The Chemical Structure, Dynamics and Mechanisms Program supports the research of Professor Michael J. Baldwin of the University of Cincinnati (UC) Main Campus to develop stimulus-responsive chelates for light-triggered release of metal ions. Several families of metal chelators based on alpha-hyrdoxyacids (AHAs) are under investigation. This research program evaluates the extent to which modifications of the ancillary functional groups in AHA-containing chelates control the photochemical properties of their corresponding Fe(III) complexes. The researchers also determine the effect of the structural position of the AHA chelates (internal or external) on the photochemical properties of their Fe(III) complexes and identify other metal ions that form photoreactive complexes with the AHA-containing chelates.
Iron has been recognized as an essential element in biological systems for centuries. Despite the recognition of this metal's importance, iron deficiency remains a problem for at least a third of the world's population and iron overload/toxicity caused by hemochromatosis is the most common genetic disease. This resesarch effort plays a role in understanding the mechanisms of iron uptake and release in bacterial pathogens, antibiotic-resistant bacterial strains, and human iron deficiency and genetic diseases. On demand iron release can also be envisioned to be useful in many materials science applications.
This project also enhances the scientific workforce. Professor Baldwin and his group have strong, synergistic collaborations with faculty at two primarily undergraduate research institutions (PUIs) - Professor Michael Goldcamp at Wilmington College and Professor Richard Holtz at the College of Mount St. Joseph. The undergraduate students at these PUIs conduct experiments and share instrumentation at the UC. The graduate students in Professor Baldwin's research group are inspired by this interaction and often seek teaching positions at small colleges. Professor Baldwin also mentors Project SEED students - high school students from economically disadvantaged backgrounds - giving them relevant research experiences in a laboratory setting.
Intellectual Merit. Developing molecular agents that make transition metals available only when an appropriate trigger is applied will provide a mechanism for control of the metals in their myriad of useful activities. Our approach to this has been to develop alpha-hydroxy acid (AHA) contining chelates that become light sensitive upon metal binding, enabling them to photochemically release that metal (Figure 1). The overall objective of this project was to create new AHA-containing chelates, and to correlate several aspects of the chelate design with their metal-binding and photochemical properties. We have advanced the project’s objective by accomplishments within its three specific aims: 1) Evaluate the extent to which modification of the ancillary (non-AHA) functional groups in AHA-containing chelates controls modulation of the photochemical properties of their Fe(III) complexes. Determined quantum yields for the photolysis of Fe(III) complexes of the X-Sal-AHA chelates (X = electron-donating or –withdrawing groups on a metal-bound phenyl ring), and showed a several-fold variation in photochemical activity through variation of X. Substituted the phenol group with a naphthol or pyridyl group to increase the UV photochemical activity, and extend it into the visible region, significantly increasing the number of potential applications for these complexes. Developed a new series of AHA-containing chelates in a "tripodal amine" motif, allowing incorporation of a significantly wider selection of ancillary functional groups (Figure 2). 2) Determine the effect of structural position of the AHA group in chelates that contain them on the photochemical properties of their Fe(III) complexes. Used studies on the Fe(Sal-AHA) complexes to demonstrate that observed photochemical product differences for Fe complexes of structurally different AHA-containing natural siderophores from marine bacteria are not due to different kinds of photochemical events, but rather to differences in air sensitivity of products resulting from the same kind of photochemical reaction (Figure 3). Initiated studies on how the length of the carbon chain to which the AHA is attached and the position of the hydroxyl group relative to the carboxylate, affect the structure and reactivity of the Fe complexes. New chelates with the tripodal amine motif are being compared to the Sal-AHA structural motif to determine how the structural framework of the chelate affects the photochemistry. 3) Identify metals other than iron that form photoactive complexes with the AHA-containing chelates. Synthesized a dimeric (UO22+)2(Sal-AHA)2 complex that is photochemically-active, extending photoactivity of the AHA chelates beyond Fe to other, very different metals. The photolysis reaction involves reduction of the uranium from U(VI) to U(IV). Showed that he Ga(III) complex of Sal-AHA has an analogous structure to the iron trimer (Figure 4), but is not photoactive. The similarity in structure allowed the mixed Fe/Ga complexes to be prepared for experiments that showed that although two Fe(III) are reduced if available in the complex, photochemistry will occur even if only a single Fe(III) is available. New directions beyond the original specific aims: The interesting structural architectures produced by these new chelates has led in new directions that are not dependent on photoactivity of the metal complexes. The structural variation observed for different metals, including the trimeric Fe and Ga clusters, the uranyl dimer, and a structurally characterized 1D polymer formed by the Cu(II) complex of a related pyridylimine-AHA chelate (Figure 5), have led us to begin investigating factors that predict the structure type. One example of useful structural aspects of these complexes include the metalloenzyme-like "reactive site in a pocket" observed for the Fe and Ga Sal-AHA clusters. Further modification of this chelate structure is also leading toward new host-guest chemistry with these molecules. Broader Impacts. Research and education were integrated in the funded activities through training student researchers at experience levels from high school through graduate school, and collaboration with faculty members from two local, primarily undergraduate institutions (College of Mount St. Joseph and Wilmington College). Graduate students involved in this work have been inspired by interaction with these collaborators to consider teaching careers at small colleges, and have gained mentoring experience by helping the PI mentor two economically disadvantaged, underrepresented-minority high school students through ACS Project SEED. This grant allowed the PI and students involved in the research to disseminate the results at regional and national conferences, including presentations by three different graduate students at ACS National Meetings. This enhances student education by providing them with the opportunity to communicate their results to other chemists in a professional setting. In the science and technology area, the development of new compounds that make metals available in situ and on demand in response to light will promote advances in molecular devices, coatings, pharmaceuticals and other applications that have yet to be imagined, providing technological, health, and economic benefits to society as a whole.
