Photo-Responsive Hydrogen-Bonded Molecular Networks Capable of Retaining Crystalline Periodicity after Isomerization

Synthesis of Compounds

Dibromodihydrodimethylbenzo[e]pyrene derivative 2 was synthesized from pristine DHP according to a previous report.⁴⁸ Suzuki–Miyaura cross-coupling reaction of 2 and 3 gave dimethyl ester derivative 4, which was hydrolyzed in the presence of KOH to give 2BDHP (Scheme 1a). Similarly, dimethyl ester derivative 5, which was prepared according to the reported method,⁴⁹ was brominated with N-bromosuccinimide, and the resultant dibromide 6 was reacted with 3 to give tetramethyl ester derivative 7 (Scheme 1b). Hydrolysis of 7 in the presence of KOH gave 4BDHP. The synthesized compounds were characterized by ¹H and ¹³C NMR spectroscopy and HR-MS. Both 2BDHP and 4BDHP were obtained as racemic mixtures of (R,R)- and (S,S)-enantiomers (no specific symbol is attached for the racemic mixture in this report).

Theoretical Calculations

Geometric optimization of 4BDHP and 4CPD was performed at the B3LYP/6-311+G** level of theory (Figure S1). Figure 2 shows superimposed molecular conformations of 4BDHP and 4CPD. Characteristic structural parameters are listed in Table 1. 4BDHP contains the C(3a¹)−C(5a¹) single bond with a bond length (d) of 1.543 Å, while the corresponding bond is cleaved in 4CPD: the distance C(17)⋅⋅⋅C(18) is 2.688 Å. The C−C bond length (d_Me) between the inner methyl carbon and C(3a¹) or C(5a¹) in 4BDHP (i.e., 1.569 Å) is slightly longer than the corresponding distance in 4CPD (i.e., 1.506 Å).

The benzene rings of the cyclophane moiety in 4CPD are slightly bent because of bridging at the meta-position of the ring: the root mean square deviation (RMSD) of the rings is 0.080 Å. Note that the peripheral tert-butyl groups in 4CPD are significantly bent up and down from the molecular plane (ω_tB: ca. 2.5° for 4BDHP and 47.9° for 4CPD), instead of the closely similar positions for the methyl groups in 4BDHP and 4CPD. This comparison also shows differences in the rotational conformation of the peripheral carboxyphenyl groups (ω_CP: 81.28–81.78° for 4BDHP and 50.72–50.91° for 4CPD) and carboxy groups (ω_C: 35.90–35.96° for 4BDHP and 37.19–37.46° for 4CPD). The TD-DFT calculations revealed that 4BDHP has lower LUMO and higher HOMO levels and a smaller HOMO–LUMO gap (−2.69 eV, −5.25 eV, and 2.56 eV, respectively) compared with the corresponding values for 4CPD (−2.46, −5.81, and 3.35 eV, respectively) due to the π-conjugated benzo[14]annulene rings of 4BDHP (Figure S2). The HOMO and LUMO of 4BDHP are delocalized throughout the BDHP skeleton, while those in 4CPD are located mainly on the cyclophane and peripheral phenylene rings. The 2BDHP and 2CPD show a similar tendency (Figure S3).

Photo-isomerization in Solution

Photo-isomerization of the BDHP derivatives was first examined in a solution state. 2BDHP and 4BDHP were subjected to irradiation with visible light (λ>430 nm) using a xenon lamp in DMF solutions, and isomerization reactions were monitored by UV/Vis and ¹H NMR spectroscopy. Figure 3a shows UV/Vis spectral changes of 4BDHP upon irradiation. 4BDHP produced absorption bands at 355 and 410 nm with shoulders and a broad band ranging from 450 to 650 nm. Upon photoirradiation, the absorption bands characteristic of 4BDHP gradually decayed and reached a steady state in 80 s, while a new band at 266 nm became prominent. These spectral changes agree well with the theoretical electronic transition calculated for 4BDHP and 4CPD (Figure 3b), indicating that the expected photo-isomerization occurred. Thermal treatment at 80 °C for 15 min prompted the ring closing reaction to give the original spectral profile. The UV/Vis spectral changes gave the isosbestic point at 315 nm, showing clean photo-isomerization without side reactions. The 2BDHP also showed similar behavior (Figure S4).

