Construction of chiral through-space luminophores via symmetry breaking triggered by sequenced chlorination

The construction of molecular chirality is crucial for exploring novel luminophores with chiroptical properties. Classic asymmetric synthesis of chiral center or axial is not powerful enough on through-space architecture. Accessible methodologies for breaking molecular symmetry could be promising but remain less investigated. Herein, we report a novel methodology for constructing chiral through-space luminophores via simple chlorination on bridged carbazole motifs. The chlorination breaks the molecular symmetry and thus results in molecular chirality by eliminating the mirror plane or rotating axis. Interestingly, continuous multiple chlorinations can rebuild and break the symmetry of the skeleton in succession. Several chiral and achiral isomeric analogues are synthesized and characterized with impressive chiroptical properties. Results of chiral high performance liquid chromatography (HPLC), single-crystal X-ray diffraction, kinetic racemization, and chiroptical property investigation demonstrate the effectiveness of our rational design strategy. It provides a feasible methodology for exploring novel chiral luminescent materials based on versatile though-space skeletons.


Introduction
Chirality, an essential attribute in nature, is fascinating for mathematics, physics, biology, and chemistry. Among them, chiral organic luminophores have drawn great attention owing to their versatile applications in three-dimensional display [1,2], optical information storage [3], light-emitting diode [4][5][6][7][8][9], asymmetric catalysis [10,11], and biological sensor [12]. These chiroptical properties should originate from molecular structural or environmental [13][14][15][16][17][18] chirality. Therefore, the construction of chirality plays a vital role in exploring novel luminophores with chiroptical properties. According to the definition, an object that is non-superposable on its mirror image is chiral. So, chiral subjects will lack a center of inversion or a mirror plane. Breaking the symmetry of an achiral object could potentially construct the chirality.
Here, we report a new methodology for constructing chiral through-space luminophores through simple chlorination on bridged carbazoles. As shown in Figure 1, the illustration model has the symmetry factors of the C 2 rotating axis and σ v mirror plane, belonging molecular point group of C 2V and thus being achiral. The introduction of chlorine atoms breaks the skeleton symmetry by eliminating the mirror plane and/ or rotating axis and leads to molecular chirality. Interestingly, continuous multiple chlorination can rebuild and break the symmetry of the skeleton in succession, together with several chiral and achiral isomeric analogues. This strategy was undoubtedly verified by chiral high-performance liquid chromatography, single-crystal X-ray diffraction analysis, kinetic racemization study, and chiroptical property investigations. Impressively, separated enantiomers exhibit considerable circular dichroism and circularly polarized luminescence performance. Overall, our design strategy provides an effective and promising methodology for constructing chiral luminescent materials based on thoughspace structures.

Results and discussion
To construct a through-space skeleton, xanthene was chosen as the bridge, and two carbazole motifs were introduced by the Ullman coupling ( Figure 2) to give OCZ as the throughspace skeleton [34], which was then subjected to chlorination. To exclude the potential influence of isomer impurity, the carbazole employed was synthesized by our lab. Due to the electronic effect, the 3-and 6-positions of carbazole were more active towards electrophilic substitution. Thus, simply controlling the equivalent of N-chlorosuccinimide yielded targeted products with varied chlorine atom substitution. For instance, OCZ-1Cl, OCZ-4Cl, OCZ-5Cl, and OCZ-6Cl were synthesized and successfully separated. However, more chlorine atoms decrease the reactivity, and all these chlorinated products have quite similar polarity. This made other possible derivatives very difficult to be separated and were thus omitted in this work. The obtained enantiomers were carefully purified by silica-gel column chromatography and recrystallization before investigating their photophysical properties. All the molecules were characterized by 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy (Charts S1-S12, Supporting Information online), high-resolution mass spectroscopy (Charts S13-S18), differential scanning calorimetry and thermogravimetric analysis (Charts S19-S24), and single-crystal X-ray diffraction analysis (Tables S5-S12, Supporting Information online).
The chirality of these molecules was then verified by a chiral stationary phase high performance liquid chromatography (HPLC). The chromatographic resolution conditions were a polysaccharide-based stationary phase and a 99:1 (v/ v) hexane/isopropanol mixture as eluent at room temperature. The optimized process is shown in Figures  The HPLC chromatograms of OCZ-1Cl and OCZ-5Cl presented two well-separated components, which could be ascribed to the two possible enantiomers in their racemic solutions. The OCZ-6Cl had three isolated components, which was consistent with its more complex isomer constituents, one cis-isomer, and two racemic trans-enantiomers. The above results clearly demonstrated the facile tuning chirality of the skeleton by simply manipulating the chlorination process.
