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Research Overview

Engineered Metallobiomolecules for Energy Conversion

Developing sustainable energy sources is a major challenge facing humanity. Among alternative fuels, hydrogen (H2) is attractive because it is energy-dense and carbon-free. To be truly carbon free, H2 needs to be produced from carbon-free sources, with water being the most attractive. The Bren group, in collaboration with the Eisenberg, Krauss, and Matson groups at U of R, is engineering systems for light-driven hydrogen evolution from water. In our part of this collaboration, the Bren group has developed methods for engineering cytochromes to act in photoinduced charge transfer and in catalysis of proton reduction. In addition, the Bren group is working to develop biomolecular catalysts to carry out the proton reduction reaction. We characterize these catalysts in electrocatalytic and photocatalytic systems. 

Selected Group Publications:
  • Semisynthetic and Biomolecular Hydrogen Evolution Catalysts, Banu Kandemir, Saikat Chakraborty, Yixing Guo and Kara L. Bren, Inorg. Chem. 2016. DOI:10.1021/acs.inorgchem.5b02054
  • Engineered Enzymes and Bioinspired Catalysts for Energy Conversion, Jennifer M. Le and Kara L. Bren. ACS Energy Lett2019. DOI: 10.1021/acsenergylett.9b01308 
  • Photochemical Hydrogen Evolution from Neutral Water with a Cobalt Metallopeptide Catalyst, Saikat Chakraborty, Emily H. Edwards, Banu Kandemir, and Kara L. Bren. InorgChem. 2019. DOI: 10.1021/acs.inorgchem.9b02067
  • Buffer pKa Impacts the Mechanism of Hydrogen Evolution Catalyzed by a Cobalt Porphyrin-peptide, Jose L. Alvarez-Hernandez, Andrew Sopchak, and Kara L. Bren. Inorg. Chem. 2020. DOI: https://doi/10.1021/acs.inorgchem.0c00362

In addition to creating H2, the Bren group is also interested in other energy-relevant small molecule reactions. Nitrate (NO3-) and nitrite (NO2-) are key players in the global nitrogen cycle. Nitrite is a significant groundwater pollutant, and is one small part of the massive and diverse human impact on the nitrogen cycle. Our lab is interested in exploring biomimetic catalysts containing cobalt and iron that can catalyze the conversion of nitrite and nitrate to high value products such as ammonia (NH3). Cleaner routes to critical molecules like ammonia can help to reduce pollutants, as well as decrease fossil fuel emissions. In a similar vein, the Bren group is also exploring the reduction of fossil fuel carbon dioxide (CO2) using cobalt porphyrin catalysts. 

Selected Group Publications:
  • A Cobalt Metallopeptide Electrocatalyst for the Selective Reduction of Nitrite to Ammonium, Yixing Guo, Jesse R. Stroka, Banu Kandemir, Claire E. Dickerson, Kara L. Bren. J. Am. Chem. Soc2018. DOI: 10.1021/jacs.8b09612
  • Electrocatalytic Multielectron Nitrite Reduction in Water by an Iron Complex, Jesse R. Stroka, Banu Kandemir, Ellen M. Matson, and Kara L. Bren. ACS Catal.  2020. DOI: https://pubs.acs.org/doi/10.1021/acscatal.0c03600

 


 

Heme Protein Dynamics and Electronic Structure

Proteins undergo conformational fluctuations on a range of time scales. Our group is investigating how protein structure modulates dynamics, and how dynamics impact function. One area that we have investigated in detail is the impact of polypeptide dynamics on heme conformation and electronic structure. We have found that polypeptide dynamics and heme dynamics are coupled to each other. In addition, polypeptide mobility impacts heme conformation and axial ligation, and thus heme electronic structure.

Selected Group Publications:
  • NMR and DFT Investigation of Heme Ruffling: Functional Implications for Cytochrome c, Matthew D. Liptak, Xin Wen, and Kara L. Bren, J. Am. Chem. Soc.2010. DOI: 10.1021/ja102098p.
  • Heme-Protein Vibrational Couplings in Cytochrome c Provide a Dynamic Link that Connects the Heme-Iron and the Protein Surface, Mary Grace I. Galinato, Jesse G. Kleingardner, Sarah E. J. Bowman, E. Ercan Alp, Jiyong Zhao, Kara L. Bren, and Nicolai Lehnert, Proc. Natl. Acad Sci. U.S.A.2012. DOI: 10.1073/pnas.1200345109
  • NMR Spectroscopy of Paramagnetic Heme Proteins, Kara L. Bren, Current Inorganic Chemistry2012. DOI: 10.2174/1877944111202030273
  • The Influence of Heme Ruffling on Spin Densities in Ferricytochromes c Probed by Heme Core 13C NMR, Jesse G. Kleingardner, Sarah E. J. Bowman, Kara L. Bren, Inorg. Chem., 2013. DOI: 10.1021/ic401250d

Cytochrome c Folding

Protein folding is characterized by a large degree of heterogeneity. We are working toward characterizing the complex process of protein folding in terms of conformational and mechanistic complexity. Conformational changes of cytochrome c are of biological interest because of the relevance to its role in apoptosis. 

Selected Group Publications
  • NMR Investigation of Ferricytochrome c Unfolding: Detection of an Equilibrium Unfolding Intermediate and Residual Structure in the Denatured State.  Brandy S. Russell, Rory Melenkivitz, and Kara L. Bren, Proc. Natl. Acad. Sci. U.S.2000. DOI: 10.1073/pnas.150239397 
  • Folding, Conformational Changes, and Dynamics of Cytochromes c Probed by NMR Spectroscopy. Kara L. Bren, Jason A. Kellogg, Ravinder Kaur, and Xin Wen, Inorg. Chem.2004. DOI: 10.1021/ic048925t
  • Zinc porphyrin: A fluorescent acceptor in studies of Zn-cytochrome c unfolding by fluorescence resonance energy transfer. Amy A. Ensign, Iris Jo, Ilyas Yildirim, Todd D. Krauss, and Kara L. Bren, Proc. Natl. Acad. Sci. U.S.A.2008. DOI: 10.1073/pnas.0802737105
  • Single-molecule Analysis of Cytochrome c Folding by Monitoring the Lifetime of an Attached Fluorescent Probe. Andrea J. Lee, Wesley B. Asher, Harry A. Stern, Kara L. Bren, Todd D. Krauss, J. Phys. Chem. Lett., 2013. DOI: 10.1021/jz401259y

Manganese Porphyrins as MRI Contrast Agents

Manganese porphyrins are effective MRI contrast agents with lower toxicity than gadolinium. Furthermore, they display enhanced relaxivity at higher magnetic field, behavior that is the opposite of gadolinium agents. In collaboration with Xiao-an Zhang of the University of Toronto, we are employing NMR to investigate the electronic structure of manganese porphyrin contrast agents to understand factors that impact their relaxivity.