[2]Catenanes Displaying Switchable Gin-Trap-Like Motion - The

Article pubs.acs.org/joc

Cite This: J. Org. Chem. 2018, 83, 5619−5628

[2]Catenanes Displaying Switchable Gin-Trap-Like Motion Chi-You Tsai,† Chien-Chen Lai,‡ Yi-Hung Liu,† Shie-Ming Peng,† Richard P. Cheng,*,† and Sheng-Hsien Chiu*,† †

Department of Chemistry, National Taiwan University, Taipei, Taiwan, R.O.C Institute of Molecular Biology, National Chung Hsing University and Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan, R.O.C

‡

S Supporting Information *

ABSTRACT: Sodium ion-controlled switching from “folded” to “linear” states results in significant changes in the molecular shape of a [2]catenane, such that it mimics the operation of a gin trap, with a fluorescent alarm signal appearing when pyrene side arms were present on its two macrocyclic components.

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INTRODUCTION Interlocked molecular switches have found use in molecular transportation,1 gelation,2 catalysis,3 and molecular machinery.4 Although the first catenanes were synthesized earlier than the first rotaxanes, the number of switchable [2]catenanes has remained significantly lower than the number of switchable [2]rotaxanes.5 [2]Rotaxane switches normally experience only slight changes in their molecular lengths and/or shapes after pirouetting of their interlocked macrocyclic components. In contrast, the arrangement of a macrocyclic component in a [2]catenane can lead to much more pronounced changes in molecular length when the two interlocked macrocycles are associated through two different pairs of recognition functionalities in the two switchable states (Figure 1). Such conformational changes should enable [2]catenane switches to serve as basic units for the construction of muscle-like materials6 or to mimic tools found in the real world. Herein, we report that the reversible “folded”-to-“linear” motion of a [2]catenane switch can be achieved through the addition/removal of Na+ ions, thereby mimicking the operation of a gin trap;7 appending a pyrene unit to the m-xylyl ring of each interlocked macrocyclic component led to the conformational transformation being reported in terms of changes to the fluorescence emission of the pyrene units.

dibromide 4 with diol 6 under basic conditions gave macrocycle 2 in 45% yield. Dibromide 7, obtained by reacting dibromide 5 with di(ethylene glycol) under basic conditions, was transformed to diamine 3 through azide substitution and a subsequent Staudinger reaction. The 1H NMR spectrum of an equimolar (10 mM) CDCl3 solution of macrocycle 2, diamine 3, NaTFPB, and isophthalaldehyde, heated at 348 K, indicated the formation of a predominant amount of imino[2]catenane [9·Na]+ after 15 h (Scheme 2 and Figure 2). Imino-[2]catenane [10·Na]+ formed at a much slower rate, displaying noticeable signals after 63 h and becoming the major product when the reaction had reached equilibrium after 495 h. We suspect that imino-[2]catenane [9·Na]+ assembled, in part, through a (presumably relatively rapid) clipping mechanism of two orthogonally aligned, Na+-templated units of diamine 3 by two units of isophthalaldehyde; in contrast, the assembly of [10·Na]+ required (presumably relatively slow) threading of diamine 3 through macrocycle 2, with the steric bulk of the tetrafluorobenzene units increasing the activation energy of this process. The yields of [2]catenanes [10·Na]+ and [9·Na]+, based on integration of their signals with reference to the signal of the TFPB anion at δ 7.74, were 54 and 27%, respectively. The imino bonds of the two [2]catenanes were reduced with NaBH4, and then the amino groups were subjected to methylation to give the hetero[2]catenane 1 and the homo[2]catenane 11 in overall yields of 39 and 15%, respectively. We determined the solid state structures10 (Figure 3) of [2]catenanes 1 and 11 through X-ray crystallographic analysis of single crystals obtained after liquid diffusion of hexane into their respective CH2Cl2 solutions, revealing the interlocked nature of the macrocyclic components corresponding to 12 and 2 (in 1) and of two copies of 12 (in 11). In the solid state, the homo[2]catenane 11 existed in a “linear” conformation, with its two ethylene glycol chains located in close proximity, each sandwiched between the tetrafluoro-p-xylyl rings of the other

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RESULTS AND DISCUSSION Previously, we demonstrated that Na+ ions can template the orthogonal alignment of oligo(ethylene glycol) units, enabling the facile syntheses of both rotaxanes and catenanes.8 Thus, we designed [2]catenane 1 with the expectation that ion−dipole interactions of a Na+ ion with the di(ethylene glycol) unit of each macrocyclic component would induce a more extended “linear” conformation (Figure 1), while the electronically complementary aromatic rings of its two interlocked macrocyclic components would stabilize a more compact “folded” conformation in the absence of Na+ ions.9 Accordingly, we prepared macrocycle 2 and diamine 3 from dibromides 42a and 5, respectively (Scheme 1). Reacting © 2018 American Chemical Society

Received: March 8, 2018 Published: April 27, 2018 5619

DOI: 10.1021/acs.joc.8b00601 J. Org. Chem. 2018, 83, 5619−5628

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The Journal of Organic Chemistry

Figure 1. Cartoon and structural representations of gin-trap-like motion in [2]catenane 1.

