Our expedition in the construction of fluorescent supramolecular metallacycles

Junlong Zhu,Xi Liu,Junhai Huang,Lin Xu

a Shanghai Key Laboratory of Green Chemistry and Chemical Processes,School of Chemistry and Molecular Engineering,East China Normal University,Shanghai 200062,China

b Zhangjiang Institute,China State Institute of Pharmaceutical Industry,Shanghai 201203,China

c State Key Laboratory of Fine Chemicals,Dalian University of Technology,Dalian 116024,China

Keywords:

Supramolecular chemistry

Fluorescent metallacycle

Coordination-driven self-assembly

Functionalized metallacycle

Supramolecular gel

ABSTRACT

During the past few years,the construction of fluorescent supramolecular metallocycles has attracted extensive attention due to their diverse applications such as sensing,photoelectric devices,and mimicking complicated natural photo-processes.In this review,we will discuss how we entered the field of fluorescent supramolecular metallacycles and what we investigated in this field.The preparation of various fluorescent supramolecular metallacycles and their applications in monitoring the dynamics of coordination-driven self-assembly,sensing,catalysts,and supramolecular gels will be summarized.

1.Introduction

It is our pleasure to write this review tracing our expedition in the construction of fluorescent supramolecular metallacycles,with a particular focus on how we entered this field and what we found in this field.During my(Lin Xu)doctoral study in the group of Prof.Xuhong Qian at East China University of Science and Technology from 2007 to 2012,I was committed to develop fluorescent probes for anions,cations,and biological small-molecules.For example,based on an excited-state intramolecular proton transfer (ESIPT)mechanism,we have prepared a new ratiometric fluorescence probe for the detection of hydrogen sulfide(H2S)in living cells[1].In July 2012,I started my independent research at East China Normal University.Since that time,in parallel with the continuous research in the development of fluorescent probes [2-4],I paid significant attention on the construction of fluorescent supramolecular metallacycles[5].In particular,using fluorescence technology to solve the partial problems in the field of supramolecular assembly,including using fluorescence method to investigate the dynamic process and mechanism of self-assembly as well as preparing functional supramolecular assemblies.

Coordination-driven self-assembly,based on the interaction between metal and ligand,is an efficient method to construct discrete supramolecular metallacycles with well-defined shapes,sizes,and geometries [6-14].Compared to stepwise covalent synthetic approaches with time-consuming process and lower yields,such strategy exhibited various synthetic superiority including fewer steps,nearly quantitative yields,defect-free assembly,and inherent self-correction.During the past few decades,Fujita [15],Stang [16],Mirkin [17],Newkome [18],and others [19-24]have constructed various metallacycles through coordination-driven self-assembly during the past three decades.

Besides the construction of complicated and delicate supramolecular metallacycles,fluorescent metallacycles have attracted extensive attention due to theirdiverse applications such as sensing,photoelectric devices,and mimicking complicated natural photoprocesses[25-39].The placement and total number of introduced fluorophores within metallacycles could be precisely controlled by coordination-driven self-assembly.Moreover,the presence of chromophores in metallacycles allows for real-time monitoring the self-assembly process and dynamics of the resultant metallacycles by highly sensitive fluorescence technique.Furthermore,compared with organic fluorescent macrocycles,the stimuliresponsive fluorescent metallacycles were easier to be realized by taking advantage of the dynamic nature of metal-ligand bonds.Therefore,we have been paying considerable attention to designing and constructing different kinds of fluorescent metallacycles and investigating their photophysical properties as well as potential applications.In this review,we will summarize our efforts in the construction of various fluorescent metallacycles and their applications in monitoring the dynamics of coordination-driven selfassembly,sensing,catalysts,and stimulus-responsive supramolecular fluorescent gels.

2.Self-assembly of supramolecular metallacycles with fluorescent properties

From the topological point of view,theoretically,there are four ways to construct fluorescent metallocycles.Firstly,the exofunctionalized fluorescent metallocycle could be constructed by incorporating the fluorophore moiety onto the exterior surface of the directional building block.Secondly,the endo-functionalized fluorescent metallocycle could be obtained by attaching the fluorophore moiety into the inner side of the directional building block with a turning angle less than 180°.Moreover,the fluorophore moiety could function as the edge or corner of the directional building block to construct the edge or cornerfunctionalized fluorescent metallocycle [40].

