Supramolecular Chirality in Metal-Organic Complexes

CONSPECTUS: Chirality is a pervasive structural feature of nature and crucial to the organization and function of nearly all biological systems. At the molecular level, the biased availability of enantiomers in nucleic and amino acids forms the basis for asymmetry. However, chirality expression in natural systems remains complex and intriguing across differing length scales. The translation of chirality toward synthetic systems therefore not only is crucial for fundamental understanding but also may address key challenges in biochemistry and pharmacology. From a structural viewpoint, a fascinating class of cavity-containing supramolecular assemblies, homochiral metal-organic complexes (MOCs), provides a good opportunity to study enantioselective processes. Chiral MOCs are constructed by coordination-driven self-assembly, wherein relatively simple molecular precursors are allowed to assemble into structurally well-defined two-dimensional (2D) metallacycles or 3D metallacages spontaneously with complex and varied functions. These aesthetically appealing structures present nanocavities with space-restricted chiral microenvironments capable of interacting distinctly with molecularly asymmetric guests, which is highly beneficial to explore the relay of chiral information from locally chiral molecules to globally chiral supramolecules, which is a significant challenge. In this Account, we specifically discuss our research toward rationally designed, synthetically accessible chiral MOCs over the past 12 years. The globally supramolecular chirality demonstrated by these well-defined MOCs prominently exceeds the constitutive molecular chirality of the components. First, we discuss chirality transfer and amplification in the context of induction and transmission from the constituent organic ligands of self-assembled chiral metallacycles. The creation of subtly chiral microenvironments in the metallacyclic architectures results from a tiny conformational bias of inner hydrophobic groups, subsequently allowing them to interact very specifically with one enantiomer over the other, thus imparting outstanding enantioseparation properties. Second, we have designed a series of chiral metallacycles and helical metallacages that are able to deploy chiral NH groups with available hydrogen bonding capacity, together with hydrophobic/CH-pi interactions, bringing about cooperativity for binding of chiral substrates. It turns out that they can be used as artificial chiral receptors capable of exceptionally high enantiorecognition toward a wide range of biologically relevant molecules. Third, we recently developed a group of highly stable chiral metallacages that feature a catalytically confined nanospace with potential as supramolecular asymmetric catalysts. It has been suggested that the use of molecularly nanocaged chiral hosts in solution to substantially increase reactivity and enantioselectivity compared with the unconfined reactions, highlighting the intermetallic synergy, rationalizes the remarkable catalytic performance. Finally, we discuss our personal perspectives on the promises, opportunities, and key issues toward the future development of chiral MOCs. Needless to say that the fundamental understanding of the translation of chirality from molecular to supramolecular to macroscopic scales is crucial to unveil biological mechanisms. We hope the described supramolecular chirality of MOCs could be extendable to develop new and valuable chiral materials in chemistry, medicine, and beyond.