Thermally induced ring closing reactions of 4CPD and 2CPD in DMF solutions were monitored by UV/Vis spectroscopy at various temperatures (Figures S5–S8), which revealed that the activation energy (E_a) of the ring closing reaction was 95.0 kJ/mol for 2CPD and 106 kJ/mol for 4CPD. These data agree well with those for other CPD derivatives reported in the literature.⁵⁰ The half-life periods of 4CPD and 2CPD at 40 °C were approximately 4 and 3 hours, respectively, and those at 70 °C were 5 and 10 min, respectively (Tables S1 and S2).

Figure 4 shows ¹H NMR spectral changes of 4BDHP upon irradiation and subsequent heating in the dark. A peak ascribable to protons of the inner methyl groups in 4BDHP resonated at −1.53 ppm almost disappeared after visible light irradiation, while a peak of the corresponding benzyl protons of 4CPD appeared at 1.46 ppm. Because of loss of aromaticity of the [14]annulene ring, signals associated with aromatic protons in the annelated benzene ring at 9.33 ppm and those for the [14]annulene ring at 8.66 and 7.21 ppm shifted up-field to 7.98, 6.87, and 6.44 ppm, respectively. Similarly, the resonance of tert-butyl protons shifted up-field from 1.34 to 1.06 ppm upon irradiation. After heating at 80 °C for 1 h, the original spectrum was recovered. The spectral changes also provided information about the rotational mobility of the peripheral phenylene rings. In the spectrum of 4BDHP, the aromatic protons of the phenylene rings resonated at four different positions of 7.87, 7.79, 7.43, and 7.16 ppm as broad doublets, while two sets of sharp doublets at 7.78 and 7.21 ppm were observed in the spectrum of 4CPD, indicating that the mobility of the phenylene rings is highly restricted in 4BDHP due to steric hindrance of the nearly planar [14]annulene ring. ¹H NMR spectral changes for 2BDHP upon visible light irradiation showed similar results (Figure S9).

Crystallography and Photo-isomerization of 2BDHP

First, pristine BDHP was recrystallized from a THF solution at room temperature, resulting in precipitation of single crystals with Pbca space group (Figure S10, Table S3). Visible light irradiation of the crystal resulted in no color changes but did increase the roughness of the crystal surface (Figure S11). Next, dicarboxylic acid derivative 2BDHP was recrystallized using a mixed solution of DMF and methyl benzoate (MeBz) at 90 °C or using a mixed solution of THF and MeBz at room temperature, where MeBz was used as a template molecule, giving single crystals suitable for X-ray analysis (Table S3). 2BDHP crystallized in space group P2₁/c with inclusion of MeBz molecules, giving crystal 2BDHP-1. The inner methyl groups and carbon atoms C(5a₁) and C(3a₁) of 2BDHP are disordered in two sites (Figure 5a). Molecules of 2BDHP form a zigzag-shaped 1D ribbon with a periodicity of 15.8386(4) Å along the b axis through intermolecular H-bonds between the carboxy groups (Figure 5b). The 1D ribbons are stacked to form a layered structure (Figure S12). The crystals in the mother liquid were exposed to visible light, resulting gradually fragmentation into small particles from the edge of the crystal, along with a color change from dark red to brown. Furthermore, yellow powders also precipitated from the liquid during the irradiation. Fortunately, a single orange crystal of relatively larger size and better quality was obtained by chance, allowing a preliminary crystallographic analysis of the open form contained crystal 2BDHP-X. In the crystal, the distance between C(3a¹) and C(5a¹) atoms is 1.85 Å, which is much longer than that in the closed form 2BDHP (1.53 Å) (Figure 5c). This observation indicated a contribution of 2CPD species coexisting in the crystal. The molecules also formed a zigzag-shaped 1D ribbon through H-bonds (Figures 5d, S14). However, its periodicity, i.e. 19.822(5) Å, is much longer than that in 2BDHP-1. These structural differences imply that isomerization from 2BDHP to 2CPD in a single crystalline state may be difficult due to the incongruence of periodicities of the H-bonded 1D structures.