The 1H NMR spectrum of the hetero[2]catenane 1 in CD2Cl2 featured significantly upfield shifted (by −0.70 and −0.95 ppm) signals for the protons of the ethylene glycol motif (H7 and H8, respectively) of its fluorinated macrocyclic component, relative to those of the free macrocycle 12 (Figure 4), consistent with an edge-to-face conformation in solution, similar to that observed in the solid state (i.e., these protons were located between the two p-xylyl rings of the nonfluorinated macrocyclic component). It is very unlikely that a face-to-face conformation, featuring π-stacking of the p-xylyl and tetrafluoro-p-xylyl rings in [2]catenane 1, would cause such strong shielding of these protons because the p-xylyl rings would not be in a position to shield them in such a conformation. The 2D NOESY spectrum of [2]catenane 1 (Figure S2) revealed cross signals between the N-methyl protons and both the aromatic (Hb, Hc) and nearby benzylic (Hd and He) protons of the m-xylyl unit of the nonfluorinated macrocyclic component, suggesting that the m-xylyl rings of the two interlocked macrocyclic components were positioned nearby, as would be expected for structures having either edge-to-face or face-to-face conformations. Nevertheless, intense correlated signals for the protons (H7 and H8) of the ethylene glycol unit of the fluorinated macrocyclic component and the benzylic protons (Hd) adjacent to the m-xylyl ring of the nonfluorinated macrocyclic component suggested that the edge-to-face conformation was predominant for [2]catenane 1 in solution (i.e., such stacking of the m-xylyl ring between the two tetrafluoro-p-xylyl rings would place these protons closer together, whereas π-stacking of the p-xylyl and tetrafluoro-pxylyl rings in a face-to-face conformation would position these protons further apart with the two m-xylyl rings closer together). Therefore, from these spectral measurements we concluded that the edge-to-face conformation would be more likely than the face-to-face conformation for the hetero[2]catenane 1 in solution. Using molecular mechanics calculations to minimize the energy of the solid state structure of [2]catenane 1 resulted in only minor movements of the atoms, resulting in essentially the same structure after minimization (Figure S13). We subjected the minimized structure to molecular dynamics calculations

Scheme 1. Synthesis of Macrocycles 2 and 14 and Diamine 3

macrocyclic component (Figure 3a). In contrast, the two tetrafluoro-p-xylyl rings of the fluorinated macrocyclic component of the hetero[2]catenane 1 sandwiched the mxylyl ring of the other macrocyclic component in an edge-toface manner in its solid state structure, forming a more compact, “folded” conformation. Although we originally suspected that face-to-face stacking of the p-xylyl and tetrafluoro-p-xylyl rings would be an important stabilizing feature of the hetero[2]catenane 1 (Scheme 2), NMR spectroscopy and computational analysis did not support such a conformation (vide inf ra). 5620


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The Journal of Organic Chemistry Scheme 2. Synthesis of [2]Catenanes 1 and 11

xylyl protons (Hc and H3) of both macrocyclic components to the ethylene glycol protons of their interlocked counterparts (H8/H9 and Hi/Hj, respectively) in the 2D NOESY spectrum (Figure S4) suggested that, after complexing a Na+ ion, the conformation of [2]catenane [1·Na]+ switched to a more extended “linear” form (Figure 1). The computer-simulated structure of [2]catenane [1·Na+] (Figure 5b) was consistent with the data observed in the 2D NOESY experiments, supporting the “linear” conformation of this [2]catenane in solution. Computer simulations of the Na+-free “folded” (Figure S13) and Na+-complexed “linear” (Figure 5b) structures revealed that the distances between their two mxylene units (in particular, the carbon atoms in the metapositions to both substituents of the two m-xylene units) were 7.15 and 18.05 Å, respectively; thus, it appeared that complexation of a Na+ ion would indeed change the distance between these two m-xylene units significantly. The addition of 1 equiv of [2.2.2]cryptand to the equimolar mixture of NaTFPB and [2]catenane 1 removed the complexed Na+ ion from [2]catenane [1·Na]+ and shifted the signals in the

using simulated annealing procedures to generate a number of conformations. Among them, the structure featuring the m-xylyl ring sandwiched between the two tetrafluoro-p-xylyl rings in a face-to-face manner was energetically similar (Figure S14a) to the minimized solid state structure. The conformation featuring sequential face-to-face π-stacking of the p-xylyl and tetrafluoro-p-xylyl rings was not among the low-energy conformations; the structure obtained from forcing an interstitial arrangement (Figure 5a) was significantly higher in energy (ΔH = 6.7 kcal/mol) than the minimized solid state structure. Because the conformations featuring edge-to-face and face-to-face stacking of the m-xylyl ring between the two tetrafluoro-p-xylyl rings were close in energy, and the distances between the protons in the computer-optimized structures were consistent with the data obtained from the 2D NOESY experiments, we believe that both conformations are important and exchange rapidly in solution. The addition of 1 equiv of NaTFPB to a solution of [2]catenane 1 resulted in significant changes to its 1H NMR spectrum (Figure 6). The appearance of cross signals for the m5621


