Nature has evolutionarily integrated metal centers in some of its most crucial/efficient functional proteins, most of which successfully mediate catalytic chemical transformations under entirely environmentally benign, ambient conditions. The pivotal nature of these metalloenzyme biochemistries often implicate them in human disease and diagnostics, whereupon a clear comprehension of their mechanistic details may lead to effective therapeutics against some of the most challenging pathological conditions humans face in present day, such as cancer, Alzheimer’s or Huntington’s. The efficiency in which nature utilizes these greener, cheaper metal systems in enzymatic catalytic turnovers also offers invaluable chemistry lessons to humans on how to move away from toxic, expensive catalytic metals that are currently in use for industrial-scale bulk transformations.
Wijeratne Research Laboratory utilizes synthetic organic and inorganic chemical tools to generate inorganic model complexes that resemble metalloprotein active sites, and then studies their reactivity profiles with small molecule biological substrates such as dioxygen (O2), its reduced derivatives such as superoxide (O2–•), peroxide (OO2–) etc., and/or nitrogen oxides (NOx’s; e.g., NO, N2O, NO2–, NO3–) under inert laboratory conditions (i.e., utilizing glovebox/Schlenk techniques). One of the primary goals of this work is to identify biologically relevant intermediates/active species using synthetic model systems. Such reaction intermediates often display impaired thermal/chemical stabilities, and thus require specialized low-temperature techniques for unequivocal characterization. An array of spectroscopic and structural characterization strategies will be applied, such as electronic absorption (UV-Vis), electronic paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), Infrared (IR), resonance Raman (rR), and X-ray absorption (XANES & EXAFS) spectroscopies, mass spectrometry, and X-ray diffraction (XRD) along with electrochemical analysis (e.g., cyclic voltammetry (CV)). Careful thermodynamic and kinetic analyses (i.e., Eyring-, Arrhenius-, Polanyi-, and Hamett-type, kinetic isotope effects (KIE), and bond dissociation (free) energy (BD(F)E) calculations) of substrate and/or self reactivities of these species will lead into crucial insights that relate to key unknowns pertaining to the corresponding metalloprotein systems. Complementary Density Functional Theory (DFT) computations will also be employed as warranted. Comprehensive understanding of the bio-related chemistry will pave the way into novel, more effective therapeutics, as well as greener (nature-inspired) methodologies for industrial scale catalytic applications. The undergraduate, graduate and postdoctoral researchers engaged in these research attempts will progress to adepts in synthetic, spectroscopic and structural approaches for tackling mechanistic ambiguities, with sound knowledge of biological, inorganic, organic and physical chemistries, and their potential roles in industrial applications. Wijeratne Research Group actively collaborates with multiple on-campus, local and international research groups and national labs/facilities, including the UAB Center for Free Radical Biology (CFRB).
Dr. Wijeratne is also the organizer of a seminar series themed “Pathways to Chemistry Careers”, which strives to provide a broader perspective on career opportunities that are available for future chemistry graduates. Both academic and industrial professionals will be invited on-campus for seminars/discussions.
