Institute of Molecular Biology

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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

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Research Interests

Research in the Pluth research group is thematically based on different aspects of molecular recognition at the interface of bioorganic and bioinorganic chemistry. Our group uses synthetic organic and inorganic chemistry, coupled with spectroscopic investigations, to investigate three main research areas:

Methods of Detection, Delivery, and Quantification of Biological Hydrogen Sulfide

Hydrogen sulfide (H2S), historically known for its unpleasant rotten-egg smell, is now accepted as an important physiological mediator and signaling agent, joining CO and NO as an endogenous gasotransmitter. Despite its recent emergence as an important biological molecule, investigations have already revealed important physiological and pathological functions of H2S including roles in diabetes, hypertension, heart failure, inflammation, and neurodegeneration. As the complex biochemical functions of H2S continue to rapidly emerge, 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 donors modulated by biological stimuli. 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.

Probing the Reactions of Hydrogen Sulfide with Biological Targets

Despite the important and diverse roles of biological H2S, little is known about the fundamental chemistry by which H2S exerts its action on discrete biological targets. Unlike gasotrasmitters NO and CO, the physiologically-accessible protonation states of H2S complicate its reactivity, but also allow for modulation of its water/lipid solubility, nucleophilicity, and reduction potential. Aligned with these physicochemical properties, most biological actions of H2S are proposed to occur through interaction with either bioinorganic transition-metal complexes or with sulfur-containing compounds. Despite the substantial consensus regarding the importance of these chemical pathways, significant controversy remains regarding the fundamental chemistry associated with these interactions. Motived by these unmet needs, we are investigating the mechanisms by which H2S reacts with biomimetic transition-metal and organosulfur compounds by using small-molecule systems to simplify the observed reactivity. By simplifying the molecular architectures involved in this chemistry and studying individual interactions, 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.

Hybrid Metal-Ligand Hydrogen-Bonding Supramolecular Architectures

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. Unlike Nature, however, chemists are not constrained to natural amino acids, bioinorganic metal ions, or the requirements to work in water at physiological pH. By leveraging this expanded chemical space and by using pre-designed components encoded with different chemical information, such as shape, symmetry, directional bonding, and makeup of functional groups, chemists have generated diverse supramolecular architectures held together by metal-ligand or hydrogen-bonding interactions. Despite the breadth of complexes and chemistries generated from the hydrogen-bonding and metal-ligand assembly strategies individually, the interface between these two assembly domains remains underexplored. This underexplored niche offers the prospect of combining different beneficial properties from each assembly strategy to develop new supramolecular complexes and chemistries. To fill this niche, we are designing different ligand components that encoded metal-ligand and hydrogen-bonding motifs to generate pre-designed, functional, self-assembled structures aimed at studying supramolecular dynamics and catalysis. Results from these studies will provide new hybrid supramolecular constructs and rational design methods for combining metal-ligand and hydrogen-bonding interactions to generate pre-designed molecular architectures.

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.

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