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Figure 2. 1H NMR spectra (400 MHz, CDCl3, 298 K) of an equimolar (10 mM) mixture of macrocycle 2, diamine 3, isophthalaldehyde, and NaTFPB that had been heated at 348 K for (a) 0, (b) 15, (c) 63, (d) 303, and (e) 495 h. Asterisks: signals for the TFPB anion.

Because the Na+-free and -complexed states of [2]catenane 1 feature its two interlocked macrocyclic components in compact “folded” and extended “linear” states with the two m-xylyl rings somewhat nearby and distant, respectively, the molecular motion during such switching appears to mimic the operation of a gin trap: the Na+-complexed “linear” state of [2]catenane 1 is a bait-ready “opened” form of the trap, and the Na+-free “folded” state is a “closed” form. Continuing the analogy, when the [2.2.2]cryptand “grabs” the Na+ ion “bait” from [2]catenane [1·Na]+ trap, rapid “linear”-to-“folded” switching occurs, much like the “opened”-to-“closed” transformation of a gin trap when its bait is grabbed by an animal. The introduction of a Na+ ion to the solution switches the conformation of [2]catenane 1 from the “folded” back to the “opened” form, analogous to the reopening of the gin trap through reloading of the bait. Thus, the reversible switching motion of [2]catenane 1 through the addition/removal of Na+ ions resembles, to some degree, the operation of a gin trap. Pyrene and its excimer have long been applied to provide fluorescence outputs in response to changes in distance associated with altered molecular structures.11 Accordingly, we synthesized [2]catenane 19, an analogue of 1, in the hope that its “folded” and “linear” conformations, with significant changes induced in the positions of the two m-xylyl rings, would be reported by the fluorescence signals of the pyrene side arms (Scheme 3). We used diol 1312 (Scheme 1) to prepare macrocycle 14 (under reaction conditions similar to those for macrocycle 2) and dialdehyde 15 (through PCC oxidation). We synthesized [2]catenane 16 through NaBH4mediated reduction of a mixture of macrocycle 14, diamine 3, dialdehyde 15, and NaTFPB (equilibrated at 348 K), followed by Eschweiler−Clarke methylation; we obtained 16, the homo[2]catenane 17, and macrocycle 18 in yields of 35, 17, and 11%, respectively. Removal of the silyl protecting group of [2]catenane 17 and subsequent appending of the pyrene side arms through N,Ń -dicyclohexylcarbodiimide (DCC)-assisted esterification gave the desired [2]catenane 19 in 66% yield.

Figure 3. Ball-and-stick representations of the solid state structures of the (a) [2]catenanes 11 and (b) 1. Atom coloring: C, gray; O, red; N, blue; and F, lime.

1

H NMR spectrum back to their original positions (i.e., before any additives were present), suggesting regeneration of the “folded” form of [2]catenane 1 in solution. We performed the same Na+ ion addition/removal processes for two more cycles, with the signals in the 1H NMR spectrum of the final “folded” state displaying no significant deviations from those of the original [2]catenane 1 (Figure S12). Thus, [2]catenane 1 can be switched reversibly between “folded” and “linear” conformations simply through the addition and removal of Na+ ions. 5622


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Figure 4. 1H NMR spectra (400 MHz, CD2Cl2, 298 K) of (a) macrocycle 2, (b) the hetero[2]catenane 1, and (c) macrocycle 12.

the solution led to a significant decrease in the intensity of the excimer signal at 476 nm (normalized at 377 nm), suggesting that the two pyrene rings of [2]catenane 19 were now spatially more distant, consistent with the coordination of the Na+ ion leading to formation of a “linear” conformation (Scheme 4). The addition of 1 equiv of [2.2.2]cryptand to the solution above reversed the changes of the excimer and monomer signals back to their original emission levels, suggesting that the conformation of [2]catenane 19 had switched from “linear” back to “folded.” Thus, [2]catenane 19 reported its own conformational switching between “linear” and “folded” states by emitting weak and strong signals, respectively, at 476 nm. Accordingly, [2]catenane 19 resembles a gin trap providing optical alarm signals, with a sudden and significant increase in the emission intensity at 476 nm indicating the loss of its Na+ “bait” to the [2.2.2]cryptand “beast.” Taking the excimer emission at 476 nm as the optical output, we switched [2]catenane 19 reversibly between its “folded” and “linear” states through four continuous cycles of sequential additions of NaTFPB and [2.2.2]cryptand to its CH2Cl2 solution (Figure 7b).13

