Experimental Studies of the Structures, Energetics, and Reactions of Gas Phase Self-Assembled Biomolecular Ionic Complexes

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Studies of complexes composed of metal cations and amino acids or DNA bases are important for our understanding of the physical chemistry of self-assembled biomaterials. The structures also have biological relevance in terms of, for example, telomere research. Part of the work proposed is to study the intrinsic structures, energetics, and spectroscopy of G-tetrads that compose G-quadruplexes—tracts of guanine residues at the ends of DNA strands which are an important part of the telomere. The assembley of these G-quadruplexes are typically initiated by metal cations. 9-ethylguanine (9-eG) is an ideal model for the nucleic acid as the 9-position is blocked, as it is in nucleic acids. Preliminary experimental work on (9eG)4M+ (M=Li+, Na+, K+, and Cs+) has revealed a remarkable stability of the (9eG)4Na+ complexes which theory shows us are square planar. In contrast, complexes with the other metal ions are non-planar, probably due to competition between hydrogen bonding between the nucleic acids and metal-ion/molecule interactions. Much more work is required to fully understand the balance of intermolecular forces that bind these structures. For example, what is the effect on structure stability and reactivity of metal cations with higher oxidation states such as the alkali earth, transition, and lanthanide metals. This research will also lead to valuable information on metal ion induced defects in nucleic acids. We plan to study the structures and energetics of higher order structures such as (9eG)8M+ and [(9eG)12M2]2+ of significance to biological and supramolecular materials research. The construction of these complexes relies on molecular recognition and self-assembly processes that occur in DNA, RNA, and proteins etc. Supramolecular complexes of the other nucleic acid bases as well as those composed of a mixture of bases will be studied. This research will have an impact health and cancer research, providing fundamental knowledge of the makeup of these biological complexes. We will carry out research on polymetallic cation-peptide supramolecular assemblies. We have done preliminary CID studies on complexes such as [Ca5(GlyGly-H)8]2+ and have also begun to model them. Our current picture has the five Ca2+ ions in a plane bridged by oxygen atoms of the peptide, similar to proposed structures of naturally occurring clusters such as ferritin and the oxygen-evolving complex of photosystem II. We propose to compare the structures, energetics and reactivities of self-assembled complexes composed of different metals and larger, varied peptides in the gas phase. These studies will be augmented by research on smaller components of the supramolecular clusters, such as metal cation-bound dimers of amino acids, DNA bases, and carbohydrates. A new tunable IR laser, far more powerful than our current one is on order. This laser will allow us to record IRMPD spectra on G-tetrads and other strongly-bound species which was not possible with our current laser. With this new laser, our spectral range increases down to 2400 cm-1 (from 3200 cm-1) allowing us to spectroscopically characterize the fundamentally important and very intense hydrogen bonded N-H stretching bands. Besides IRMPD spectroscopy and computational techniques to determine structures of gaseous ions we will use energy-resolved CID, CID coupled with isotopic substitution, blackbody infrared radiative dissociation coupled with master equation modeling to determine binding energies, and radiative association with kinetic modeling to study bimolecular ion-molecule reactions. We are also adding simulated annealing to our repertoire of techniques to help ensure we have explored the full geometric space of our large clusters.