Pyrene and its derivatives have been extensively investigated for their fascinating fluorescent properties.For example,they poessess high fluorescent quantum,relatively long excited-state lifetime,and extraordinary distinction of the fluorescence bands for monomers and excimers[41-45].In consequence,the incorporation of multiple pyrene subunits into a single scaffold to construct supramolecular metallacycles with fluorescent properties has evolved to be one charming subject[46,47].However,it is challenging to introducted multiple pyrene groups into a well-defined discrete supramolecular systems in a controlled way.We constructed varioustris-and hexakis(pyrene)hexagonal metallocycles 4 and 5 with precise shapes and sizes through the coordination-driven self-assembly of the pyrenemodified 120°acceptor 1 and its complementary 120°donor ligand 2 or 180°donor ligand 3,respectively(Scheme 1)[48].Analogously,another series of“isomeric”multipyrene hexagons 9 and 10 were constructed through the coordination-driven self-assembly of the pyrene-modified 120°donor 6 and its complementary 120°acceptor ligand 7 or 180°acceptor ligand 8,respectively.These hexagonal metallocycles exhibited a similar geometry,but luminescent behaviors of them differed from each other dramatically(Fig.1).For example,hexagonal metallocycles 9(3.3×10-6mol/L)and 10 (1.7×10-6mol/L) in dichloromethane exhibited a longer emission band at λmax550 nm corresponding the excimer emission of the pyrene chromophore,while hexagonal metallocycles 4(3.3×10-6mol/L) and 5 (1.7×10-6mol/L) in dichloromethane disabled to form excimers due to the relatively lower charge densities of 4 and 5 compared to that of 9 and 10.This investigation indicated the structural effect could impact the formation of pyrene excimer.

There have been some successful examples in preparation of fluorescent metallacycles by coordination-driven self-assembly[49,50],but the construction of fluorescent metallacycles with highly emissive property,especially in situ generated by external stimuli,is still a challenge.Light is often chosen as the source of stimuli-response because it is the cleanest energy [51-53].More recently,we constructed the highly emissive fluorescent metallacycles 18 and 19 upon irradiating non-fluorescent metallacycles 14 and 15,respectively [54].Through the reaction of the 120°diarylethene-based dipyridyl donors 12 and 16 with 120°acceptor 11 in a 1:1 ratio in dichloromethane at room temperature,respectively,non-fluorescent metallacycles 14 and 15 could be readily obtained without further purification (Scheme 2).The highly emissive fluorescent metallacycles 18 and 19 could be formed from non-fluorescent metallacycles 14 and 15 by UV irradiation with high conversion yields,respectively,due to the photoswitchable property of diarylethene ligands (Fig.2).This“turn-on” fluorescent switch differed from the most common photochromic systems,where the fluorescence is often quenched by UV irradiation.

Scheme 1.Cartoon representation of the formation of multi-pyrene hexagons 4,5 and 9,10.

Fig.1.Emission spectra of 1 (10-5 mol/L),6 (10-5 mol/L),4 (3.3×10-6 mol/L),5(1.7×10-6 mol/L),9 (3.3×10-6 mol/L),and 10 (1.7×10-6 mol/L) in CH2Cl2.Reproduced with permission [48].Copyright 2013,American Chemical Society.

Scheme 2.Cartoon representation of the formation of dithienylethene hexagons 14,15,18 and 19.

Fig.2.(a) Absorption spectral changes of 12 (10-5 mol/L in CH2Cl2) upon UV irradiation at 365 nm.(b)Emission spectral changes of 12(10-5 mol/L in CH2Cl2,EX= 450 nm)upon UV irradiation at 365 nm.Copied with permission[54].Copyright 2019,Wiley-VCH.

Carbazole has been extensively explored owing to its wide application such as charge-hole transport material in organic light-emitting diodes (OLEDs) and light-emitting photosensitizer[55-61].Dendrimers are hyperbranched macromolecules consisting of some dendritic wedges which extend from a core [62-69].Recently,we prepared a series of carbazole-containing metallodendrimers 22a-c and 23a-c by self-assembly of carbazolecontaining dendrimers donors 21a-c with 60°acceptor 20 or 120°acceptor 11 in a 1:1 M ratio,respectively (Scheme 3) [70].The research of fluorescent properties of dendrimers 21a-c,22a-c,and 23a-c displayed that all of them possessed aggregation-induced emission (AIE) properties (Fig.3).Especially,metallodendrimers 22a-c and 23a-c exhibited generation-dependent AIE properties compared to ligands 21a-c proved by emission spectra in solvent mixtures of DCM and n-hexane with different volume ratio,as well as Tyndall effect,SEM and DLS consequence.This work provided the first examples of coordination-driven self-assembly of carbazole-containing metallodendrimers with generation-dependent AIE properties.

