Yisong (Alex) Guo
Associate Professor, Chemistry
Education2003–2009 Ph.D. Department of Applied Science, University of California, Davis
Spectroscopy, bioinorganic chemistry, Mössbauer and EPR spectroscopy, synchrotron radiation techniques, nuclear resonance vibrational spectroscopy (NRVS), synchrotron Mössbauer, metalloproteins, enzyme mechanisms, transition metal complexes, electronic structures, density functional theory.
Metalloproteins play essential roles in many key biological processes, including photosynthesis, respiration, nitrogen fixation and carbon cycle, antibiotics biosynthesis, gene regulation, post transcriptional modification, bio-signal sensing, and DNA/RNA repair. In these biological processes, an astounding array of chemical transformations with high stereo- and regio-selectivities is achieved by metal centers buried inside the protein scaffold of metalloproteins. Studies of these metal centers in both geometric and electronic level not only can help us reveal the fundamental chemical principles underpinning these biological processes, also provide valuable guidelines for designing and synthesizing efficient and inexpensive catalysts to perform some of these important yet challenging chemical transformations, such as water oxidation, dinitrogen reduction, selective C-H functionalization.
Our main research focus is iron containing metalloproteins, in particular, small molecule (N2, H2, O2 etc.) activating enzymes, such as nitrogenases, hydrogenases, and oxygenases. Various advanced spectroscopic methods are utilized to gain information regarding iron center changes, both geometric and electronic, during enzyme catalytic cycles. Spectroscopic studies are coupled with Density Functional Theory (DFT) calculations to establish structural models and further identify reaction mechanisms. The ultimate goal of our research is to impact favorably on alternative energy research and human health.
The spectroscopic methods we use include Mössbauer Spectroscopy, Electron Paramagnetic Resonance (EPR) Spectroscopy, Nuclear Resonance Vibrational Spectroscopy (NRVS), and Synchrotron Mössbauer.
Mössbauer spectroscopy arguably has the highest information content of any spectroscopic methods on studies of iron containing systems. It detects all iron in a given sample, and determines their oxidation, spin states, and precise quantification of iron in different local environments. It is a high-resolution technique, which allows one to probe the electronic structure of iron sites in great detail through the hyperfine coupling between electronic states and nuclear states. EPR spectroscopy is a high sensitivity technique; it detects paramagnetic systems and reveals their electronic structures through electronic Zeeman Effect.
Recent developments of synchrotron radiation (SR) facilities enable us to utilize SR sources for Mössbauer spectroscopy in replacement of traditional radioactive sources. The advantage of Synchrotron Mössbauer over the conventional lab-based Mössbauer is that it can have higher spectral resolution, shorter measurement time, and the capability of measuring smaller samples, which are crucial for studies on metalloproteins. The advancement of modern synchrotron radiation sources also promotes the development of a new type of vibrational spectroscopic technique, Nuclear Resonance Vibrational Spectroscopy (NRVS). NRVS detects nuclear excitation coupled molecular vibration excitation (or de-excitation), which conceptually resembles Raman scattering. Yet, compared with Raman and Infrared techniques, NRVS has much higher element selectivity and less restrictive selection rules. It allows us study structures and dynamics of iron centers in metalloproteins by selectively probing iron related vibrations in the far IR region (essentially down to 0 cm-1) without the interference of protein scaffold and solvent vibrations.
With continuous development of synchrotron radiation facilities, new synchrotron radiation with many orders of magnitude higher in intensity and extremely smaller beam size (sub-micron to nanometers) than those in use today will be available in the near future. In collaboration with groups at synchrotron radiation facilities, we will develop imaging techniques using Mössbauer spectroscopy to study iron cofactors in organelles and whole cells.
