Review
doi: 10.1021/cr900138t.
Applications of orthogonal "click" chemistries in the synthesis of functional soft materials
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- PMID: 19905010
- PMCID: PMC3165017
- DOI: 10.1021/cr900138t
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Review
Applications of orthogonal "click" chemistries in the synthesis of functional soft materials
Chem Rev.
2009 Nov.
No abstract available
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This article highlights examples employing “click” chemistry for the preparation and functionalization of complex polymer materials, three-dimensional substrates, two-dimensional surfaces, and biological systems. The types of chemical reactions include those that involve reactive functional groups, which undergo efficient, orthogonal couplings (REO chemistry), selectively and in high yield with limited by-products.
Retrosynthetic analysis for a homopolymer containing a single REO reactive group at one chain end. In this example, a mediator represents some species that controls polymerization at the active end of a polymer chain (e.g. halogen in ATRP, nitroxyl in NMRP, catalyst in ROP/ROMP, etc.), and a `non-functional' initiator is one that does not include a moiety capable of undergoing an REO transformation.
Retrosynthetic analysis for a homopolymer containing REO reactive groups at both chain ends. The upper method can produce heterobifunctional materials, while the bottom two methods can only successfully make homobifunctional polymers. In this example, a mediator represents some species that controls polymerization at the active end of a polymer chain (e.g. halogen in ATRP, nitroxyl in NMRP, catalyst in ROP/ROMP, etc.), and a `non-functional' initiator is one that does not include a moiety capable of undergoing an REO transformation. In the case of ATRP, the halogen, which serves as the mediator, can be replaced by a nucleophile to give some useful end-group that can undergo an REO transformation (e.g. organic azide).
Retrosynthetic analysis for ABC triblock copolymers using REO chemistry by either a one-pot coupling of three unique mono- or hetero-bifunctional end-functionalized homopolymers (upper pathway) or by a step-wise growth and coupling of a homopolymer and diblock copolymer, each having a single complementary reactive chain end (lower pathway).
Retrosynthetic analysis for graft copolymers made using REO chemistry by the “grafting from” (upper), “grafting onto” (middle) or “grafting through” (lower) approaches.
Illustration of the three general strategies for star polymer synthesis.
Retrosynthetic analysis for miktoarm star polymers prepared using REO chemistry.
The two main synthetics strategies for preparation of dendronized polymers.
Conjugation of functional dendrons to a vesicle surface. (Reproduced with permission from ref 230. Copyright 2007 The Royal Society of Chemistry).
Gelation model for amphiphilic, dendronized polymers. (Reproduced with permission from ref 231. Copyright 2008 Wiley-VCH).
Retrosynthetic analysis for well-defined networks made by crosslinking telechelic polymers with multi-functional crosslinkers using REO reactions.
Schematic illustration of test substrates produced by sequential Diels-Alder and azide-alkyne cycloadditions of azide-bearing biotin, carbohydrates, and proteins, and the resultant interactions with fluorescently-tagged proteins to demonstrate that substrates were not only covalently attached to the surface, but that upon conjugation, the ligands retained bioactivity post-conjugation.
Fabrication of a protein micro array by a) site-specific covalent-bond (1,2,3-triazole formation and b) random amide-bond formation, contrasting the differences in fluorescence obtained after incubation with biotinylated maltose and a fluorescently-tagged streptavadin. c) X-ray structure of MBP with blue regions representing Lys and Arg residues that may react with the NHS-decorated surface. (Reproduced with permission from ref 358. Copyright 2006 Wiley-VCH).
A) Mixed monolayers presenting NVOC protected hydroquinone and tetra(ethylene)glycol are illuminated with UV light to afford the hydroquinone. Subsequent oxidation of the hydroquinone produces the corresponding benzoquinone, which can then undergo reaction with aminooxy-terminated ligands. B) A photochemical strategy for generating patterns and gradients of immobilized ligands onto an electroactive monolayer.
Depiction of the patterned photo-deprotection of aminooxy-terminated SAMs and the subsequent functionalization with ketone-containing ligands to generate a functional patterned surface.