Besides preparing homo-functional fluorescent metallocycles,we constructed hetero-functional fluorescent metallocycles 26a-c and 27a-c by coordination-driven self-assembly of the pyrenemodified 120°donors 1 or 24 and their complementary 60°dendritic acceptors 25a-c,respectively (Scheme 4) [71].The investigation of photochemical behavior showed that fluorescence quantum yields of 27a-c in DCM(0.47-0.61)are higher than those of 26a-c(0.14-0.17).Moreover,all fluorescence quantum yields of metallocycles 26a-c and 27a-c are higher than those of their pyrene-modified precursors 1 (0.03) and 24 (0.09),respectively,which may result from the inhibition of the aggregation of pyrene by dendrons.This strategy can be applied to construct high emission fluorescent metallodendrimers with well-defined shapes and sizes.

Scheme 3.Cartoon representation of the formation of metallodendrimers 22a-c and 23a-c.

3.Functionalized fluorescent supramolecular metallacycles

3.1.Real-time monitoring the dynamics of coordination-driven selfassembly

Fig.3.Fluorescence spectra of 21a(a),22a(b),and 23a(c)in mixtures of n-hexane/CH2Cl2 with different fh.Changes in the photoluminescence(PL)signal intensities of 21a(d),22a (e),and 23a (f) in mixtures of n-hexane/CH2Cl2 with different fh are also shown.Reproduced with permission [70].Copyright 2015,Wiley-VCH.

Up to now,a large variety of intricate and fascinating metallacycles with well-defined shapes and sizes have been efficiently prepared through coordination-driven self-assembly[72-76].However,it is a huge challenge to investigate the dynamic process of coordination-driven self-assembly owing to the presence of numerous intermediates and uncertain processes within self-assembly.Recently,we chose coumarin and rhodamine moieties as the fluorescence-resonance energy transfer (FRET)donor and receptor,respectively,resulting from most overlap between the emission spectrum of coumarin and the excitation spectrum of rhodamine.Thus,the dipyridyl ligand 28 modified by 7-(diethylamino)-coumarin and the diplatinum(II) ligand 29 modified by rhodamine were successfully synthesized.Then,the fluorescent metallacycle 30 was prepared through coordinationdriven self-assembly of the ligand 28 and the ligand 29(Scheme 5)[77].As shown in Fig.4a,the rhodamine emission increased obviously accompanied by a decrease in coumarin emission during the self-assembly of the dipyridyl ligand 28 and the diplatinum(II)ligand 29,which attributed to FRET between coumarin and rhodamine moieties.In addition,we mix coumarin-based metallacycle and rhodamine-based metallacycle in a 1:1 ratio in acetone/water(5:1,v/v).As a result,coumarin emission decreased obviously accompanied by an increase in rhodamine emission,which was consistent with FRET progress resulting from the formation of new metallacycles containing both coumarin and rhodamine.Moreover,we designed disassembly and reassembly experiment by adding and removing competitive ligands such as halide ions to bring about reversible disassembly and reassembly through FRET approach (Scheme 6).As shown in Fig.4b,the gradual addition of 6.0 equiv.of Br-into the solution of metallacycle 30 resulted in an obvious decrease in rhodamine emission accompanied by an increase in coumarin emission,which indicated the disassembly of metallacycle 30 with the addition of Br-.After that,the addition of 6.0 equiv.of Ag+into the halogenated solution of 30 brought about the reassembly of metallacycle 30 proved by the reappearance of the FRET process.All results indicated that the self-assembly process and dynamics of the fluorescent metallacycle could be monitored in real time by employing FRET.

3.2.Sensing

Proton plays a vital role in many chemical and biological processes [78,79].Therefore,it is urgent to develop methods for detecting the change of pH.We chose 1,8-naphthalimide as the fluorophore owing to its great photostability,high quantum yield,and good compatibility [80-85].Therefore,naphthalimide fluorophore was connected to 120°dipyridyl donor by the nonconjugate incorporation way,which was able to avert the quenching of fluorescence.Weak fluorescent metallacycle 32 was obtained by self-assembly of naphthalimide-modified 120°dipyridyl donor 31 with 120°diplatinum acceptor 11 in mild condition(Scheme 7)[86].As shown in Fig.5a,as the pH decreased from 7.5 to 3.5,the fluorescence of metallacycle 32 gradually became stronger.This resulted from the inhibition of PET channel along with the protonation of the N atom in the N-methyl piperazine moiety [87-92].Furthermore,the enhancement of fluorescence intensity of 32 at 514 nm corresponded to the concentration of H+(0-60 μmol/L)in a linear relationship(linearly dependent coefficient: R2=0.9906),which suggested that the metallocycle 32 could quantitatively detect H+concentration below 60 μmol/L.This study provided such a non-conjugate incorporation method to prepare metallacycles with various fluorophore for fluorescence detection of different analytes.

