Click chemistry CuAAC

Keywords Nucleic acid Cycloaddition Click chemistry CuAAC LEDDA Metabolic labeling... 

Furthermore, a dialdehyde, a diisocyanide, and a carboxylic acid were applied in the Passerini one-pot polymerization (Scheme 4c). For this combination of reactants, Li et al. used adipaldehyde, 1,6-diisocyanohexane, and undecanoic acid, resulting in polyamides with functional side groups [35]. Optimization of the reaction conditions revealed that a IM chloroform solution of bifunctional components and a 2.2-fold excess of the carboxylic acid at 40°C gave the best results, yielding polymers with of up to 16.6 kDa in a yield of 90%. Here, m-alkene- or a)-alk5me-functionalized carboxylic acids were used as monomers in order to allow post-polymerization modifications via thiol-ene addition or copper-catalyzed azide-alkyne click chemistry (CuAAC). 

The Cu -catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) click chemistry has also been used to synthesize a library of a,/ -D-glucopyranosyl triazoles (iii). The synthesized triazoles proved to be potential glycosidase inhibitors [15]. 

Dedola S, Hughes DL, Nepogodiev SA et al (2010) Synthesis of a- and ) -D-glucopyranosyl triazoles by CuAAC click chemistry Reactant tolerance, reaction rate, product structure and glucosidase inhibitory properties. Carbohydr Res 345 1123-1134... 

Among these reactions, the Cu(l)-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely used. This reaction has been implemented for the preparation of segmented block copolymers from polymerizable monomers by different mechanisms. For example, Opsteen and van Hest [22] successfully prepared poly(ethylene oxide)-b-poly(methyl methacrylate) (PEO-b-PMMA) and PEO-b-PSt by using azide and alkyne end-functionalized homopolymers as the click reaction components (Scheme 11.2). Here, PEO, PSt, and PMMA homopolymers were obtained via living anionic ring-opening polymerization (AROP), atom transfer radical polymerization (ATRP), and postmodification reactions. Several research groups have demonstrated the combination of different polymerization techniques via CuAAC click chemistry, in the synthesis of poly(e-caprolactone)-b-poly(vinyl alcohol) (PCL-b-PVA)... 

Click Chemistry in Polymer Science CuAAC and Thiol-Ene Coupling for the Synthesis and Functionalization of Macromolecules... 

This chapter will serve to highlight recent advances in polymer science that have been aided by the use of click chemistry. The copper(l)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene reactions will be discussed first, after which the utilization of these chemical transformations in the construction and fimction-ahzation of a multitude of different polymeric materials will be outlined. Particular attention will be focused on the preparation of highly complex polymer architectures, such as dendrimers and star polymers, which exempHfy the essential role that chck chemistry has assumed in the polymer science community. 

Scheme 30.8 Preparation of macromolecular brushes via the grafting-onto method, using a combination of ATRP and CuAAC click chemistry. Reproduced with permission from Ref [85] 2007, American Chemical Society.

The use of click chemistry has also influenced the construction of more sophisticated star polymers, such as those with block copolymer arms. Maty-jaszewski has eloquently demonstrated the preparation of three-arm star block copolymers by again combining ATRP with CuAAC click couphng [109]. In these studies the ATRP of styrene, starting from a trifunctional initiator, yielded the three-arm star homopolymer bearing bromide end groups that subsequently were transformed by substitution with sodium azide. CuAAC reaction with PEO-alkyne... 

Scheme 30.17 The convergent synthesis of triazole dendrimers using CuAAC click chemistry, (a) CuAAC coupling reaction and (b) nucleophilic substitution with sodium azide. R = chain-end group, X = internal repeat unit. Reproduced with permission from Ref [112] 2004, john Wiley. Sons, Inc.

In potentially the ultimate demonstration of the power of click chemistry for the construction of dendrimers, both thiol-ene and CuAAC coupling reactions were combined in a single accelerated growth strategy [133], This rapid synthetic... 

Hyperbranched polymers can be prepared by a variety of techniques, including the polycondensation of AB monomers as originally described by Flory [113], the reaction of A2 + B3 monomers, and self-condensing vinyl polymerization [139-141]. The first report [142] of using click chemistry in the synthesis of hyperbranched materials appeared at about the same time as the initial report for dendrimers prepared using CuAAC however, but much fewer examples have been reported that describe hyperbranched materials involving click chemistry. Nevertheless, these polymers represent an important class of materials, and both CuAAC [142-147] and thiol-ene [148] chemistry have found their way into the hyperbranched hterature. 

A review of click chemistry and its application to material synthesis would not be complete without a discussion of the network-forming abilities of CuAAC and fhiol-ene coupling reactions. In particular, thiol-ene chemistry has been well established in the field, and has been used extensively in network formation for over... 

Gonzaga, F. Yu, G. Brook, M. A., Polysiloxane Elastomers via Room Temperature, Metal-Free Click Chemistry. Macromolecules 2009,42, 9220-9224. Schmidt, U. Zehetmaier, P. C. Rieger, B., Direct Synthesis of Poly(dimethylsiloxane) Copolymers with TPE-Properties via CuAAC (Click Chemistry). Macromol. Rapid Commun. 2010, 31, 545-548. 

Hanni KD, Leigh DA (2010) The application of CuAAC click chemistry to catenane and rotaxane synthesis. Chem Soc Rev 39(4) 1240-1251. doi 10.1039/b901974j... 

CuAAC click chemistry has further been used to cross-link complementary DNA strands to form stable duplexes employing alkyne- and azide-modified nucleobases. Increased melting temperatures up to 30 °C could be achieved [19]. PNA/DNA-peptide conjugates can easily be prepared by CuAAC click chemistry using 3 -azido-modified oligonucleotides and alkyne-modified peptides [24, 25]. 

Rentmeister et al. developed a two-step approach to site-specifically label the 5 -cap of eukaryotic mRNAs via CuAAC [15] and SPAAC [14] click chemistry. For this, a variant of trimethylguanosine synthase 2 from Giardia latnblia is employed. 

Hexagonal DNA modules have been self-assembled and stabiUzed via CuAAC click chemistry by six simultaneous reactions, a method which is applicable for stabilization of various DNA nanostructures [176]. 

DNA nanopatterns on surfaces have been immobilized using click chemistry [177], and branched, Y-shaped DNA molecules can be prepared from tripropar-gylated oligonucleotides [178] by CuAAC click reactions, which are useful building blocks for higher DNA nanostructures. Moreover, SPAAC click chemistry in combination with orthogonal photochemical fixation has been used to synthesize oligomeric DNA scaffolds from cyclic DNA nanostructures which are stable towards denaturation and allow facile purification [179]. 

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