Deciphering Pyrrolidine and Olefin Formation Mechanism in Kainic Acid Biosynthesis
Tzu-Yu Chen, Shan Xue, Wei-Chih Tsai, Tun-Cheng Chien, Yisong Guo, Wei-chen Chang, ACS Catal. 11: 278-282, 2021. DOI: 10.1021/acscatal.0c03879
Epoxidation Catalyzed by the Non-Heme Iron- and 2-Oxoglutarate-Dependent Oxygenase, AsqJ: Mechanistic Elucidation of Oxygen Atom Transfer by a Ferryl Intermediate
Jikun Li, Hsuan-Jen Liao, Yijie Tang, Jhih-Liang Huang, Lide Cha, Te-Sheng Lin, Justin L. Lee, Igor V. Kurnikov, Maria G. Kurnikova, Wei-chen Chang, Nei-Li Chan, Yisong Guo, J. Am. Chem. Soc. 142: 6268-6284, 2020. DOI: 10.1021/jacs.0c00484
Pathway from N-Alkylglycine to Alkylisonitrile Catalyzed by iron(II) and 2-Oxoglutarate Dependent Oxygenases
Tzu-Yu Chen, Jinfeng Chen, Yijie Tang, Jiahai Zhou, Yisong Guo, Wei-chen Chang, Angew. Chem. Int. Ed. 59: 7367-7371, 2020. DOI: 10.1002/anie.201914896
A Highly Reactive CoIII,IV2(μ-O)2 Diamond Core Complex that Cleaves C-H Bonds
Yan Li, Suhashini Handunneththige, Erik R. Farquhar, Yisong Guo, Marat R. Talipov, Feifei Li, Dong Wang, J. Am. Chem. Soc. 141: 20217-20136, 2019. DOI: 10.1021/jacs.9b09531
Elucidating the Reaction Pathway of Decarboxylation-Assisted Olefination Catalyzed by a Mononuclear Non-Heme Iron Enzyme
Cheng-Ping Yu, Yijie Tang, Lide Cha, Sergey Milikisiyants, Tatyana I. Smirnova, Alex I. Smirnov, Yisong Guo, Wei-chen Chang, J. Am. Chem. Soc. 140: 15190-15193, 2018. DOI: 10.1021/jacs.8b10077
Probing Hydrogen Bonding Interactions to Iron-Oxido/Hydroxido Units via 57Fe Nuclear Resonance Vibrational Spectroscopy
Andrew C. Weitz, Ethan A. Hill, Victoria F. Oswald, Emile L. Bominaar, Andy S. Borovik, Michael P. Hendrich, Yisong Guo, Angew. Chem. Int. Ed. 2018. 57: 16010-16014. DOI: 10.1002/anie.201810227
Spectroscopic and DFT Characterization of a Highly Reactive Nonheme FeV-oxo Intermediate
Ruixi Fan, Joan Serrano-Plana, Williamson N. Oloo, Apparao Draksharapu, Estefanía Delgado-Pinar, Anna Company, Vlad Martin-Diaconescu, Margarida Borrell, Julio Lloret-Fillol, Enrique García-España, Yisong Guo, Emile L. Bominaar, Lawrence Que, Jr., Miquel Costas, Eckard Münck, J. Am. Chem. Soc. 140: 3916-3928, 2018. DOI: 10.1021/jacs.7b11400
Identification of a Catalytic Iron-Hydride at the H-cluster of [FeFe]-Hydrogenase
David W. Mulder, Yisong Guo, Michael W. Ratzloff, Paul W. King, J. Am. Chem. Soc. 139: 83-86, 2017. DOI: 10.1021/jacs.6b11409
The Nitrogenase FeMo-cofactor Precursor Formed by NifB Protein: A Diamagnetic Eight Iron Atoms
Yisong Guo, Carlos Echavarri-Erasun, Marie Demuez, Emilio Jiménez-Vicente, Emile L. Bominaar, Luis M. Rubio, Angew. Chem. Int. Ed. 41: 12764-12767, 2016. DOI: 10.1002/anie.201606447
Mechanistic Investigation of a Non-Heme Iron Enzyme Catalyzed Epoxidation in (-)-4’-Methoxycyclopenin Biosynthesis
Wei-chen Chang, Jikun Li, Justin L. Lee, Andrea A. Cronican, Yisong Guo, J. Am. Chem. Soc. 138: 10390-10393, 2016. DOI: 10.1021/jacs.6b05400
Mechanism of the C5 Stereoinversion Reaction in the Biosynthesis of Carbapenem Antibiotics
Wei-chen Chang, Yisong Guo, Chen Wang, Susan E. Butch, Amy C. Rosenzweig, Amie K. Boal, Carsten Krebs, J. Martin Bollinger, Jr., Science, 343: 1040-1144, 2014. DOI: 10.1126/science.1248000
The Crystal Structure of a High-Spin Oxoiron(IV) Complex and Characterization of Its Self-Decay Pathway
Jason England, Yisong Guo, Erik R. Farquhar, Victor G. Young Jr. Eckard Münck, and Lawrence Que Jr., J. Am. Chem. Soc.132: 8635-8644, 2010. DOI: 10.1021/ja100366c
|2020–present||Associate Professor, Department of Chemistry, Carnegie Mellon University|
|2014–2020||Assistant Professor, Department of Chemistry, Carnegie Mellon University|
|2012–2013||Postdoctoral Research Associate, Department of Chemistry, the Pennsylvania State University.
Advisors: Prof. J. Martin Bollinger and Prof. Carsten Krebs
|2009–2012||Postdoctoral Research Associate, Department of Chemistry, Carnegie Mellon University.
Advisors: Prof. Eckard Münck and Prof. Emile L. Bominaar (theory)
Awards and Distinctions
|2017||NSF CAREER Award|