Furthermore, sequenced-chlorination-induced symmetry breaking and chirality alternating process was investigated by point-group analysis. As shown in Figure 3b, the symmetry character of the skeleton is decreased from C 2v to C 1 , resulting in four chiral OCZ-1Cl, OCZ-3Cl, OCZ-5Cl, and OCZ-7Cl compounds. Then, it can be partially recovered to C s in cis-OCZ-2Cl and cis-OCZ-6Cl or C 2 in trans-OCZ-2Cl and trans-OCZ-6Cl by one more chlorination. Finally, C 2v is fully recovered in achiral OCZ-4Cl and OCZ-8Cl derivatives. The HPLC results perfectly matched the theoretical symmetry analysis. In a word, by sequenced chlorination, chiral through-space luminophores could be facilely constructed by symmetry breaking. Considering the relatively good separation of retention time in chiral HPLC, the racemic mixtures of OCZ-5Cl and OCZ-6Cl were separated into their pure enantiomers by a semi-preparative chiral HPLC column ( Figures S4, S5, S8 and S9). The absolute conformations are then checked by single-crystal X-ray diffraction analysis. As the representative in Figure 3c, molecular structures of (P)-OCZ-6Cl and (M)-OCZ-6Cl in their single crystals have the expected mirror images. Based on these single-crystal struc-tures, a clockwise arrangement of chlorine atoms is selected as P-configuration, and thus the P, M, cis and achiral isomers are determined and labeled in Figure 3a, accordingly.
To better understand the stability of the chiral isomers, we studied the thermodynamics and kinetics of the isomerization process using chiral HPLC. The isomerization situation of OCZ-6Cl is more complex as cis-trans and racemization transitions are twined. So, we selected OCZ-5Cl as a demonstration for clarity ( Figure 4a). Heating solutions of  (c) Single-crystal X-ray structure of (P)-OCZ-6Cl and (M)-OCZ-6Cl with carbon, oxygen, nitrogen, and chlorine atoms shown as grey, red, blue, and green ellipsoids at the 20% probability level (color online). different OCZ-5Cl isomers in toluene at 373 K for days led to the mixture with the same equilibrium of (P)-OCZ-5Cl and (M)-OCZ-5Cl in a ratio of 1:1, which was determined from the integrations in the chiral HPLC chromatograms as shown in Figure 4b. Based on the equilibrium ratio, the racemization equilibrium constant K eq = k 1 /k −1 was given as 1.0. This was in agreement with their mirror-imaged configurations with the same energy. Starting from a 98.5% ee solution of (P)-OCZ-5Cl in toluene, continuous heating at 373 K for 5.5 h resulted in partial thermal isomerization to (M)-OCZ-5Cl. The kinetic progress was carefully monitored with chiral HPLC. Given the reversible and first-order unimolecular nature of the racemization reaction, the racemization rate constants can be estimated by using the equation of ln(C 0 /C t ) = (k 1 + k −1 )t, where C 0 /C t is the ratio of (P)-OCZ-5Cl that has been depleted at a specific time t, which represents the extent of the reaction and could be determined by integrations in the chiral HPLC chromatograms. k 1 and k −1 are the rate constants for the forward and reverse reactions, respectively. Plotting ln(C 0 /C t ) versus time leads to a slope of 3.28 × 10 −6 s −1 , as shown in Figure 4c. From this slope and the reaction equilibrium constant K eq , the rate constant k 1 at 373 K is determined as 1.64 × 10 −6 s −1 . Using the Eyring equation k = κ(k B T/h)exp(−ΔG/RT) and assuming a value of unity for the transmission coefficient (κ) [35,36], the activation free energy ΔG is calculated as 31.9 kcal/mol for the racemization of (P)-OCZ-5Cl, which is close to the density functional theory (DFT)-calculated energy barrier of 28.7 kcal/mol. The details of ΔG estimation are given in the Supporting Information online.
The racemization energy barriers of other chiral derivatives were also estimated by theoretical calculations. Judging from the geometries of transition states (Figures S10-S12), the energy minimum was achieved by slightly bending the xanthene bridge and pushing away the carbazole motif for facile rotation. As the number of substituted chlorine atoms was increased, the free energy barrier ΔG went uphill from 25.1 to 39.9 kcal/mol without temperature correction (Table  S3). It was reasonable because more chlorine atoms at carbazole would contribute to higher steric repulsion and bigger structural deformation during the racemic rotation process [37]. Nevertheless, the considerably high racemic ΔG endowed these chiral isomers with robust thermal stability at ambient conditions for investigating their photophysical properties in solution.
