Design and synthesis of novel functionalized sensors for the biological imaging of zinc(II) and nitric oxide

Abstract

CHAPTER 1: Fluorescent Sensors for the Biological sensing of Zinc(II) A variety of fluorescent techniques have been developed for the in vivo sensing of Zn2+. This chapter presents a brief overview of techniques used to image chelatable zinc(II) in neuronal cells. Ratiometric sensors have been developed for more precise zinc sensing. These sensors exhibit differentiable changes in fluorescence in the presence and absence of zinc. CHAPTER 2. An Esterase-Activated System for the Ratiometric Sensing of Biological Zinc A ratiometric two-fluorophore sensing system has been developed by coupling Zinpyr- 1, a zinc-sensitive fluorophore, to the zinc-insensitive coumarin-343. The two fluorophores are bound by an ester linkage, which allows cell permeability; cytoplasmic esterases hydrolyze the sensor into its parent fluorophores. CHAPTER 3: Syntheses of Zinpyr Derivatives for Localized Applications in Zn2+ Sensing This chapter describes the preparation of reactive Zinpyr-1 derivatives for the direct functionalization of biological targets. A Zinpyr alkyne has been synthesized as a click chemistry substrate to couple to azides, and a Zinpyr succinimidyl ester has been developed to couple to amines.

(cont.) Applications of these derivatives include directly coupling the derivatives to glutamate receptor antagonists and small peptides for more localized sensing applications. CHAPTER 4: Conjugated Polymer-Based Sensors for the Biological Imaging of NO A variety of monomers featuring hydrophilic constituents have been synthesized for use in polymer synthesis via Pd-catalyzed cross-coupling reactions. CP-transition metal complexes have been made, using a variety of CPs including poly(p-phenylene vinylenes) (PPVs) and poly(p-phenylene ethynylenes) (PPEs). Metal binding functionalities have been incorporated into the conjugate polymer main chains. The optical properties of the CPs have been examined, as well as the interactions of these CP-metal complexes with NO.