Investigation of zinc metalloneurochemistry with fluorescent sensors based on fluorescein platforms

Chapter 1. CoordinationChemistry for the Neurosciences Metal ions are integral components of numerous enzymes and proteins. Although the field of bioinorganic chemistry has not focused on the brain and central nervous system, metal ions are vital to many neurological functions and are implicated in several neurological disorders. In this chapter, I present a brief overview of the functions of metal ions in neurobiology and highlight recent advances in the use of fluorescent sensors to study the neurotransmitters zinc and nitric oxide. Chapter 2. Fluorescent Sensors for Zn2' Based on a Fluorescein Platform: Synthesis, Properties and Intracellular Distribution Two new fluorescent sensors for Zn2' that utilize fluorescein as a reporting group, Zinpyr-1 (ZP1) and Zinpyr-2 (ZP2), have been synthesized and characterized. ZP1 is prepared in one step via a Mannich reaction, and ZP2 is obtained in a multi-step synthesis that utilizes 4',5'-fluorescein dicarboxaldehyde as a key intermediate. Both ZP sensors have excitation and emission wavelengths in the visible range (500 nm), dissociation constants (Kdl) for Zn2* of less than 1 nM, quantum yields approaching unity ... and cell permeability, making them well suited for intracellular applications. A 3- to 5-fold fluorescent enhancement occures under simulated physiological conditions corresponding to the binding of the Zn2+ cation to the sensor, which inhibits a photo-induced electron transfer (PET) quenching pathway. The X-ray crystal structure of a 2:1 Zn2/ZP1 complex has been solved. It is the first structurally characterized example of a complex of fluorescein substituted with metal binding ligands.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2003

Author dc:creator

• Burdette, Shawn C. (Shawn Christopher), 1975-

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/1721.1/17567

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/17567