Spontaneous Resolution of Racemic Cage-Catenanes via Diastereomeric Enrichment at the Molecular Level and Subsequent Narcissistic Self-Sorting at the Supramolecular Level

Abstract

The spontaneous resolution of racemates, from natural compounds to artificial structures, has long been pursued to shed light on the origin of homochirality in life. Even though diverse synthetic systems have been elegantly devised to elaborate the underlying principles of spontaneous symmetry breaking, their complexity is still unparalleled to the natural masterpieces including DNA helix and proteins, which convey remarkable coalescence at both molecular and supramolecular levels. Here, we report on the spontaneous resolution of a pair of homochiral entities from a racemic mixture of a triply interlocked cage-catenane comprising 720 possible stereoisomers. This cage-catenane comprises six methyldithiane ring-containing linkers (denoted rac-2). As each methyldithiane ring has two chiral centers, it exhibits four possible diastereomers. These otherwise equimolar diastereomers are preferentially differentiated with the equatorial conformers over their axial analogues, leading to the dominant formation of ( S , R )-2 and ( R , S )-2, i.e., diastereomeric enrichment at the molecular level. This diastereomeric enrichment is unbiasedly transferred from precursor rac-2 to cage-catenane rac-4, from which a pair of homochirals ( S , R ) 6 -4 and ( R , S ) 6 -4 is narcissistically self-sorted upon crystallization. This powerful symmetry breaking is attributed to a supramolecular synergy of directional π–π stacking with the multivalency of erstwhile weak S···S contacts (with an unusual distance of 3.09 Å) that are cooperatively arranged in a helical fashion. This work highlights the attainability of complex homochiral entities by resorting to coalesced covalent and noncovalent contributions and therefore provides additional clues to the symmetry breaking of sophisticated yet well-defined architectures.

Heterochiral Diastereomer-Discriminative Diphanes That Form Hierarchical Superstructures with Nonlinear Optical Properties

“…With the aids of single-crystal X-ray diffraction (SC-XRD) and circular dichroism (CD), we reveal that this configurational change of the cages yields superstructures with dramatically different molecular packing. 9 It in turn results in distinct emergent functions, as demonstrated by their second-order nonlinear optical (NLO) properties as a proof of concept ( Figure 1 ).…”

“…We also investigate the self-assembly of homochiral and achiral diphanes , which serve as supramolecular building blocks for the construction of hierarchical superstructures. With the aids of single-crystal X-ray diffraction (SC-XRD) and circular dichroism (CD), we reveal that this configurational change of the cages yields superstructures with dramatically different molecular packing . It in turn results in distinct emergent functions, as demonstrated by their second-order nonlinear optical (NLO) properties as a proof of concept (Figure ).…”

Dynamic Covalent Chemistry for Synthesis and Co‐conformational Control of Mechanically Interlocked Molecules

“…It is also possible to use other interactions such as donor‐acceptor or π‐π interactions to drive templated dynamic imine MIM formation [46] . These interactions can be used for the high‐yielding thermodynamic synthesis of some very impressive molecular architectures, such as cryptand‐based [2]rotaxanes [47–48] and catenated molecular cages [49] . In an recent impressive example, Zhang and co‐workers also showed that the mechanically interlocked nature of a pair of catenated imine cages could be synthetically useful [50] .…”

Light‐Fueled Transformations of a Dynamic Cage‐Based Molecular System

“…The development of molecular machines by the incorporation of photoswitches in more complex molecular systems and architectures, such as macrocycles and molecular cages, has the potential to exhibit emergent behaviors that resemble their biological counterparts. [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] An example of this emergent behavior is the influence of switching in the reactivity of constrained molecular architectures. Particularly, the effect of the geometric change in the switch can introduce strain in the macrocycle, and by doing so, it can promote the reactions in which the strain directly affects the rate limiting step.…”

“…Molecular photoswitches are attractive synthetic tools that use light as an energy source to induce a reversible change in their properties. The development of molecular machines by the incorporation of photoswitches in more complex molecular systems and architectures, such as macrocycles and molecular cages, has the potential to exhibit emergent behaviors that resemble their biological counterparts [30–45] …”