Welcome to the Roth Group

Dr. Justine P. Roth       Associate Professor        2009-present Phone: 410-516-7835 Office: 121 Remsen Email: jproth@jhu.edu Assistant Professor:         Johns Hopkins University,    2003-2009 Dreyfus Teacher-Scholar (2008), Sloan Fellow (2007), Reseach Corp. Cottrell Scholar (2006), NSF CAREER (2005) NIH Postdoctoral Fellow:         U. California, Berkeley        2000-2003        PhD: U. Washington, Seattle  1995-2000

BIO-INORGANIC & BIO-PHYSICAL INTERESTS.  The Roth group pursues problems related to health, energy and the environment at the interfaces of biological, inorganic and physical chemistry. 

Biological Proton-Coupled Electron Transfer:  In enzymes that catalyze oxidative processes vital to life, redox-active metal ions mediate the coupled transfer of electrons and protons.  Such transformations are classified as proton-coupled electron transfers (PCETs) when the particle motions are concerted.  PCETs can be highly selective, forming radicals derived from amino acid side chains at specific sites with a protein.  These protein radicals can catalyze subsequent redox reactions or lead to oxidative protein modification as well as enzyme deactivation. The PCETs of greatest interest are central to physiological function and range from the biosynthesis of prostanoids in mammals to the transduction of light to chemical energy in photosynthetic organisms.  To address how PCET determines structure-function relationships, we are investigating a variety of related proteins and the quantum mechanical features that allow PCET over short and long distances.  Through these efforts we hope to characterize the first unambiguous example of enzymatic long-range PCET.

Oxygen Isotope Effects: Interaction and processing of small molecules (oxygen, superoxide, hydrogen peroxide and water) by redox-metals (e.g. Cu, Co, Fe and Mn) are amenable to study at natural abundance using isotope ratio mass spectrometry.  A recurring theme in our research is developing techniques for using competitive oxygen isotope effects to probe oxygen-derived intermediates and their mechanisms. Because of their transient nature, reactive oxygen species and other intermediates containing a form of activated oxygen are often undetectable by conventional molecular spectroscopy.  Furthermore, insight concerning mechanisms at the level of specific changes in bonding in transition states is best probed by isotopic substitution and discrimination. Presently we are applying competitive oxygen kinetic isotope effects to determine mechanisms of O-O bond formation during water oxidations of major relevance to the energy problem.  We also continue to examine more fundamental inner-sphere and outer-sphere  electron transfer as well as PCET reactions of molecular oxygen and its partially reduced forms (e.g. superoxide, peroxyl radicals and peroxides).  This research encompasses developing experimental methods for measuring heavy atom isotope effects and applying computational methods to predict isotope effects from changes in molecular vibrations. Through such analyses we can deduce structure and mechanism within theoretic contexts. 

Principles of Catalysis: An overriding objective of our research is to understand catalysis and underlying mechanistic strategies used by enzymes, as well as some inorganic molecules, to effect difficult chemical transformations. To this end, we examine the origins of selectively and rate acceleration.  Through the application of theory, the importance of intrinsic and thermodynamic factors can be delineated.  At this stage, it is crucial to illuminate the importance of quantum mechanical events and how they may manifest differently in an enzyme active site than outside of the protein environment in homogenous solution.