Catenanes: fifty years of molecular links

Abstract

Half a century after Schill and Lüttringhaus carried out the first directed synthesis of a [2]catenane, a plethora of strategies now exist for the construction of molecular Hopf links (singly interlocked rings), the simplest type of catenane. The precision and effectiveness with which suitable templates and/or noncovalent interactions can arrange building blocks has also enabled the synthesis of intricate and often beautiful higher order interlocked systems, including Solomon links, Borromean rings, and a Star of David catenane. This Review outlines the diverse strategies that exist for synthesizing catenanes in the 21st century and examines their emerging applications and the challenges that still exist for the synthesis of more complex topologies.

Keywords: catenanes; interlocked molecules; links; supramolecular chemistry; template synthesis.

Scheme 1

a) Attempted synthesis of a [2]catenane by Lüttringhaus and Cramer (1958). Complexation between dithiol 3 and α-cyclodextrin 4 led to a threaded inclusion complex (2), but subsequent oxidation did not afford catenane 1.[11] b) Wasserman's 1960 synthesis of a [2]catenane (7) by statistical threading of diester 6 through macrocycle 5 during an acyloin condensation.[1]

Scheme 2

Schill and Lüttringhaus's directed synthesis of a [2]catenane (1964).[14]

Scheme 3

Schill's directed synthesis of a [3]catenane (1969).[15]

Figure 1

The “Möbius strip” approach to generating different topological isomers. The macrocyclization of a ladder-shaped molecule (a) can form a range of cyclic molecules containing different numbers of twists (b). Cleavage of the rungs yields different topological isomers (c).

Scheme 4

Walba′s synthesis of a molecular Möbius strip.[19]

Figure 2

A selection of prime links with up to eight crossing points, and their Alexander–Briggs notation.

Figure 3

Four different representations of a Solomon link (${4_12 }$).

Figure 4

a) Electron micrograph of circular DNA revealing a catenane topology. b,c) Highlighting the two component rings of the DNA catenane as a Hopf link. Modified from Ref. [23] with permission.

Figure 5

The “chainmail” arrangement of proteins found in bacteriophage HK97s capsid (colored sections highlight the individual protein rings). a) The repeating pattern of interlocking proteins which constitute the spherical capsid. b) A cross-section of the capsid in which three protein rings interlock with one another. c) Magnified view of the position at which protein rings overlap (cross-linking isopeptide bonds are highlighted). Reprinted from Ref. [28] with permission.

Figure 6

Forming catenanes from single strands of synthetic DNA. Complementary sequences of DNA (represented by colored spheres) fold into helicates, the subsequent ligation of the strands affords catenanes.

Scheme 5

Sauvage's metal-template synthesis of a [2]catenane by Williamson ether macrocyclization of the tetrahedral coordination complex 23-Cu^I, formed by coordination of ligand 21 and macrocycle 22 to Cu^I.[43]

Scheme 6

Sauvage's high-yielding olefin metathesis macrocyclization to form [2]catenane 26-Cu^I.[44] Electrostatic interactions between the glycol ether oxygen atoms and the aromatic protons of the metal-coordinated dpp ligands may help promote intramolecular macrocyclization.

Scheme 7

Octahedral [2]catenanes 29-M^II formed around a range of divalent metal ions through double RCM reactions from precatenane 28-M^II or assembled by imine bond formation.[ The quoted yields refer to the double RCM route. Stabilizing π–π interactions between the phenyl and the pyridyl rings likely play a significant role in the assembly process.

Scheme 8

Beer's mixed-valence [2]catenane generated from partial oxidation of macrocycle 31-Cu^II.[53] Alkyl side chains have been omitted from the crystal structure for clarity.

Scheme 9

Catenane formation driven by aurophilic interactions from a) Mingos et al. (34-Au^I₁₂)[55] and b) Che et al. (36-Au^I₁₁).[56] In the crystal structure of 36-Au^I₁₁, the sugars have been omitted for clarity, whilst the sulfur atoms that constitute the pentameric ring are shown in blue.

Scheme 10

The active metal-template synthesis of a) heterocircuit [2]catenane 39 and b) homocircuit [2]catenane 41 by CuAAC macrocyclization reactions.[

Scheme 11

Stoddart's first [2]catenane, featuring π-electron-rich/π-electron-poor aromatic stacking.[65]

Scheme 12

Sanders' use of neutral π-electron-rich and poor motifs to form a [2]catenane by oxidative coupling of alkynes.[68]

Scheme 13

Ogoshi's synthesis of a [2]catenane assembled by threading of a pyridinium salt through the cavity of a pillar[5]arene cyclophane.[69]

Figure 7

Hunter's benzoquinone receptor.