A) Schematic procedure showing a one-pot functionalization. B) Fluorescence image of (a) “click”-functionalized red dye excited at 545 nm, (b) NHS-functionalized green dye excited at 491 nm, (c) overlapped images of (a) and (b). Each scale bar represents 30 μm. (Reproduced with permission from ref 373. Copyright 2008 American Chemical Society).
a) Electron beam crosslinking of end-functionalized eight-arm PEG polymers for protein patterning, each PEG was end-functionalized with one of four protein reactive handles (biotin, maleimide, aminooxy, or nitrilotriacetic acid). b) Streptavidin was attached to the biotin. c) bovine serum albumin was immobilized through a reaction with a cysteine side chain and maleimide. d) Myoglobin bearing an N-terminal oxo moiety was attached to the surface through oxime formation. e) Histidine-tagged calmodulin was immobilized through a nickel-histidine affinity interaction using nickel(II) chelated by the nitrilotriacetic acid substituents.372 (Reproduced with permission from ref 374. Copyright 2009 American Chemical Society)
Modification of the chain terminus of P(NIPAM) polymers derived from functional initiators and post-polymerization CuAAC chain end modification. This study revealed significant effects of only changing the end group on the LCST, which varied by over 10 °C.
Small-molecule azides representative of acrylic, cyanoacrylic, styrenic and methacrylic polymer chain ends are used to probe reactivity of azide terminal polymers made by ATRP and halogen displacement.
Formation of diblock copolymers by CuAAC, and cleavable diblock copolymers using disulfide chemistry.,
Production of heterobifunctional, telechelic polystyrene, followed by application of CuAAC conditions affords macrocyclic and/or extended polymer structures. The polymer concentration determines whether the major product is cyclic polymer, or chain-extended materials by a step growth mechanism.,
Orthogonal functionalization of the α- and ω-chain ends of a polystyrene derivative using orthogonal thiolene and CuAAC chemistries.
Orthogonal strategies based on CuAAC chemistry for the preparation of ABC triblock copolymers in one pot from two mono-end-functional and one hetero-bifunctional telechelic homopolymers.,
Demonstration of the effectiveness of CuAAC both before and after polymerization.
“Click”able polyesters with a number of functional groups introduced.
Alkyne-functional polyesters allow for incorporation of biologically-active peptides.
Thiol-ene modification of structurally diverse polymers with various thiols.
Synthesis of an orthogonally reactive block copolymer by RAFT.
Synthesis of a block graft copolymer with PCL-b-PBA side chains from a PHEMA backbone.
Synthesis of a polymer brush with PMA and PMA-co-POct grafts using sequential RAFT and ATRP polymerizations.
Fabrication of a shell-crosslinked molecular brush and a hollowed nanostructure via a core-shell brush block copolymer prepared via ROMP of inimer 1, followed by growth of polymer grafts by NMP from the multi-functional macroinitiator 4. (Reproduced with permission from ref 149. Copyright 2006 American Chemical Society).
One-pot synthesis of a core-shell graft block copolymer via ROMP of an inimer and then RAFT grafting from the multi-functional macroinitiator.
A) Synthesis of PS-b-PBA macromonomer using ATRP and CuAAC, and B) graft copolymers achieved by the conventional radical polymerization of PBA and PS macromonomers.
Synthesis of a block graft copolymer by ATRP and then ROMP (direct pathway downward), followed by acidolysis to release an amphiphilic graft block copolymer. A similar product was afforded by acidolysis at the macromonomer stage followed by ROMP under emulsion polymerization conditions.
Synthesis of a densely grafted amphiphilic brush block copolymer employing both the “grafting from” and “grafting through” strategies.
Synthesis of block graft copolymers via a combination of ATRP for the construction of the backbone and the functional grafting polymer chains, followed by CuAAC “click” chemistry for the grafting onto strategy.
copolymer prepared using RAFT, MADIX, and CuAAC cycloaddition.
Synthesis of a low density grafted brush copolymer using CuAAC “click” chemistry and the “grafting onto” approach.