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CONCLUSION We have demonstrated that changing the recognition pairs from edge-to-face-interacting m-xylyl and tetrafluoro-p-xylyl rings to Na+-bound di(ethylene glycol) chains allows [2]catenanes to undergo reversible switching between “folded” and “linear” states, with significant changes in molecular shape that can be reported by the emission signals of pyrene units attached to the two macrocyclic components. If we consider the Na+ ion as the “bait,” the “linear”-to-“folded” conformational transformation of the [2]catenane mimics the operation of a gin trap with the emission signal at 476 nm reporting the loss of the bait and possible capture of the prey. We hope that our results encourage further applications of catenane structures as basic functional units in muscle-like materials.

Figure 5. Energy-minimized structures of the (a) [2]catenane 1 with sequential stacking to the two p-xylyl rings (forcing interstitial) and (b) [1·Na+] (the Na+ ion appearing in CPK form). Atom coloring: C, gray; H, white; N, blue; O, red; F, cyan; Na, magenta.

The emission spectrum of [2]catenane 19 (1 μM) displayed (Figure 7a) the characteristic emission peaks of pyrene monomers and excimers at 377/397 and 476 nm, respectively; the intense signal of the excimer suggested that the two pyrene units must have been spatially proximal, consistent with a “folded” conformation. The addition of 1 equiv of NaTFPB to 5623


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Figure 6. 1H NMR spectra (400 MHz, CD2Cl2, 298 K) of (a) [2]catenane 1 (5 mM), (b) the sample obtained after the addition of NaTFPB (1 equiv) to the solution in a, (c) the sample obtained after the addition of [2.2.2]cryptand (1 equiv) to the solution in b, (d) the sample obtained after the addition of NaTFPB (1 equiv) to the solution in c, and (e) the sample obtained after the addition of [2.2.2]cryptand (1 equiv) to the solution in d. Hashtags: Signals for the TFPB anion. Asterisks: Signals for the [2.2.2]cryptand.

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HR-MS (ESI): calcd for [M + H]+ C20H17Br2F8O3+, m/z 614.9411; found, 614.9417. Diazide 8. A mixture of dibromide 7 (216 mg, 0.351 mmol) and sodium azide (91.3 mg, 1.40 mmol) in DMF (7.00 mL) was stirred at room temperature for 3 h. After evaporating the solvent under reduced pressure, the residue was partitioned between H2O (50 mL) and CH2Cl2 (50 mL × 2). The combined organic phases were dried (MgSO4) and concentrated to afford a pale-yellow oil (171 mg, 91%). 1 H NMR (400 MHz, CDCl3, 298 K): δ = 3.62−3.68 (m, 8H), 4.44 (s, 4H), 4.67 (s, 4H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 41.9, 60.2, 70.3, 70.5, 114.3 (t, JC−F = 15.6 Hz), 117.1 (t, JC−F = 16.0 Hz), 143.4−144.1 (m), 145.9−146.5 (m). HR-MS (ESI): calcd for [M + H]+ C20H17F8N6O3+, m/z 541.1229; found, 541.1234. Diamine 3. A solution of the diazide 8 (340 mg, 0.632 mmol) and triphenylphosphine (497 mg, 1.90 mmol) in THF (6.32 mL) was treated with H2O (171 mg, 9.48 mmol) and then stirred at room temperature for 16 h. The organic solvent was evaporated under reduced pressure and the residue purified chromatographically (NHSilica gel; CH2Cl2/MeOH, 98:2) to afford a pale-yellow oil (274 mg, 89%). 1H NMR (400 MHz, CDCl3, 298 K): δ = 3.63 (s, 8H), 3.95 (s, 4H), 4.64 (s, 4H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 34.1, 60.0, 69.9, 70.4, 114.8 (t, JC−F = 18.7 Hz), 121.6 (t, JC−F = 18.0 Hz), 143.0−143.9 (m), 145.4−146.4 (m). HR-MS (ESI): calcd for [M + H]+ C20H21F8N2O3+, m/z 489.1419; found, 489.1424. [2]Catenanes 1 and 11 and Macrocycle 12. A solution of macrocycle 2 (265 mg, 0.590 mmol), diamine 3 (288 mg, 0.590 mmol), isophthalaldehyde (79.1 mg, 0.590 mmol), and NaTFPB (523 mg, 0.590 mmol) in CHCl3 (59.0 mL) was stirred at 70 °C for 495 h. After cooling to room temperature, the mixture was slowly added to a solution of NaBH4 (890 mg, 23.5 mmol) in MeOH (236 mL), and then the organic solvents were evaporated under reduced pressure. The residue was partitioned between NaOH(aq) (150 mL) and CH2Cl2 (150 mL × 2). The organic phases were combined, dried (MgSO4), and concentrated. The residue was dissolved in DMF (59.0 mL) and treated with paraformaldehyde (915 mg, 29.5 mmol) and formic acid (1.11 g, 29.5 mmol); the mixture was then heated at 70 °C for 16 h. After cooling to room temperature, the solvents were evaporated

