John Toscano

John Toscano

Professor of Chemistry

PhD, Yale University

New Chemistry Building 115
Group/Lab Website

John P. Toscano is a professor of chemistry in the School of Arts and Sciences. He was previously vice dean for natural sciences, where he served as liaison with the chairs of the school’s natural science departments to ensure the highest quality undergraduate experience, as well as to think through space planning and research infrastructure needs and opportunities for interdisciplinary endeavors. He was an important partner to the science chairs and the dean in the recruitment of faculty and issues concerning tenure and promotion, and he represented the school and cultivated ties with other science-intensive divisions of the university, as well as with external institutions for scientific research. Moreover, Dr. Toscano worked with the university’s technology transfer office and maintained 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 biology of small molecule bioactive signaling agents such as nitric oxide (NO).  In particular, his research has focused on two such small molecules of recent interest – nitroxyl (HNO) and hydrogen sulfide (H2S) and their cardioprotective properties.

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.

Our research group is largely focused on the exploration of the fundamental chemistry and biology of physiologically important signaling molecules including nitroxyl (HNO), hydrogen sulfide (H2S), and related species.

HNO has been shown to have biological activity distinct from that of its redox cousin, nitric oxide (NO), and related nitrogen oxides. Much of the recent interest in HNO has been catalyzed by research suggesting that it may be a novel therapeutic for the treatment of heart failure. At neutral pH in the absence of chemical traps, HNO efficiently dimerizes to hyponitrous acid (HON=NOH), which subsequently dehydrates to nitrous oxide (N2O).  Given this inherent reactivity, HNO cannot be used directly; donor molecules are required for the generation of HNO in situ.

Hydrogen sulfide is believed to be involved in a myriad of physiological processes including smooth muscle relaxation and inhibition of inflammation. Recent reports have shown that much of the biological activity associated with H2S is due to its oxidized congeners, namely hydropersulfides (RSSH) and polysulfides (RSSnSR; n ≥1). Hydropersulfides are highly reactive species with poorly understood chemical properties when compared to their thiol counterparts. Recent studies have shown that hydropersulfides are commonly found in vivo as low molecular weight persulfides (i.e., cysteine persulfide, glutathione persulfide) or as modifications on cysteine residues in proteins. Protein hydropersulfides can be made post-translationally following cysteine oxidation or incorporated during translation using cysteinyl-tRNA synthetase (CARS). These modifications are expected to alter the activity of proteins depending on the site of S-persulfidation; however, methods to persulfidate specific residues of interest have yet to be developed.

In order to explore the chemistry and biology of these reactive sulfur species we aim to explore:

  1. Novel ways to generate hydropersulfides
  2. The fundamental properties of hydropersulfides
  3. Biochemical effects of hydropersulfides
  4. Reagents capable of specific and efficient protein persulfidation

“Reaction of Nitroxyl (HNO) with Hydrogen Sulfide and Hydropersulfides” Zarenkiewicz, J.; Khodade, V. S.; Toscano, J. P. J. Org. Chem. 202186, 868-877

“Predicting the Possible Physiological/Biological Utility of the Hydropersulfide Functional Group Based on Its Chemistry: Similarities Between Hydropersulfides and Selenols” Fukuto, J. M.; Lin, J.; Khodade, V. S.; Toscano, J. P. Antioxid. Redox Signal. 202033, 1295-1307

“The reactions of hydropersulfides (RSSH) with myoglobin” Álvarez, L.; Suarez Vega, V.; McGinity, C.; Khodade, V. S.; Toscano, J. P.; Nagy, P.; Lin, J.; Works, C.; Fukuto, J. M.; Arch. Biochem. Biophys. 2020687, 108391

“Alkylamine-Substituted Perthiocarbamates: Dual Precursors to Hydropersulfide and Carbonyl Sulfide with Cardioprotective Actions” Khodade, V. S.; Pharoah, B. M.; Paolocci, N.; Toscano, J. P. J. Am. Chem. Soc. 2020, 142 (9), 4309-4316

“Nitroxyl (HNO) targets phospholamban cysteines 41 and 46 to enhance cardiac function” Keceli, G.; Majumdar, A.; Thorpe, C. N.; Jun, S.; Tocchetti, C. G.; Lee, D. I.; Mahaney, J. E.; Paolocci, N.; Toscano, J. P. J. Gen. Physiol. 2019151 (6), 758–770

“Speciation of reactive sulfur species and their reactions with alkylating agents: do we have any clue about what is present inside the cell?” Bogdandi, V.; Ida, T.; Sutton, T. R.; Bianco, C.; Ditroi, T.; Koster, G.; Henthorn, H. A.; Minnion, M.; Toscano, J. P.; van der Vliet, A.; Pluth, M. D.; Feelisch, M.; Fukuto, J. M.; Akaike, T.; Nagy, P. Br. J. Pharmacol. 2019, 176, 646-670

“The Reaction of Hydrogen Sulfide with Disulfides: Formation of a Stable Trisulfide and Implications to Biological Systems” Bianco, C. L.; Akaike, T.; Ida, T.; Nagy, P.; Bogdandi, V.; Toscano, J. P.; Kumagai, Y.; Henderson, C. F.; Goddu, R. N.; Lin, J.; Fukuto, J. M. Br. J. Pharmacol. 2019, 176, 671-683

“Development of S-Substituted Thioisothioureas as Efficient Hydropersulfide Precursors” Khodade, V.; Toscano, J. P. J. Am. Chem. Soc. 2018140, 17333-17337

“Amphiphilic Copolymers Capable of Concomitant Release of HNO and Small Molecule Organics” Church, D.C.; Nourian, S.; Lee, C.; Yakelis, N. A.; Toscano, J. P.; Boydston, A. J. ACS Macro Lett. 20176, 46-49

“Chemical Biology of Hydropersulfides and Related Species: Possible Rolles in Cellular Protection and Redox Signaling” Alvarez, L.; Bianco, C. L.; Toscano, J. P.; Lin, J.; Akaike, T.; Fukuto, J. M. Antioxid. Redox Signal. 201727, 622-633

“The chemical biology of HNO signaling” Bianco, Christopher L.; Toscano, J. P.; Bartberger, Michael D.; Fukuto, Jon M. Arch. Biochem. Biophys. 2017617, 129-136

“Development of N-Substituted Hydroxamic Acids with Pyrazolone Leaving Groups as Nitrosocarbonyl Precursors” Nourian, Saghar; Zilber, Zachary A.; Toscano, J. P. J. Org. Chem201681, 9138-9146

“Nitrosocarbonyl release from O-substituted hydroxamic acids with pyrazolone leaving groups” Nourian, Saghar; Lesko, Robert P.; Guthrie, Daryl A.; Toscano, J. P. Tetrahedron 201672, 6037-6042

“Selenols are resistant to irreversible modification by HNO” Bianco, Christopher L.; Moore, Cathy D.; Fukuto, Jon M.; Toscano, J. P. Free Radic. Biol. Med.  201699, 71-78

“The chemical biology of the persulfide (RSSH)/perthiyl (RSS•) redox couple and possible role in biological redox signaling” Bianco, Christopher L.; Chavez, Tyler A.; Sosa, Victor; Saund, Simran S.; Nguyen, Q. Nhu N.; Tantill, Dean J.; Ichimura, Andrew S.; Toscano, J. P.; Fukuto, Jon M. Free Radic. Biol. Med.  2016101, 20-31

“Time-resolved Infrared (TRIR) Studies of Oxycarbonylnitrenes” Chavez, Tyler A.; Liu, Younglin; Toscano, J. P. J. Org. Chem. 201681, 6320-6328

“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.