CHEMICAL SCIENCE

ECNU constructs a high-order topology through chiral auxiliary base strategy


On December 6, 2022, Beijing time, Zhang Liang’s research group in the School of Chemistry and Molecular Engineering of East China Normal University made progress in the emerging field of molecular nanotopology, and published back-to-back titles entitled “Completely Stereospecific Synthesis of a Molecular Cinquefoil (51) Knot” and “A” in the international journals Chem Star of David [2]catenane of Single Handedness” two papers, realizing the molecular five-leaf knot (51) and the Star of David, respectively[2]Efficient, specific stereoselective synthesis of Star of David.

In the two papers, researcher Zhang Liang from the School of Chemistry and Molecular Engineering of East China Normal University is the corresponding author of the two papers, Zhang Zhihui, a postdoctoral fellow at the School of Chemistry and Molecular Engineering of East China Normal University, is the first author of the molecular conclusion, doctoral student Haina Feng and Sun Zhanhu are the co-first authors of the molecular hydrocarbon paper, and Yanhang Ma of ShanghaiTech University and Professor Li Zhiming of Fudan University also participated in the research work.

The history of molecular nanotopology dates back to 1961, when Frisch and Wasserman proposed chemical topology in order to elucidate the topological isomerism of molecules. With Professor Jean-Pierre Sauvage (Nobel Prize in Chemistry 2016) creatively proposing the strategy of “Metal-template Synthesis” that opened the door to the synthesis of complex topologies, scientists are witnessing the advent of a new era in molecular nanotechnology. Based on summarizing the development of chemical topology, mechanical bonding and mechanically interlocking molecules including molecular junctions and molecular hydrocarbons, Professor Fraser Stoddart (Nobel Prize in Chemistry 2016) first proposed the concept of “molecular nanotopology” in 2020 to define this emerging discipline (Nano Lett. 2020, 20, 5597; CCS Chem. 2021, 3, 1542.)。

Molecular junctions and cord hydrocarbons can be divided into three categories: achirism, conditional topological chirality, and unconditional topological chirality. Topological chirality refers to the property that molecules with topological structures cannot be converted into mirror images by continuous deformation in three-dimensional space, which is a “flexible” non-Euclidean handiness that distinguishes it from Euclidean handiness. At present, there are three strategies for constructing single topological chiral molecular junctions and hydrocarbons: stereoselective preparation by chiral infrastructure units, kinetic disassembly, and separation of enantiomers by chiral high performance liquid chromatography. Some low-order topological molecules such as three-leaf knot and solomon hydrocarbons have been prepared and synthesized by these methods, but there is still a lack of stereoselective synthesis of higher-order topological molecules with single chirality. In response to this scientific problem, Zhang Liang’s research team used metal ions as a template, using ligands containing stereoscopic (chiral) centers, to transfer point-chirality from ligands to polymetallic spirochetes with spiral chirality, and then further to topological molecules with intrinsic topological chirality, and finally accurately constructed a molecular five-leaf knot with a single topological chirality and the Star of David. The stereoselective synthesis of nanotopological molecules with specific topological kinks using chiral information transfer strategy opens up a new way to explore the potential of topological stereochemistry in chemistry, materials and biology.

1. Stereoselective construction of molecular five-leaf knots

In the first work, the researchers used the pyridine-thiazole ligand reported by Professor Rice’s group and used two chiral valines as chiral inducers to successfully construct the molecular five-leaf knot of Δ and Λchiral. Different from the previously reported topology based on polypyridine, the unique torsion angle of the pyridine-thiazole ligand allows it to spontaneously form an “up-down” staggered arrangement when coordinating with metals, which has the characteristics of easy synthesis and modification, making it possible to construct topological molecules with different functional groups and their applications.