EXPERIMENTAL SECTION

General. All glassware, syringes, needles, and stir bars were ovendried prior to use. All reagents, unless otherwise indicated, were obtained from commercial sources. Reactions were conducted under N2 atmospheres. Thin layer chromatography (TLC) was performed on Merck 0.25 mm silica gel (Merck Art. 5715). Column chromatography was performed using Kieselgel 60 (Merck, 70−230 mesh) or Chromatorex NH-DM1020. High-resolution mass spectrometry (HRMS) was performed using a Sciex QStar Elite Q-TOF or a Bruker Daltonics autoflex MALDI-TOF mass spectrometer. Melting points were determined using a commercial hot stage apparatus and are uncorrected. Macrocycle 2. A solution of dibromide 4 (3.28 g, 6.95 mmol) and 1,3-benzenedimethanol (961 mg, 6.95 mmol) in THF (150 mL) was added slowly to a suspension of NaH (1.39 g, 34.8 mmol) in THF (546 mL) over 24 h, and then the mixture was heated under reflux for 5 days. After cooling to room temperature, the solvent was evaporated under reduced pressure and the residue purified chromatographically (SiO2; EtOAc/hexane, 3:7) to afford a white solid (1.41 g, 45%). Mp = 75.5−76.5 °C. 1H NMR (400 MHz, CDCl3, 298 K): δ = 3.66−3.73 (m, 8H), 4.52 (s, 4H), 4.54 (s, 4H), 4.60 (s, 4H), 7.22 (s, 1H), 7.30− 7.34 (m, 10H), 7.51 (s, 1H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 69.4, 70.8, 71.3, 71.3, 72.7, 126.9, 126.9, 127.5, 127.8, 128.2, 137.3, 137.8, 138.5. HR-MS (ESI): calcd for [M + H]+ C28H33O5+, m/z 449.2323; found, 449.2328. Dibromide 7. NaH (368 mg, 9.19 mmol) was added to a solution of di(ethylene glycol) (390 mg, 3.67 mmol) in THF (36.7 mL) at 0 °C, and then the mixture was stirred at room temperature for 30 min before dibromide 5 (4.91 g, 14.7 mmol) was added. The mixture was heated under reflux for 16 h and then cooled to room temperature. After evaporating the solvent under reduced pressure, the residue was purified chromatographically (SiO2; EtOAc/hexane, 1:5) to afford a pale-yellow oil (472 mg, 21%). 1H NMR (400 MHz, CDCl3, 298 K): δ = 3.62−3.67 (m, 8H), 4.49 (s, 4H), 4.65 (s, 4H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 16.3, 60.2, 70.3, 70.5, 116.9 (t, JC−F = 20.5 Hz), 117.1 (t, JC−F = 16.5 Hz), 143.0−144.0 (m), 145.5−146.6 (m). 5624


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The Journal of Organic Chemistry Scheme 3. Synthesis of the Pyrene-Containing [2]Catenane Switch 19

calcd for [M + H]+ C60H61F16N4O6+, m/z 1237.4330; found, 1237.4386. Data for Macrocycle 12. 1H NMR (400 MHz, CDCl3, 298 K): δ = 2.26 (s, 6H), 3.62 (s, 4H), 3.72 (s, 8H), 3.76 (s, 4H), 4.70 (s, 4H), 7.22 (d, J = 7.6 Hz, 2H), 7.28−7.32 (m, 1H), 7.47 (s, 1H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 41.8, 48.2, 60.2, 61.7, 69.9, 70.4, 115.1 (t, JC−F = 7.6 Hz), 117.0 (t, JC−F = 16.0 Hz), 127.6, 127.8, 129.7, 138.8, 143.7−144.1 (m), 146.1−146.5 (m). HR-MS (ESI): calcd for [M + H]+ C30H31F8N2O3+, m/z 619.2201; found, 619.2202. Macrocycle 14. A solution of dibromide 4 (1.22 g, 2.58 mmol) and diol 13 (1.13 g, 2.58 mmol) in THF (45.0 mL) was added slowly to a suspension of NaH (516 mg, 12.9 mmol) in THF (215 mL) over 24 h, and then the mixture was heated under reflux for 5 days. After cooling to room temperature, the solvent was evaporated under reduced pressure and the residue purified chromatographically (NHsilica gel; EtOAc/hexane, 7:3) to afford a white solid (293 mg, 22%). Mp = 92.5−93.0 °C. 1H NMR (400 MHz, CDCl3, 298 K): δ = 1.99 (t, J = 6.4 Hz, 1H), 3.66−3.73 (m, 8H), 3.94−3.97 (m, 2H), 4.10 (t, J = 4.8 Hz, 2H), 4.49 (s, 4H), 4.51 (s, 4H), 4.60 (s, 4H), 6.81(s, 2H), 7.09 (s, 1H), 7.31−7.35 (m, 8H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 61.3, 69.2, 69.5, 70.9, 71.1, 71.2, 72.7, 113.0, 119.7, 127.6, 127.8, 137.2, 137.9, 140.1, 158.8. HR-MS (ESI): calcd for [M + Na]+ C30H36NaO7+, m/z 531.2353; found, 531.2372. Dialdehyde 15. Pyridinium chlorochromate (2.08 g, 9.66 mmol) was added to a solution of diol 13 (1.41 g, 3.22 mmol) in CH2Cl2

