Halogen Bonding Tetraphenylethene Anion Receptors: Anion‐Induced Emissive Aggregates and Photoswitchable Recognition

Abstract A series of tetraphenylethene (TPE) derivatives functionalized with highly potent electron‐deficient perfluoroaryl iodo‐triazole halogen bond (XB) donors for anion recognition are reported. 1H NMR titration experiments, fluorescence spectroscopy, dynamic light scattering measurements, TEM imaging and X‐ray crystal structure analysis reveal that the tetra‐substituted halogen bonding receptor forms luminescent nanoscale aggregates, the formation of which is driven by XB‐mediated anion coordination. This anion‐coordination‐induced aggregation effect serves as a powerful sensory mechanism, capable of luminescence chloride sensing at parts per billion concentration. Furthermore, the doubly substituted geometric isomers act as unprecedented photoswitchable XB donor anion receptors, where the composition of the photostationary state can be modulated by the presence of a coordinating halide anion.


Introduction
Organic luminescent materials frequently exhibit significant concentration dependent photophysical properties.T raditional chromophores,s uch as extended planar aromatic systems,a re typically strongly fluorescent under dilute conditions,b ut suffer considerable attenuation in emissive properties with increasing concentration. This phenomenon is known as aggregation-caused quenching (ACQ), [1][2][3] which is attributable,i nm ost cases,t oe xcimer or exciplex formation. Whilst undesirable,A CQ was widely accepted as an immutable characteristic of fluorescent material design. However,T angss eminal report of aggregation-induced emission (AIE) in at etraphenylsilole derivative challenged this precept. [4] Extensive experimental and theoretical studies revealed that the origin of this atypical fluorescent response upon aggregation was,a mongst other factors,a ttributable to the restriction of intramolecular rotation which acts to suppress non-radiative decay pathways of the excited state. Indeed, the discovery of this behaviour stimulated intense interest in the search for other AIE molecules,a nd recent years have seen an ever-increasing library of AIE luminogenic (AIEgens) materials developed. [5] In this context, tetraphenylethene (TPE) derivatives have risen to prominence as synthetically accessible,m odular,m ultivalent scaffolds for AIEgens in the construction of bio-imaging probes, [6,7] optoelectronic devices [8] and responsive materials. [9][10][11][12] In addition to their role as highly sensitive luminescent reporter groups,T PE derivatives are also of interest by virtue of their potential to serve as photoswitchable platforms with large degrees of spatial control. [13] TPE derivatives have also received significant interest in the development of supramolecular sensors which couple aluminescent response with molecular recognition events. [14][15][16][17][18] However,the considered employment of TPE-derivatives within supramolecular host systems remains scarce, [19][20][21][22] with the overwhelming majority of reported examples reliant on irreversible chemical modification of the AIEgen core to sense the guest species. [23] Within the rapidly expanding field of supramolecular anion host-guest chemistry,h alogen bonding and chalcogen bonding intermolecular interactions have emerged as av aluable addition to the supramolecular toolbox. [24][25][26][27] These sigma hole interactions frequently confer enhanced anion affinity and unique selectivity profiles relative to hydrogen bonding (HB) interactions within anion receptors, [28][29][30][31][32][33][34][35][36][37] sensors [38][39][40] and transmembrane anion transporters. [41][42][43][44] Herein, we report as eries of multidentate TPE-based anion receptors containing highly potent perfluoroaryl iodotriazole XB donor motifs.D etailed 1 HNMR anion titration experiments reveal the significant influence of XB donor geometry and multivalency on anion coordination mode and binding affinity.P hotophysical experiments,i nc ombination with dynamic light scattering (DLS) measurements,T EM imaging and X-ray structure determination, reveal the formation of XB-mediated anion-coordination-induced aggregates,a ccompanied by as ignificant turn-on luminescence response which serves as apowerful transduction mechanism for chloride sensing.T he bidentate iodo-triazole TPE derivatives may be switched between strong and weak chloride binding states by photoisomerisation, representing-to the best of our knowledge-the first example of ap hotoswitchable XB anion receptor.A nalysis of the photoswitching process reveals as trong correlation between halide anion affinity and the position of the photostationary state.

Synthesis of mono-and bi-dentate anion receptors
To determine the effect of varying the geometrical arrangement of XB donor motifs around the TPE core on the multi-dentate anion-recognition behaviour,s ynthetic efforts were first directed towards preparing the mono-and di-functionalised anion receptors 1·XB, 2·XB, 2·XB E and 2·XB Z (Scheme 1).
