Conventional approaches to the synthesis of molecular knots and links mostly rely on metal templation. We present here an alternative strategy that uses the hydrophobic effect to drive the formation of complex interlocked structures in water. We designed an aqueous dynamic combinatorial system that can generate knots and links. In this system, the self-assembly of a topologically complex macrocycle is thermodynamically favored only if an optimum packing of all its components minimizes the hydrophobic surface area in contact with water. Therefore, the size, geometry, and rigidity of the initial building blocks can be exploited to control the formation of a specific topology. We illustrate the validity of this concept with the syntheses of a Hopf link, a Solomon link, and a trefoil knot. This latter molecule, whose self-assembly is templated by halides, binds iodide with high affinity in water. Overall, this work brings a fresh perspective on the synthesis of topologically complex molecules: Solvophobic effects can be intentionally harnessed to direct the efficient and selective self-assembly of knots and links.

The hydrophobic effect promotes the self-assembly of imine-based [2]catenanes in pure water.

Ar apid screening method based on traveling-wave ion-mobility spectrometry (TWIMS) combined with tandem mass spectrometry provides insight into the topology of interlocked and knotted molecules,e ven when they exist in complex mixtures,s uch as interconverting dynamic combinatorial libraries.ATWIMS characterization of structure-indicative fragments generated by collision-induced dissociation (CID) together with af loppiness parameter defined based on parent-and fragment-ion arrival times provideastraightforward topology identification. To demonstrate its broad applicability,t his approach is applied here to six Hopf and two Solomon links,atrefoil knot, and a[3]catenate.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Achiral [2]catenanes composed of rings with inequivalent sides may adopt chiral co-conformations. Their stereochemistry depends on the relative orientation of the interlocked rings and can be controlled by sterics or an external stimulus (e.g., a chemical stimulus). Herein, we have exploited this stereodynamic property to amplify a mechanically chiral ( P )-catenane upon binding to ( R )-1,1′-binaphthyl 2,2′-disulfonate, with a diastereomeric excess of 85%. The chirality of the [2]catenane was ascertained in the solid state by single crystal X-ray diffraction and in solution by NMR and CD spectroscopies. This study establishes a robust basis for the development of a new synthetic approach to access enantioenriched mechanically chiral [2]catenanes.