Development of Stimulus-Responsive Ligands for the Modulation of Copper and Iron Coordination

The ability to manipulate the coordination chemistry of metal ions has significant ramifications for the study and treatment of metal-related health concerns, including iron overload, UV skin damage, and microbial infection among many other conditions. To address this concern, chelating agents that change their metal binding characteristics in response to external stimuli have been synthesized and characterized by several spectroscopic and chromatographic analytical methods. The primary stimuli of interest for this work are light and hydrogen peroxide.

Herein we report the previously unrecognized photochemistry of aroylhydrazone metal chelator ((E)-N′-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide) (HAPI) and its relation to HAPI metal binding properties. Based on promising initial results, a series of HAPI analogues was prepared to probe the structure-function relationships of aroylhydrazone photochemistry. These efforts elucidate the tunable nature of several aroylhydrazone photoswitching properties.

Ongoing efforts in this laboratory seek to develop compounds called prochelators that exhibit a switch from low to high metal binding affinity upon activation by a stimulus of interest. In this context, we present new strategies to install multiple desired functions into a single structure. The prochelator 2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (E)-3-(2,4-dihydroxyphenyl)acrylate (PC-HAPI) is masked with a photolabile trans-cinnamic acid protecting group that releases umbelliferone, a UV-absorbing, antioxidant coumarin along with a chelating agent upon UV irradiation. In addition to the antioxidant effects of the coumarin, the released chelator (HAPI) inhibits metal-catalyzed production of damaging reactive oxygen species. Finally a peroxide-sensitive prochelator quinolin-8-yl (Z)-3-(4-hydroxy-2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)phenyl)acrylate (BCQ) has been prepared using a novel synthetic route for functionalized cis-cinnamate esters. BCQ uses a novel masking strategy to trigger a 90-fold increase in fluorescence emission, along with the release of a desired chelator, in the presence of hydrogen peroxide.

Redeeming Faustus: Tracing the pacts of Mariken and Faust from the 1500s to the present

This dissertation uncovers and analyzes the complicated history of the devil’s pact in literature from approximately 1330 to 2015, focusing primarily on texts written in German and Dutch. That the tale of the pact with the devil (the so-called Faustian bargain) is one of the most durable and pliable literary themes is undeniable. Yet for too long, the success of Johann Wolfgang von Goethe’s Faust I (1808) decisively shaped scholarship on early devil’s pact tales, leading to a misreading of the texts with Goethe’s concerns being projected onto the earliest manifestations. But Goethe’s Faust really only borrows from the original Faust his name; the two characters could not be more different. Furthermore, Faustus was not the only early pact-maker character and his tale was neither limited to the German language nor to the Protestant faith. Among others, tales written in Dutch about a female, Catholic, latemedieval pact-maker, Mariken van Nieumeghen (1515), illustrate this. This dissertation seeks to redeem the early modern Faustus texts from its misreading and to broaden the scholarship on the literature of the devil’s pact by considering the Mariken and Faust traditions together.

The first chapter outlines the beginnings of pact literature as a Catholic phenomenon, considering the tales of Theophilus and Pope Joan alongside Mariken of Nijmegen. The second chapter turns to the original Faust tale, the Historia von D. Johann Fausten (1587), best read as a Lutheran response to the Catholic pact literature in the wake of the Reformation. In the third chapter, this dissertation offers a new, united reading of the early modern Faust tradition. The fourth and fifth chapters trace the literary preoccupation with the pacts of both Mariken and Faustus from the late early modern to the present.

The dissertation traces the evolution of these two bodies of literature and provides an in-depth analysis and comparison of the two that has not been done before. It argues for a more global literary scholarship that considers texts across multiple languages and one that takes into consideration the rich body of material of the pact tradition.