5 research outputs found

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

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    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

    3-(Phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole: a fascinating molecular framework to study the enantioseparation ability of the amylose (3,5-dimethylphenylcarbamate) chiral stationary phase. Part I. Structure-enantioselectivity relationships

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    Chiral stationary phases (CSPs) based on amylose (3,5-dimethylphenylcarbamate) (ADMPC) exhibit awide-range of enantioselectivity in high-performance liquid chromatography (HPLC) and supercriticalfluid chromatography (SFC). Although this class of CSPs has been extensively used, chiral discriminationsat receptorial level, which are useful to develop predictive molecular models, have been rarely reportedin the literature.Herein, we describe the results obtained in the enantioselective HPLC of a set of six C5-chiral 4,5-dihydro-(1H)-pyrazole derivatives on the ADMPC-based Chiralpak AD-3 CSP (CSP) under normal-phaseand polar organic conditions. Using pure methanol as a mobile phase the exceptional enantioseparationfactor value of 50 at 25â—¦C was found for one of the investigated analytes. To the best of our knowledge, theenantiomeric bias represents the most outstanding enantioseparation ever recorded on ADMPC-basedCSPs.Systematic variations in chemical groups in specific positions of the 3-(phenyl-4-oxy)-5-phenyl-4,5-dihydro-(1H)-pyrazole molecular framework resulted in peculiar changes in retention andenantioselectivity. A careful analysis of the chromatographic data permitted to advance some hypothesesconcerning the role played by the individual chemical groups in determining the exceptional enantiosep-aration.In particular, under methanol-rich mode, the prenyl moiety of the second eluted enantiomer of thebetter resolved analyte was recognized as a critical structural element to establish direct and favorablesolvophobic interactions with apolar portions of selector
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