B.S., University of Oregon, 2004. Ph.D., University of California, Berkeley, 2008 (Robert G. Bergman and Kenneth N. Raymond). Postdoctoral: Massachusetts Institute of Technology, 2008-11 (Stephen J. Lippard).
Selected Honors and Awards: Barry M. Goldwater Scholar, 2003-04; NSF Graduate Research Fellow, 2004-07; ACS Young Investigator Award, 2008; NIH National Research Service Award, 2008-10; NIH Pathway to Independence Award, 2010-14; NSF CAREER Award 2015; Sloan Fellow, 2015; Camille Dreyfus Teacher Scholar, 2016; UO Oustanding Early Career Award, 2016; UO Fund for Faculty Excellence Award, 2017; UO Center for Undergraduate Research & Engagement (CURE) Award, 2018; Richard T Jones New Investigator Award, 2018; UO COVID-19 Innovation Award, 2021; AAAS Fellow, 2022; NSF Creativity Award, 2023. At Oregon since 2011.
Research in the Pluth group is thematically based on different aspects of molecular recognition at the interface of chemistry and biology. Our group uses synthetic chemistry to enable new investigations into chemical biology and catalysis. Our main research areas include:
Chemical Biology of Carbonyl Sulfide (COS)
Carbonyl sulfide (COS) is the most prevalent sulfur-containing gas in Earth’s atmosphere, but few studies have investigated its role as an important small gaseous biomolecule. Drawing parallels to the other small important gases NO, CO, H2S, and SO2, COS is poised to play a unique role in living systems. Already detected in living systems, COS has emerged as a potential biomarker for organ rejection and other diseases. Aligned with these opportunities, our group has pioneered the development of COS-releasing small molecules and is at the forefront of leveraging these developed tools to further the investigations of the role of COS in biology. These platforms allow for new chemistry to be developed to access COS-on-demand platforms and provide a first line of investigative tools to expand our understanding of the emerging roles of COS in chemical biology.
Detection, Delivery, and Quantification of Biological H2S
Hydrogen sulfide (H2S), commonly known for its unpleasant rotten-egg smell, is now accepted as an important enzymatically-produced biomolecule that plays important roles in living systems. Joining CO and NO in a class of molecules often referred to as ‘gasotransmitters’, H2S plays important roles diabetes, hypertension, heart failure, inflammation, neurodegeneration. As the biomedical applications of H2S continue to emerge rapidly, the development, refinement, and application of robust, reliable and purpose-inspired chemical tools for studying its multifaceted roles are paramount. Aligned with this need, our group is developing new chemical tools to detect and modulate biological H2S. Such tools include fluorescent, chemiluminescent, and colorimetric methods for H2S detection and quantification as well as slow-releasing H2S donor molecules. These investigations have included collaborations with the Parthasarathy (UO) focused on imaging H2S in live zebrafish as well as with the Kevil group (LSUHSC) focused on different applications of H2S analytical methods. Drawing parallels to the positive impacts of chemical tools for detection, quantification, and delivery of biological NO, we anticipate that these newly-developed chemical tools will enable new investigations into the multifaceted roles H2S in biology and facilitate new discoveries into the roles of H2S in human health and disease.
Bio(in)organic Sulfide Chemistry
Despite the important and diverse roles of H2S in biology, the fundamental chemistry by which H2S exerts its action on discrete biological targets remains uncertain. For example, H2S, persulfides (RSSH) and polysulfide (RSSxR) likely contribute to the complex landscape of H2S chemical biology. Furthermore, HS– is the primary form of H2S under physiological conditions which allows for modulation of water/lipid solubility, nucleophilicity, and reduction potential, but also complicates direct investigations of important reactions with metalloenzymes and interactions with the thiol pool. Motived by these challenges, we use small molecule bioorganic and bioinorganic model systems to investigate how H2S/HS– with transition-metal containing compounds, small sulfur-rich biomolecules, and other reactive sulfur, oxygen, and nitrogen species (RSONS). In addition, we collaborate with the Johnson and Haley groups at the UO to expand investigations into the role of HS– as an overlooked biologically-relevant anion and as a target for synthetic molecular receptors. As a whole, by studying the reactivity of H2S/HS– with simplified molecular architectures, our long-term goal is to develop and use model systems that allow for greater understanding into the fundamental chemistry associated with the storage, translocation, and action of biological H2S.
