Pasteur-like Separation of Silver Nanocluster Racemates by Conglomerate Crystallization

Chirality is a ubiquitous observation in an extremely wide spectrum from molecules to galaxies. It has attracted special interest among chemists as molecular chirality determines the optical, biomedical, and catalytic applications of many compounds. Since Pasteur’s first separation of enantiopure tartaric acid from their conglomerate crystals in the 1840s, chiral resolution has become a decisive task for the development of fine chemical and pharmaceutical industries. Now, Zhao-Yang Wang, Shuang-Quan Zang, and co-workers have made the enantioseparation of intrinsically chiral silver nanoparticles possible through a similar conglomerate crystallization method.¹

In this work, intrinsically chiral silver nanoparticles consisting of a 30-silver-atom core (typically referred to as Ag₃₀ nanoclusters), stabilized by 8 achiral carboranetrithiolate and 6 achiral phosphine ligands, were synthesized and crystallized as a racemic mixture in a dual-solvent system of tetrahydrofuran and acetonitrile. The X-ray crystallography analysis of single crystals of racemic nanoclusters (Ag₃₀-rac) reveals an “outside-in” chirality transfer scheme of cluster chirality origin. Specifically, the interaction of B–H···π and C–H···π in the cluster between neighbored ligands organizes the surface phenyl ring (from the phosphine ligand) into a spiral pattern, which induces chiral arrangement of carboranetrithiolate and phosphine ligands at the metal–organic interface. In addition to the establishment of intrinsic cluster chirality, the rich surface functionality also provides a good means for the enantioseparation of racemic Ag₃₀ nanoclusters by conglomerate crystallization. Recrystallization of racemic Ag₃₀ nanoclusters in dimethylacetamide (DMAc) produces enantiomorphic crystals (R- or L-Ag₃₀, Figure 1), where enantiopure nanoclusters are organized into a helical architecture reminiscent of double-stranded DNA (Figure 1a,b,d,e). The double-helical arrangement is maintained through diverse noncovalent interactions between clusters (e.g., B–H···π, π···π, C–H···O, and H···H interactions), among which the most notable one is the host–guest binding between DMAc molecules and enantiopure nanoclusters. With this facile chiral resolution method, Zhao-Yang Wang, Shuang-Quan Zang, and co-workers also demonstrated the circularly polarized luminescence (CPL) activity of the enantiopure conglomerates, in which the mirror responses were recorded at ∼650 nm with a dissymmetry factor of 7.0 × 10^–4 (Figure 1g,h).

Figure 1.

(a, b) Crystal packing structure, (g) photograph, and (h) circularly polarized luminescence (CPL) spectra of (a) R-Ag₃₀ and (b) L-Ag₃₀ crystals; the red, blue, and black lines in part h are CPL spectra of R-Ag₃₀, L-Ag₃₀, and Ag₃₀-rac, respectively. Helical arrangement of (c, f) dimethylacetamide molecules and (d, e) Ag₃₀ nanoclusters observed in (c, d) R-Ag₃₀ and (e, f) L-Ag₃₀ crystal lattices. Red, blue, and cyan balls in parts a, b, d, and e are silver atoms. Reproduced with permission from ref (1). Copyright 2020 American Chemical Society.

With the accelerated development of nanochemistry in recent decades, chiral arrangements have been widely observed in various inorganic nanoparticles at the intra- and interparticle level.² As the structure of conventional nanoparticles becomes ambiguous in atomic resolution, metal nanoclusters protected by organic ligands, which can be synthesized and characterized with atomic precision, have recently emerged as paradigm particles for revealing the origin of chirality at the nanoscale. The discovery of optical activity in metal nanoclusters can be traced back to the seminal work by Whetten and co-workers in 1998, where chiral glutathione (H-SG) ligands were used to induce circular dichroism (CD) response in Au₂₅(SG)₁₈ nanoclusters.³ Since then, many other chiral ligands including thiols, dithiols, and diphosphines have been used to synthesize chiral metal nanoclusters. One of the most significant findings in cluster chirality research is the generation of intrinsic chirality in the absence of chiral ligands.^4,5 In 2007, Kornberg and co-workers reported for the first time the crystal structure of thiolate-protected metal nanoclusters, where a pair of racemic Au₁₀₂(p-MBA)₄₄ (p-MBA denotes p-mercaptobenzoic acid) nanoclusters were identified in their single crystals.⁴ Although the p-MBA ligand is achiral, the asymmetric arrangement of the (p-MBA)-Au-(p-MBA) protecting motifs on the Au₇₉ core (Marks’ decahedron-based structure) establishes the intrinsic chirality of Au₁₀₂(p-MBA)₄₄. In addition to the asymmetric arrangement of metal–ligand protecting motifs, the intrinsic chirality of the clusters can also be attributed to the chiral atom packing in their metal core.

