Award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports Professor Kristin Bowman-James to explore: anion binding, to evaluate the role of lone protons in chemical processes, and the binding and manipulation of neutral triatomic gases. A systematic approach is used by linking a series of similar amide/amine-based hydrogen-bond donor building blocks to give hosts with increasing complexity and dimensionality, and differing degrees of rigidity. The five specific goals are: 1) Simple amide/amine containing hosts will be strategically modified to probe the addition of more hydrogen bonding sites as well as redox switches, the latter using pendant sulfhydryl groups. 2) Structural data on binding of linear and V-shaped anions will be used to expand the project to neutral gases, specifically CO2, N2O, and SO2. Both traditional hydrogen bonding strategies will be used as well as dynamic covalent chemistry (DCC), the formation of covalent bonds that can be readily broken. 3) Complex cyclophane-capped multicycles will be explored as hosts for larger polyanionic guests, including metallates, polyphosphates, nucleotides, and carboxylates. These hosts will provide more rigid architectures than earlier ligands. 4) The prototype phenyl host caps will be replaced by triazine, pyrazine and naphthalene to examine a) the influence of heteroatoms in the preorganization of the side chains and stacking distances, and b) the use of naphthalene to circumvent an acid decomposition of the host with four linkers (tetrad) as well as undesirable intramolecular NHC hydrogen bonds. 5) Structural data indicating that a lone proton could play a role in shaping the conformations of molecules will be pursued to assess the generality of this phenomenon.
The goal of this work is to design more complex hosts that will show high affinity for larger and more challenging guests with two targets being neutral gases and single protons. The broader impacts are the educational component that spans students from undergraduate to postdoctoral status, and outreach that includes women and underrepresented minorities. The societal impacts are in understanding not only the complex chemistry involved in anion recognition but also the more elusive targets of neutral gas recognition and the role that lone protons could play in supramolecular and biological chemistry.
This project has involved an in-depth study of the design, synthesis, and chemistry of molecules (hosts) capable of interacting with negatively charged ions, anions (guests). The intellectual merit of this work is derived from the systematic, planned design of host molecules that use simple amide/amine building blocks to obtain large organic molecules made up of two or more connected molecular rings. The goal was to use these more complex molecules to bind either multiple groups of molecules and/or ions or larger more complex negatively charged guests. A secondary goal was to explore whether these hosts could also provide new transition metal catalysts when bound to metal ions, with a focus on catalyzing carbon-carbon coupling reactions. The intellectual merit of this aspect of the program relates to the fact that two new classes of potentially useful transition metal catalysts have been identified, pincer-like frameworks containing either two amide or two thioamide units (>N(H)=O or >N(H)=S). One of the key accomplishments during this funded cycle was the isolation of a large organic molecule shaped like a tetrahedron and capable of sequestering small clusters of molecules. In one case an encapsulated pentameric water cluster known as Walrafen’s pentamer was isolated and characterized by X-ray crystallography. The pentamer has long been predicted to be the simplest small water cluster, but this is possibly the first case in which such a pentamer was captured in a cage. The tetrahedron molecule also was found to encapsulate what is known as an aquated fluoride ion, i.e., a fluoride ion surrounded by four water molecules. The use of multiple nuclear magnetic resonance (NMR) techniques allowed for the study of the chemistry of the caged, aquated fluoride ion in solution. Such studies can shed light on ion solvation patterns governing the behavior of ions in solution, including real world situations such as in lakes and ponds, leading to a better understanding of groundwater contamination chemistry. Another key accomplishment was the isolation and characterization of a cylindrical organic molecule. This new host represents the second class of molecules enabled by this funding. The cylindrical host was found to be especially selective for a particular class of long organic dianions, dicarboxylates, containing two carboxylate groups in one molecule. These are important ions in biological systems because of their involvement in a number of metabolic cycles. They are also useful in industrial applications in the production of adhesives, polymers, and fragrances. The cylinder showed an unusual aptitude for changing its shape by shrinking or expanding depending on whether a dicarboxylate guest was encapsulated within its cylindrical framework. In particular the degree to which the host compressed was found to be dependent on the length of the dicarboxylate guest. Ultimately the new host could be used for transport of desired anions across membranes such as in drug delivery. A third key finding was that some of the building blocks used for the new anion hosts were found to bind transition metal ions, forming complexes that can catalyze organic transformations. As a result two new classes of palladium(II) complexes were found to catalyze Heck-type carbon-carbon coupling reactions. These reactions are extremely useful in the synthesis of complex organic compounds such as in natural product synthesis or in various aspects of industrial synthesis. Broader impacts fall into both chemical and workforce categories. The ability to study an isolated unit cluster of water will enable a better understanding of the chemistry of bulk water systems as well as how water "solvates" other ions. The new dicarboxylate-binding cylindrical hosts may help to unravel some of the complex metabolic pathways involving anion transport across cell membranes. Because of the flexible and simple synthetic methodologies used, the new class of palladium catalysts may also lead to further development of multi-metallic catalysts. Additionally, the PI actively promotes the participation of underrepresented groups in the chemical sciences. These efforts occur both in the lab, as in the current group of three researchers, including one woman and one minority, as well as outside of the lab in expanded efforts to promote diversity in the STEM workforce. She has been especially proactive in workshops and organizations for women and scientists with disabilities. Finally, the techniques that students learn in doing this research are used to train future chemists with a broad-base of knowledge, including synthetic organic, analytical, inorganic, catalytic, NMR, and crystallographic techniques.
