Professor of Chemistry and Vice Dean for Natural Sciences
John P. Toscano, vice dean for natural sciences, is a professor of chemistry in the School of Arts and Sciences.
Dr. Toscano serves as liaison with the chairs of the school’s natural science departments to ensure the highest quality undergraduate experience, particularly in introductory level courses, as well as to think through space planning and infrastructure needs and opportunities for interdisciplinary endeavors. He is an important partner to the science chairs and the dean in the recruitment of faculty and issues concerning tenure and promotion, and he represents the school and cultivates ties with other science-intensive divisions of the university, as well as with external institutions for scientific research. Moreover, Dr. Toscano works with the university’s technology transfer office and maintains responsibility for research reporting and compliance issues.
A highly accomplished scientist, Dr. Toscano’s main interests are currently focused on the study of the fundamental chemistry and biochemistry of nitroxyl (HNO). HNO has been shown to have biological activity distinct from that of its redox cousin, nitric oxide (NO), but many mechanistic questions remain. Recent interest in HNO has been catalyzed by research suggesting that it may be a novel therapeutic for the treatment of heart failure.
Dr. Toscano received his baccalaureate degree in chemistry from Princeton University and his doctoral degree in organic chemistry from Yale University. After completing a National Institutes of Health postdoctoral fellowship in organic chemistry at Ohio State University, he joined the Johns Hopkins University Department of Chemistry in 1995 as an assistant professor. He became a full professor in 2003, vice-chair of the department in 2004, and served as chair from 2005 to 2011 and again from 2013 to 2014.
The Toscano group’s main interests have focused on the application of nanosecond time-resolved infrared (TRIR) spectroscopy to the study of organic reactive intermediates and the development of novel photochemical precursors to nitric oxide (NO). More recently, our research activities have turned to study of the fundamental chemistry and biochemistry of nitroxyl (HNO). This one-electron reduced and protonated congener of NO has recently received significant attention, especially as a potential alternative to current treatments of cardiac failure.
Although unique biological responses have been attributed to HNO, compared with its redox sibling NO, much less is known about the fundamental solution chemistry of this deceptively complicated system. A major reaction pathway for HNO is dimerization (through hyponitrous acid HON=NOH) to produce ultimately nitrous oxide (N2O) and water. Thus, HNO cannot be stored and must be produced from an appropriate precursor. Unfortunately, only a very limited number of precursors suitable for biological studies currently exist.
In order to advance our understanding of HNO chemistry and biochemistry we are actively pursuing research in the following areas:
(1) Development of new thermal and photochemical precursors to HNO
(2) Development of new analytical tools for the detection and study of HNO
(3) Elucidation of fundamental HNO solution-phase chemistry
(4) Characterization of HNO-induced modifications of phospholamban, an important regulatory protein involved in the control of cardiac function
“Curtailing the Hydroxylaminobarbituric Acid – Hydantoin Rearrangement to Favor HNO Generation” Guthrie, D. A.; Nourian, S.; Takahashi, C. G.; Toscano, J. P. J. Org. Chem. 2015, 80, 1349-1356.
Featured Article: “Catch and Release of HNO with Pyrazolones” Guthrie, D. A.; Ho, A.; Takahashi, C. G.; Collins, A.; Morris, M.; Toscano, J. P. J. Org. Chem. 2015, 80, 1338-1348.
“Comparison of HNO Reactivity with Tryptophan and Cysteine in Small Peptides” Keceli, G.; Toscano, J. P. Bioorg. Med. Chem. Lett. 2014, 24, 3710-3713.
“Trans-Cis Isomerization of Vinylketones through Triplet 1,2-Biradicals” Upul Ranaweera, R. A. A.; Scott, T.; Li, Q.; Rajam, S.; Duncan, A.; Li, R. Evans, A. S.; Bohne, C.; Toscano, J. P.; Ault, B. S.; Gudmundsdottir, A. D. J. Phys. Chem. A 2014, 118, 10433-10447.
“Reactivity of C-terminal Cysteines with HNO” Keceli, G.; Toscano, J. P. Biochemistry 2014, 53, 3689-3698.
“Post-Study Caffeine Administration Enhances Memory Consolidation in Humans” Borota, D.; Murray, E.; Keceli, G.; Chang, A.; Watabe, J. M.; Ly, M.; Toscano, J. P.; Yassa, M. A. Nature Neurosci. 2014, 17, 201-203.
“2-Diazo-1-(4-hydroxyphenyl)ethanone: A Versatile Photochemical and Synthetic Reagent” Senadheera, S.; Evans, A. S.; Toscano, J. P.; Givens, R. S. Photochem. Photobiol. Sci. 2014, 13, 324-341.
“HNO Enhances SERCA2a Activity and Cardiomyocyte Function by Promoting Redox-Dependent Phospholamban Oligomerization” Sivakumaran, V.; Stanley, B. A.; Tocchetti, C. G.; Ballin, J. D.; Caceres, V.; Zhou, L.; Keceli, G.; Rainer, P. P.; Lee, D. I.; Huke, S.; Ziolo, M. T.; Kranias, E. G.; Toscano, J. P.; Wilson, G. M.; O’Rourke, B.; Kass, D. A.; Mahaney, J. E.; Paolocci, N. Antiox. Redox Signal. 2013, 19, 1185-1197.
“NMR Detection and Study of Hydrolysis of HNO-Derived Sulfinamides” Keceli, G.; Moore, C. D.; Labonte, J. W.; Toscano, J. P. Biochemistry 2013, 52, 7387-7396.
“Oxidation of N-hydroxy-L-arginine by Hypochlorous Acid to Form Nitroxyl (HNO)” Cline, M. R.; Chavez, T.A.; Toscano, J. P. J. Inorg. Biochem. 2013, 118, 148-154.
“Nanosecond Time-Resolved IR Study of Thiobenzoylnitrene” Liu, Y.; Evans, A. S.; Toscano, J. P. Phys. Chem. Chem. Phys. 2012, 14, 10438-10444.
“Reactivity of Nitroxyl-Derived Sulfinamides” Keceli, G.; Toscano, J. P. Biochemistry 2012, 51, 4206-4216.
“Development of N-Substituted Hydroxylamines as Efficient Nitroxyl (HNO) Donors” Guthrie, D. A.; Kim, N. Y.; Siegler, M. A.; Moore, C. D.; Toscano, J. P. J. Am. Chem. Soc. 2012, 134, 1962-1965.
“Optimization of HNO Production from N,O-bis-Acylated Hydroxylamine Derivatives” Sutton, A. D.; Williamson, M.; Weismiller, H.; Toscano, J. P. Org. Lett. 2012, 14, 472-475.