Here, we try to address some of the challenges faced during the discovery of biological activity in polymers. For instance, identifying structure-activity relationships for polymers is often confounded by the nature of the polymerisation: Kinetics of polymerisation is affected by the nature of the polymers often leading to polymers with very different lengths and topologies for different monomers. Post-polymerisation is often used to address this limitation. However, most of the current post-polymerisation chemistries are done in organic solvents, and thus, libraries of polymers have to be purified before identifying their biological activity.
To address these limitations, we have investigated the use of poly(acryloyl hydrazide)s, that can be readily reacted under aqueous condition to yield functional polymers. Moreover, these functional polymer can be evaluated, under biological relevant conditions, without the need for purification/isolation steps. The effciency of the hydrazide-aldehyde coupling is modulated by tuning the reaction conditions, including the use of both aqueous and organic conditions, to yield polymers with a consistent degree of functionalisation. You can find more details in Crisan, D. et al. Poly(acryloyl hydrazide) as a versatile scaffold for the preparation of functional polymers: Synthesis and post-polymerisation modification. Polym. Chem. (2017).
In collaboration with Javier Montenegro (USC, E), we have demonstrated the potential of this approach in the synthesis of novel polymeric amphiphiles capable of delivering siRNA. Our methodology has allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa-EGFP), and better performance than one of the best commercial reagents (lipofectamine RNAiMAX). You can read the full paper in J. M. Priegue et al., In Situ Functionalized Polymers for siRNA Delivery. Angew. Chem., Int. Ed. (2016), doi:10.1002/anie.201601441.