The ultraviolet-visible (UV-vis) absorption and photoluminescence (PL) spectra in dilute 2-MeTHF were investigated for OCZ-nCl. As displayed in Figure 5a, the absorption spectra exhibit similar shapes and intensities with three main regions. The longest wavelength absorption bands could be attributed to the locally excited states ( 1 LE) of carbazole motifs with multiple vibronic structures. As the number of substituted Cl atoms was increased, they exhibited an obvious bathochromic shift. It is reasonable as Cl substitution is effective in lowering molecular-orbital energies, especially for LUMOs [38] and the conjugation effect of the Cl atom increases the overall π-conjugation of substituted carbazoles ( Figure 5 and Figure S13). Both effects exert the same effect on lowering the energies of the first singlet excited states (S 1 ). This trend is also verified in the PL spectra of their 2-MeTHF solutions and crystals as shown in Figure 5c, d. The emission maxima are gradually red-shifted from 360 to 383 nm in solutions and from 376 to 415 nm in crystals, respectively. Time-resolved decay curves give short lifetimes in nanoseconds, indicating their fluorescence characteristics ( Figure S14). Careful investigations of the PL spectra reveal the typical emission profile of the carbazole motif, with two finely resolved peaks and one shoulder peak. This is in accordance with that S 1 is mainly contributed by locally excited carbazole motif. It is worth noting that full width at half maximum is significantly deduced in OCZ-nCl to ca. 24 nm as listed in Table S4. The possible reason is that the bridged skeleton of OCZ-nCl forces the carbazole motif into a tightly confined molecular geometry by through-space interaction. Thus, the vibration extent is restricted and narrowed emission profiles are yielded. Besides, the PL was quantified, which gave relatively low Φ PL values, particularly for multiple chorine substitutions. Their fluorescent and nonradiative decay constants were estimated and summarized in Table S4. These results demonstrate that chlorination and through-space configuration play important roles in the photophysical properties with tuned spectral profiles and narrow emission bands.
The successful separation of absolute chiral enantiomers allows investigating the chiroptical property. The circular dichroism (CD) and circularly-polarized luminescence (CPL) spectra were measured. Firstly, CD spectroscopies of (M)-OCZ-6Cl and (P)-OCZ-6Cl solutions show the alternating positive and negative Cotton effect from 250 to 370 nm at room temperature, which matches well with their absorption bands in 2-MeTHF and their absolute chiral molecular configuration (Figure 5a, b). The calculated CD spectra of OCZ-1Cl, OCZ-5Cl, and OCZ-6Cl were found a good match with experimental results of OCZ-6Cl and their UV-vis absorption spectra. There is also a trend of bathochromic shift from OCZ-1Cl to OCZ-5Cl, and to OCZ-6Cl, which is in accordance with the electronic and conjugation effects of more chlorine substitution ( Figure S15).
Secondly, the CPL spectra were measured on an Edinburgh FLS-1000 spectrometer with the CPL accessory. The total PL spectra in 2-MeTHF solutions at 77 K give the intense and resolved phosphorescence bands at 415-565 nm, which are verified by delayed PL spectra and their lifetime decay curves ( Figure S16). The ΔI exhibit the structured emission profiles with the prominent circularly-polarized phosphorescence emission bands (Figure 6a). They are coinciding with the steady-state PL spectra. Typically, the CPL magnitude is evaluated by the dissymmetry factor (g lum ), which can be defined as g lum = 2 (I L − I R )/(I L + I R ) = 2 ΔI/I, where I L and I R indicate the intensity of L-CPL and R-CPL, respectively. Theoretically, the g lum of −2 and +2 describe the pure R-CPL and L-CPL, respectively. Peak dissymmetric factor g lum around 0.7 × 10 −2 -2.3 × 10 −2 was obtained for (M)-OCZ-6Cl and (P)-OCZ-6Cl solutions at 77 K under 300 nm excitation (Figure 6b), giving the impressive CPL performance.
To ensure the samples are solutions, we increase the temperature from 77 to 150 K. The obvious CPL signal is still existing ( Figure S17). Different from the pure phosphorescence emission at 77 K, a significantly fluorescence emission band emerges at 150 K due to the reduced intersystem crossing. Further increasing the temperature to room temperature, the 2-MeTHF solutions of (M)-OCZ-6Cl and (P)-OCZ-6Cl lost their CPL signals ( Figure S18), which could be attributed to the enhanced nonradiative decay rate and molecular flexibility at high temperature, resulting in luminescence performance far inferior to that at 77 K. The other possible reasons include light-induced deterioration or racemization of molecules. Besides, solutions of racemic OCZ-6Cl at 77 and 150 K keep CPL silence ( Figure S19), indicating the above CPL signals must stem from chiral molecular structures rather than solvent environments. Then, we measured the solvent effect on the CPL spectra of (M)-OCZ-6Cl and (P)-OCZ-6Cl at 77 K. There were weak to no CPL signals from isopropanol to toluene and to acetonitrile ( Figures S20-S22) [39]. Overall, the absolute chiral molecular structures, cryogenic conditions, and suitable solvent are the decisive conditions to achieve the impressive CPL performance.