Crystallography and Photo-isomerization of 4BDHP

4BDHP was crystallized by slow evaporation from a mixed solution of DMF and MeBz at 90 °C, yielding monoclinic P2₁/c crystal 4BDHP-1 (Figure 6a–d, Table S4). The inner methyl groups and carbon atoms C(3a¹) and C(5a¹) of 4BDHP are disordered in two sites with a chemical occupancy of 0.64 and 0.36. The 4BDHP forms a sql-networked flat sheet through intermolecular H-bonds of the carboxy groups. The network has periodicities of 33.18 Å and 15.25 Å along the b axis and ac diagonal axis directions, respectively. This type of sql-network is typical for tetracarboxylic acid tectons with rigid planar skeletons.^{51, 52} Neighboring tert-butyl groups divide the rhombic void into two triangular voids with a side length of ca. 8.2 Å. The solvent-accessible volume was estimated to be 13 % by PLATON software using a probe radius of 1.2 Å.⁵³ In the void, molecules of MeBz are accommodated with a 1 : 2 host–guest ratio. The solvent molecules were fixed through π/π stacking between the carboxy dimer and the benzene ring of MeBz and multiple CH/O contacts (Figure S15). Molecules with the same chemical occupancy constitute one sql-networked sheet, and therefore chirality of the sheet slightly leaned to one side, such as the (S,S)-rich sheet. The layers are, however, stacked in an inverted manner, resulting in the achiral layered framework of 4BDHP-1. The layers are stacked with an interlayer distance of 5.08 Å through contacts between the methyl groups and the [14]annulene ring as well as CH/O contacts of the carbonyl oxygen atoms and the aromatic hydrogen atoms (Figure S16).

Meanwhile, crystallization from a mixed solution of DMF and 1,2-dimethoxybenzene (DMB) at 90 °C yielded orthorhombic Pbcn crystal 4BDHP-2 (Figure 6e–h). The molecule has a two-fold axis. The inner methyl groups and carbon atoms at C(3a¹) and C(5a¹) of 4BDHP are disordered in two sites with chemical occupancies of 0.61 and 0.39. The 4BDHP forms a sql-networked undulate sheet parallel to the ab plane through intermolecular H-bonds of the carboxy groups. The network has periodicity of 33.89 Å and 13.97 Å along the b- and a-axis directions, respectively. In the sheet, R,R-rich and S,S-rich molecules are alternately connected through H-bonds with opposite inclines of 18.4° against the ab plane (Figures 6g and S17). Because of the incline, the tert-butyl groups are out of the plane. The undulate layers are stacked in an inverted manner with interlayer distances of 5.47 Å through contacts between the methyl groups and the annelated benzene ring as well as CH/O contacts of the carbonyl oxygen atoms and the aromatic hydrogen atoms (Figure S18). Molecules of DMB in the inclusion space of 4BDHP-2 were severely disordered and were not able to be refined crystallographically. The void ratio of the inclusion space was 10 %.

Thermal analyses of 4BDHP-2 revealed that the crystallinity was lost by heating up to ca. 220 °C due to removal of included DMB molecules and thermal decomposition of the molecules themselves (Figures S19–S21). ¹H NMR spectrum of the decomposed compounds indicates that the thermal decomposition was proceeded by 1,5-sigmatropic shift of the inner methyl groups and irreversible cascade reactions (Figure S22), which was reported on DHP derivatives.⁵⁴ These indicate thermal limitation of the present systems.

