Janet R. Morrow

PhD

Janet Morrow.

Janet R. Morrow

PhD

Janet R. Morrow

PhD

UB Distinguished Professor
Larkin Professor

Research Interests

Bioinorganic chemistry: Magnetic resonance imaging contrast agents based on iron, cobalt or nickel, bimodal (fluorescent) probes, ligand synthesis, self-assembled multinuclear iron complexes for imaging, yeast cell labeling with inorganic complexes.

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

  • UB exceptional scholar (sustained achievement) 2015
  • 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 for applications in tumor imaging
  • Yeast cell labeling with metal complex probes to track infections
  • Bimodal imaging agents
Chemical diagram and MRI image.

Students working on this project will become familiar with macrocycle synthesis, coordination chemistry, CEST NMR and MR imaging methods.  Animal imaging collaborators are at Roswell Park Comprehensive Cancer Center.

Magnetic resonance imaging probes 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 and are in high spin form. 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 Comprehensive Cancer Center 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 (see figure below). 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. Co(II) complexes have been incorporated into liposomes to increase the sensitivity of these probes through lipoCEST.

Figure 1.

Figure 1. Two isomeric Co(II) paraCEST MRI probes produce a signal correlated to pH in solution and in tissue homogenate.   Research featured in Dalton Trans. 2020, 49, 279-284.

Iron(III) coordination complexes as alternatives to Gadolinium(II) MRI contrast agents.

High spin Fe(III) complexes show great promise as contrast agents that increase relaxation of water protons for T1 weighted MRI. Our group has produced a new class of macrocyclic Fe(III) complexes that produce water proton relaxivity in serum that rivals that of clinically used Gd(III) complexes. These iron complexes do not have an exchangeable water ligand, but function through second-sphere water interactions and also through proton exchange. 

The synthetic chemistry of the Fe(III) macrocyclic complexes is quite versatile, allowing us to change ancillary groups to tune the biodistribution and pharmacokinetics of clearance from mice. The overall charge and lipophilicity of the complexes is varied in order to produce a strong signal in the vasculature and for rapid renal clearance.  Complexes that bind tightly to serum albumin for use as blood pool agents are also being studied.

Yeast-derived Β-glucan particles (GPs) are hollow shells that act as carriers for drugs and imaging probes. The GPs are promising for targeting immune cells including macrophages and monocytes.  Fe(III) complexes with open coordination sites bind strongly to GPs  and are released upon treatment with mild acid or a chelator. The iron-loaded GPs are taken up by macrophages, opening up the possibility of targeting macrophages in tumors for imaging.

Figure 2.

Figure 2. Iron complexes bound to glucan particles derived from yeast for MRI applications.

Cell labeling with metal complexes for tracking in vivo.

Studies are underway to label yeast cells for tracking yeast infections in animals. Fe(III) complexes bind to the cell wall of yeast enhance the T2 water proton relaxation in a shape dependent manner. Studies are underway to optimize conditions for uptake in various types of yeast including in Candida Albicans in yeast and hyphal form.

Selected Recent Publications

  • 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. PMCID: PMC5553446 PMID: 27934305 DOI: 10.1021/acs.inorgchem.6b02159.
  • 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. https://doi.org/10.1016/j.ica.2016.02.008.
  • 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. 201693, 1115-1119. https://doi.org/10.1021/acs.jchemed.5b00818.
  • 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. PMID:28358208, DOI:10.1021/acs.inorgchem.7b00176.
  • 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. PMID:28929548, DOI:10.1002/chem.201704381.
  • 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. PMID: 29260180, DOI:10.1039/c7dt03812g.
  • 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. PMID: 29412653, DOI:10.1021/acs.inorgchem.7b02977.
  • 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, 1902-1908.   https://doi.org/10.1002/ejic.201800021.
  • Tsitovich, P. B.;  Gendron F.; Nazarenko, A. Y.; Livesay, B. N.; Lopez, A. P.; Shores, M. P.; Autschbach, J. A.; Morrow, J. R.*  “Low Spin Fe(III) Macrocyclic Complexes of Imidazole-appended TACN as Paramagnetic Probes”  Inorg. Chem. 2018, 57, 8364-8374. PMID:29939736, DOI:10.1021/acs.inorgchem.8b01022.
  • Bond, C. F.; Sokolow, G. E.; Crawley, M. R.; Burns, P. J.; Cox, J. M.; Mayilmurugan, R.; Morrow, J. R.* “Exploring inner-sphere water interactions of Fe(II), Fe(II) and Co(II) complexes of 12-member macrocycles to develop CEST MRI probes”  Inorg. Chem. 2019, 58, 8710-8719. PMID:31247845, DOI: 10.1021/acs.inorgchem.9b01072.
  • Patel, A.; Asik, D.; Spernyak, J. A.; Cullen, P.; Morrow, J. R.* “Fe(III) based bimodal imaging agents for yeast cells”  J. Inorg. Biochem. 2019, 201, 11083-.  Issue dedicated to Debbie Crans. PMID:31522137, PMCID: PMC6859208, DOI: 10.1016/j.jinorgbio.2019.110832.
  • Snyder, E. M.; Asik, D.; Abozeid, S. M.; Burgio, A.; Bateman, G.; Turowski, S. G.; Spernyak, J. A.; Morrow, J. R.* “A class of Fe(III) macrocyclic complexes with alcohol donor groups as effective T1 MRI contrast agents”  Angew. Chem. Int. Ed. 2020, 59, 2414-2419. PMID:31725934, DOI:10.1002/anie.201912273.
  • Bond, C. J.; Cineus, R.; Nazarenko, A. Y.; Spernyak, J. A.; Morrow, J. R.*, “Isomeric Co(II) paraCEST agents as pH responsive MRI probes” Dalton Trans. 2020, 49, 279-284   PMID: 23102112, DOI: 10.1021/ja307909x.
  • Snyder, E. M.; Chowdhury, M. S. I.; Morrow, J. R.* “Co(II) and Fe(II) Triazole-Appended 4,10-diaza-15-crown-5-ether Macrocyclic Complexes for CEST MRI Applications” Inorg. Chim. Acta 2020, 509, 119649. issue in honour of Prof. Tara Dasgupta. doi.org/10.1016/j.ica.2020.119649
  • Patel, A.; Asik, D. Snyder, E. M.; Delillo, A. E.; Cullen, P. J.; Morrow, J. R.* “Binding and release of Fe(III) complexes from glucan particles for delivery of T1 MRI contrast agents” ChemMedChem 2020, March 13. PMID:32168421, DOI:10.1002/cmdc.202000003.
  • Abozeid, S. M.; Asik, D.; Sokolow, G. E.; Nazarenko, A. Y.; Lovell, J. F.; Morrow, J. R. “Co(II) complexes as liposomal CEST agents” Angew. Chem. Int. Ed.  2020, 59, 12093-97.    doi.org/10.1002/anie.202003479.
  • Asik, D.; Smolinski, R.; Abozeid, S. M.; Michell, T. B.; Spernyak, J. A.; Morrow, J. R. “Modulating the Properties of Fe(III) Macrocyclic MRI Contrast Agents by Appending Sulfonate or Hydroxyl Groups”  Molecules 2020, 25, 2291; doi:10.3390/molecules25102291.
  • Patel, A.; Patel, A. Asik, D. Snyder, E. M.; Apernyak, J. A.; Cullen, P. J.; Morrow, J. R.* “Saccharomyces cerevisiae and Candida albicans Yeast Cells Labeled with Fe(III) Complexes as MRI Probes” Magnetochemistry 2020, 6, 41 DOI:10.3390/magnetochemistry6030041.