A) The synthesis of anthracene- and azide-functionalized PS derivatives, and B) the one-pot preparation of PS-g-(PMMA-PEG) heterograft copolymers using two different “click” reactions.
Alkyne-functional polyesters allow for A) the incorporation of biologically-stealth PEG grafts, and B) the preparation of PEG-grafted polyester-camptothecin conjugates by a CuAAC “grafting onto” approach., (GPC reproduced with permission from ref 114. Copyright 2005 American Chemical Society).
Synthesis of A) PPGL-g-PEO homopolymer and B) (PPG-g-PEO)-co-PLA using CuAAC chemistry.
Preparation of PCL-g-PEO using ketoxime ether formation.
Examples of A) three- and four-arm star polymers made by “click” coupling of azido-terminated polystyrene onto a central tri- or tetra-alkynyl core, respectively, and B) three-arm stars made by independent coupling of several types of azido-terminated polymers to a tri-alkynyl core.,
An example of “click” chemistry to make star-shaped PCL via grafting of alkynyl-terminated PCL to a cyclodextrin core bearing seven azides.
Construction of three-arm star polymers using an anthracene-maleimide based Diels-Alder “click” reaction.
Use of RAFT polymerization and subsequent hetero Diels-Alder reaction to construct two-,three-, and four-arm star topologies.
Star polymer synthesis utilizing Michael addition of a dithioester-terminated linear polymer to a multifunctional diene core.
One-pot synthesis of a three-arm star block copolymer through two selective and sequential “click” reactions.
One-pot synthesis of chain end functional, stereoregular, star-shaped poly(lactide) and subsequent chain end functionalization via 1,3-dipolar cycloaddition and Michael-addition chemistry.
Chain end functionalization with a RAFT chain-transfer agent and chain extension with styrene to yield star-shaped block copolymers.
Synthesis of PS-b-PEO three-arm star block copolymers by a combination of the “core first” and “coupling to” methods.
Synthesis of multi-arm star block copolymers using the Diels-Alder “click” reaction between anthracene and maleimide derivatives.
Synthetic routes to produce an alternating, six-arm PCL-PMMA miktoarm star polymer.
Syntheses of ABC miktoarm stars employing ROP, NMP, ATRP and a “core-first” approach.,
“Click” coupling of PS-b-PMMA, at an alkyne site located between the PS and PMMA chain segments, with either azido-PEO or azido-PtBA to give ABC miktoarm star copolymers.
A) A one-pot, one-step technique for the preparation of three-miktoarm star terpolymers, and B) a one- pot, two-step method for the preparation of three-miktoarm star terpolymers.
A) Preparation of a PS-b-PCL copolymer with an azide at the junction point, B) preparation of PEG-b-PMMA or PEG-b-PtBA with an alkyne at the junction point, and C) preparation of PCL-PS-PEG-PMMA and PCL-PS-PEG-PtBA heteroarm star polymers via “click” cycloadditions.
An ABCD four-arm star quarterpolymer made using a combination of RAFT polymerization, ROP, and “click” coupling.
Examples of multifunctional polyester dendrimer constructs for nanomedical applications.,
Asymmetrically-functionalized polyester dendrimers (top), and multifunctional polyester dendrimers (bottom) that allow for modification via orthogonal chemistry.
Orthogonally-functionalized dendritic polyamides.
Examples of multifunctional dendrimers from the group of Simanek.
Synthesis of a doubly-dendronized polymer through “click” cycloaddition. (Reproduced with permission from ref 226. Copyright 2005 The Royal Society of Chemistry).
Block copolymer containing dendronized blocks.
Step polymerization of hydrocarbon based dendritic monomers through CuAAC chemistry.
The synthesis and formation of PEG-based hydrogels using CuAAC as the crosslinking reaction.
Synthesis and degradation of photodegradable model networks made by ATRP and CuAAC.,,
Chemical strategy for construction of liquid crystalline networks crosslinked in a well-defined manner from metathesis-based telechelic polymers containing either 1 or 2 mesogens per repeat unit.
