In this project supported by the Chemical Structure, Dynamics and Mechanisms Program of the Division of Chemistry, Professor Scott Reid of Marquette University will study non-covalent interactions involving halogen atoms, which are fundamentally important in diverse areas in chemistry and biochemistry from protein-ligand interactions and drug discovery to molecular recognition and self-assembly to electron transfer and organic synthesis. The strength of halogen bonds can rival or exceed that of hydrogen bonds, and just as our ever-evolving understanding of the hydrogen bond has been aided to a great degree by the study of model systems, the study of halogen bonding requires fundamental probes of interactions in prototypical systems, which is the focus of this proposal. In particular, the need exists to systematically correlate properties of the donor/acceptor with structural characteristics of halogen bonding. Prof. Reid and co-workers will probe the structure, properties, reactivity and electron transfer dynamics of prototypical halogen bonded systems, using matrix isolation methodologies in combination with spectroscopic probes from the far-IR to UV region, with assistance from high level ab initio theory. A key aspect of this work is the combination of experimental and computational methods that will be brought to bear on this important problem. The charge transfer character of donor-acceptor complexes and the dynamics of electron transfer in these systems are key issues that underpin much of organic reactivity, and the photochemical studies described herein will provide valuable information on the dynamics associated with photoinduced electron transfer across halogen bonds. Through the study of model complexes in the key classes of halogen bonded interactions (Ã -systems, O and S atom donors, N and P atom donors), fundamental new insights will be provided into the nature of halogen bonding, which will aid the development and refinement of theoretical methods.
The project results will be disseminated by publication in high quality journals and participation at national and international scientific meetings such as the International Symposium on Molecular Spectroscopy, for which the PI currently serves as Chair of the International Advisory committee. The PI will also use this project to broaden the participation of underrepresented groups in research.
Non-covalent molecular forces, the most famous of which is hydrogen bonding, are crucially important in directing and mediating the path of chemical reactions. In comparison with hydrogen bonding, much less is known about non-covalent interactions involving halogens, despite the fact that organic halogens are widely distributed throughout nature, and it has been estimated that roughly half of all drug candidates used in high throughput screening are halogenated. In this project, our goal was to better understand the nature of the halogen bond, an important non-covalent donor-acceptor interaction which often rivals the hydrogen bond in both importance and strength. Specifically, we are set out to examine the spectroscopy, structure, and electron transfer dynamics in prototypical halogen bonded assemblies, using a complementary suite of gas-phase and condensed phase methodologies which were capable of stabilizing these weakly bound aggregates, using the low temperatures accessible in supersonic beams or cryogenic matrices. Our experimental studies were complemented by high level theoretical investigation of the structure and properties of these complexes, and our studies have provided valuable new insights into the structure and dynamics of halogen bonded assemblies. Our work is anticipated to impact many other fields; e.g., providing insights for chemical biologists seeking to understand ways in which halogen-bonding interactions can enhance drug interactions, and organic chemists seeking new supramolecular architectures based on self-assembly through halogen bonding.
