An Enantiopure Cyclotriphosphazenium Chloride Salt for Effective Enantioselective Recognition of Organic Molecules

Abstract

Chirality manifests across different scales, from the subatomic to the supramolecular, extending to macroscopic and even galactic levels. While molecular chirality plays a vital role in pharmaceuticals and functional materials, supramolecular chirality in host guest systems is a particularly fascinating and promising area of research as it plays a significant role in biological processes, enantioselective separation, and biochemical sensing. By optimizing the cumulative effect of different noncovalent interactions and steric effects, host–guest systems can be optimized for enhanced enantioselective recognition. In this study, we introduce an enantiomeric pair of cyclotriphosphazenium salt, of the formula: [R* = (R)-(CH(CH₃)PhCl)] (1-RH·Cl) and [(S)-(CH(CH₃)PhCl)] (1 SH·Cl), functionalized with a chiral (1-(4-chlorophenyl)ethylamine) substituent. This novel design enables the system to act as a hydrogen bond donor and acceptor, making it a promising host for the chiral recognition of organic molecules. The recognition ability of the R-enantiomer of the cyclotriphosphazenium salt was investigated for a range of chiral organic compounds containing various functional groups such as mandelic acid (MA), styrene oxide (SO), 2-phenyl succinic acid (PA), and epichlorohydrin (EP). Notably, 2-phenyl succinic acid demonstrated a remarkable selectivity value of 6425 in favor of its R-enantiomer. Furthermore, density functional theory (DFT) studies provided more insights into the binding mechanism for each host guest system, revealing that multiple noncovalent interactions contribute significantly to the selective complexation of the guest molecules with the chiral host. These findings highlight the importance of the molecular rigidity and specific functional group compatibility of the host-guest systems in determining binding affinities with the guest molecules. This study underscores the versatility of enantiopure cyclotriphosphazenium chloride salt as a potential host for chiral recognition studies.