Scheme 14

Hunter's synthesis of an amide-based [2]catenane 56 and its X-ray crystal structure (solvent molecules and non-amide hydrogen atoms omitted for clarity).[72], [73] Vögtle reported the synthesis of a very similar [2]catenane shortly afterwards.[74]

Scheme 15

The eight-molecule condensation to form benzylic amide [2]catenane 57.[76]

Scheme 16

Beer's synthesis of [2]catenane 60-Br⁻ directed by halogen bonding.[80]

Scheme 17

Beer's synthesis of a [2]catenane stabilized by a pyridinium iodide–pyridine interaction.[81]

Scheme 18

Stoddart's synthesis of [2]catenane 65, promoted by hydrophobic binding.[82]

Scheme 19

Fujita's “magic ring” [2]catenane synthesis. Reversible coordination of ligand 66 with Pd^II generates an interconverting mixture of macrocycle 67-Pd^II and [2]catenane 68-Pd^II, with the [2]catenane energetically favored at high concentrations through hydrophobic binding.[83], [84]

Scheme 20

Chiu's Na^I-template synthesis of a [2]catenane.[86]

Scheme 21

Beer's synthesis of a [2]catenane using a chloride anion template.[88]

Scheme 22

Stoddart's synthesis of a [2]catenane through radical-pairing interactions.[91]

Scheme 23

Sanders' [2]catenane formed within a DCL and amplified by acetylcholine biding.[93]

Scheme 24

Sanders' partial control over the composition of [2]catenanes formed from a disulfide-based DCL can be achieved by choice of the DN building block. In both cases, the DCLs initially also contained non-interlocked macrocycles. Amplification of [2]catenane 85 was achieved by the addition of either cationic templates to intercalate between the catenanes inner NDI units, or polar salts to enhance hydrophobic effects. Amplification of [2]catenane 87 was achieved by the addition of polar salts, whilst amplification of 88 was achieved by employing a threefold excess of DN 86 relative to NDI 83, and increasing the solvent ionic strength.[95], [96]

Figure 8

Classification of higher order [n]catenanes (n>2). a) [3]Catenane topoisomers. b) The addition of macrocycles to a linear [3]catenane generates further topoisomers.

Scheme 25

Sauvage's synthesis of a [3]catenane by linking two Cu^I-complexed pseudorotaxanes.[97], [98]

Scheme 26

Stoddart's assembly of [3]catenanes.[100]

Scheme 27

Stoddart's linear [5]catenane “Olympiadane”.[101]

Scheme 28

Sauvage's radial [n]catenanes generated by the oxidative homocoupling of alkyne-functionalized pseudorotaxanes, detected by ESI-MS. The yields are approximate and are based on m/z signal intensities from electrospray mass spectrometry. Catenanes 100-Cu^I₂, 101-Cu^I₃, and 102-Cu^I₄ could be isolated by chromatography, structures 103-Cu^I₅ and 104-Cu^I₆ could not.[106]

Scheme 29

Anderson's synthesis of the radial [4]catenane 110-Zn^II.[

Scheme 30

Kim's synthesis of a radial [4]catenane “molecular necklace” 112-Pt^II, assembled from threaded cucurbituril macrocycles and Pt^II connecting units.[108]

Scheme 31

Kim's radial [5]catenane.[109]

Scheme 32

Böhmer's [8]catenane-like structure based on interlocked calix[4]arene dimers. Hydrogen bonding between the urea motifs is illustrated with dashed lines.[111]

Scheme 33

Gunnlaugsson's lanthanide-template synthesis of an apparent ${6_33 }$ link.[

Scheme 34

a) Endo's polycatenane networks obtained from polymerization of 1,2-dithiane. b) Synthesis of linear poly(1,2-dithiane).[114]

Scheme 35

Fujita's triply interlocked cage complex formed by the self-assembly of four organic ligands with six square-planar-coordinating metal cations (Pd^II or Pt^II).[116] The interplanar distance between the aromatic faces of the cages is ideal for generating strong π–π stacking interactions with a separate intercalated cage.

Scheme 36

Beer's sulfate anion template synthesis of a catenane cage molecule.[120]

Scheme 37

Cooper's formation of discrete interlocked cages mediated by reversible imine bond formation.[121] Non-interlocked cage monomers 133 a–c are formed in the absence of CF₃CO₂H.[122]

Scheme 38

Nitschke and Sanders' [7]catenane based on the dynamic threading of macrocycles around each of the cage vertices.[124]

Scheme 39

Sauvage's use of trimetallic double-stranded linear helicates to generate a Solomon link in a) a single Williamson ether macrocyclization[125] and b) double macrocyclization by RCM.[126]

Scheme 40

The one-pot synthesis of a Solomon link based on a tetrameric circular helicate.[129]

Scheme 41

Puddephatt's Solomon link generated from the rearrangement of a dialkyne–Au^I polymer on introduction of coordinating diphosphine ligands. Phosphophenyl groups are omitted from the crystal structure for clarity. Au-Au distances; 3.130(2) and 3.239(2) Å.[130]

