Synthesis and self-assembly properties of the first fluorescein-based hexacatenar mesogens

Abstract First series of fluorescein-based hexacatenar mesogens consisting of a central fluorescein unit and two 1,2,3-triazole dendritic wings were designed and synthesized by using the Williamson reaction and Cu-assisted alkyne-azide cycloaddition reaction. Polarized optical microscopy textures, differential scanning calorimetry curves, and X-ray diffraction (XRD) data demonstrated that all the compounds can self-assemble into hexagonal columnar mesophases. Organogel test demonstrated that these compounds could form organogel in some moderate polar solvents with irregularly winkled morphologies. Density functional theory calculation demonstrated that these mesogens adopted distorted conformation which might be the reason why narrow mesogenic temperature ranges and irregularly winkled morphologies in these compounds are observed.


Introduction
Supramolecular self-assembly caused by intermolecular interactions between organic molecules is an important method to construct stable, well-defined, and complex micronano structures under some certain conditions [1][2][3][4].Liquid crystals and organogels are important supramolecular materials, that have specific features of both liquid and solid, and display distinct advantages of reversible stimulus responsibility, good thermal reversibility, and well adjustability [5][6][7][8].As a result, these materials various exhibit wide potentials in smart windows [9], display devices [10], chemical sensors [11], supramolecular chirality [12], stimulus-response materials [13][14][15], and fluorescent materials [16,17].The molecular structures of liquid crystals and organogelators including p-conjugated aromatic core, type of linkages, appended groups, and the symmetry heavily affected the molecular self-assembly processes, the phase transition behaviors, and applications [5][6][7][8].Therefore, a diverse range of building blocks have been employed to construct novel liquid crystals and organogelators.
Fluorescein is an important fluorochrome with high fluorescence quantum efficiency, characteristics of multipoint modification, and high photostability [18,19] leading to fascinating applications in chemosensors, indicators, medicine, and bioimaging [20][21][22][23].Although the synthesis and self-assembly of some novel fluorescein-based compounds were well demonstrated, only limited fluorescein-based liquid crystals or/and organogelators were reported [24,25].For instance, Yang et al. reported a series of fluoresceintriphenylene dimers that exhibited columnar mesophase and distinct fluorescence behaviors (compounds I-IV in Fig. 1) [24].The elongation of the length of alkyl chains on fluorescein led to an increase in emission efficiencies.Recently, they reported fluorescein-bridged perylene bisimide dimer which could self-organize into hexagonal columnar phase in a wide temperature range (compound V in Fig. 1) [25].The fluorescence resonance energy transfer effect between the central fluorescein and perylene bisimide units could induce strong fluorescence.These investigations demonstrated that the incorporation of fluorescein into liquid crystalline molecules could induce complex selfassembly structures and interesting emission properties.
Though, both fluorescein and 1,2,3-triazole heterocycle have been well investigated, however no report about liquid crystals and organogelators containing fluorescein and 1,2,3-triazole heterocycle.Therefore, herein we wish to synthesize the first fluoresceinbased hexacatenar molecules and report the self-assembly properties in both bulk and solution states.A series of hexacatenar molecules containing fluorescein and 1,2,3-triazole heterocycle were synthesized by CuAAC reaction between fluorescein contained diacetylene and 3,4,5-trialkoxybenzyl azides.These hexacatenar molecules could selforganize into hexagonal columnar mesophase in bulk state and form organogels with multiple morphologies in solution.

Synthesis
The synthetic route of fluorescein-based hexacatenars was designed as shown in Scheme 1. Fluorescein was etherified with propargyl bromide in the presence of dimethyl formamide (DMF) and weak base to yield fluorescein propargyl diether 2 [36].The synthetic process of 3,4,5-trialkoxybenzyl azides 3/n had been indicated in our previous literature [37].The target compounds YGS/n were synthesized by CuAAC reaction between 2 and 3/n in 74.2-77.1% yield.The structures of these fluoresceinbased hexacatenars were confirmed by nuclear magnetic resonance (NMR) spectra.The correlative spectra of these intermediates and target compounds reported here were provided in the Supplementary Materials.

