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Mike Pluth

  • Title: Assistant Professor
  • Additional Title: Organic Chemistry, Chemical Biology, Bioinorganic Chemistry
  • Phone: (541) 346-7477
  • Office: 355B Klamath Hall
  • Affiliated Departments: Institute of Molecular Biology, Materials Science Institute
  • Website: Website

Education

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).

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.

Research

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.

Publications

Selected publications:

Google Scholar Profile

Bailey, T.S.; Zakharov, L.N.; Pluth, M.D. Understanding Hydrogen Sulfide Storage: Probing Conditions for Sulfide Release from Hydrodisulfides. J. Am. Chem. Soc. 2014, 136(30), 10573-10576. [link]

Hammers, M.D.; Pluth, M.D. Ratiometric Measurement of Hydrogen Sulfide and Cysteine/Homocysteine Ratios Using a Dual-Fluorophore Fragmentation Strategy. Anal. Chem. 2014, 86(14), 7135–7140. [link]

Montoya, L.A.; Pluth, M.D. Hydrogen Sulfide Deactivates Common Nitrobenzofurazan-Based Fluorescent Thiol Labeling Reagents. Anal. Chem. 2014, 86(12), 6032-6039. [link]

Hartle, M.D.; Sommer, S.K.; Dietrich, S.R.; Pluth, M.D. Chemically Reversible Reactions of Hydrogen Sulfide with Metal Phthalocyanines. Inorg. Chem. 2014, 53(15), 7800-7802. (Cover Article) [link]

McGrath, J.M.; Pluth, M.D. Understanding the Effects of Pre-Organization, Rigidity, and Steric Interactions in Synthetic Barbiturate Receptors. J. Org. Chem. 2014, 79(2), 711-719. [link]

Bailey, T.S.; Pluth, M.D. Chemiluminescent Detection of Enzymatically-Produced Hydrogen Sulfide: Substrate Hydrogen Bonding Influences Selectivity for H2S over Biological Thiols. J. Am. Chem. Soc. 2013, 135(44), 16697-16704. [link]

Montoya, L.A.; Pearce, T.F.; Hansen, R.J.; Zakharov, L.N.; Pluth, M.D. Development of Selective Colorimetric Probes for Hydrogen Sulfide Based on Nucleophilic Aromatic Substitution. J. Org. Chem. 2013, 78(13), 6550-6557. [link]

Montoya, L.A.; Pluth, M.D. "Selective Turn-On Fluorescent Probes for Imaging Hydrogen Sulfide in Living Cells" Chem. Commun. 2012, 48(39), 4767-4769. [link]