Reversible reduction drives anion ejection and C₆₀ binding within an Fe^II₄L₆ cage

Abstract

Fe^II₄L₆ tetrahedral cage 1 was prepared from a redox-active dicationic naphthalenediimide (NDI) ligand. The +20 charge of the cage makes it a good host for anionic guests, with no binding observed for neutral aromatic molecules. Following reduction by Cp₂Co, the cage released anionic guests; subsequent oxidation by AgNTf₂ led to re-uptake of anions. In its reduced form, however, 1 was observed to bind neutral C₆₀. The fullerene guest was subsequently ejected following cage re-oxidation. The guest release process was found to be facilitated by anion-mediated transport from organic to aqueous solution. Cage 1 thus employs electron transfer as a stimulus to control the uptake and release of both neutral and charged guests, through distinct pathways.

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Introduction

Self-assembled metal–organic cages¹ have found uses across various fields, ranging from chemical separations,² catalyzing organic reactions,³ sensing specific analytes⁴ and acting as photoreactors,⁵ among others. These applications are often based on encapsulation of guests within the well-defined inner cavities of cages. Guest uptake and release by a host molecule can be controlled using stimuli such as heat,⁶ light,⁷ pH⁸ and competing guests,⁹ as understanding has increased as to how to design stimuli-responsive behaviour.¹⁰ The use of redox stimuli is particularly attractive¹¹ because electrons are ‘clean’ stimuli, producing no chemical by-products. Thus far, several redox-active metal–organic cages have been successfully synthesized.^11c Recently Sallé, Goeb and co-workers reported several tetrathiafulvalene based coordination cages, which can reversibly uptake and release perfluorocarborate^11d or corronene^11a guests under redox control. Inspired by these achievements, we sought to develop new redox-active metal–organic cage systems capable of reversible guest uptake. In the present system, electron transfer was used to stimulate the uptake and release of both anionic and neutral guests, via distinct pathways.

Naphthalenediimides (NDIs) and their derivatives are redox-active electron-deficient compounds, and can be readily substituted with a wide variety of functional groups,¹² making them ideal building blocks for metal–organic cages.¹³ We have reported several NDI-diamine based tetrahedral metal–organic cages, with the redox behaviour of one catalyzing the oxidative coupling of arylborates to give biphenyls.¹⁴ However, reduction of that cage¹⁴ resulted in precipitation due to charge neutralization. This behaviour prevented further study of its redox dependent host–guest chemistry in solution. In order to solve this issue, we designed a new dicationic subcomponent, A (Fig. 1). We hypothesised that the permanent charges of A would improve the solubility of the corresponding cage 1, following reduction of the NDI moieties. This Fe^II₄L₆ cage, 1, did indeed remain in solution upon NDI reduction, enabling different guests to be taken up and released upon reduction and oxidation of the cage.

Fig. 1 The synthesis of Fe^II₄L₆ cage 1 (top) and crystal structure of 1 with three carborate anions encapsulated (bottom). Cage hydrogen atoms, counterions, solvents and disorder are omitted for clarity.

Results and discussion

Tetrahedral Fe^II₄L₆ cage 1 was synthesized from quaternary-ammonium-functionalized NDI subcomponent A (6 equiv.), 2-formylpyridine (12 equiv.) and Fe(NTf₂)₂ (4 equiv.) in acetonitrile (Fig. 1). The ¹H NMR spectrum of 1 was consistent with a single symmetric species (Fig. S2–S7†). ESI-MS of 1 confirmed the formation of an assembly with Fe^II₄L₆ stoichiometry (Fig. S8–S11†). Subcomponent A was not observed to form the Zn₄L₆ analogue of 1 when Zn(NTf₂)₂ was used in place of the iron salt. We infer this lack of reactivity to be due to the weaker metal–ligand bonds involving zinc not being able to compensate for coulombic repulsion among the cationic ligands.

Single crystals of 1 were obtained from vapour diffusion of diisopropyl ether into an acetonitrile solution of 1 containing cesium carborane (10 equiv.). The crystal structure of 1 revealed a T-symmetric framework (Fig. 1), with six ligands bridging four octahedral iron(II) centres of the same handedness. The solid state structure is consistent with NMR data, in which all ligands are magnetically equivalent. The metal–metal distances are in the range 18.771(3)–19.345(2) Å (average 19.1 Å). The NDI moieties lie tangent to the edges of the tetrahedron, affording an enclosed cavity which is further blocked by the –(CH₂)₂N⁺(Me)₃ substituents of the ligands. A cavity volume of 1100 ų was determined using VOIDOO¹⁵ (Fig. S26†). Three carborate anions were found in the cavity in the solid state.