Formation of self-reparable networks using reversible Diels-Alder reactions for crosslinking from a single component system.
Examples of shell crosslinked knedel-like (SCK) nanoparticles functionalized via combinations of 1,3-dipolar cycloadditions and carbodiimide-based amidations., (Reproduced with permission from ref 299 and . Copyright 2005 American Chemical Society).
Combination of Michael additions and 1,3-dipolar cycloadditons. (Reproduced with permission from ref 303. Copyright 2008 The Royal Society of Chemistry).
Example of “click” modifications of a polymersome to couple enhanced green fluorescent protein units and produce hybrid synthetic-biologic nanostructures. (Reproduced with permission from ref 306. Copyright 2007 The Royal Society of Chemistry).
Example of aldehyde-based strategies for preparation of folate receptor-targeted polymeric micelles with pH-sensitive drug cargos.
Example of a mixed micelle preparation strategy for introducing orthogonal functional groups. (Reproduced with permission from ref 320. Copyright 2007 American Chemical Society).
Nanocage modification using amidation and reductive amination chemistries.
Examples from Kataoka et al. on preparing thiol-functionalized cationic poly(L-lysine) segments within block copolymers with poly(ethylene oxide) (upper portion) and their transformation into disulfide crosslinked polyplexes for delivery of plasmid DNA (lower portion)., (Reproduced with permission from ref 328. Copyright 2004 American Chemical Society).
Diels-Alder based functionalization of a polymeric nanoparticle with antibodies. (Reproduced with permission from ref 348. Copyright 2007 Wiley-VCH).
Structure of a self-assembled monolayer used to immobilize thiol-terminated ligands. The maleimide reacts selectively with thiol groups in a contacting solution while the oligo(ethylene glycol) groups are present to minimize non-specific adsorption of proteins and peptides onto the monolayer.
A) 6-ferrocenyl-1-hexanethiol and B) cytochrome C protein functionalization of phenylmaleimide thin films. C) Direct functionalization of a surface with phenylmaleimide diazonium conjugated to ferrocene-labelled ssDNA via a thiol-Michael addition.
The redox-active hydroquinone monolayer undergoes electrochemical oxidation to the benzoquinone and then undergoes a chemoselective reaction with an aminooxy-containing compound to yield the corresponding oxime.
Following exposure to UV light through a mask, acetals were selectively deprotected to afford aldehydes (1). A biotinylated hydroxylamine was attached to the surface through oxime formation (2). The films were exposed to UV light to remove additional protecting groups (3), and convert remaining acetals to aldehydes (4). Aminooxy-terminated PEG was allowed to react with the background aldehydes while streptavidin was immobilized to the biotin patterns (5). Any biotinylated protein can then be immobilized onto the streptavidin foundation (6).
A) After covalently linking the copolymer to the surface, a photoacid generator was spin-coated on top and the films were exposed to UV light through a mask. B) At the locations exposed to the UV light, and subsequent acid exposure, the Boc protecting groups were removed affording a pattern of aminooxy functionalities. C) An α-ketoamide modified streptavidin was immobilized on the surface through oxime formation.
Functional assemblies of CPMV particles and various functional units.
Examples of 1,3-dipolar cycloaddition modifications of tobacco mosaic virus wires.
Example of aldehyde-based conjugation strategies for the selective functionalization of the exterior (K106, K113, and N-terminus) or interior (Y85) of MS2 viral capsids with 90 ligands in both cases.
Porphyrin-functionalized tobacco mosaic virus. (Reproduced with permission from ref 403. Copyright 2007 Wiley-VCH).
Amidation strategies for viral functionalization. (Reproduced with permission from ref 406. Copyright 2007 American Chemical Society).
Oxidative coupling of peptides to the exterior surface of MS2 viral capsids.
Synthetic glycopolymers based on BSA. (Reproduced with permission from ref 42. Copyright 2007 American Chemical Society).
Thermoresponsive BSA.
PEGylation via the formation of thiol cleavable conjugates.
Diels-Alder functionalization of oligonucleotides with PEG and various small molecules.
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