This award in the Chemical Synthesis (SYN) program of the Chemistry Division supports work by Professor David Goldberg of the Department of Chemistry of Johns Hopkins University to develop the synthesis and reactivity of a class of porphyrinoid compounds known as corrolazines and corroles. These molecules are designed to stabilize high-valent transition metals, including high-valent metal-oxo species. The porphyrinoid ligands to be employed will provide access to these species, allowing for their reactivity to be assessed directly in biologically relevant and synthetically important processes such as hydrogen-atom transfer and C-H bond cleavage. The anticipated findings should yield new mechanistic information of relevance to both heme and nonheme enzymes, and may provide insights into why Nature selects iron or manganese for a particular function. The structure/function correlations to be obtained should also aid in the design and development of synthetic porphyrinoid-based oxidation catalysts.
The research described in this proposal will provide new knowledge regarding key intermediates proposed for a range of metalloenzymes and synthetic metal-based catalysts. The knowledge obtained will advance our understanding of catalytic processes in biology, and may translate into the development of new, environmentally compatible, bio-inspired catalysts that can be used in oxidative transformations of industrial importance. Undergraduate and graduate students will receive training in chemical synthesis and mechanism, and more broadly in the methods of experimental science. The research program also includes active collaborations with scientists at several U.S. and international institutions. These interactions will provide expanded training opportunities for students participating in the research. Outreach programs aimed at broadening the participation of underrepresented groups in the physical sciences are planned at the high school and university level.
Intellectual Merit. This project was focused on the development of new organic and inorganic compounds for modeling key aspects of iron- and manganese-containing heme proteins and enzymes. A heme group is an organic porphyrin compound with an iron atom held inside the cyclic structure of the porphyrin. Nature utilizes heme, and analogous porphyrin structures, to perform biological functions that are critical to many organisms including humans. Many of these functions rely on heme enzymes to catalyze key transformations of biologically relevant organic and inorganic substrates. Chemists have also sought to reproduce some of the features of heme enzymes by synthesizing porphyrin-like molecules, which could then be used as potent and selective catalysts for organic reactions. Porphyrin-like compounds have many advantages over traditional catalysts, including environmentally and biologically benign components, high stability, and a controllable architecture at the molecular level. In the current work, our group synthesized and studied the reactivity of a unique class of porphyrin-like compounds called corrolazines. The corrolazines have a modified porphyrin scaffold such that they are able to generate and maintain metal-based species in unusual electronic structures, and with specialized groups, or ligands, bonded to the metal ion. We discovered that corrolazines containing manganese atoms were capable of catalyzing the oxidation of certain carbon-hydrogen bonds with only visible light and air as the other components of the catalytic reaction. These results provided a novel mechanism for combining oxygen in the air with organic C-H compounds to give alcohol and aldehyde products. In other work we found that iron atoms deficient in electrons, i.e. in high oxidation states, could be greatly stabilized by being bound in the corrolazine cavity. These iron complexes also yielded new chemical reactivity in terms of nitrogen group transfer chemistry, not seen in normal porphyrins. Other fundamental studies led to new information regarding the influence of axial donor ligands and certain acids on the reactivity of high-valent manganese-oxo complexes. These latter studies provided insights into why Nature chooses certain amino acid residues to chelate heme in the axial position, including the unique axial cysteine group found in the heme enzyme Cytochrome P450. Broader Impacts. The fundamental discoveries made during this project helped to advance our understanding of heme enzymes as well as synthetic, bio-inspired transition metal oxidation catalysts. The work provided new knowledge on how oxygen can be utilized by transition metals to carry out important synthetic transformations. This knowledge can be used to design future catalysts of importance to the chemical industry. Graduate and undergraduate students also received a broad education and training in scientific research and the chemical sciences. High school students were mentored and exposed to the scientific endeavor through an outreach program that involved a Baltimore City High School.