The electrochemical properties of cage 1 and subcomponent A were investigated by cyclic voltammetry, carried out in 0.1 M ⁿBu₄N⁺Tf₂N⁻ in MeCN at a scan rate of 500 mV s⁻¹. Similar to other NDI derivatives,^14,16 cage 1 exhibited a quasi-reversible process upon reduction (Fig. 2), in which the first reduction wave appeared at −0.81 V vs. Fc/Fc* and the second occurred at −1.19 V. The related oxidation waves were found at −1.29 and −0.78 V. Reduction was reversible over several cycles. In comparison, two similar reduction waves (at −0.96 and −1.36 V) were also observed for subcomponent A (Fig. S25†). However, the intensity of the CV signals decreased with each cycle in the case of A, consistent with irreversible reactions following redox events for A, but not for 1. We thus infer that self-assembly rendered the NDI panels more robust to redox processes.

Fig. 2 Cyclic voltammetry (5 scans, 500 mV s⁻¹) of 1 in MeCN (0.1 M ⁿBu₄N⁺Tf₂N⁻) at 25 °C.

In light of our electrochemical studies, we investigated the reactions of 1 with chemical reductants and oxidants. Cp₂Co and AgNTf₂ were selected as an appropriate one-electron reductant and oxidant, respectively, for 1. Following the addition of Cp₂Co (10 equiv.), a sharp signal attributed to Cp₂Co⁺ appeared at 5.67 ppm in the ¹H NMR spectrum, indicating that cage reduction had occurred. Following reduction, the cage signals became NMR silent due to the formation of radical species, as was observed previously in the case of related systems.^14,17 When AgNTf₂ (12 equiv.) was added to the mixture, the cage signals reappeared cleanly (Fig. S41†), demonstrating the reversibility of the process.

Next we investigated the binding behaviour of 1 with various prospective guests using ¹H NMR spectroscopy in CD₃CN. Cage 1 did not show measurable affinity towards the neutral species investigated (Fig. 3 and S27–S32†) despite the enclosed cavity observed in the crystal structure (Fig. 1).

Fig. 3 Top, neutral aromatic non-guests and anionic guests for cage 1; bottom, a stacked plot of the ¹H NMR titration (500 MHz, 298 K) of KBF₃Ph into a solution of 1 (0.17 mM) in CD₃CN. The signals from the guest (KBF₃Ph) have been labelled with red and blue dots, and the others belong to cage 1.

Only the anions BF₄⁻, PhBF₃⁻ and CB₁₁H₁₂⁻ were observed to bind in fast exchange on the NMR chemical-shift timescale (Fig. 3 and S33–S40†). For instance, the ¹H NMR signals of PhBF₃⁻ were shifted upfield by up to 0.91 ppm in the presence of 1. Similar chemical shift changes were also observed in the ¹⁹F NMR spectrum of this anion (Fig. S37†); host signals were also observed to shift in the presence of guests. However, the binding stoichiometries of these anions in cage 1 could not be established due to their fast exchange binding, and attempts to crystallize these host–guest adducts were also not successful. The ¹⁹F NMR signal of triflimide shifted upon the addition of KBF₃Ph, suggesting that the encapsulated Tf₂N⁻ anions were released in the presence of the competing guest PhBF₃⁻ (Fig. S36†). We infer the cationic nature of subcomponent A to impart the cage with a higher binding affinity for anionic guests relative to neutral guests.

PhBF₃⁻ was chosen as a model guest to probe the binding behaviour of 1 under redox control. During the stepwise addition of Cp₂Co, the ¹H NMR signals of PhBF₃⁻ gradually shifted downfield, towards the values for the free guest (Fig. 4).

Fig. 4 Redox control of KBF₃Ph binding within 1.

We infer the reduction of the NDI panels of 1 to result in repulsion between the anionic guest and the reduced cage panels, leading to release of the bound guests. The signals of 1 broadened into the baseline during the reduction process due to the formation of radical anion species. After the addition of 10 equivalents of Cp₂Co, the ¹H NMR signals of PhBF₃⁻ were found at the same chemical shift values as the free anion, suggesting complete ejection of the guest from the cage cavity. Full recovery of the ¹H NMR spectrum of PhBF₃⁻ ⊂ 1 was observed after the addition of AgNTf₂ (12 equiv.).