Ty pically,t he synthesis of the target receptors was accomplished by treatment of the proto-alkyne precursors with n-BuLi in anhydrous THF solution at À78 8 8C, followed by reaction of the lithiated alkynes with iodine to afford the respective iodo-alkynes (Scheme 1a). Thet arget receptors were subsequently synthesized via ac opper(I)-catalysed azide alkyne cycloaddition (CuAAC) reaction between the appropriate iodo-alkyne derivative and perfluorophenyl azide,i nt he presence of Cu(MeCN) 4 PF 6 and the Cu I stabilising ligand tris(benzyltriazolylmethyl) amine (TBTA), which afforded 1·XB and 2·XB in yields of 83 %a nd 57 % respectively.I nt he case of 2·XB E and 2·XB Z ,amixture of both isomers was obtained with ac ombined yield of 58 %, because the parent bis-iodoalkyne was used as an inseparable mixture of the geometric isomers.P leasingly,h owever, the introduction of the aryl-iodotriazole motifs enabled resolution of the stereoisomers by silica gel column chromatography,facilitating the isolation of 2·XB E and 2·XB Z in 33 %and 25 %y ield, respectively.F ull synthetic procedures and characterisation data are available in the Supporting Information.

Anion-recognition experiments
With the series of mono-and di-functionalised TPE receptors in hand, we examined their chloride anion-recognition behaviour by 1 HNMR anion titration experiments. Aliquots of chloride,a st he tetrabutylammonium salt, were added to solutions of the respective receptor in [D 8 ]THF, monitoring the binding induced chemical shift perturbations. In the case of 1·XB, 2·XB and 2·XB E ,c hloride binding induced adownfield shift of the aryl signal directly adjacent to the iodo-triazole moiety,c onsistent with XB mediated anion complexation. Analysis of the titration isotherm for 1·XB using the Bindfit programme [45,46] generated a1 :1 stoichiometric association constant, K 1:1 (1·XB) = 2380 M À1 ,r epresenting the binding affinity of chloride to one iodotriazole XB donor. Thei ntegration of additional XB donors to the TPE core enables higher host-guest complex stoichiometries to be achieved, which in the case of 2·XB, 2·XB Z and 2·XB E corresponds to a1 :2 host-anion stoichiometry.D epending on the geometric arrangement of the two XB donors,a nion complexation occurs with either no cooperativity (binding of the first anion does not affect binding of the second) or negative cooperativity (binding of the first anion inhibits binding of the second). In the former case,t he 1:1a nd 1:2 host-guest binding constants, K 1:1 and K 1:2 respectively,a re related by the expression K 1:1 = 4 K 1:2 ,a ccounting for statistical factors.Analysis of the chloride binding isotherms for the di-iodotriazole derivatives 2·XB, 2·XB Z and 2·XB E (Figure 1c)r evealed that the two XB donors in 2·XB and 2·XB E bind the chloride anions in anon-cooperative manner,with an interaction parameter a = 1, where a = 4 K 1:2 /K 1:1 ( Table 1).
Thec hloride binding isotherm of 2·XB Z exhibits am ore complex profile,i nw hich addition of up to 1equivalent of chloride induced an upfield shift in proton a (Figure 1b), after which an inflection point is observed and subsequent addition of chloride resulted in ad ownfield shift. This behaviour is consistent with the initial formation of a1:1 complex, and the formation of ac onsiderably weaker 1:2c omplex at higher concentrations of chloride.T he reversal of chemical shift perturbation is interpreted to be aconsequence of conformational rearrangement upon changing from 1:1t o1 :2 stoichiometry to maximise the inter-anion separation (Figure 1a).
Analysis of the 1:1s toichiometric binding constants for the three di-iodotriazole geometric isomers 2·XB, 2·XB E and 2·XB Z provided evidence for the presence or absence of bidentate anion binding with chelate cooperativity for each isomer.T he chloride binding constant obtained for the reference mono-dentate compound 1·XB, K 1:1 (1·XB), quantifies the binding of the anion to asingle iodotriazole binding site.T he 1:1b inding constant for the di-iodotriazole derivatives 2·XB, 2·XB E and 2·XB Z is given by 2 K 1:1 (1·XB)i nt he absence of chelate cooperativity and when statistical factors   associated with binding of one anion to ad itopic host are considered. Inspection of the values of K 1:1 for the diiodotriazole derivatives reveals that, in the case of 2·XB and 2·XB E ,the two iodotriazole donors are too far apart to allow for chelation of the anion in ab identate fashion: K 1:1 (2·XB) and K 1:1 (2·XB E ) % 2 K 1:1 (1·XB). In contrast, in 2·XB Z the two iodotriazole derivatives are closer in space,w hich allows for effective bidentate cooperative binding of the first chloride anion, such that K 1:1 (2·XB Z ) % 10K 1:1 (1·XB). Thepronounced negative cooperativity in binding of the second equivalent of anion to 2·XB Z ,r eflected in the interaction parameter a = 0.17, presumably therefore arises due to the combination of mutual anion-anion electrostatic repulsion and the requirement to break the bidentate XB-chloride interactions upon formation of the ternary complex. Subsequent 1 HNMR anion titration experiments of 2·XB Z with the heavier halides revealed that bromide and iodide produced similar binding isotherms with somewhat attenuated association constants,c onsistent with anion basicity trends (Table 2).