Crystals of 4BDHP-1 were subjected to visible light irradiation for 8 h and showed no changes in either appearance (Figure 6a) or crystal structure (Table S5, Figure S23) due to tight packing of the molecules in the crystals. In contrast, crystals of 4BDHP-2 underwent color changes from dark red to yellowish red accompanied by generation of cracks upon irradiation (Figure 6e). This indicates that 4BDHP-2 undergoes photo-isomerization due to loose packing of the undulate layers. Single-crystalline X-ray diffraction experiments revealed a structure of a photoirradiated crystal containing 4BDHP with an elongated C(5a¹)−C(3a¹) bond (Table S5 and Figure S23). Further irradiation, however, resulted in loss of single-crystallinity. ¹H NMR spectrum of the well-irradiated crystal dissolved in DMSO-d₆ indicated that side reactions also might occur (Figure S25). Since 4BDHP-2 is composed of disordered racemic 4BDHP molecules, photoisomerized crystals can contain (R,R)-4BDHP, (S,S)-4BDHP, (R_p)-4CPD, and (S_p)-4CPD. Particularly, the coexistence of (R_p)-4CPD and (S_p)-4CPD must disturb the crystallinity because of their prominent structural differences. Based on this hypothesis, the enantiomers of 4BDHP were separated.

Enantiomer Separation of 4BDHP

Resolution of 4BDHP was conducted as shown in Figure 7. As described earlier, the BDHP and CPD derivatives are chiral compounds. Two chiral centers at C(3a¹) and C(5a¹) in 4BDHP results in (S,S)- and (R,R)-isomers. Similarly, 4CPD has planar chirality.^{55, 56} The definition of planar chirality in 4CPD is shown in Figure S26. The (S_p)-4CPD and (R_p)-4CPD can be provided by ring opening reactions of (S,S)-4BDHP and (R,R)-4BDHP, respectively.

The racemic mixture of methyl ester precursor (rac)-7 dissolved in chloroform was irradiated with a white LED light until (rac)-7 was isomerized into (rac)-7 o. The resultant solution was immediately subjected to preparative HPLC equipped with a chiral column (Figures S27, S28), allowing isolation of enantiomers (S_p)-7 o and (R_p)-7 o with 99.1 %ee and 94.9 %ee, respectively (Figures S29 and S30). The enantiomers also were confirmed to isomerize into the corresponding BDHP isomer upon heating (Figure S31 and S32). Optical properties of the separated enantiomers (S_p)-7 o and (R_p)-7 o and the corresponding BDHP isomers (S,S)-7 and (R,R)-7 are shown in Figure 7c and 7d, respectively. The absolute structures of the enantiomers of 7 and 7o were assigned by comparison with the theoretical CD signals calculated for each of the enantiomers (Figure 7e,f). The enantiomers of 7 showed CD bands in the range of 450–650 nm, which corresponds to the HOMO–LUMO transition, although the intensity of the CD spectra was weak because of subtle differences in the structures. These bands are characteristic of BDHP and were also predicted by the theoretical calculation. The CD spectra of 7 o show prominent bands at 273, 314, 343, and 402 nm. The separated (S_p)-7 o and (R_p)-7 o were isomerized back to (S,S)-7 and (R,R)-7, respectively, and subjected to hydrolysis, giving (S,S)-4BDHP and (R,R)-4BDHP, respectively, which were used for construction of enantiopure H-bonded framework. The absolute structure of enantio-pure 4BDHP was also confirmed by X-ray crystallography with Cu−Kα X-ray source (vide infra).