Scheme 42

Severin's Solomon link containing a 2:1 mixture of square-planar and tetrahedral coordinated metal cations. Dppp ligands on the Pt^II metal centers are omitted from the crystal structure for clarity.[131]

Scheme 43

A Star of David [2]catenane synthesized by RCM of a hexameric circular helicate scaffold. A PF₆⁻ ion occupies the central cavity of the helicate in the X-ray crystal structure of 150-Fe^II, oriented to direct the fluorine atoms towards the twelve electron-poor protons that line the walls of the cavity (CH⋅⋅⋅F distances 1.88–2.43 Å).[135]

Scheme 44

Stoddart's Borromean rings, with the carbon atoms in each ring of the interlocked topology highlighted in different colors (light blue, orange, and gray). Additional anions occupying the sixth coordination site in the Zn^II cations have been omitted for clarity. The Zn^II centers are all crystallographically equivalent, with distorted octahedral geometries (cis-N-Zn^II-N bond angles 72.5(2)–109.5(3)8). Extensive π stacking occurs between the phenyl rings and bipyridine groups (distances: 3.51 and 3.72 Å).[137]

Scheme 45

Jin's Borromean rings comprised of RhCp* metallarectangles. The Cp* ligands on the Rh metal centers are omitted from the crystal structure for clarity.[140]

Scheme 46

a) Sauvage's switchable heterocatenate 158.[143] b) Oxidation-state-controlled switching of [2]catenate 159 between three distinct co-conformations.[144]

Scheme 47

Stoddart's co-conformational switching of a [2]catenane mediated by the relative strengths of intermacrocycle electron-rich/poor aromatic stacking interactions.[145]

Scheme 48

Stoddart's reversible switching in a [2]catenane by alternating between electron-rich/poor aromatic stacking interactions and radical-pairing interactions as dominant intermacrocycle forces, after bipyridinium reduction and oxidation, respectively.[146]

Scheme 49

Sauvage's pH-induced switching between co-conformations following demetalation of a Cu^I-template-directed [2]catenane.[147]

Scheme 50

A three-state switching process between two co-conformations for a [2]catenane utilizing variable coordination modes of suitable Pd^II cations.[148]

Scheme 51

A [2]catenane in which modifying the binding affinity of three different stations to a benzylamide macrocycle allows switching between three discrete co-conformations. a) Structure of [2]catenane 164-(E,E). b) Illustration of the switching process.[

Scheme 52

A [3]catenane rotary motor. a) Structure of [3]catenane 165-(E,E).[ b) Illustration of the directional switching process. Conditions: i) UV (350 nm); ii) UV (254 nm); iii) heat.

Scheme 53

Cleavage and switching sequences in rotary motor [2]catenane 166, which is capable of directional and reversible circumrotation.[

Scheme 54

Beer's incorporation of a ferrocene motif into a catenane allows electrochemical sensing of anion binding in 167, which was found to selectively bind chloride anions. The corresponding non-interlocked macrocycles of 167 were found to display binding selectivity dictated by the basicity of the anions (BzO⁻>H₂PO₄⁻>Cl⁻>HSO₄⁻).[152]

Scheme 55

Beer's selective binding of chloride and bromide anions detected by optical sensing of their influence on the naphthalene emission spectra.[80]

Scheme 56

Yashima's cation-sensing catenane which undergoes a switch from a “locked” state to one in which macrocycles can freely rotate.[154]

Figure 9

A main-chain poly[2]catenane.

Scheme 57

Geert and Sauvage's synthesis of main-chain poly[2]catenanes incorporating dpp-Cu^I catenanes or their demetalated analogues.[158], [159]

Scheme 58

The solid-state polymerization of [2]catenane monomer 172 and bisphenol A polycarbonate oligomers to generate a main-chain poly[2]catenane copolymer.[

Figure 10

Side chain poly[2]catenanes in which (A) a single macrocycle forms part of the polymer main chain or (B) the entire catenane is a pendent group.

Scheme 59

Stoddart's side-chain poly[2]catenane in which a single macrocycle of the [2]catenane constitutes part of the polymer backbone.[

Scheme 60

Bria's side-chain [2]catenane polymer.[166]

Scheme 61

Stoddart and Yaghi's synthesis of metal–organic frameworks containing [2]catenane organic struts.[168], [169] The interlocked macrocycles which do not form part of the MOF backbone have been colored blue, and represented as space-filled structures for clarity.

Figure 11

Three different forms of [2]catenanes attached to surfaces.

Scheme 62

A thiol-functionalized [2]catenane tethered to a Au(111) surface.[172]

Scheme 63

Beer's chloride-containing pseudorotaxane which forms a [2]catenane with a Au(111) surface.[152]

Scheme 64

Stoddart's switchable [2]catenane layered between electrodes.[175]

Scheme 65

Stoddart's switchable [2]catenane tethered to a metal nanoparticle. TOAB=tetraoctylammonium bromide.[176]