Students and researchers in the Pluth research group can look forward to working in an interdisciplinary group with research interests at the interfaces between organic/inorganic chemistry and chemical biology. Our research relies on many preparative and analytical techniques ranging from organic and organometallic synthesis to tissue culture preparation and computational chemistry. Spectroscopic methods include UV-vis and fluorescence spectroscopy, fluorescence microscopy, X-ray crystallography, advanced multidimensional NMR techniques, and other forms of spectroscopy.
Selected publications:
Google Scholar Profile (Full Publication List)
Newton, T.D.; Li, K.; Sharma, J.; Champagne, P.A.; Pluth, M.D. “Direct Hydrogen Selenide (H2Se) Release from Activatable Selenocarbamates.” Chem. Sci., 2023, 14, 7581-7588. [link]
Li, K.; Zakharov, L.N.; Pluth, M.D. “Taming the Dichalcogenides: Isolation, Characterization, and Reactivity of Elusive Perselenide, Persulfide, Thioselenide, and Selenosulfide Anions.” J. Am. Chem. Soc., 2023, 145, 12435-13443. [link]
Gilbert, A.K.; Pluth, M.D. “Subcellular Delivery of Hydrogen Sulfide Using Small Molecule Donors Impacts Organelle Stress.” J. Am. Chem. Soc., 2022, 144, 17651-17660. [link]
Garcia, A.C.; Zakharov, L.N.; Pluth, M.D. “Supramolecular Activation of S8 by Cucurbiturils in Water and Mechanism of Reduction to H2S by Thiols: Insights into Biological Sulfane Sulfur Trafficking.” J. Am. Chem. Soc. 2022, 144, 15324-15332. [link]
Sherbow, T.J.; Fu, W.; Tao, L.; Britt, D.R.; Pluth, M.D. “Thionitrite (SNO–) and Perthionitrite (SSNO–) are Simple Synthons for Nitrosylated Iron Sulfur Clusters.” Angew. Chem. Int. Ed. 2022, 61, e202204570. [link]
Fosnacht, K.G.; Cerda, M.M.; Mullen, E.J.; Pigg, H.C.; Pluth, M.D. “Esterase-Activated Perthiocarbonate Persulfide Donors Provide Insights into Persulfide Persistence and Stability.” ACS Chem. Biol. 2022, 17, 331-339. [link]
Newton, T.D.; Bolton, S.G.; Garcia, A.C.; Chouinard, J.E.; Golledge, S.L.; Zakharov, L.N.; Pluth, M.D. "Hydrolysis-Based Small-Molecule Hydrogen Selenide (H2Se) Delivery." J. Am. Chem. Soc. 2021, 143(46), 19542-19550. [link]
Sherbow, T.J.; Zakharov, L.N.; Johnson, D.W.; Pluth, M.D. "Hydrosulfide Oxidation at at a Molybdenum-Tetrasulfido Complex." Inorg. Chem. 2020, 59(21), 15574-15578. [link]
Bolton, S.G.; Pluth, M.D. "Modified Cyclodextrins Solubilize Elemental Sulfur in Water and Enable Biological Sulfane Sulfur Delivery." Chem. Sci. 2020, 11, 11777-11784. [link]
Cerda, M.M.; Mancuso, J.L.; Mullen, E.J.; Hendon, C.H.; Pluth, M.D. “Dithiasuccinoyl-Caged Amines Enables COS/H2S Release Lacking Electrophilic Byproducts” Chem. Eur. J. 2020, 26(24), 5374-5380. [link]
Newton, T.D.; Pluth, M.D. “Development of a Hydrolysis-Based Small-Molecule Hydrogen Selenide (H2Se) Donor” Chem. Sci. 2019, 10, 10723-10727. [link]
Levinn, C.M.; Cerda, M.M.; Pluth, M.D. “Development and Application of Carbonyl Sulfide-Based Donors for H2S Delivery.” Acc. Chem. Res. 2019, 52(9), 2723-2731. [link]
Zhao, Y.; Cerda, M.M; Pluth, M.D. “Fluorogenic Hydrogen Sulfide (H2S) Donors Based on Sulfenyl Thiocarbonates Enable H2S Tracking and Quantification.” Chem. Sci. 2019,10, 1873-1878. [link]