under reduced pressure and the residue partitioned between NaOH(aq) (50 mL) and CH2Cl2 (50 mL × 2). The organic phases were combined, dried (MgSO4), and concentrated; the residue was purified chromatographically to afford [2]catenane 1 (NH-silica gel; EtOAc/ toluene, 1:2), [2]catenane 11 (diol-silica gel; EtOAc/hexane, 1:5), and macrocycle 12 (diol-silica gel; EtOAc/hexane, 1:9) in yields of 39% (245 mg; colorless sticky liquid), 15% (54.1 mg, white sticky liquid), and 7% (25.8 mg; colorless sticky liquid), respectively. Data for [2]Catenane 1. 1H NMR (400 MHz, CD3COCD3, 298 K): δ = 1.99 (s, 6H), 2.63 (br, 4H), 2.97 (br, 4H), 3.38−3.41 (m, 8H), 3.62 (s, 4H), 4.00 (s, 4H), 4.33 (s, 4H), 4.35 (s, 4H), 4.40 (s, 4H), 4.47 (s, 4H), 7.15−7.35 (m, 16H). 13C NMR [100 MHz, CD3COCD3, 298 K]: δ = 40.3, 50.1, 60.3, 61.4, 69.2, 70.0, 70.1, 70.7, 71.9, 73.3, 116.7 (t, JC−F = 19.5 Hz), 117.2 (t, JC−F = 18.0 Hz), 126.4, 127.7, 128.2, 128.4, 129.1, 129.4, 130.3, 138.5, 138.7, 139.6, 139.9, 144.5− 145.1 (m), 147.0−147.5 (m) (two signals are missing, possibly because of signal overlap). HR-MS (ESI): calcd for [M + H]+ C58H63F8N2O8+, m/z 1067.4451; found, 1067.4437. Data for [2]Catenane 11. 1H NMR (400 MHz, CDCl3, 298 K): δ = 2.05 (s, 12H), 3.12 (s, 8H), 3.19 (s, 8H), 3.56 (s, 8H), 3.94 (s, 8H), 4.40 (s, 8H), 7.06 (s, 2H), 7.24−7.29 (m, 6H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 39.7, 49.5, 59.9, 60.7, 69.0, 69.6, 115.2−115.7 (m), 127.5, 128.4, 129.4, 138.8, 143.7−144.0 (m), 146.1−146.5 (m) (one signal is missing, possibly because of signal overlap). HR-MS (ESI): 5625


