Twisted Host–Guest Systems Exhibit Superamplification of Asymmetry via Coupled Allosteric and Conformational Cooperativity

Chiral host-guest systems are central to applications in chiral separation, chiral sensing, and asymmetric catalysis. Chiral interactions involving multiple guest molecules exhibit two cooperative effects: allosteric binding and amplification of asymmetry (i.e., chiral amplification). Coupling of these effects can lead to a phenomenon that surpasses conventional amplification of asymmetry, which we propose to term 'superamplification of asymmetry'. Despite its potential, no established theoretical framework exists. In this work, we developed three models: a general 1:2 twisted host-guest interaction model; a 1:n model assuming independent binding events at multiple sites equivalent to the majority rule effect type host-guest inter-action (MRHG) model for short polymers; and the MRHG model combined with allosteric binding (MRHG-AB model). These models were applied to twisted macrocycles and triple-stranded metallohelicates, offering new insights into the amplification of asymmetry mechanisms. Superamplification of asymmetry unlocks powerful new strategies for chiral separation, asymmetric catalysis, and chiral sensing through highly cooperative molecular interactions.