Liquid crystalline self-assembly
The liquid crystalline self-assembly behaviors of the fluorescein-based hexacatenars YGS/n were investigated by polarized optical microscopy (POM), differential scanning calorimetry (DSC), and small angle X-ray diffraction (SAXS).The thermodynamic and DSC data were provided in Table 1 and Fig. S1.The thermodynamic data obtained from DSC and POM showed that all the hexacatenar mesogens YGS/n are enantiotropic liquid crystals (Table 1, Figs.S1-S3, and Fig. 2).The melting temperatures gradually decrease, clearing temperatures change irregularly and mesogenic temperature range become wide with the elongation of alkyl chains.The highest homolog YGS/16 shows the widest mesogenic temperature range (Table 1 and Fig. S1).
The liquid crystalline textures of these hexacatenars were observed under POM measurements showed typical pseudo focal conic fan-shaped textures indicating that all the hexacatenars should self-assemble into columnar mesophases (Fig. 2a, c, and e).The dark regions under POM demonstrated these columnar mesophases were optically uniaxial (Fig. 2a c, and e).The liquid crystalline textures with a k-retarder plate showed different colors (yellow and blue fans), which could well deduce that these columnar mesophases were optically negative, demonstrating that the preferred direction of the central fluorescein cores is on average perpendicular to the column long axis (Fig. 2b, d, and f) [38].
The type of mesomorphism and molecular packing structures of the mesophase were furtherly investigated by SAXS (Fig. 3a, Tables 1 and S1).In the SAXS patterns, there were three small-angle reflections at 3.40 nm, 1.96 nm, and 1.70 nm for YGS/10, 3.74 nm, 2.15 nm, and 1.87 nm for YGS/14, and 3.76 nm, 2.18 nm, and 1.88 nm for YGS/16, corresponding to (10), (11), and (20) reflections having spacing ratios of 1:(1/3) 1/2 :1/2.Therefore, all the three hexacatenars YGS/n (n ¼ 10, 14, 16) could selfassemble into hexagonal columnar phase (Col hex /p6mm) (Fig. 3a, Tables 1 and S1).According to the small-angle reflections, the lattice parameters of Col hex /p6mm formed by YGS/10, YGS/14, and YGS/16 are about 3.92 nm, 4.31 nm, 4.35 nm, respectively (Table 1).The number of molecules in each unit cell in these Col hex /p6mm phases was about 2, deducing that two fluorescein-based hexacatenar molecules aggregated into an oval-shaped disk which further stacked into columns and then arranged into p6mm lattice with the aid of the dipole-dipole interaction, p-p staking, etc.The corresponding self-assembly process and self-assembly model were proposed in Fig. 3b.The molecular dynamics (MD) annealed models (Fig. 3c) are well in line with the proposed self-assembly process and self-assembly model.It is worth noting that it is the first report about unconventional hexacatenar liquid crystals containing fluorescein fluorophore as the aromatic core.The DSC traces and POM data showed that all the compounds displayed a narrow mesogenic temperature range (about 30 � C) owing to the nonplanar configuration of fluorescein and flexible methylene units (Fig. 4).On the one hand, the presence of flexible methylene units could increase the microsegregation between incompatible molecular parts (alkyl chains and p-conjugated aromatic core), which promoted the formation of mesophases.On the other hand, the large molecular distortion hindered intermolecular close p-p staking, leading to the decrease in the stability of the liquid crystal phase.Therefore, Col hex /p6mm phase with lower stability was formed.

Gel self-assembly
In addition, the self-assembly of the fluorescein-based hexacatenar in different solvents was also investigated (Table S2 and Fig. 5).The gelation ability of representative hexacatenar YGS/16 was examined in some frequently-used solvents by means of the ''stable to inversion of a test tube'' method as shown in Table S2.YGS/16 could gelate only in the organic solvents with medium polarity including ethyl acetate, acetone, and 1, 4-dioxane with critical gelation concentration of 31 mg/mL, 30 mg/mL, and 27 mg/mL, respectively.The morphologies of xerogels obtained from above-mentioned solvents were furtherly investigated by field-emission scanning electron microscopy (FESEM) (Fig. 5).The FESEM images demonstrated that all the xerogels showed similar irregularly winkled morphologies.Although the presence of the ester group and 1,2,3-triazole could increase the intermolecular interaction between gelators and solvent molecules, the non-planar configuration of fluorescein hindered the intermolecular interaction between gelators and gelators (Fig. 4).Therefore, only irregular organogel morphologies could be observed in these organic solvents.

