an advantage of this approach as the reactive thiocarbonylthio group may cause concentrationdependent cytotoxicity if the bioconjugates are intended to be used in living organisms.…”

“…56,67,[68][69][70]136 This approach produces PDS-functional polymers with high yields (close to 90%) without accompanying side-reactions such as disulfide or thiolactone formation. The ''in situ aminolysis'' approach can also be performed in the presence of ene-bearing molecules to generate polymers with different u-functionality with high yields.…”