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Design, Synthesis and Characterization of Zinc(II)-Selective Ratiometric Fluorescent Sensors

by Wu, Yonggang

Abstract (Summary)
Zinc is an important micronutrient but the biological function of its labile form is poorly understood. Zinc selective fluorescence sensors, recognized as the major tool to gain information about the role of zinc in living systems, have been attracting more and more interest. The most promising solution currently being studied comes in the form of ratiometric sensors. Unlike sensors based on the switch-on mechanism, ratiometric sensors determine the free metal concentration directly from the ratio of the emission intensities at two wavelengths. The major restriction on the design of this type of sensor is from the necessity for a spectral-shift upon binding metal ions. To develop novel ratiometric sensors, we have developed designs based on excited-state intramolecular proton transfer (ESIPT). In the absence of ZnII at neutral pH, the 2-(2-sulfonamidophenyl)benzimidazole family undergoes ESIPT to yield a highly Stokes-shifted emission from the proton-transfer tautomer. Coordination of ZnII inhibits the ESIPT process and yields a significant hypsochromic shift of the fluorescence emission maximum. By implementing structural modifications, we were able to gauge free ZnII concentrations in the millimolar to picomolar range. To tune the peak excitation towards lower energy, a property that is of particular importance in the light of biological applications, we modified the platform molecule with extended pi-conjugation and by substituent engineering. The position of the modification and the nature of the substituents strongly influenced the photophysical properties of the investigated derivatives. Several fluorophores revealed emission ratiometric properties with a large dynamic range combined with a peak absorption beyond 350 nm, rendering these probes promising candidates for applications. To further understand the origin of the substituent effect, we studied five derivatives for the solvatochromic shift analysis and quantum chemical studies. The results showed that the negative solvatochromic shift behavior was most pronounced in protic solvents presumably due to specific hydrogen-bonding interactions. The extrapolated gas-phase emission energies correlated qualitatively with the trends in Stokes shifts, suggesting that solute-solvent interactions do not play a significant role in explaining the divergent emission energy shifts. Detailed quantum chemical calculations not only confirmed the moderately polarized nature of the ESIPT tautomers but also provided a rationale for the observed emission shifts based on the differential change in the HOMO and LUMO energies. This study revealed the great potential of 2-(2-arylsulfonamidophenyl)- benzimidazoles, such as tunable peak absorption and emission, a very wide dynamic range regarding to zinc binding, very little solvent polarity dependence, and especially, the emission ratiometric property. All these properties make this system a unique candidate to tackle the problems in the research of zinc biology.
Bibliographical Information:

Advisor:Fahrni, Christoph J.; Doyle, Donald F.; Wilkinson, Angus P.; Zhang, Z. John; Murthy, Niren

School:Georgia Institute of Technology

School Location:USA - Georgia

Source Type:Master's Thesis

Keywords:chemistry and biochemistry

ISBN:

Date of Publication:11/14/2007

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