Synthesis and anion recognition of tetradentate receptors
Attention then turned towards the synthesis of the tetrasubstituted receptors 4·XB, 4·XB Ph and 4·HB,w hich were prepared from the corresponding tetra-iodo/proto alkyne TPE derivatives using analogous procedures to those used for 1·XB (see the Supporting Information for further details). 1 HNMR chloride titration experiments were conducted on 4·XB, 4·XB Ph and 4·HB,toelucidate the role and potency of XB interactions on the anion-recognition process.Chloride binding titration experiments with 4·XB revealed achemical shift perturbation profile with an inflection point similar to that observed with 2·XB Z ,i nw hich up to two equivalents of TBACli nduced an almost linear upfield perturbation of the aryl proton a,i ndicative of near quantitative formation of a1:2 receptor:anion complex. Addition of further equivalents caused aprogressive downfield shift, indicating the formation of higher receptor:anion stoichiometries,p resumably up to 1:4( Figure 2b). [ * ] Similar chemical shift perturbations were observed for 4·XB Ph ,whilst binding to the hydrogen bonding analogue 4·HB was weak (see Supplementary information for further details). Furthermore,t he preference for the lighter halides observed for 2·XB Z appears to also translate to 4·XB, [a] Anions added as their tetrabutylammonium salts, errors < 10 %.
[b] Fitted to afull 1:2host-guest binding model. Forf ull details of the binding models and raw data see the ESI. [*] The binding data could not be reliably fitted to a1:4 host:guest isotherm, presumablyd ue to the presence of anion-induced aggregates. However,visual inspection of the isotherm (noting the inflection point at 2equiv.ofanion) indicates that the binding of the first and second anion is strong (K ! 10 4 M À1 ,likely via the same bidentate binding mode seen in 2·XB Z ), with weaker binding of the third and fourth equivalent.
upon visual analysis of the bromide and iodide binding isotherms (Figure 2c). [ * ]

Solid-state structure determination
Further insight into the anion-binding mode of the halogen bonding TPE systems was obtained by solid-state characterisation of 4·XB ( Figure 3) and in the presence of asource of chloride anion (Figure 4).
It is noteworthy that repeated attempts to crystallize 4·XB with an on-coordinating organic countercation (e.g.t etraethylammonium, tetrabutylammonium or benzyltrimethylammonium) persistently yielded the NaCl complex of 4·XB (Figure 4a). Thepropensity of 4·XB to crystalize with an adventitious sodium cation may be rationalized by inspection of the solid-state structure in which the Na + forms ap roximal ion-pair with ac hloride anion simultaneously exhibiting four CÀI···Cl À XB interactions with four distinct 4·XB molecules (Figure 4b). Close examination of the structure reveals that the four-fold coordination of chloride, in concert with other interactions (Figure S86), enforces close proximity of the TPE aromatic cores,a sclearly visualised in the space filling representation (Figure 4c). To establish the relative roles of the Na + and Cl À in the formation of these aggregated structures observed in the solid state,efforts were then directed towards obtaining structural information in the presence of other halides.Crystals suitable for X-ray diffraction were obtained by slow diffusion of pentane into a9 :1 CHCl 3 :acetone (v/v) solution of 4·XB in the presence of excess NaI. Single-crystal X-ray analysis revealed the  NaI·4·XB complex displays an analogous four-fold anion coordination via C À I···I À XB interactions in an approximately square planar geometry around the iodide,h owever the sodium cation in this case resides in av acancy between the central aromatic units constituting the tetraphenylethene core ( Figure S82). This is presumably due to the reduced electrostatic interaction between the larger iodide anion and the sodium cation. Thes tructural similarity of the obtained sodium halide complexes reveals the crucial role of potent XB-anion interactions in the assembly of the aggregates. Encouraged by these findings,a ttention then turned to investigating whether these anion-induced aggregates persist in solution phase.

