Stereodynamic Helicenes for Chirality Sensing and Enantiomeric Assay through Diastereomeric Helical Enrichment

Although several molecular systems that lead to helically twisted structures upon binding with chiral analytes and produce strong Cotton effects (CEs) in CD for chirality sensing and assay have been reported, helicene-based platforms as probes have not been much explored. We designed and synthesized three stereodynamic regioisomeric oxahelical dialdehydes (ODs)OH-Prox, OH-Dist, and OH-Asymalong with an analogous carbohelical dialdehyde (CH-Prox), and investigated them as probes for sensing chiral monoamines (MAs) and diamines (DAs). Reactions of all ODs with a cyclic chiral diamine, 1,2-cyclohexanediamine (DA1), produced macrocyclic imine products with a 2:2 OD/DA1 stoichiometry, which exhibited strong CEs in their CD spectra. Notably, the imine derived from OH-Prox displayed intense CEs characteristic of helical structures, appearing in the 300-400 nm region with a bisignate feature near the absorption edge. In contrast, the imines formed from OH-Dist and CH-Prox lacked this signature. Theoretical energy minimizations of the structures of imine products suggest that the compact and rigid structure of the OH-Prox_DA1 imine is responsible for the edge CE with bisignation observed in its CD spectrum. Analogous but significantly weaker CEs (5-7 fold lower), also indicative of helical structures, were observed for the imine products of OH-Prox with monoamines MA1 and MA2, reflecting reduced rigidity and partial enrichment of one helical form. For opposite stereoconfigurations of amine analytes, mirror-image CEs were consistently observed for all dialdehyde probe systems. It is shown that the pronounced CEs, arising from conformational locking with DA1 and enantiomeric helical enrichment with MAs, enable the determination of absolute configuration as well as rapid assay of enantiomeric excess of chiral amine analytes at very low concentrations (μM). The stereodynamic helical molecular platforms are thus compellingly demonstrated as powerful systems for chirality sensing and assaymarking an advance in a field dominated heretofore by helically twisted molecular frameworks.