Analysis of self-assembling complexes via supramolecular mass spectrometry.

摘要

Self-assembling supramolecular complexes are stable configurations of two or more molecules stabilized by noncovalent intermolecular interactions, which aggregate independently according to molecular recognition principles. Noncovalent, e.g., cation-pi and hydrogen-bonding, interactions make important contributions to the structure and function of many biomolecules. They are vital to protein folding and stabilization and so to substrate specificity and enzyme action. Host-guest inclusion complexes stabilized by these interactions are used in areas such as enzyme mimicry, catalysis, and therapeutic drug development and delivery. Modeling and analysis of these noncovalent interactions are essential to the development of selective synthetic hosts. Thorough analytical characterization of diverse supramolecular systems is necessary to contribute to the wealth of data required to gain a better understanding of the inherent chemical behavior involved in molecular recognition and noncovalent complex formation. Mass spectrometry, as a gas-phase analytical technique, has the ability to provide vital information concerning supramolecular chemistry in the absence of interference from a solvent shell. The advancement of supramolecular mass spectrometry was the major goal of this research.;A pair of designed synthetic receptors for alkali-metal cations based on the natural product 1,3,5-trihydroxybenzene (phloroglucinol) was thoroughly characterized in the gas phase using advanced supramolecular mass spectrometric techniques. Following additional solution-phase characterization using absorbance spectroscopy in the ultraviolet region, it was determined that the mass spectrometric approach and the optical spectroscopic approach combined to yield useful complementary characterization information.;Following the configuration of a home-built source with a time-of-flight mass analyzer, desorption electrospray ionization (DESI) was developed and validated as a useful novel analytical tool for this area of application, through the design and implementation of a rapid screening experiment for potential guest compounds for supramolecular encapsulation by a beta-cyclodextrin host. Comparison experiments, using nuclear magnetic resonance spectroscopy as the standard solution-phase validation technique, revealed that DESI is a superior ionization technique to the commonly-employed electrospray ionization (ESI) for this type of work. DESI is not as prone to the detection of false-positive nonspecific complexes resulting from the formation of artifacts during the electrospray process. Thus a useful addition to the supramolecular mass spectrometry toolkit has been contributed.