Institute of Molecular Biology

Home | About | Faculty | Calendar | Facilities | Graduate program | Contact | Apply

This page is optimized for viewing with javascript.

Michael D. Pluth

Michael D. Pluth

Assistant Professor, Chemistry and Biochemistry
Associate Member, IMB

Ph.D., University of California, Berkeley
B.S., University of Oregon

Lab website
Office: Klamath Hall Room 355B
Office Phone: 541-346-7477

Loading profile for Michael D. Pluth

Research Interests

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.

Self-Assembled Allosteric Catalysts

Inspired by the remarkably complex structures generated from Nature’s simple catalog of assembly components, chemists have devised different strategies to harness molecular self-assembly and develop diverse supramolecular constructs. Similarly, Nature has developed remarkable enzyme catalysts in which catalytic activity can be regulated by co-factor binding, conformational changes, or allosteric regulation. Unlike Nature, synthetic chemists are not constrained to natural amino acids, bioinorganic metal ions, or the requirements to work in water at physiological pH. Although chemists have developed diverse platforms for chemical catalysis, the ability to regulate catalytic activity through external stimuli remains a significant challenge. Motivated by this under-investigated area, we are expand the interface between supramolecular chemistry and catalysis by developing responsive ligand architectures in which catalytic activity is modulated upon guest binding.

Recent publications

(pulled from pubmed)

Recent publications

(pulled from pubmed)

A simple bioluminescent method for measuring D-amino acid oxidase activity.
Bailey TS, Donor MT, Naughton SP, Pluth MD
Chem Commun (Camb) 2015 Mar 28;51(25):5425-8
Chemiluminescent detection of enzymatically produced H2S.
Spencer Bailey T, Pluth MD
Methods Enzymol 2015;554:81-99
A Bright Fluorescent Probe for H2S Enables Analyte-Responsive, 3D Imaging in Live Zebrafish Using Light Sheet Fluorescence Microscopy.
Hammers MD, Taormina MJ, Cerda MM, Montoya LA, Seidenkranz DT, Parthasarathy R, Pluth MD
J Am Chem Soc 2015 Aug 19;137(32):10216-23
Inhibition of endogenous hydrogen sulfide production in clear-cell renal cell carcinoma cell lines and xenografts restricts their growth, survival and angiogenic potential.
Sonke E, Verrydt M, Postenka CO, Pardhan S, Willie CJ, Mazzola CR, Hammers MD, Pluth MD, Lobb I, Power NE, Chambers AF, Leong HS, Sener A
Nitric Oxide 2015 Sep 15;49:26-39
Selection for a Single Self-Assembled Macrocycle from a Hybrid Metal-Ligand Hydrogen-Bonded (MLHB) Ligand Subunit.
Sommer SK, Henle EA, Zakharov LN, Pluth MD
Inorg Chem 2015 Jul 20;54(14):6910-6
Chloride-catalyzed, multicomponent self-assembly of arsenic thiolates.
Carnes ME, Collins MS, Lindquist NR, Guzmán-Percástegui E, Pluth MD, Johnson DW
Chem Commun (Camb) 2014 Jan 4;50(1):73-5
Chemically reversible reactions of hydrogen sulfide with metal phthalocyanines.
Hartle MD, Sommer SK, Dietrich SR, Pluth MD
Inorg Chem 2014 Aug 4;53(15):7800-2
Understanding hydrogen sulfide storage: probing conditions for sulfide release from hydrodisulfides.
Bailey TS, Zakharov LN, Pluth MD
J Am Chem Soc 2014 Jul 30;136(30):10573-6
Development of selective colorimetric probes for hydrogen sulfide based on nucleophilic aromatic substitution.
Montoya LA, Pearce TF, Hansen RJ, Zakharov LN, Pluth MD
J Org Chem 2013 Jul 5;78(13):6550-7
Selective turn-on fluorescent probes for imaging hydrogen sulfide in living cells.
Montoya LA, Pluth MD
Chem Commun (Camb) 2012 May 16;48(39):4767-9
Reversible binding of nitric oxide to an Fe(III) complex of a tetra-amido macrocycle.
Pluth MD, Lippard SJ
Chem Commun (Camb) 2012 Dec 21;48(98):11981-3
Biochemistry of mobile zinc and nitric oxide revealed by fluorescent sensors.
Pluth MD, Tomat E, Lippard SJ
Annu Rev Biochem 2011;80:333-55
Seminaphthofluorescein-based fluorescent probes for imaging nitric oxide in live cells.
Pluth MD, Chan MR, McQuade LE, Lippard SJ
Inorg Chem 2011 Oct 3;50(19):9385-92
External and internal guest binding of a highly charged supramolecular host in water: deconvoluting the very different thermodynamics.
Sgarlata C, Mugridge JS, Pluth MD, Tiedemann BE, Zito V, Arena G, Raymond KN
J Am Chem Soc 2010 Jan 27;132(3):1005-9
Cell-trappable fluorescent probes for nitric oxide visualization in living cells.
Pluth MD, McQuade LE, Lippard SJ
Org Lett 2010 May 21;12(10):2318-21
Enzymelike catalysis of the Nazarov cyclization by supramolecular encapsulation.
Hastings CJ, Pluth MD, Bergman RG, Raymond KN
J Am Chem Soc 2010 May 26;132(20):6938-40
Mechanism of nitric oxide reactivity and fluorescence enhancement of the NO-specific probe CuFL1.
McQuade LE, Pluth MD, Lippard SJ
Inorg Chem 2010 Sep 6;49(17):8025-33
Structural consequences of anionic host-cationic guest interactions in a supramolecular assembly.
Pluth MD, Johnson DW, Szigethy G, Davis AV, Teat SJ, Oliver AG, Bergman RG, Raymond KN
Inorg Chem 2009 Jan 5;48(1):111-20
Proton-mediated chemistry and catalysis in a self-assembled supramolecular host.
Pluth MD, Bergman RG, Raymond KN
Acc Chem Res 2009 Oct 20;42(10):1650-9
Supramolecular catalysis of orthoformate hydrolysis in basic solution: an enzyme-like mechanism.
Pluth MD, Bergman RG, Raymond KN
J Am Chem Soc 2008 Aug 27;130(34):11423-9