In this project supported by the Experimental Physical Chemistry Program, Professor Mary T. Rodgers of Wayne State University and her group will carry out research designed to obtain absolute quantitative thermochemical, dynamical, and structural information regarding noncovalent interactions between metal ions and ligands. The systems chosen for study are of either biological relevance or analytical utility and include: model aromatic ligands, crown ethers, nucleic acid bases, model phosphate esters, and mono- and dinucleotides interacting with alkali, alkaline-earth, and transition metal ions. Experimental techniques will include guided ion-beam tandem mass spectrometry (GIBMS)and threshold collision-induced dissociation (TCID).
The experiments are designed to measure directly either the absolute strength of the metal-ligand interaction, or the activation energy for activated dissociation processes of the metal-ligand complexes. These studies also provide structural and mechanistic information regarding such bond activation processes obtained in the form of concomitant theoretical work and through the analysis of decomposition pathways. Outcomes are expected to provide accurate thermodynamic information on a wide variety of metal-ligand complexes; this information is being compiled into thermochemical databases that will enable the characterization and understanding of periodic properties and trends.
Biological mass spectrometry is a rapidly growing and evolving technology that has captured the interest of a broad community of researchers. Outcomes from this research will contribute to the underpinnings of the methodology, and add to its continuing development.
The most significant goal and outcome of our NSF supported work is the training and development of scientists at the undergraduate and Ph.D. levels. To this end, the PI has involved 19 Ph.D. and 16 undergraduate students including both minority and female students in the work supported under this grant. More than half of these students have completed their degrees and have gone on to pursue advanced degrees (Ph.D., M.D. or D.D.S.) or are productively employed in academia and industry. The next most significant goal and outcome of our NSF supported work is the acquisition of structural and energetic information for biologically relevant systems that bind via noncovalent and/or metal-ligand interactions. Our studies have examined the effects of protonation and noncovalent interactions on the structures and stabilities of the building blocks of nucleic acids (i.e., nucleobases, phosphate esters, nucleosides, and nucleotides) and have laid the ground work for determining how these interactions evolve in larger systems. In particular, protonation is found to stabilize alternative structures of DNA and RNA nucleobases and nucleobase pairs, and to facilitate cleavage of glycosidic bonds (i.e., the bonds that hold the nucleobase and sugar building blocks of nucleosides and nucleotides together). Thus, protonation is used by nature to alter structure and stability of molecules. Such changes may occur to facilitate various desirable biochemical processes including, for example, nucleobase salvage and DNA repair processes. However, protonation can also stabilize noncanonical folded structures of DNA such as the DNA i-motif, which is associated with Fragile-X syndrome the leading cause of mental retardation in humans. Our studies have also provided insight into the roles that permethylation plays in advancing Fragile-X syndrome. Our studies have also sought to elucidate the factors that lead to selectivity in molecular recognition processes involving macrocyclic crown ether ligands as these interactions can be useful for the separation of metals and for various technological applications. By examining a variety of cation-crown ether complexes, we have been able to elucidate the effects of cation size, charge and structure as well as the nature and number of the donor atoms responsible for binding to the crown ether and its size and flexibility on the strength of binding. Size and structure are clearly the key determinants in the selectivity of binding. However, the nature and number of the donor atoms are also critical. The chelation effect, which leads to stronger more selective binding to such macrocyclic ligands was also been shown to be almost entirely entropically driven. Our studies have also provided fundamental insight into both electron transfer and proton transfer charge fission reactions, which are of great importance in various electrochemical processes and in the activated dissociation of multiply charged ions. The ability to characterize the extent of charge transfer in transition metal cation-ligand complexes via these charge fission processes can be used to optimize and control the properties of an inorganic metal-ligand complexes being developed for materials applications. Insight into the activated dissociation of multiply charged ions is particularly relevant today, as electrospray ionization has become the most widespread ionization technique used for mass spectral analyses, and produces predominantly multiply charged ions. The thermochemical data determined in our NSF supported work has been disseminated in 34 research manuscripts that have been published in the literature and has also been included in recent updates to the CRC Handbook of Chemistry and Physics as well as the National Institute of Standard of Standards and Technology Chemistry Webbook. Thus our results are freely available to all scientists that could benefit from this information. In addition to being useful to a variety of experimental scientists, it is anticipated that the availability of such accurate thermochemical data as determined in our work will motivate theoreticians to improve the model theories and basis sets employed for theoretical electronic structure calculations that have become an important component of many scientific studies.
