The Untapped Potential of Twisted Molecular Hoops

In the molecular world, chirality—the property where an object cannot be superimposed onto its mirror image—is a defining feature of life and chemistry. While chemists typically focus on molecules defined by specific chiral centres or axes, a fascinating class of compounds known as inherently chiral macrocycles (ICMs) has largely flown under the radar. Unlike conventional chiral molecules, ICMs lack standard stereogenic elements. Instead, their specific 'handedness' arises solely from the curvature introduced into their planar, ring-like structure.

A defining characteristic of these unique compounds is that their geometric magic is fragile; if you break the ring to form a linear chain, the molecule immediately becomes achiral. Despite their intrigue, ICMs have remained chemically elusive. Synthesising them in highly pure, enantiomerically enriched forms has historically been a significant hurdle, often requiring tedious separation techniques like high-performance liquid chromatography (HPLC).

However, recent advancements have shifted this landscape. Researchers have successfully developed three primary strategies to construct these twisted hoops efficiently: de novo synthesis from linear precursors, the desymmetrisation of symmetric macrocycles, and dynamic kinetic resolution. These breakthroughs allow scientists to finally explore the properties of ICMs systematically. The findings suggest these compounds offer an extraordinary platform for creating advanced functional materials. By acting as chiral catalysts in supramolecular chemistry or forming the basis of new chiroptical materials, ICMs represent a frontier of molecular design that is no longer out of reach.