A multidisciplinary approach to the development of innovative tools for pharmaceutical and technological applications

The research activity carried out during the Ph.D. in Chemical and Pharmaceutical Sciences has regarded the design, synthesis, and characterization of innovative tools relevant to both pharmaceutical and technological fields. Great interest has been dedicated to the investigation of the “affinity polymerization” mechanism of novel polymeric materials founded on repetitive monomeric units based on the 3-phenylbenzofulvene scaffold that spontaneously polymerize by simple removal of the solvent. In this context, the attention has been focused on the synthesis of novel benzofulvene-based derivatives bearing complexed and non-complexed pyridine rings in different positions of the benzofulvene scaffold, to evaluate the effects generated by the insertion of a bulky substituent in the aggregation/polymerization behavior. The experience acquired with this study has been then capitalized on the design, synthesis, and characterization of a novel visible-light-sensitive biomimetic molecular switch inspired by the benzofulvene scaffold and the Green Fluorescent Protein (GFP) chromophore. The chemical-structural manipulation of the benzofulvene structure has made possible the development of a novel set of biomimetic photoswitches inspired by the supramolecular properties of the 3-phenylbenzofulvene scaffold and the molecular features of the GFP chromophore. In the framework of material chemistry, the well-known click-chemistry reaction of hyaluronic acid (HA) derivatives bearing propargylated ferulic groups has been exploited to obtain biomimetic and biocompatible materials useful in different biopharmaceutical fields. In particular, low molecular weight HA has been anchored on the hydrophobic surface of low-generation poly(propylene imine) (PPI) dendrimers by the click-chemistry reaction between their azido-functionalized surfaces and low molecular weight HA derivatives bearing propargylated ferulic groups. The resulting materials have been proposed as biocompatible drug delivery systems (DDSs) of Doxorubicin. Another application of HA has concerned the hyaluronan-based graft copolymers showing low and medium molecular weight values that have been exploited in cross-linking by the click-chemistry reaction. Interestingly, the interaction of resulting HA materials with water led to the formation of hydrogels, and the tunable rheological behavior of these materials led to their applicability in different biomedical fields. Lastly, the knowledge in medicinal chemistry has guided the design and synthesis of innovative bioactive compounds such as novel Cyclooxygenase‑2 (COX-2) inhibitors containing Nitric Oxide (NO) donor moiety (CINODs) endowed with vasorelaxant properties. The outcomes of these studies would provide fertile ground for future projects that will hopefully contribute to accelerate the research in several fields. Indeed, the increased knowledge on the behavior of these innovative tools, by means of a multidisciplinary approach, is the key for boosting the development of novel materials for pharmaceutical and technological applications.