Electrospray ionization mass spectrometric techniques for the study of molecular recognition
Abstract
The ability of electrospray ionization mass spectrometry (ESI-MS) to
quantitatively analyze the distribution of complexes resulting from molecular recognition
in solution was modeled, and ESI-MS techniques were developed to analyze complexes
involving several different types of novel compounds in different areas of molecular
recognition and supramolecular chemistry.
To better understand the relationship between ion abundances observed by ESI-MS and concentrations of host-guest complexes in solution, mathematical models based
on equilibrium partitioning theory were developed to relate ESI-MS ion abundances to
relative solution concentrations of complexes resulting from host-guest binding. The
predictions of these new models were evaluated and experimentally confirmed through
the analysis of complexes of crown ethers with alkali metal cations in an ESI quadrupole ion trap mass spectrometer, yielding a greater understanding of the behavior of host-guest
complexes in ESI-MS, allowing for more accurate measurements of solution binding
interactions.
The self-assembly of ligand-metal-ligand sandwich complexes involving a novel
quinoxaline-containing crown ether was studied to evaluate the contribution of pi-stacking interactions between the ligands towards the overall stability of the complexes.
Donor-acceptor pi-stacking interactions between the electron-poor quinoxaline group and
electron-rich benzene groups from benzo- or dibenzo-18-crown-6 were found to
significantly enhance the formation of mixed-ligand sandwich complexes.
A synthetic pyrrole-inosine nucleoside, capable of forming an extended three-point Hoogsteen-type hydrogen-bonding interaction with guanine, was shown to bind
guanosine selectively over other individual nucleosides, and ESI-MS results indicated the
formation of specific complexes between the pyrrole-inosine nucleoside and two different
quadruplex DNA structures. The specificity of the pyrrole-inosine nucleoside for
quadruplex DNA suggests that it or similar structures based on this binding modality may
ultimately demonstrate utility as anti-tumor agents.
The interactions between a novel enediyne drug and various cytidine-containing
oligonucleotides were studied, and the structures of the DNA-enediyne adducts known to
lead to cytidine-specific DNA cleavage were examined. Collisionally activated
dissociation of the adducts confirmed their strength and suggest a direct linkage between
the enediyne and the cytidine nucleobase, likely the result of a nucleophilic attack by the
cytidine amine.