Synthesis, self‐association and chiroselectivity of isotopically labeled trianglamine macrocycles in the ion trap mass spectrometer

Abstract

Abstract:The synthesis and self-association of chiral isotopically labeled trianglamine macrocycles under electrospray mass spectrometer conditions in an ion trap are described. A moderate diastereoselectivity in the self-association process was observed providing a synthetic model system for the investigation of chiral selfassociation in the gas phase. The first non-covalently bound dimer exclusively bonded through aromatic-aromatic interactions was observed in the gas phase. Evidence for self-association in solution was observed by diffusion nuclear magnetic resonance spectroscopy. Copyright # 2007 John Wiley & Sons, Ltd.Keywords: deuterium labeling; supramolecular chemistry; mass spectrometry; chiral recognition; macrocyclic chemistry Molecular recognition is an area of chemistry aiming at the understanding of complementarity of size shape and functionality at the supramolecular level. It explores weak interaction between two or more molecules over short distances resulting in complex molecular assemblies.1,2 At this supramolecular level chirality can be expressed through the diastereoselective formation of molecular clusters through selfassembly of homochiral building blocks. 3,4 Mass spectrometry has been shown to provide an experimental technique suitable for the study of these diastereoselective self-assembly processes in the gas phase. Early reports demonstrated the self-association of homochiral tartrate derivatives in the gas phase. 5,6 Most prominently homochiral amino acids, in particular serine, were reported to form non-covalent clusters readily generated by electrospraying or sublimation and observed and characterized through ESI mass spectrometry. 7-9Studies on such chiral supramolecules have been motivated to a large extent by the possibility that such self-assembled clusters of homochiral molecules play an important role in the origin of homochirality in biological systems, exemplified by the preference of amino acids for the l-configuration or sugars for the d-configuration.Our group has studied for some time the chemistry of homochiral polyamine and polyimine macrocycles, which we named trianglimines and trianglamines. [10][11][12][13][14][15] In the course of our investigation we observed frequently that under ESI mass spectrometric conditions the homochiral macrocycles did assemble in the gas phase into larger clusters. Since trianglamines are readily available in both enantiomeric forms we decided to investigate the chiroselection of this self-assembly process in detail and report the finding of our studies in this publication. Results and discussions Synthesis of triangliminesFor our studies concerned with the chiroselection of homochiral trianglamine macrocycles through mass spectrometry we required macrocycles in both enantiomeric forms that were isotopically labelled in order to distinguish between diastereomeric clusters in the mass spectrometer. If one of either enantiomers of a given compound is isotopically labelled the two