Chain Click chemistry

Finally, Lecomte and coworkers reported the synthesis of mikto-arm star-shaped aliphatic polyesters by implementing a strategy based on click chemistry (Fig. 36) [162]. Firstly, the polymerization of sCL was initiated by a diol bearing an alkyne function. The chain-ends were protected from any further undesired reaction by the esterification reaction with acetyl chloride. The alkyne was then reacted with 3-azidopropan-l-ol. The hydroxyl function located at the middle of the chain was then used to initiate the ROP of sCL and y-bromo-s-caprolactone. Finally, pendant bromides were reacted successfully with sodium azide and then with N, N-dimethylprop-2-yn-l-amine to obtain pendant amines. Under acidic conditions, pendant amines were protonated and the polymer turned out to exhibit amphiphilic properties. 

An approach to inducing an ot-helical conformation in peptides that is more definitive than relying on salt-bridging interactions involves chemical ligation of side-chain residues using either ring-closing olefin metathesis or Cu-catalyzed azide cycloaddition to an alkyne (click chemistry) [147-153]. This approach,... 

The modification of polymers can be readily conducted by chemical coupling reactions when the chain to be modified possesses groups such as vinyl, hydroxyl, or azide [23], etc. The Diels-Alder reaction between a diene and a dienophile, discovered by Otto Diels and Kurt Alder in 1928 [24], is the most important example of click chemistry. These robust and efficient click coupling reactions have been widely exploited in the construction of tailor-made functional polymeric materials with complex molecular architectures... 

Recently, well-defined AB2 dual (temperature and pH) sensitive miktoarm star copolymers of (PNIPAm)-(PLL)2 were synthesized through the combination of ATRP, ROP and click chemistry. " Propargylamine was used to initiate ROP of ZLL-NCA for the preparation of all nyl-terminated polypeptide. The use of a diazide-functional ATRP initiator afforded PNIPAm with two azide groups at the chain end. The subsequent click reaction led to the formation of a (PNIPAm)-(PZLL)2 star. The final double hydrophilic structure was obtained after deprotection of the polypeptide arms. 

O Mahony et al. modified cyclodextrin structurally, for enhanced siRNA deliveiy to the brain. In this study, an amphiphilic cationic p-cyclodextrin with hydrocarbon chains (C12) on the primacy face and a polar (propyl-amino) group on the secondary face was synthesized by applieation of copper(I)-catalyzed click chemistry. The results showed a signifieant inerease in siRNA delivery, with at least 80% eell viability after modification of cyclodextrin in both immortalized hypothalamic neurons and primary hippocampal neurons. Other physicoehemical properties of modified CDs were also found to be suitable for a gene deliveiy system. On the other hand, an investigation of modified amphiphilic p-cyclodextrin was done by Godinho et al. In this particular study, efficient HTT siRNA delivery with limited toxicity was reported. 

Bria et al. synthesized a tetracationic cyclophane-aromatic crown ether-type side-chain poly[2]catenane 59 by employing click chemistry, via route iii (Scheme 17.18) [111]. First, the template-directed coupling reaction between bis(bipyridinium) salt 28 and the alkyne-substituted p-xylylene dibromide 55, in the presence of dinaphtho crown ether 54, afforded an alkyne-functionalized [2]catenane 56 [112], Substitution of the chloro group on styrene-vinylbenzyl chloride copolymer 57 (M = 3.7 kDa, M , = 6.3 kDa) with sodium azide gave the azide-functionalized polymer 58 [83,113-115]. By employing CuS04/ascorbic acid as catalyst [116-120], click chemistry between azide-functionaUzed polymer 58 and alkyne-functionalized [2]catenane 56 afforded the side-chain poly[2]catenane 59, the successful formation of which was confirmed with Fourier transform infrared (FTIR) and NMR analyses. Unfortunately, both of these techniques revealed that the reaction of the azide groups was incomplete, and the observation was ascribed to a Coulombic repulsion of the cyclophane units and steric hindrance caused by the bulky catenane units[121]. 

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