3.3.Catalysts

Metallacycles are instable under relatively severe conditions due to the dynamic property of coordination bonds[93-95].As for fluorescent metallacycles,their luminescent properties suffer from the aggregation-cause quenching(ACQ)effect[96,97].Therefore,it is essential to construct the isolated fluorescent metallacycles with great stability and dispersity refraining from ACQ effect.Recently,we fabricated the hybrid materials(34?C)composed of porphyrinbased metallacycle 34,which is obtained through self-assembly of the 120°donor precursor 33 modified by porphyrin with typical 120°diplatinum(II) acceptor 11 within the cavity of mesoporous carbon FDU-16 (Scheme 8) [98].The hybrid materials possessed higher1O2generation efficiency than that of free metallacycles in solution and greatly improved stability and activity of metallacycles 34 inside the confined cavity,which could function as heterogeneous catalyst for photooxidation of sulfides (Fig.6a).Full conversion from sulfides to sulfoxides catalyzed by 34?C was observed after 4 h of white LED irradiation monitored by NMR and GC--MS.Under the same reaction conditions,the reaction catalyzed by metallacycle 34 or composites 34/C gave 42% and 54% conversion,respectively,and the conversion efficiency without a catalyst became lower (Fig.6b).More importantly,the catalytic activity of 34?C reduced a little bit after five reuse cycles.In contrast,the pristine metallacycle 34 was observed to deactivate remarkably even after two cycles (Fig.6c).This work was the first example of isolated functionalized metallacycle in the confined space,which presented a novel strategy to improve the dispersity and stability of metallacycles.

Scheme 4.Cartoon representation of the formation of metallodendrimers 26a-c and 27a-c.

Scheme 5.Cartoon representation of the formation of metallacycle 30.

Fig.4.(a)Time-dependent changes in the emission spectra of the mixture of ligand 28 (30 μmol/L) and ligand 29 (30 μmol/L) in acetone; (b) Emission spectra of metallacycle 30 (5.0×10-6 mol/L) upon titration of TBAB in acetone-d6/D2O=5:1(v/v).Reproduced with permission [77].Copyright 2017,American Chemical Society.

Scheme 6.Cartoon representation of reversible disassembly and reassembly of 30 induced by addition and removal of Br-.

Scheme 7.Cartoon representation of the formation of metallacycle 32.

Fig.5.(a)Fluorescence spectra of 32(20 μmol/L)upon addition of proton in aqueous solution(acetone/water,4/1,v/v);Inset(a)and(b):Curves of fluorescence intensity at 514 nm of 32 (20 μmol/L) versus increasing concentrations of CF3COOH.Reproduced with permission [86].Copyright 2014,Royal Society of Chemistry.

Scheme 8.Cartoon representation of the formation of trisporphyrin metallacycle 34 in cavities of mesoporous carbon FDU-16.

Fig.6.(a)Scheme for the photooxidation of sulfides(34?C as catalyst);(b)Photooxidation profile of sulfides; (c) Reusability hybrids 34?C and metallacycle 34.Reproduced with permission [98].Copyright 2018,American Chemical Society.

3.4.Supramolecular gels

Supramolecular gels are generated by self-assembly of small molecules or complexes through non-covalent interactions including π-π stacking,hydrogen bond,and coordination bond.As smart soft materials,they have been widely applied in many fields such as drug delivery,wound healing,tissue engineering,nanoelectronics,and chemical sensing [99,100].Metallacycles with well-defined shape and size can be readily modified by multiple functional moieties with non-covalent interactions to form supramolecular gels via hierarchical self-assembly [101-103].Furthermore,the reversible non-covalent interaction gave supramolecular gels with stimuli-response.