Since intrinsically chiral metal nanoclusters synthesized with achiral ligands are usually produced in the form of racemic mixtures, chiral resolution is generally required before chiroptical and many other applications. Bürgi and co-workers designed a chiral high-performance liquid chromatography (HPLC) method (Figure 2a) for the enantioseparation of chiral nanoclusters such as Au₃₈(SR)₂₄, Au₄₀(SR)₂₄, Au₂₈(SR)₂₀, and Au₃₈Cu(SR)₂₄ (SR denotes the thiolate ligand).⁶ In addition to chiral HPLC, the enantioseparation of chiral metal nanoclusters can also be achieved by ion-pairing reactions with chiral cations (Figure 2b). The chiral resolution by this method has been successfully applied to Au₁₀₂(SR)₄₄ and [Ag₂₈Cu₁₂(SR)₂₄]^4–.^7,8 More recently, chiral molecules such as α-cyclodextrin have also been used as chiral resolution agents.⁹ Although previous chiral resolution methods inevitably depend on external “chiral stimuli” (e.g., chiral stationary phases, cations, and molecules), the conglomerate crystallization method developed in this work does not require external chiral stimuli (Figure 2c). This suggests that the “chiral–achiral” supramolecular interaction can be used as an alternative to the widely explored “chiral–chiral” supramolecular interaction, to selectively separate the cluster enantiomers. In addition, since the conglomerate crystallization method is essentially a recrystallization process, it can provide a sufficient amount of enantiopure nanoclusters for further chiroptical exploration. One fascinating example is the CPL responses investigated in this work. It is also important to note that the rich surface functionality of Ag₃₀ nanoclusters can provide abundant sites to rigidify the cluster surface, which may further increase the CPL intensity through the aggregation-induced emission (AIE) mechanism.¹⁰

Figure 2.

Schematic illustration of chiral resolution strategies for metal nanoclusters.

The formation of the double helix structure by regularly organizing cluster enantiomers is another interesting discovery. The double-helical assembly of metal nanoparticles can be obtained by using DNA and peptide templates, and the resulting helical architecture is a combination of the chirality and noncovalent interactions of building blocks (i.e., nucleotides and amino acids).² Coincidently, both the intracluster chirality and intercluster noncovalent interactions are strongly observed in the enantiopure L/R-Ag₃₀, which implies the biomimetic formation mechanism of the cluster double helix. We envision that the proteinlike hierarchical structure of metal nanoclusters lays the structural foundation for the biomimetic self-assembly behavior and may help produce more complex architectures in the near future. Moreover, it has been observed that the host–guest binding between DMAc molecules and nanoclusters promotes the helical arrangement of DMAc molecules to be encapsulated in a cluster lattice (Figure 1c,f). This indicates that the enantiopure metal nanoclusters (particularly in their organized forms) may provide unique binding sites for selected molecules, thereby satisfying highly stereoselective catalytic reactions.

In summary, the conglomerate crystallization methodology developed in this study by Zhao-Yang Wang, Shuang-Quan Zang, and team provides a facile and efficient way for the enantioseparation of intrinsically chiral metal nanoclusters. This can not only unravel atomic-level clues for understanding the chirality origin and self-assembly behavior of metal nanoclusters but also pave the way for further applications of chiral metal nanoparticles.