The single crystals of achiral 1, OCZ, and OCZ-4Cl, racemic single crystals of OCZ-5Cl and OCZ-6Cl, chiral single crystals of (M)-OCZ-5Cl, (M)-OCZ-6Cl, and (P)-OCZ-6Cl were successfully obtained by careful solvent diffusion (details are shown in the Supporting Information online). Their absolute molecular conformations were determined by single-crystal X-ray diffraction (Tables S5-S12). As shown in Figure 7, the xanthene rings are assigned as plane A, the carbazoles are assigned as plane B and C. The dihedral angles of θ A/B and θ A/C in OCZ, OCZ-4Cl, OCZ-5Cl, and OCZ-6Cl are in the range of 57.46°-67.27°, revealing that they endow the highly twisted molecular conformations and also weak electronic conjugation between xanthene and carbazole units. While, the θ B/C in these compounds are in the range of 3.19°-13.35°, confirming that adjacent planar carbazole units are arranged in parallel or nearly parallel configurations. Furthermore, the intramolecular interactions are investigated. The vertical distances between the carbazole planes are 3.67-3.95 Å, which are short enough to generate through-space π-conjugations. In comparison, carbazole unit in crystal of 1 fails to achieve such interactions. To confirm through-space conjugation, the theoretical calculations were performed by the density functional theory at the B3LYP/6-31G(d) level. At the ground-state molecular geometry, there are considerable overlaps in the frontier LUMO and LUMO + n, suggesting the existence of intramolecular throughspace interactions (Table S13).
In addition, chiral crystals of (M)-OCZ-5Cl, (M)-OCZ-6Cl, and (P)-OCZ-6Cl were analyzed. The molecules of (M)-OCZ-5Cl, (M)-OCZ-6Cl, and (P)-OCZ-6Cl ( Figure S23) were packed in a chiral orthorhombic space-group of P21 with the Flack parameters of +0.061(10), −0.003(5), and +0.013 (7), respectively, verifying the absolute axial chirality of molecules. In comparison, pairs of (P)-OCZ-6Cl and (M)-OCZ-6Cl molecules packed in an achiral P1 group in racemic OCZ-6Cl single crystal. Crystal structures shown in Figure  S23 confirmed that the adjacent planar carbazole motifs also aligned in parallel or close parallel configurations with the shortest π-π distances from 3.88 to 3.95 Å, resulting in the considerable through-space π-conjugation. On the other hand, the dihedral angles between the carbazole and xanthene was close to orthogonal ranged from 86.2°to 89.8°. Such large dihedral angles led to the poor through-bond  conjugation from xanthene bridge in OCZ-6Cl, giving similar emission profiles to carbazole motif.
Breaking symmetry is powerful in constructing molecular chirality but less investigated. Here, five kinds of compounds with different numbers of chlorine substitutions were synthesized by simple chlorination reaction on bridged-carbazole. Simple chlorination on bridged carbazole puts forth a novel methodology for constructing nonconventional chiral through-space luminophores by eliminating mirror plane or rotating axis. Interestingly, continuous chlorination rebuilds and breaks the skeleton symmetry in succession. The different substitution on carbazole subunits could introduce the charge-transfer charcter to initial the thermally-activated delayed fluorescence property. However, these chlorinated through-space derivatives are quite difficult to be purified and resolved into their enantiomers. The tedious chiral HPLC is still required, which blocks in-depth investigations. Besides, the luminescent properties are also quite poor as multiple chlorinations harm the emission. Probably, novel through-space architectures can be applied to solve these problems, as our methodology is general in constructing chirality.

Conclusions
In summary, we report a novel methodology for constructing chiral through-space luminophores based on chlorinating bridged carbazole skeleton. The chlorination process breaks the symmetry of the molecular configuration, resulting in chirality. Three chiral isomers (P)-OCZ-5Cl, (M)-OCZ-6Cl, and (P)-OCZ-6Cl were isolated by semi-preparative HPLC, and their absolute configurations were determined by singlecrystal X-ray diffraction. In addition, the investigation of kinetic racemization and chiroptical properties proves the effectiveness of our design strategy. We are applying the strategy in developing new chiral through-space architectures for cutting-edge applications in our lab.