Bioinorganic chemistry: Fluorescent sensors for metal ions, MRI contrast agents based on Fe(II) and Ln(III), ligand synthesis, structure selective interactions of compounds with DNA and RNA
526 Natural Sciences Complex
Buffalo NY, 14260
Phone: (716) 645-4187
Fax: (716) 645-6963
The central theme in our research is the synthesis of inorganic complexes for biomedical diagnostics, sensing or catalytic applications.
Current research in our laboratories focusses on the following topics:
Magnetic resonance imaging contrast agents that are responsive to biological environment
Paramagnetic metal ion complexes are widely used in clinical medicine as contrast agents for MRI. We have developed the first examples of paramagnetic transition metal complexes that act as chemical exchange saturation transfer agents (paraCEST). ParaCEST agents produce contrast that can be turned on and off with a presaturation pulse, eliminating the need for pre- and post-contrast agent MRI scans.
Metal ions with excellent magnetic properties for paraCEST include the biologically relevant metal ions Fe(II), Co(II) and Ni(II). We have prepared macrocyclic complexes of these metal ions that are inert towards dissociation. These complexes produce intense CEST contrast that is shifted far from the signal from bulk water in tissue. These complexes are being further developed and tested in vivo in collaboration with Roswell Park Cancer Institute imaging scientists.
Our paraCEST contrast agents are sensitive to temperature and to pH and are under development for mapping temperature and pH in tissue. Complexes that have multiple CEST peaks are especially promising in this regard for ratiometric imaging. Tuning the redox properties of the iron and cobalt complexes produces paraCEST agents that switch on and off according to redox potential. For example, cobalt complexes are magnetic switches that proceed from paramagnetic Co(II) to diamagnetic Co(III) complexes upon reaction with oxygen.
Recognition of unusual DNA and RNA structures
A long standing interest is the design of metal ion complexes for the recognition of unusual DNA or RNA structures. Structural biology aspects of this project are carried out in collaboration with Professor Matthew Fountain of SUNY, Fredonia. Our current focus is on complexes that specifically bind single-base bulges, and the design of G-quadruplex specific binders, especially for G-quads with unpaired thymine or uracil. Our complexes are bifunctional and contain Zn(II) and a pendent aromatic group. Some systems function as Zn(II) dependent switches or fluorescent sensors. Shown below is a potential binding mode for a Zn(II) complex with the human telomeric G-quadruplex.