Janet R. Morrow

PhD

Janet Morrow.

Janet R. Morrow

PhD

Janet R. Morrow

PhD

UB Distinguished Professor
Larkin Professor

Research Interests

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

Contact Information

526 Natural Sciences Complex

Buffalo NY, 14260

Phone: (716) 645-4187

Fax: (716) 645-6963

jmorrow@buffalo.edu

Education

  • NSF Visiting Professor, University of Rochester
  • Postdoctoral Fellow, University of California, San Diego
  • NSF Postdoctoral Fellow, University of Bordeaux
  • PhD, University of North Carolina – Chapel Hill
  • BS, University of California, Santa Barbara

Awards and Honors

  • Jacob F. Schoellkopf Medal, ACS, 2014
  • Co-chair of the NSF workshop in Inorganic Chemistry, 2010
  • Elected council member, Society of Biological Inorganic chemistry, 2009-2012
  • National Science Foundation Award for Special Creativity, 2007-2009
  • Chair, Bioinorganic chemistry section of the Inorganic division of the ACS, 2005
  • Director, Research Experiences for Undergraduates Site in the Chemistry Department at the University at Buffalo, 2004-present
  • NSF Visiting Professor, University of Rochester, 1996-1997
  • Alfred P. Sloan Fellow, 1994-1996

Specializations

The central theme in our research is the synthesis of inorganic complexes for biomedical diagnostics, sensing or catalytic applications.

Research Summary

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
Chemical diagram and MRI image.

Students working on this project will become familiar with macrocycle synthesis, coordination chemistry, CEST NMR and MR imaging methods.

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.

Chemical diagram.

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.

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.

Selected Recent Publications

  • 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.
  • 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, 53, 11540-11551.
  • Siters, K. E.; Sander, S. A.; Devlin, J.; Morrow, J. R.* “Bifunctional Zn(II) Complexes for Recognition of Non-Canonical Thymines in DNA Bulges and G-Quadruplexes” Dalton Trans. 2014, 3708-3716.
  • Sander, S. A.; Van Hall, A. K.; Morrow, J. R.* “Zn2+ Selective Switch of Duplex to Hairpin DNA” Inorg. Chem. 2015, 54, 3084-3086.
  • Olatunde, A. O.; Bond, C. J.; Dorazio, S. J.; Daddario, M. D.; Spernyak, J. A.; Cox, J. M.; Benedict, J. B.; Morrow, J. R.* “CoII, FeII and NiII Amide-Appended Tetraazamacrocyclic Complexes as ParaCEST Agents for Thermometry” Chem. Eur. J. 2015, 21, 18290-18300.
  • Tsitovich, P. B.; Cox, J. M.; Benedict, J. B.; Spernyak, J. A.; Morrow, J. R.* “Six-coordinate Co(II) and Fe(II) paraSHIFT agents for temperature measurement.” Inorg. Chem. 2015, 55, 700-716.
  • Morrow, J. R. “Virtual issue on Emerging investigators in Bioinorganic Chemistry” Inorg. Chem. 2015, 54(23), 11039-11042.
  • Burns, P. J.; Tsitovich, P. B.; Morrow, J. R.* “Preparation of Cobalt(II) Cages: An Undergraduate Laboratory Experiment that Produces a paraSHIFT Agent for Magnetic Resonance Spectroscopy” J. Chem. Educ. 2016, 93, 1115-1119.
  • Sanders, S. A; Morrow, J. R.* “Zn(II) Complexes that trigger a DNA conformational Switch” Submitted to special issue on metal nucleic acid interactions: state of the art in Inorg. Chim. Acta 2016, 452, 90-97.
  • Tsitovich, P. B.; Cox. J. M. Morrow, J. R.* “Gearing up for pH Shift: a Responsive Iron(II) 2-amino-6-picolyl-appendent Macrocyclic paraCEST Agent” Inorg. Chem. 2016, 55, 12001-10.
  • Burns, P. J.; Cox, J. M.; Morrow, J. R.* “Imidazole-appended macrocyclic complexes of Fe(II), Co(II) and Ni(II) as paraCEST agents” Inorg. Chem. 2017, 56, 4545-4554.
  • Morrow, J. R.; Toth, E. “Next Generation MRI Contrast Agents” virtual issue, Inorg. Chem. 2017, 56, 6029-34.
  • Tsitovich, P. B.; Kosswattaarachchi, A. M.; Crawley, M. R.; Tittiris, T. Y.; Cook, T. R.; Morrow, J. R., ”An Fe(III) Aza-macrocyclic Complex as pH-Tunable Catholyte and Anolyte for Redox-Flow Battery Applications” Chem. Eur. J. 2017, 23(61), 15327-15331.
  • Tsitovich, P. B.; Tittiris, T. Y.; Cox, J. M.; Benedict, J. B.; Morrow, J. R., “Fe(II) and Co(II) N-methylated CYCLEN complexes as paraSHIFT agents with large temperature dependent shifts” Dalton Trans. 2018, 47, 916-924.
  • Abozeid, S. M.; Snyder, E. M.; Tittiris, T. Y.; Steuerwald, C.M.; Nazarenko, A. Y.; Morrow, J. R., “Co(II) complexes with innersphere and outersphere water interactions for CEST MRI applications” Inorg. Chem. 2018, 57, 2085-2095.
  • Abozeid, S. M.; Snyder E. M.; Lopez, A. P.; Steuerwald, C. M.; Sylvester, E.; Ibrahim, K. M; Zaky, R. R; Abou-El-Nadar, H. M.; Morrow, J. R. “Nickel(II) complexes as paramagnetic shift and paraCEST agents” Eur. J. Inorg. Chem. 2018 in revision.