Density functional theory calculation
Geometry optimization, frontier molecular orbitals, and molecular electrostatic potential (MEP) of model compound YGS/OCH 3 in which the methoxy groups replace the  terminal alkoxy chains had been executed by using B3LYP/6-31G basis sets (Fig. 4).The dihedral angle between isobenzofuran-1(3H)-one unit and 9H-xanthene unit in the optimal conformation of YGS/OCH 3 is about 90 � , the dihedral angles between 9H-xanthene unit and 1,2,3-triazole units are about 43.34 � and 46.96 � , respectively, and dihedral angles between 1,2,3-triazole units and the terminal phenyls are 75.81� and 74.24 � , respectively, indicating that these hexacatenar mesogens adopted twisted conformation (Fig. 4a).The extremely large dihedral angles between isobenzofuran-1(3H)-one unit and 9H-xanthene unit and between 1,2,3-triazole units and the terminal phenyls would be attributed to the heavy steric hindrance induced by the ester group and flexible methylene units, respectively.The frontier molecular orbitals and energy gaps are regarded as important parameters in determining the charge transfer and photostability [39].As shown in Fig. 4c, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of YGS/OCH 3 mainly distribute on the 9H-xanthene unit and isobenzofuran-1(3H)-one unit, respectively, indicating distinct intramolecular charge transfer.The LUMO þ 1 and LUMO þ 2 are the second and third LUMOs, respectively and the majority of the LUMO þ 1 and LUMO þ 2 all mainly distribute on the central fluorescein unit (Fig. 4c).HOMO þ 1 and HOMO þ 2 are the second and third HOMOs, respectively and the majority of the HOMO þ 1 and HOMO þ 2 mainly distribute on the one terminal phenyl and central fluorescein unit, respectively (Fig. 4c).The calculated energy gaps of the YGS/OCH 3 between HOMO-LUMO, HOMO-1-LUMO þ 1, and HOMO-2-LUMO þ 2 are about 4.70 eV, 5.50 eV, and 5.53 eV, respectively (Fig. 4c), demonstrating higher kinetic stability and lower chemical reactivity [40].In addition, the MEP is a visual model to display the charge distribution over the molecules and is also an important tool in investigating the interand intramolecular interactions [39,41].In the MEP map, the maximum negative charge center (red region) is the carbonyl oxygen of the ester and nitrogen atoms of 1,2,3-triazole, whereas the minimum negative charge center (blue region) is methine units of 1,2,3-triazole (Fig. 4b).The asymmetrical charge distribution could induce large molecular dipole.The balance of twisted conformation which could increase steric hindrance and decrease intermolecular close p-p stacking and charge distribution which could increase molecular dipole led to the formation of liquid crystal and organogel.

Conclusion
In conclusion, the first example of fluorescein-based hexacatenar mesogens containing one fluorescein and two 1,2,3-triazole units as the rigid core was synthesized by CuAAC reaction.All the compounds could self-assemble into hexagonal columnar mesophase in bulk state and self-assemble into organogel with irregularly winkled morphologies in moderate polar solvents.Density functional theory calculations showed that these hexacatenar mesogens adopted twisted conformation, showed distinct intramolecular charge transfer, and showed asymmetrical charge distribution.The balance of these factors of structure and property has benefits to the formation of complex self-assembly structures in both bulk state and solution state.

Figure 1 .
Figure 1.The chemical structures of the reported fluorescein-based liquid crystals.

Table 1 .
Phase transitions, lattice parameters, and other data of fluorescein-based hexacatenars YGS/n.a a Transition temperatures and transition enthalpies determined by DSC on first heating and cooling (10 K min −1 ); Cr ¼ crystal; Col hex /p6mm ¼ hexagonal columnar phase; Iso ¼ isotropic state; a ¼ lattice parameter determined by XRD; n cell ¼ number of molecules in each unit cell which was calculated by the equation: n cell ¼ (a 2 /2) ffi ffi ffi 3 p h(N A /M)q. b Observed by POM.