Small molecule based optical monitors: synthesis, characterization, and applications in bioimaging (PhD)

Abstract

Given the potential applications of sensing materials in our daily life and also the market size of such materials, starting from electronics to biomedical applications, efforts are being made throughout the world toward their development with improved properties. On the other hand, development of cell permeable materials for staining/imaging bio-relevant analytes in living system has attracted great attention of scientific community as this non destructive technique helps in understanding various biological events. Often chemical sensing agents with low toxicity are employed extensively for bioimaging. The present thesis entitled ‘Small molecule based optical monitors: synthesis, characterization and applications in bioimaging’ contains six chapters. Chapter 1 provides brief introduction about fluorescent chemical sensors, their sensing mechanisms, and about the importance of metal ion sensing. Chapter 2 describes an approach for fabrication of fluorescent imine and the applications of such imine as a ratiometric sensor (CRZ 1) for paramagnetic metal ions Fe3+/Cu2+. Probe CRZ 1 contains one carboxylated unit, which act as a ‘locking unit’ restricting the possibility of E/Z-isomerization and ESIPT making CRZ 1 fluorescent. CRZ 1 was found to be an efficient fluorescent chemical sensor for the selective sub-micromolar ratiometric detection of Fe3+/Cu2+ over a wide range of metal ions. Chapter 3 mainly focuses on the utility of an unsymmetric benzophenone-based imine. A benzophenone-based half condensed Schiff base BZP has been applied for selective detection of Al3+. Due to combined effect of photoinduced electron transfer (PET), excited state intramolecular proton transfer (ESIPT) and E/Z isomerization, the half condensed probe was found to be almost non-fluorescent. Remarkable fluorescence enhancement was noticed upon the addition of Al3+ into a methanolic solution of BZP. This probe (BZP) can detect micromolar level of Al3+ and can distinguish Al3+, Ga3+, In3+ from the absorption and emission profile. The selectivity was tested over 24 different metal and non-metal ions (Li+, Na+, K+, NH4+, Ba2+, Ca2+, Mg2+, Mn2+, Cu2+, Fe2+, Fe3+, Cr3+, Sn2+, Zn2+, Cd2+, Co2+, Ni2+, Hg2+, Sr2+, Ag+ and Pb2+). As demonstrated in the beginning, in many occasions fluorescent chemical sensors are widely applied as bioimaging agents for tracking/imaging metal ions in living systems. Chapter 4 offers a quick look on the importance of metal ions in living systems followed by a brief history on the development of bioimaging materials for metal ion tracking/imaging. Utilization of a benzo[h]chromene derivative (synthesized following a multicomponent one pot procedure), 2 amino-4-phenyl-4H-benzo[h]chromene-3-carbonitrile 1, as a chemical sensor for Pb2+ via ‘turn on’ fluorescence signaling was described in Chapter 5. The selectivity was tested over a range of seventeen different metal and non-metal ions. Addition of Pb2+ to a methanolic solution of 1 changed the weak blue emission of 1 to a glowing green emission along with a prominent red shift (26 nm) in the emission band. Sensor 1 can easily penetrate the cell membrane without causing any harm to the living cells and can image Pb2+ inside living system. Chapter 6 describes our systematic approach towards the development of cell permeable molecular probes with higher wavelength excitation and emission profile for imaging of zinc in living systems. Probes such as Tris 2, L5 and TRZ were found to be efficient fluorescent chemical sensors for zinc in bio friendly medium. All these three probes were non-fluorescent initially. The metal-induced turn-on fluorescence was used as a potential tool to image zinc in living cells, both in vitro and in vivo.