Anion-coordination-induced aggregation and anion sensing
As anticipated from the well-established emission behaviour of TPE derivatives,m easurement of the fluorescence spectra in THF solution (10 À5 M) revealed that 4·XB is weakly emissive (l ex = 350 nm). As ignificant increase in emission intensity with increasing water fractions (f w )w as observed at f w > 60 %, indicative of the anticipated aggregation-induced emission behaviour of TPE derivative 4·XB (Figure 5a,t op), and the formation of aggregates confirmed by dynamic light scattering (DLS) measurements (Figure 5a, bottom).
Addition of increasing equivalents of chloride to aT HF solution of 4·XB led to an increase in fluorescence intensity (l max = 520 nm), with athree-fold increase observed after the addition of 10 equivalents (Figure 5b,t op), accompanied by aconsiderable hypsochromic shift ( % 20 nm). Recent studies shedding light on the mechanism of AIE in TPE derivatives have demonstrated that the direction of l max perturbation can be closely correlated with the relative orientations of the central aromatic units to the alkene core.Increasing planarity between the constituent phenyl rings leads to increasing pconjugation and red-shifting of the emission, whilst adoption of aperpendicular conformation decreases p-conjugation and results in blue-shifted emission. [47,48] Close examination of the solid state structures for 4·XB and its NaCl complex readily rationalise the observed changes in the emission profile, whereby the intermolecular coordination of the halide by halogen bond interactions not only induces the formation of closely intertwined complexes,r estricting possible rotational degrees of freedom, but also enforces am ore perpendicular geometry of the core aromatic scaffold (See Figure S85 and Table S5). Addition of the non-coordinating anion hexafluorophosphate did not affect the emission spectrum, further demonstrating that XB-mediated coordination to chloride is required to mediate aggregation ( Figure S79). Dynamic light scattering (DLS) measurements of freshly prepared THF solutions (10 À5 M) of 4·XB indicate that the free receptor is non-aggregated in the absence of chloride,but the addition of 1equivalent of TBAClinduces the formation of aggregates on the order of 100 nm in diameter (Figure 5b,bottom). Further evidence for anion-induced aggregate formation of 4·XB was provided by transmission electron microscopy (TEM) which, consistent with results from DLS,r evealed that the addition of 1equiv.ofTBACl to a1mM solution of 4·XB in THF led to the formation of % 100 nm sized particles,w hile no such species were observed for the free receptor in the absence of chloride (Figures S87 and S88).
To further explore the role of spatial orientation and potencyo ft he halogen bond donors in the formation of the anion-mediated aggregates,t he relative fluorescence re- sponse for all receptors was recorded in the presence of 10 equivalents of TBACl, and the data summarised in Figure 6. Thel argest emission intensity increases are observed for 4·XB and 2·XB,a nd the formation of aggregates in the presence of 1equivalent of TBACli nb oth cases was confirmed by DLS measurements.I nc ontrast, 1·XB, 2·XB Z and 2·XB E exhibited minor perturbations in fluorescence intensity upon the addition of 10 equivalents of TBACl, and DLS analysis revealed no evidence of aggregated species. Together,t hese results confirm that the observed emission enhancement arises from XB-mediated chloride induced aggregation. Thea bsence of anion-coordination-induced aggregation with 2·XB Z ,d espite the receptor possessing enhanced chloride affinity relative to all other mono-and di-substituted TPE derivatives,d emonstrates that spatial orientation of the XB donors is crucial in the formation of the chloride induced XB aggregates.U nder analogous conditions 4·XB Ph and the hydrogen bonding analogue 4·HB also demonstrated no significant emission intensity change,p roviding further strong evidence for the requirement for multiple potent XB-anion interactions to drive aggregate formation.
