Research Projects

Heme centers that activate dioxygen (O₂) and nitrogen oxides (NOx) play crucial roles in biological systems and have been the focal point of many intense research efforts for decades. Nonetheless, chemistries involving mid-valent (i.e., Fe(III)) heme oxidants/reaction intermediates are still unclear, despite their multifarious implications in various pathogenic conditions in humans, including cancer (such as nitric oxide synthase (NOS) and heme oxygenase (HO)). Many heme enzymes where mid-valent heme oxidants are active species, are therefore drug targets, and there is an urgent need to elucidate the mechanistic details pertaining to their physiological activities. Even so, it is often cumbersome and complicated to implement enzymatic systems in mechanistic studies, which in most instances can be effectively circumvented by utilizing small molecule synthetic model complexes; these are often simpler and straightforward to both analyze and modify. Research idea of this work seeks to utilize synthetic mimics of mid-valent heme-O₂/NOx intermediates to gain insight into the mechanistic details and probing the reactivities of multiple heme enzymes such as heme dioxygenases, heme oxygenase, nitric oxide synthase, and aromatase. These details have important implications in human pathogenesis and therapy, and we anticipate that the outcome of this work will vertically advance this area and offer new insights on how to maneuver subtle mechanistic details into the amelioration of next generation therapeutics. Secondly, despite the economic importance of natural rubber and substantial amount of permanently released rubber waste into the environment, the fate/degradation of rubber materials is still in its infancy. Rubber oxygenase A (RoxA), a di-heme enzyme, is known to catalyze the oxidative cleavage of latex for biodegradation. However, details pertaining to its mechanism of action are still elusive. Therefore, we intend to design the efficient modeling of the active site of interest, utilizing synthetic porphyrinic models possessing divergent geometric and electronic properties. Moreover, the electronic attributes of the active oxidant will be probed with axially coordinating ligands as well as Lewis acids. In addition to unlocking the mechanistic insights, this research is anticipated to nurture the biotechnological/industrial application of rubber-degrading systems. Furthermore, highly warranted, yet severely understudied reactivity landscapes of high-valent oxo intermediates of such di-heme model systems will also be targeted.