As shown in Figure 1, the authors would (R,R)-1The ligand was mixed with 1 equivalent Zn(OTf)2 in CH3CN solution, and then quantitatively formed a product with a high symmetric structure, and then the single crystal diffraction results confirmed that the product was a circular pentanolic, where ligand (R,R)-1and (S,S)-1The formation of Δ and Λchiral annular treponemals was selectively induced respectively, and their d.e. values were as high as 100%. By introducing terminal olefins with suitable chain length at the three positions of pyridine, the metal five-leaf knot was successfully constructed by cycloaddition reaction. Finally, by Li2S demetalization, the organic molecule five-leaf knot Δ- was obtained by gel permeation chromatography.2and Λ-2

Figure 1: Schematic diagram of the synthetic route of the molecular five-leaf junction

Since the organic molecule five-leaf junction Δ-2and Λ-2In cases where NMR and carbon spectra and mass spectrometry are indistinguishable, the authors utilized circular dicography to continue characterizing the product (Figure 2). Chiral molecule five-leaf knot Δ-2and Λ-2The CD curve shows a perfect mirror image coincide, indicating that the two have opposite chiralities. At the same time, compared with the ligands that only have point-chirality, the CD signal of chiral molecular nodes is enhanced, indicating that the contribution of topological chirality in chiral molecular nodes to the overall chirality of molecules is greater than the sum of point-chiral molecules.

Figure 2: Circular dichromatograms of organic molecules Δ-2 and Λ-2 and ligands (R,R)-1 and (S,S)-1

In addition, the authors also explore the application of metal five-leaf junctions in the direction of anion recognition and ion transport, and the results show that organometallic junctions can form channels in phospholipid bilayers, which are expected to become carriers for ion transport and thus be used in the biological field. In summary, this work fixes the chirality of the circular pentanolic helix by using the coordination of Zn(II) metal with chiral amino acids, synthesizes high-order molecular junction 51 with high stereoselectivity, and explores the application prospect of metal junction in biology and materials.

2. Three-dimensional selective construction of the Star of David

The family of pyridine and bipyridine ligands with stereocentric centers developed by von Zelewsky and colleagues are called CHIRAGENs, which can fix the chirality of metal coordination sites in a highly stereoselective manner, unlike Lehn-type spirochetes that are difficult to functionalize, the introduction of CHIRAGENs provides an efficient way to construct higher-order molecular junctions and cord hydrocarbons with controlled chirality.

The authors by modifying the pinene bipyridine ligand1Hexameric annular treponemal treponemal was obtained by highly stereoselective self-assembly with monovalent metallic silver or copper ions (Figure 3), and the main product David Star Λ- was successfully constructed by ring closure by olefin metathesis reaction for ring closure, and finally the metal David Star was demetallized by Na4EDTA, and the main product David Star Λ- was obtained by gel permeation chromatography2and the Great Ring3The topology was characterized by NMR, ESI-MS, CD, etc.

Figure 3: Stereoselective synthesis of Λ- [Ag616](PF6)6、Λ-[Cu616](PF6)6 and Star of David Λ-2

Tandem mass spectrometry (MS/MS) clearly confirmed the interlocking structure of David Star Λ-2 (Figure 4). Select Will[Λ-2+3H]The 3+ ions (m/z 1430.83) underwent collision-induced dissociation, and two peaks were detected at m/z 715.49 and 1072.98, corresponding to large rings3target[M+3H]3+ and[M+2H]2+ ion peaks. The result is related to[2]The typical fragmentation process of soloxamines is consistent, where one of the macrocyclic covalent connections is broken and slips, eventually forming a single large ring that remains charged.

Figure 4: Low-resolution ESI MS and MS/MS characterization of David Star Λ-2

In addition, the authors measured the ligand1, large ring3and Star of David Λ-2Circular dichroic spectroscopy (CD), Star of David Λ-2The induced CD signal appears weaker than the ligand1and the Great Ring3(Figure 5). This is due to the organic Star of David Λ-2Through the asymmetric conformation with multiple mutual transformations of skeleton peristalsis, the CD with its average effect is obtained, indicating that a single element of its topological chirality affects the asymmetry of the chromophore environment more effectively than the sum of chiral stereocarbon centers.

Figure 5: UV-Vis and CD spectra of ligand 1, macroring 3, and David Star Λ-2(Source: Science Network)

Related paper information:

https://doi.org/10.1016/j.chempr.2022.11.009

https://doi.org/10.1016/j.chempr.2022.11.010



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