Analogous experiments were also undertaken to investigate how the nature of the anionic guest influences aggregate formation, in which the emission intensity of 4·XB in THF was measured in the presence of 10 equivalents of arange of anions (Figure 7). In all cases except acetate,the addition of an anion induced afluorescence intensity increase. In accordance with the anion basicity trend this increase followed the order of Cl À > Br À > I À .Notably,despite its dianionic nature,S O 4 2À elicited ad iminished enhancement in emission intensity in comparison to the strong chloride response.T he considerable fluorescence response for Cl À corresponds to al imit of detection (LOD) of 5.14 mM (183 ppb), constituting one of the most sensitive supramolecular anion sensors to-date ( Figure S75). [23,49] Photo-switchable anion recognition In addition to the highly desirable luminescent properties of TPE, unsymmetrical doubly substituted TPE derivatives have the capability to function as molecular photo-switches in which photoisomerisation switches between different spatial arrangements of functional groups.P hoto-switchable anion receptors in particular have attracted interest for applications including ion extraction and transport, enabling control over when and where the hosts bind or release their targets. [50] However,t he utilization of TPE as ap hotoswitch has been hindered by practical issues in their synthesis,d ue to ac ombination of poor stereoselectivity and challenging chromatographic separation of the closely related geometric isomers.C onsequently,t he vast majority of reports to date using these di-functionalised TPE derivatives in material or polymer sciences have used mixtures of the isomers.C ompounds 2·XB E and 2·XB Z are prime candidates for developing photo-switchable anion receptors due to the contrast in chloride binding affinity of the two geometric isomers (K 1:1 of 4970 and 23 200 M À1 ,respectively), and fortuitously,could be isolated by column chromatography.
Irradiation of as olution of ap ure sample of 2·XB E with 405 nm light triggered photo-isomerisation, generating an approximately equal ratio of both isomers in the photostationary state (52:48 2·XB Z :2·XB E ), as determined by integration of the NMR signals of the mixture.T he effect of 405 nm irradiation on the UV vis spectrum of as olution of 2·XB E is shown in Figure 8a,resulting in abathochromic shift of the absorption at low wavelength (ca. 265 nm) and adecrease in the absorption at 335 nm, with isosbestic points at 270 nm and 310 nm confirming the unimolecular nature of the isomerisation process.T he photo-stationary state was reached within 120 s, as deduced by the absence of further changes in the absorption spectrum. No thermal isomerization of 2·XB Z or 2·XB E was observed under ambient conditions in THF solution over the course of the experiment when excluded from light. Analogous irradiation experiments starting with 2·XB Z generated as imilar, but reversed set of perturbations in the UV-vis profile,n amely an increase in absorption at 335 nm and ah ypsochromic shift in the local l max absorption at approximately 265 nm.
Given the contrasting anion-binding properties of the isomers,weanticipated that the photostationary state may be biased in favour of the Z isomer by coordination to an anion.  To this end, analogous photoisomerisation experiments were conducted by irradiating the sample with 405 nm light in the presence of 10 equivalents of TBACl. In the presence of the halide,t he PSS is biased in favour of the Z isomer,d ue to strong XB coordination to the chloride (68:32 2·XB Z :2·XB E ) (Figure 8b). Similar experiments were undertaken with 10 equivalents of bromide and iodide (Table 3), revealing that the bias of the PSS in favour of the Z isomer correlates with the anion-binding affinity to 2·XB Z ,namely Cl À > Br À > I À .I nc ontrast, in the presence of non-coordinating anion, PF 6 À ,w hich demonstrated no binding to either receptor in 1 HNMR titration experiments,n op erturbation of the position of the PSS was detected. Together,this data provides evidence for photo-switchable XB-mediated anion recognition, in which strong binding to the 2·XB Z and weaker binding to 2·XB E enables switching of binding using light, as well as modulation of the obtained ratio of isomers in the photostationary state.

Conclusion
In conclusion, we report aseries of halogen bonding TPEbased anion receptors,inwhich the multivalencyand relative orientation of the strongly potent perfluoroaryl XB donors is systematically investigated. 1 HNMR anion titration experiments elucidate the varied binding modes and stoichiometries of the family of halogen bonding TPE derivatives.F luorescence anion titration experiments demonstrate that the tetrasubstituted perfluorinated 4·XB receptor,e xperiences ad ramatic increase in emission intensity upon the addition of chloride,w hilst the non-fluorinated 4·XB Ph or hydrogen bonding 4·HB analogues elicit no photophysical response. Detailed analysis of the fluorescence spectra, dynamic light scattering measurements,T EM imaging and X-ray crystal structure determination demonstrate that the origin of this sensory response is an unprecedented XB-anion coordination-induced aggregation mechanism. Furthermore,s uccessful isolation of difunctionalised geometric isomers 2·XB Z and 2·XB E facilitated the investigation of these TPE derivatives as photoswitchable anion receptors,inwhich it was demonstrated that the position of the photostationary state could be significantly biased towards 2·XB Z on the basis of enhanced halide anion affinity.T hese results not only provide further evidence for the advantages of XB interactions in the design of potent anion receptors,but also point to new opportunities in the development of XB anion-responsive materials, switches and sensors.