A biocompatible post-polymerization functionalization reaction takes advantage of a polymer's structural motif for the controllable attachment of biotin as a model biosensor that responds to streptavidin.
10Strategies for the post-polymerization functionalization (PPF) of polymers are advantageous in that they allow for tuning of a polymer's properties without synthetically retreating to the monomer stage. Further, PPF permits the incorporation of functional groups that may be incompatible with 15 polymerization conditions. Several strategies have been reported for conjugated polymers. A number of designs involve substitution reactions with pendant halogen, 1 alcohol, 2 or carboxylic acid moieties, 3 and application of high yielding click chemistries 4 like the 1,3-dipolar cycloaddtion of alkynes 20 and azides 5 or thiol-conjugate addition 6 have also been reported. Two potential drawbacks are characteristic of the above strategies: (i) an appropriately functionalized monomer specific for the intended PPF must be incorporated into the polymer synthesis--often in protected form and (ii) it can be 25 difficult to control the extent of functionalization.We recently reported the synthesis of a rigid hydrophilic monomer (1) that--when incorporated into poly(p-phenylene ethynylenes) (PPEs) 7 (P1)--leads to increased spectral purity 30 by preventing hydrophobically induced aggregate emission. 8 We envisioned that the three dimensional array of vicinal hydroxyl groups might be further elaborated through periodate oxidation and reductive amination (P1→2→3, Scheme 1). 9 Similar processes have been widely applied for 35 bioconjugation through periodate oxidation of carbohydrate residues, making this process compatible with existing bioconjugation schemes. Herein we report a biocompatible post-polymerization biotinylation of P1, where (i) the need for a PPF specific monomer is negated by activation of an 40 existing structural motif, and (ii) the extent of functionalization can be controlled by the equivalents of the NaIO 4 reagent. Further, the improved spectral purity imparted by the presence of 1 in 3a is not lost. In turn, this demonstrates an improved signal amplified biosensor 10 45 response to fluorophore-labeled streptavidin, a tetrameric protein with high biotin affinity (4 x 10 -14 M) 11 that has been applied to a variety of conjugated polymer affinitychromic 3,12 and agglutination 2b biosensor designs.
50Scheme 1 Periodate oxidative activation and reductive amination Treatment of P1 with 0.2 equivalents of NaIO 4 in water generated 1,6-dialdehyde moieties at random positions along the backbone (2, Scheme 1). 13 Subsequent incubation with an excess of amine-containing compound (a or b) in aqueous 55 alkaline solution generated the putative Schiff base, which was reduced in situ to the tertiary amine 3 with NaCNBH 3 (vide infra, Scheme 2).The azepane linkage in 3 is proposed based on two model studies. Firstly, the broad nature of the 1 H NMR signals of 3a 60 overlapped with the weaker biotin signals making dete...