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[2]Catenanes 16 and 17 and Macrocycle 18. A solution of macrocycle 14 (170 mg, 0.334 mmol), diamine 3 (163 mg, 0.334 mmol), dialdehyde 15 (144 mg, 0.334 mmol), and NaTFPB (296 mg, 0.334 mmol) in CHCl3 (33.4 mL) was stirred at 70 °C for 264 h. After cooling to room temperature, the mixture was added slowly to a solution of NaBH4 (505 mg, 13.4 mmol) in MeOH (134 mL), and then the solvents were evaporated under reduced pressure. The residue was partitioned between NaOH(aq) (100 mL) and CH2Cl2 (100 mL × 2). The organic phases were combined, dried (MgSO4), and concentrated. The residue was dissolved in DMF (14.6 mL) and treated with paraformaldehyde (226 mg, 7.28 mmol) and formic acid (335 mg, 7.28 mmol); the mixture was then heated at 70 °C for 16 h. After cooling to room temperature, the solvent was evaporated under reduced pressure and the residue partitioned between NaOH(aq) (50 mL) and CH2Cl2 (50 mL × 2). The organic phases were combined, dried (MgSO4), and concentrated; the residue was purified chromatographically to afford [2]catenane 16 (NH-silica gel; EtOAc/hexane, 3:7), [2]catenane 17 (NH-silica gel; EtOAc/hexane, 1:19), and macrocycle 18 (NH-silica gel; EtOAc/hexane, 1:19) in yields of 35% (165 mg; sticky colorless liquid), 17% (106 mg, sticky yellow liquid), and 11% (34.5 mg; sticky yellow liquid), respectively. Data for [2]Catenane 16. 1H NMR (400 MHz, CD3COCD3, 298 K): δ = 1.07 (s, 9H), 2.03 (s, 6H), 2.65 (br, 4H), 2.77 (s, 1H), 3.02 (br, 4H), 3.34 (br, 8H), 3.60 (s, 4H), 3.85−3.89 (m, 2H), 3.98 (s, 4H), 4.00−4.09 (m, 4H), 4.18 (s, 2H), 4.31 (s, 4H), 4.36 (s, 4H), 4.41 (s, 4H), 4.48 (s, 4H), 6.83 (s, 3H), 6.86 (s, 3H), 7.10−7.21 (m, 8H), 7.42−7.49 (m, 6H), 7.76−7.78 (m, 4H). 13C NMR (100 MHz, CD3COCD3, 298 K): δ = 19.3, 27.2, 40.5, 50.1, 60.3, 61.4, 61.5, 63.8, 69.0, 69.9, 70.0, 70.1, 70.4, 70.5, 71.8, 73.2, 112.7, 114.5, 116.6−117.6 (m), 119.8, 122.4, 128.6, 129.2, 130.6, 134.4, 136.4, 138.4, 138.7, 141.1, 141.4, 144.6−145.1 (m), 147.0−147.5 (m), 159.8, 160.3 (three signals are missing, possibly because of signal overlap). HR-MS (ESI): calcd for [M + Na]+ C78H88F8N2NaO12Si+, m/z 1447.5871; found, 1447.5858. Data for [2]Catenane 17. 1H NMR (400 MHz, CD2Cl2, 298 K): δ = 1.06 (s, 18H), 2.05 (s, 12H), 3.09 (br, 8H), 3.17 (br, 8H), 3.52 (s, 8H), 3.91 (s, 8H), 4.01 (br, 4H), 4.12 (br, 4H), 4.40 (s, 8H), 6.68 (s, 2H), 6.81 (s, 4H), 7.37−7.45 (m, 12H), 7.68−7.74 (m, 8H). 13C NMR (100 MHz, CD2Cl2, 298 K): δ = 19.5, 27.0, 40.2, 49.9, 60.3, 61.1, 63.4, 69.4, 69.6, 70.0, 113.9, 115.9−116.4 (m), 121.9, 128.1, 130.1, 134.1, 136.1, 140.9, 144.2−144.5 (m), 146.6−146.9 (m), 159.7 (one signal is missing, possibly because of signal overlap). HR-MS (ESI): calcd for [M + Na]+ C96H104F16N4NaO10Si2+, m/z 1855.6928; found, 1855.6849.

Figure 7. (a) Emission spectra (normalized at 377 nm) recorded after sequential additions of 1 equiv of NaTFPB (blue) and 1 equiv of [2.2.2]cryptand (red) to a CH2Cl2 solution (1 μM) of [2]catenane 19. (b) Plot of the fluorescence intensities during four on−off cycles of switching of [2]catenane 19. Excitation, 344 nm; emission, 476 nm. (37.0 mL) and THF (25.0 mL), and then the mixture was stirred at room temperature for 16 h. After evaporating the organic solvents under reduced pressure, the residue was purified chromatographically (SiO2; EtOAc/hexane, 1:19) to afford a colorless oil (1.38 g, 99%). 1H NMR (400 MHz, CDCl3, 298 K): δ = 1.03 (s, 9H), 4.02 (t, J = 4.8 Hz, 2H), 4.19 (t, J = 4.8 Hz, 2H), 7.34−7.43 (m, 6H), 7.59 (s, 2H), 7.66− 7.68 (m, 4H), 7.93 (s, 1H), 10.02 (s, 2H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 19.2, 26.7, 62.5, 69.9, 120.0, 124.0, 127.7, 129.8, 133.3, 135.6, 138.3, 160.2, 190.8. HR-MS (ESI): calcd for [M + Na]+ C26H28NaO4Si+, m/z 455.1649; found, 455.1651.

