(Accepted: June 23, 2026; Published: 2026)
Helicenes are well known for their strong chiroptical properties, including high optical rotations and pronounced Cotton effects (CEs), but their application as molecular probes for chirality sensing has remained largely unexplored. In this work, we designed and synthesized a carbopentahelical dialdehyde (CH-Prox) and three stereodynamic oxapentahelical dialdehydes, namely OH-Prox, OH-Dist, and OH-Asym, as molecular platforms for sensing chiral amine analytes and determining their enantiomeric excess. The stereodynamic helicenes undergo covalent imine formation with chiral amines, resulting in diastereomeric helical enrichment and, in favourable cases, dynamic kinetic locking of one helical form. Reactions of the oxapentahelical dialdehydes with cyclic chiral 1,2-cyclohexanediamine (DA1) produced macrocyclic imine products with a 2:2 dialdehyde/diamine stoichiometry and exhibited pronounced Cotton effects in their circular dichroism (CD) spectra. Among the systems investigated, the OH-Prox-derived imine displayed particularly intense and characteristic helical Cotton effects in the 300–400 nm region, including a distinctive bisignate feature near the absorption edge. Theoretical energy-minimization and noncovalent interaction analyses revealed that the compact and rigid conformation of OH-Prox_DA1, supported by collective dispersion interactions within the molecular cavity, is responsible for its enhanced chiroptical response. In contrast, OH-Dist_DA1 adopts a more stretched-out structure, while OH-Asym_DA1 exhibits an intermediate conformation. Chiral monoamines produced 1:2 dialdehyde/amine imine products and generated weaker but diagnostically significant Cotton effects arising from partial enrichment of one of the diastereomeric helical forms. Mirror-image CD responses were consistently observed for opposite configurations of the chiral amine analytes, enabling determination of absolute configuration. The pronounced CD responses generated by OH-Prox with chiral diamines were further exploited for quantitative chiroptical assays of enantiomeric excess and analyte concentration. A linear correlation between CD intensity and enantiomeric excess was obtained, with R² values of 0.998 and 0.997 at 255 and 281 nm, respectively, while experimentally determined enantiomeric excess values were within ±3.01% of the actual values. Concentration-dependent assays exhibited a linear response, with experimentally determined concentrations within 2.0% of the actual values. The limits of detection for the OH-Prox_DA1, OH-Dist_DA1, and OH-Asym_DA1 systems were 1.1–1.2 μM, while the limits of quantification were 3.33–3.40 μM. Overall, this study establishes stereodynamic helicenes, particularly OH-Prox, as powerful molecular platforms for chirality sensing, absolute configuration determination, and rapid chiroptical assay of chiral amines at very low concentrations through diastereomeric helical enrichment and dynamic kinetic locking.