We next investigated the use of electron transfer to control the uptake and release and of neutral molecules. Although cage 1 possesses a +20 charge, which favours the binding of anions, we reasoned that reduction of the NDI panels with Cp₂Co would partially neutralize the charge and potentially modify the guest preference.

The X-ray structure of 1 (Fig. 1) suggested that cage 1 would have a suitable volume (Fig. S26†) to accommodate C₆₀, and analogous cages have been shown to bind fullerenes well.^14,18 C₆₀ thus appeared to be an ideal guest molecule to test the catch-and-release cycle shown in Fig. 5. This cycle is inferred to have three distinct stages. First, after the addition of Cp₂Co, reduced cage 1 released the anionic guest in favour of neutral C₆₀. Second, treatment with AgNTf₂ oxidized the cage back to its initial state, giving C₆₀ ⊂ 1 as a kinetically-trapped species. Third, the thermodynamically-unfavourable C₆₀ ⊂ 1 released neutral C₆₀, generating the more stable triflimide adduct.

Fig. 5 The encapsulation and release of C₆₀ within cage 1 following reduction and subsequent re-oxidation.

To test the cycle of Fig. 5, a solution of reduced cage 1, prepared through addition of Cp₂Co (10 equiv.) to 1 in CD₃CN, was mixed with C₆₀ (4 equiv.), and the mixture was kept at room temperature overnight. AgNTf₂ (12 equiv.) was added to oxidize the cage back to its initial state. The presence of C₆₀ was confirmed by ¹³C NMR (Fig. S15 and S21†) in CD₃CN, a solvent in which free C₆₀ displays negligible solubility.¹⁹

Cage 1 exhibited T point symmetry in solution, as reflected in its ¹H NMR spectra,²⁰ however, the encapsulation of C₆₀ within 1 resulted in the formation of diastereomers having all possible combinations of Δ and Λ metal stereochemistries with T, S₄, and C₃ point symmetries (Fig. S13†).^13d,20 Interestingly, the C₆₀ ⊂ 1 complex was found to be a kinetically trapped species. After 5 days the S₄ and C₃ diastereomers²⁰ (Fig. S19†) of C₆₀ ⊂ 1 released their encapsulated C₆₀ with concomitant formation of free 1 and a reduction in the intensity of ¹³C NMR signal for C₆₀ (Fig. S21†). Only the T diastereomer²⁰ of C₆₀ ⊂ 1 (14% by ¹H NMR integration) remained in solution after 30 days, indicating its greater kinetic stability relative to the other diastereomers of C₆₀ ⊂ 1 (Fig. 6).

Fig. 6 The release of C₆₀ from C₆₀ ⊂ 1 monitored by ¹H NMR (500 MHz, CD₃CN) over the course of a month.

Counteranions have been shown to drive the phase transfer of cationic coordination cages, permitting guests to be conveyed across phase boundaries.^1a,1c The treatment of a solution of cage 1 in MeCN/EtOAc (1 : 1) with aqueous Na₂SO₄ resulted in transfer of 1 from the organic phase into water (Fig. S42 and S43†) as the sulfate salt.^1a Treatment with aqueous Na₂SO₄ likewise stimulated phase transfer of the C₆₀ ⊂ 1 host–guest complex. This complex, however, was observed to release C₆₀ upon phase transfer, allowing cargo recovery by filtration (Fig. 7, S44 and S45†). This novel use of phase transfer to effect guest ejection could enable new means of chemical purification, whereby a guest is separated from its recyclable host in a single step, rather than requiring a separate purification step.²¹

Fig. 7 (a) Mixture of cage 1 and C₆₀ in MeCN. (b) Formation of C₆₀ ⊂ 1. (c) The release of C₆₀ and transfer of cage 1 from the EtOAc/MeCN to the water layer.

Conclusions

In this study, we reported a new redox-switchable Fe^II₄L₆ tetrahedral cage. Although, the cage shows binding affinity for anionic guests, following reduction the cage was observed to encapsulate neutral C₆₀ with ejection of the anionic guests. Current efforts are focused on expanding redox-stimulated guest uptake and release to a broader set of guest species, and applying these concepts to design new systems where electrical energy may be used directly to effect chemical separations and transport.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by the European Research Council (695009) and the UK Engineering and Physical Sciences Research Council (EPSRC, EP/P027067/1 and EP/M008258/1). Z. L. thanks the Deutsche Forschungsgemeinschaft (DFG) for a Postdoctoral fellowship. We thank Diamond Light Source (UK) for synchrotron beamtime on I19 (MT15768).

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. CCDC 1935513. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c9sc05728e

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