Janet R. Morrow
UB Distinguished Professor
Office: 526 Natural Sciences Complex
Phone: (716) 645-4187
Fax: (716) 645-6963
B.S., University of California, Santa Barbara
Ph.D., University of North Carolina – Chapel Hill
NSF Postdoctoral Fellow, University of Bordeaux
Postdoctoral Fellow, University of California, San Diego
NSF Visiting Professor, University of Rochester
Awards and Honors:
Alfred P. Sloan Fellow (1994-1996)
NSF Visiting Professor, University of Rochester (1996-1997)
Director, Research Experiences for Undergraduates Site in the Chemistry Department at the University at Buffalo (2004-present)
Chair, Bioinorganic chemistry section of the Inorganic division of the ACS (2005)
National Science Foundation Award for Special Creativity (2007-2009)
Elected council member, Society of Biological Inorganic chemistry (2009-2012)
Co-chair of the NSF workshop in Inorganic Chemistry (2010)
Jacob F. Schoellkopf Medal, ACS (2014)
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 containing iron, cobalt or nickel
Temperature, pH or redox responsive MRI contrast agents
Optical sensing of metal ions, especially iron
Recognition of unusual DNA or RNA structures by metal complexes
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.
Students working on this project will become familiar with macrocycle synthesis, coordination chemistry, CEST NMR and MR imaging methods.
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.
Students working in this area become familiar with ligand synthesis, coordination chemistry fluorescence spectroscopy, gel electrophoresis, PCR and use isothermal calorimetry, and surface plasmon resonance to study binding.
Optical sensing of iron
A new direction in our laboratory is the development of optical sensors for Fe(II) in cell culture and in tissue. We have prepared new ligands that bind Fe(II) specifically over Zn(II) and contain fluorophores that register metal ion binding through changes in emission peak intensity.
Students working on this project will be familiar with ligand synthesis, fluorescence and photophysics of metal ion complexes, and metal ion trafficking in cells.
Selected Recent Publications:
- Olatunde, A. O.; Cox, J. M.; Daddario, M. D; Spernyak, J. A.; Benedict, J. B.; Morrow, J. R. “Seven-Coordinate CoII, FeII and Six-Coordinate NiII Amide-Appended Macrocyclic Complexes as ParaCEST Agents in Biological Media” Inorg. Chem. 2014, 53, 8311-8321.
- Siters, K. E.; Fountain, M. A.; Morrow, J. R. “Selective binding of Zn(II) complexes to Human Telomeric G-quadruplex DNA” Inorg. Chem. 2014, in press.
- Dorazio, S. J.; Olatunde, A. O.; Tsitovich, P. B.; Morrow, J. R. “Comparison of Divalent Transition metal ion paraCEST MRI Contrast Agents”, J. Biol. Inorg. Chem. 2014, 19, 191-205.
- Tsitovich, P. B.; Burns, P. J.; McKay, A. M.; Morrow, J. R. “Redox-activated MRI Contrast Agents Based on Lanthanide and Transition Metal Ions”, J. Inorg. Biochem. 2014, 133, 143-154.
- Siters, K. E.; Sander, S. A.; Morrow, J. R. “Selective Binding of Zn2+ Complexes to Non-Canonical Thymine or Uracil in DNA or RNA”, Prog. Inorg. Chem. K. D. Karlin, Ed., Wiley 2014, vol. 59, pp. 245-298.
- Dorazio, S. J.; Olatunde, A. O.; Spernyak, J. A.; Morrow, J. R. “CoCEST: Cobalt(II) Amide-appended ParaCEST MRI Contrast Agents”, Chem. Commun. 2013, 49, 10025-10027.
- Tsitovich, P. B.; Spernyak, J. A.; Morrow, J. R. “A redox-activated MRI Contrast Agent that Switches between Paramagnetic and Diamagnetic States”, Angew. Chem. Int. Ed. 2013, 52, 13997-14000.
- Dorazio, S. J.; Tsitovich, P. B.; Gardina, S. A.; Morrow, J. R. “The Reactivity of Macrocyclic Fe(II) paraCEST MRI Contrast Agents towards Biologically Relevant Anions, Cations, Oxygen or Peroxide”, J. Inorg. Biochem. 2012, 117, 212-219.
- Tsitovich, P. B.; Morrow, J. R. “Macrocyclic ligands for Fe(II) paraCEST and Chemical Shift MRI Contrast Agents”, Inorg. Chim. Acta 2012, 393, 3-11.
- Olatunde, A.; Dorazio, S. J.; Spernyak, J. A.; Morrow, J. R. “The NiCEST Approach: Ni(II) PARACEST MRI Contrast Agents”, J. Am. Chem. Soc. 2012, 134, 18503-18505.