Recently,we constructed a fluorescent metallacycle 37 with AIE property via coordination-driven self-assembly of the dipyridyl donor 36 modified with multiple amide groups and long hydrophobic alkyl chains and diplatinum(II)acceptor 35 decorated with tetraphenylethylene (Scheme 9) [104].Fluorescence emission-enhanced supramolecular gel was successfully prepared in acetone/water (5:1) at a low critical gelator concentration (CGC)(21.3 mg/mL)of metallacycle 37 by hierarchical self-assembly due to the intermolecular interactions derived from amide groups and long alkyl chains.Furthermore,the reversible gel-sol transitions were realized via disassembly and reassembly of metallacycle 37 by adding and removing bromine ions or fluorine ions because of the dynamic nature of coordination bond and hydrogen bond(Fig.7).Meanwhile,the apparent fluorescence switch was observed during the reversible gel-sol transitions.This research presented the interesting supramolecular metallogel possessing fluorescence emission-enhanced property with multiple stimuliresponsive behaviors via hierarchical self-assembly.

Scheme 9.Cartoon representation of the formation of metallacycle 37.

Fig.7.Photographs demonstrating the reversible stimuli-responsive gel-sol transition of hexagonal metallacycle 37 in acetone/water (5:1) by the addition of(a)TBAB and AgPF6 and(b)TBAF and HClO4.Digital photos of the reversible stimuliresponsive gel-sol transition of hexagonal metallacycle 37 by the addition of (c)TBAB and AgPF6 and(d)TBAF and HClO4 under irradiation by a UV lamp at 365 nm.Copied with permission [104].Copyright 2017,Royal Society of Chemistry.

Scheme 10.Cartoon representation of the formation of metallacycles 39 and 40.

Fig.8.Gel-sol transitions of supramolecular polymer gel 41?40 triggered by a variety of stimuli.Copied with permission [105].Copyright 2018,Royal Society of Chemistry.

Besides the above supramolecular gel obtained via hierarchical self-assembly based on metal-ligand coordination bond and hydrogen bond,we prepared another kind of supramolecular gel via hierarchical self-assembly based on metal-ligand coordination bond and host-guest interactions [105].Through coordinationdriven self-assembly of 120°tetraphenylethylene-based dipyridyl donor 39 decorated with pillar[5]arene and the corresponding complementary 60°diplatinum(II) acceptors 20 or 120°diplatinum(II) acceptors 11,two different metallacycles 39 and 40 with different shapes and sizes were obtained,respectively(Scheme 10).The metallacycles host 39 or 40 and the neutral ditopic guest 41 can form the cross-linked supramolecular polymers with AIE properties under high concentration conditions through hostguest interactions.Interestingly,cross-linked supramolecular gels were generated with further increase of the concentrations.Furthermore,both gels 41?39 and 41?40 displayed reversible gel-sol transitions under different stimuli of temperature,competitive guest molecules,and halides,along with the “onoff”of fluorescence by taking the advantages of the dynamic nature of metal-ligand bonds and host-guest interactions (Fig.8).This investigation offered another new strategy to fabricate smart soft materials efficiently.

4.Conclusion

In this review,we summarized the recent advances of our group on the construction of fluorescent metallacycles via coordinationdriven selfassembly.A variety of fluorescent metallacycles with different shapes,sizes,and fluorescent moieties were designed and synthesized successfully,which indicated that coordinationdriven self-assembly was a simple and highly efficient strategy with numerous synthetic superiority,including fewer steps,nearly quantitative yields,defect-free assembly,and inherent selfcorrection.Furthermore,their photophysical properties and applications in monitoring the dynamics of coordination-driven self-assembly,sensing,catalysts,and supramolecular gels were also discussed.

Although much progress has been made with the fluorescent metallacycles,three vital aspects should be considered in my opinion.On one hand,except for fluorescence intensity,the combination of electrospray ionization mass spectrometry (ESIMS),NMR,and super-resolution fluorescence microscopy techniques would be an effective method for monitoring the dynamic the self-assembly process of metallacycles.On the other hand,research focus should be shifted from the two-dimensional (2D)fluorescent metallacycles towards three-dimensional (3D) fluorescent metallacages,because metallacages,which contain guests by host-guest interactions,could be uesd for drug delivery,sensing,and catalysts.Thirdly,there have been relatively fewer reports on biological applications of fluorescent metallocycles and metallocages.Thus,fluorescent metallocycles and metallocages with high water solubility,good biocompatibility,or near-infrared emission should be constructed.Generally,3D metallacages display larger volume and higher molecular weight than those of 2D metallacycles,thus,the challenges of high stability,good solubility,and low toxicity need to be considered particularly for 3D fluorescent metallacages in biological application.

Acknowledgments

Thanks to all excellent authors whose names appear in the references.We acknowledge the National Natural Science Foundation of China (Nos.21871092 and 21672070),Shanghai Pujiang Program (No.18PJD015),and the State Key Laboratory of Fine Chemicals (No.KF1801) for the financial support.