An improved understanding of fluorescent Zn(II) sensors and their uses in biological settings

Chapter 1. An Introduction to Fluorescent Zn(II) Sensors and Their Applications in Biological Systems This chapter opens with an overview of the numerous roles of zinc in biology, with an emphasis on labile Zn(II), that is, loosely bound or kinetically available stores of the ion. The synthesis, characterization, and application of fluorescent sensors for Zn(II) detection constitute an active field of research. A survey of the history and development of these sensors is presented, along with a sample of the knowledge acquired through their use in biological systems. An examination of methods for the subcellular localization of fluorescent probes is included. Chapter 2. Solution and Fluorescence Properties of Symmetric Dipicolylamine- Containing Dichlorofluorescein-Based Zn2+ Sensors The syntheses of five new analogues of the 2',7'-dichlorofluorescein-based Zn2+ sensor Zinpyr-1 (ZP1) are reported. Analysis of these fluorophores by absorption and emission spectroscopy, in combination with potentiometric titrations, produced a detailed molecular picture of the Zn2+ and H+ binding properties of the ZP1 family of sensors. The two separate N30 donor atom sets on ZP1 converge to form binding pockets in which all four heteroatoms participate in coordination to either Zn2+ or protons. The position of the pyridyl group nitrogen atom, 2-pyridyl or 4-pyridyl, has a large impact on the fluorescence response of the dyes to protons in spite of relatively small changes in pKa values. Despite the structural complexity of ZP1, we provide evidence that the pyridyl arms of the DPA appendages participate in the quenching process, in addition to the contribution from the tertiary nitrogen amine atom.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Wong, Brian Alexander

Advisor dc:contributor.advisor

• Stephen J. Lippard.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/55100

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/55100