Synthetic Models for Copper Electron Transfer Sites and Their Reactivity with Nitric Oxide and Dinitrogen
Warren, Timothy H
Nitric oxide (NO) has been recently recognized as an important gaseous signal transmitter that participates in many biological processes, including vasorelaxation, neurotransmission, and immune responses. S-nitrosothiols (RSNO), such as such as S-nitrosocysteine and S-nitrosoglutathione, are important oxygen stable reservoirs for nitric oxide. Due to the therapeutical value of NO, interconversion between RSNO and NO as well as metalloenzymes that involving in these processes have become a new target of bioinorganic chemistry. This thesis centers on understanding the fundamental reactivity between copper thiolate and nitric oxide by using model complexes that emulate the common coordination environments of mono- or multi- copper electron transfer sites.To better understand the electronic structure of copper electron transfer sites, we developed several functional model complexes for the binuclear CuA site and type 1 copper site (T1Cu). While previous models were much harder to reduce than native sites, our model complexes are first to closely and reversibly reproduce their reduction potentials. More importantly, these electronic and steric modifications of copper model complexes allow for the isolation of a series of unprecedented copper S-nitrosothiol complexes in different binding modes (1-N(O)SR, 1-S(NO)R, 1-S(O)NR). These results demonstrate that the NO binding mode and binding affinity on copper thiolate are strongly dependent on the redox potential of copper and the steric bulk around the coordinate site.Along with the rich nitric oxide reactivity on copper sites, we also discovered that the prototypical tris(pyrazolyl)borate copper fragments that serve as model for the reversible O2 binding at hemocyanin, also reversibly binds dinitrogen. Isolation of the first example of end-on -N2 dicopper complex and its intriguing formation from a unique mixed-valence, dicopper hydride complex are presented. Preliminary mechanistic studies employing isolated dicopper hydride complex are suggestive of a highly reducing terminal copper(II) hydride species.
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Williams, Kamille D. (Georgetown University, 2016)The N-O functionality is ubiquitous endogenously. The wide range of oxidation states of the nitrogen atom, (+5 to -3), is attributed to the various biologically relevant congeners containing the NO functionality. The ...
Nitric Oxide Reactivity at Biomimetic Copper and Zinc Complexes and Metal-free Frustrated Lewis Pairs Cardenas, Allan Jay Pascasio (Georgetown University, 2013)Since the discovery of nitric oxide (NO) in 1772, this simplest, stable free radical with one unpaired electron has been a target of ongoing research as an industrial intermediate, environmental pollutant, and more recently, ...
Varonka, Matthew Stephen (Georgetown University, 2009)Nitric oxide (NO) and biologically relevant sources of NO such as S-nitrosothiols (RSNOs) have become a topic of great interest due to their regulation of biological functions including vasorelaxation, neurotransmission, ...