Scheme 4. Na+-Controllable Switching of the Fluorescence-Active [2]Catenane 19

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Data for Macrocycle 18. 1H NMR (400 MHz, CDCl3, 298 K): δ = 1.06 (s, 9H), 2.19 (s, 6H), 3.51 (s, 4H), 3.65 (s, 8H), 3.70 (s, 4H), 3.92−4.00 (m, 2H), 4.08−4.13 (m, 2H), 4.64 (s, 4H), 6.73 (s, 2H), 6.99 (s, 1H), 7.35−7.43 (m, 6H), 7.66−7.72 (m, 4H). 13C NMR (100 MHz, CDCl3, 298 K): δ = 19.2, 26.8, 41.8, 48.2, 60.2, 61.7, 62.8, 69.1, 69.9, 70.4, 113.7, 114.9−115.4 (m), 116.6−117.2 (m), 122.0, 127.6, 129.6, 133.6, 135.6, 140.1, 143.8−144.1 (m), 146.3−146.7 (m), 158.8. HR-MS (ESI): calcd for [M + Na]+ C48H52F8N2NaO5Si+, m/z 939.3410; found, 939.3425. [2]Catenane 19. TBAF (1 M in THF, 149 μL, 0.149 mmol) was added to a solution of [2]catenane 17 (96.8 mg, 679 μmol) in THF (3.40 mL) at room temperature, and then the mixture was stirred at room temperature for 16 h. The solvent was evaporated under reduced pressure and the residue partitioned between H2O (15 mL) and EtOAc (15 mL × 3). The combined organic phases were concentrated under reduced pressure and the residue dissolved in CH2Cl2 (3.40 mL). This solution was treated with 1-pyrenebutyric acid (43.1 mg, 0.149 mmol), DCC (30.8 mg, 0.149 mmol), and 4-dimethylaminopyridine (1.66 mg, 0.014 mmol). The mixture was stirred at room temperature for 24 h, then concentrated. The residue was purified chromatographically (SiO2; CH2Cl2/MeOH, 98:2) to give a sticky pale-yellow liquid (77.6 mg, 66%). 1H NMR (400 MHz, CD2Cl2, 298 K): δ = 1.90 (s, 6H), 2.17 (quint, J = 7.2 Hz, 4H), 2.48 (t, J = 7.2 Hz, 4H), 2.57 (s, 4H), 2.89 (s, 4H), 3.35−3.39 (m, 12H), 3.44 (s, 4H), 3.73 (s, 4H), 4.10−4.12 (m, 4H), 4.16 (s, 4H), 4.20 (s, 4H), 4.30 (s, 4H), 4.32 (s, 4H), 4.36−4.38 (m, 4H), 6.68 (s, 2H), 6.71 (s, 1H), 6.75 (s, 2H), 6.78 (s, 1H), 7.07−7.12 (m, 8H), 7.85 (d, J = 7.6 Hz, 2H), 7.92−8.01 (m, 6H), 8.02−8.18 (m, 8H), 8.25−8.31 (m, 2H). 13C NMR (100 MHz, CD2Cl2, 298 K): δ = 27.2, 27.3, 33.1, 33.1, 34.1, 34.2, 40.3, 49.7, 60.0, 60.9, 63.2, 63.3, 66.3, 66.4, 69.0, 69.6, 69.8, 70.5, 71.4, 73.0, 73.2, 112.1, 113.9, 116.7−116.5 (m), 120.0, 122.7, 123.8, 125.1, 125.1, 125.2, 125.4, 126.3, 127.0, 127.0, 127.6, 127.7, 127.9, 128.8, 128.9, 129.1, 129.1, 130.3, 130.3, 131.3, 131.3, 131.8, 131.8, 136.5, 136.5, 137.9, 138.0, 140.5, 141.0, 143.9−144.4 (m), 146.4− 146.8 (m), 158.7, 159.2, 173.6 (13 signals are missing, possibly because of signal overlap). HR-MS (MALDI): calcd for [M + H]+ C102H99F8N2O14+, m/z 1727.6963; found, 1749.6876.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00601.

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Article

NMR spectra, computational data, and X-ray crystallography data of [2]catenanes (PDF) X-ray crystallography data for [2]catenane 1 (CIF) X-ray crystallography data for [2]catenane 11 (CIF)

AUTHOR INFORMATION

Corresponding Authors

*(R.P.C.) E-mail: [email protected]. *(S.-H.C.) E-mail: [email protected]. ORCID

Sheng-Hsien Chiu: 0000-0002-0040-1555 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the Ministry of Science and Technology (Taiwan) (MOST-106-2628-M-002-002 and MOST-106-2113-M-002011) and National Taiwan University (NTU-106R880202) for financial support. We thank the Computer and Information Networking Center at National Taiwan University for supporting the high-performance computing facilities. 5627


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The Journal of Organic Chemistry Corradini, R. A bifunctional monomer for on-resin synthesis of polyfunctional PNAs and tailored induced-fit switching probes. Org. Lett. 2016, 18, 5452−5455. (d) Bai, Y.; Zhao, Q. Rapid fluorescence detection of immunoglobulin E using an aptamer switch based on a binding-induced pyrene excimer. Anal. Methods 2017, 9, 3962−3967. (12) Lu, D.; Hossain, M. D.; Jia, Z.; Monteiro, M. J. One-pot orthogonal copper-catalyzed synthesis and self-assembly of l-lysinedecorated polymeric dendrimers. Macromolecules 2015, 48, 1688− 1702. (13) The fluorescence change may allow the [2]catenanes to be applied as molecular sensors for alkali metal ions.

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[2]Catenanes Displaying Switchable Gin-Trap-Like Motion - The

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