Manipulating Ligand Binding Affinity in Allosteric Coordination Complexes through Inherent Ring Strain Design

Organometallic complexes are highly versatile given that their binding affinities are sensitive to their chemical makeup and environment. Indeed, these differences in binding affinities can be leveraged with the use of hemilabile ligands to construct spatially responsive structures. However, modifying binding affinities usually involves adding specific electron groups to binding atoms, a process that is not only synthetically complex but also can limit the integration of other functional groups. One solution to this challenge is to use ring strain in cyclic compounds to act as a binding affinity modulator combined with a hemilabile coordination system. The Weak-Link Approach (WLA) is a particularly powerful hemilabile coordination system that contains chemical modularity by exploiting binding affinities with combinations of strong binders, weak binders, and metal nodes.<br/><br/>Here, we introduce a new WLA system by replacing an asymmetric P,S ligand with a symmetrical bis-carbene and explore the effects of ring strain on allosteric reactivity. By studying ligand displacement in 4- to 8-membered rings, a correlation between ring size and coordination reactivity is established. Adjusting the ring size proved to be an effective way to alter binding affinities without further complex chemical modifications. Moreover, we observed that increased ring strain also leads to changes in overall allosteric reactivity, and even reversing conventional coordination binding to prefer weaker binders vs stronger ones in highly strained 4-, 7-, and 8-membered cyclic systems. Overall, through careful selection of metal-binder coordination, and thus enthalpy, along with the formation energy associated within a strained ring-forming system, we precisely define a desired allosteric state. In sum, this work not only represents a paradigm shift in harnessing ring strain as a strategy for binding affinity manipulation, but also redefines our understanding of coordination dynamics in these systems.