We have recently developed a class of antiproliferative chelators that scavenge intracellular iron ions upon reduction/activation by glutathione in cancer cells. This approach, which is aimed at the development of new molecular tools for the study and treatment of cancer, seeks to exploit an emerging vulnerability of malignant cells, namely their altered iron metabolism and increased demand for this essential metal ion.
We are inspired by bioinorganic chemistry for the design of novel metal complexes featuring both metal-based and ligand-based redox chemistry. Our current work in this area is focused on naturally occurring pyrrole-based compounds (e.g., bacterial prodigiosins, biopyrrins from heme metabolism) and on their role as redox-active ligands in coordination chemistry and catalysis.
Because of the interdisciplinary nature of our queries, the design of research plans in the Tomat laboratory combines principles of synthetic and coordination chemistry with current knowledge of cell metabolism and molecular biology. We employ the tools of synthetic chemistry and a variety of spectroscopic techniques (e.g., NMR, EPR, UV-visible absorption, fluorescence emission) and electrochemical methods for the preparation and characterization of metal complexes both in vitro and in cultured mammalian cells.
- Akam, E. A.; Chang, T. M.; Astachkine, A. V.; Tomat*, E. "Intracellular reduction/activation of a disulfide switch in thiosemicarbazone iron chelators" Metallomics 2014, 6, 1905-1912.
- Chang, T. M.; Sinharay, S.; Astachkine, A. V.; Tomat*, E. "Prodigiosin analogue designed for metal coordination: Stable zinc and copper pyrrolyldipyrrins" Inorg. Chem. 2014, 53, 7518-7526.
- Chang, T. M.; Tomat*, E. "Disulfide/thiol switches in thiosemicarbazone ligands for redox-directed iron chelation" Dalton Trans. 2013, 42, 7846-7849.
- Blakemore, L. J.; Tomat, E.; Lippard, S. J.; Trombley, P. Q. "Zinc Released from Olfactory Bulb Glomeruli by Patterned Electrical Stimulation of the Olfactory Nerve" Metallomics 2013, 5, 208-213.
- Pluth, M. D.; Tomat, E.; Lippard S. J. "Biochemistry of Mobile Zinc and Nitric Oxide Revealed by Fluorescent Sensors" Annu. Rev. Biochem. 2011, 80, 333-355.
- Tomat, E.; Lippard, S. J. "Ratiometric and Intensity-Based Zinc Sensors Built on Rhodol and Rhodamine Platforms" Inorg. Chem. 2010, 49, 9113-9115.
- You, Y.; Tomat, E.; Hwang, K.; Atanasijevic, T.; Nam, W.; Jasanoff, A. P.; Lippard, S. J. "Manganese Displacement from Zinpyr-1 Allows Zinc Detection by Fluorescence Microscopy and Magnetic Resonance Imaging" Chem. Commun. 2010, 4139-4141.
- Tomat, E.; Lippard, S. J. "Imaging Mobile Zinc in Biology" Curr. Op. Chem. Biol. 2010, 14, 225-230.
- Tomat, E.; Nolan, E. M.; Jaworski, J.; Lippard, S. J. "Organelle-specific Zinc Detection Using Zinpyr-labeled Fusion Proteins in Live Cells" J. Am. Chem. Soc. 2008, 130, 15776-15777.
- Cuesta, L.; Tomat, E.; Lynch, V. M.; Sessler, J. L. "Binuclear Organometallic Ruthenium Complexes of a Schiff-Base Expanded Porphyrin" Chem. Commun. 2008, 3744-3746.
- Tomat, E.; Cuesta, L.; Lynch, V. M.; Sessler, J. L. "Binuclear Fluoro-Bridged Zinc and Cadmium Complexes of a Schiff Base Expanded Porphyrin: Fluoride Abstraction from the Tetrafluoroborate Anion" Inorg. Chem. 2007, 46, 6224-6226.
- Sessler, J. L.; Tomat, E. "Transition Metal Complexes of Expanded Porphyrins" Acc. Chem. Res. 2007
- NSF CAREER Award, 2015
- Young Investigator Award of the International Society for Zinc Biology, 2009
- Robert A. Welch Professional Development Fellowship, 2006
- BASF Endowed Fellowship, University of Texas, 2002
- Elio Russo Award, University of Trieste, 2002