Structure and Photo-isomerization of Enantiopure Crystal

Crystallization of (S,S)-4BDHP from a mixed solution of DMF and MeBz gave monoclinic P2₁ crystal (S,S)-4BDHP-1 (Table S6, Figure S33). The crystal had a molecular arrangement closely similar to that in racemic 4BDHP-1 (Figure S34). Crystallization of (S,S)-4BDHP from a mixed solution of DMF and DMB yielded orthorhombic P2₁2₁2 crystal (S,S)-4BDHP-2 (Figure 8a). The crystal is composed of crystallographically independent two (S,S)-4BDHP molecules (A and B) (Figure 8b). (S,S)-4BDHP-2 also has a structure closely similar to that of racemic 4BDHP-2. Molecules A and B are connected alternately through H-bonds of the carboxy groups to form a sql-networked undulate layer (Figure 8c). The molecules A and B are inclined by 15.4° and 20.5°, respectively, against the bc plane (Figure S35). The undulate layers are stacked with interlayer distances of 5.43 Å through interlayer contacts similar to those in the racemic crystal. Further detailed structural comparison revealed that the relative positions of the inner methyl groups and the dihedral angle between the peripheral phenylene rings were different in the racemic and enantiopure crystals (Figure S36). Molecules of DMB in voids of the framework were severely disordered.

Interestingly, one of the independent molecules (molecule A) has a longer C(3a¹)−C(5a¹) bond with a length of 1.601(8) Å, while that of molecule B shows a typical length of 1.472(7) Å. This implies that the photo-isomerization of 4BDHP may start even under an ambient condition before affirmative irradiation. Indeed, X-ray diffraction analyses, performed on four different single crystals of (S,S)-4BDHP-2 (Table S7), revealed that the C(3a¹)−C(5a¹) bond length in molecule A varied from 1.565(4) Å to 1.726(14) Å (Table S8), although the crystals had the same space group, i.e. P2₁2₁2, and the same networked structures (Figure S37).

Visible light irradiation to a single crystal of (S,S)-4BDHP-2 changed the color of the crystal from dark red to brown (Figure 8a). Simultaneously, cracks were generated parallel to the (100) face, on which the H-bonded sql-network sheets are laid. Single crystal X-ray diffraction analysis successfully revealed a structure of the crystal irradiated for 7 h, (S,S)-4BDHP-2-Vis-7h (Figure 8d, e). Surprisingly, only molecule A changes its structure into a chair-like configuration corresponding to (S_p)-4CPD. The C(3a¹)−C(5a¹) bond was cleaved: the distance between carbon atoms C(17) and C(18) was 2.345 Å. In addition, the two peripheral tert-butyl groups were bent up and down by 33° compared with those of 4BDHP. Molecule B, in contrast, shows the same structure with that before irradiation. However, the well-organized alternate arrangement of molecules A and B strongly indicates that both molecules A and B experienced reversible ring opening and closing reactions, and consequently reached a thermodynamically stable steady state to yield (S,S)-4BDHP-2-Vis-7h. Otherwise, the photo-isomerization reaction would have occurred in a random manner, resulting in one averaged molecular structure.

Further structural analysis revealed the following structural changes. Surface shapes of the inclusion channel in the crystals changed upon the isomerization (Figure S38). The dihedral angles of the carboxy groups ω_C(A) and carboxyphenyl groups ω_CP(A) of molecule A against the molecular plane changed from 46.17° to 59.56° and from 83.89° to 66.88°, respectively, upon the isomerization (Table 1, Figure 8f, g). Similarly, the corresponding angles of molecule B, ω_C(B) and ω_CP(B) changed from 44.14° to 43.78° and from 86.20° to 69.57°, respectively. Additionally, only molecule A inclined by ca. 11° from the bc plane after the isomerization to maintain the approximate position of the bulky tert-butyl groups in the alternating alignment of molecules A and B (Figures 8h, i and S39). The distance between the quaternary carbon atoms of the tert-butyl groups of neighboring molecules A and B is 6.480 Å in (S,S)-4BDHP-2, and is 6.410 Å in (S,S)-4BDHP-2-Vis-7h. These structural adjustments help prevent changes in the framework periodicity and maintain crystallinity of the frameworks.

It is remarkable that molecule A in (S,S)-4BDHP-2-Vis-7h has an intermediate conformation between 4BDHP and geometrically optimized 4CPD, as shown in Figure 9. When these three structures are superimposed to match the molecular plane defined by C2, C3, C10, and C11, the positions of the inner methyl groups are approximately the same in all three structures. However, the positions of the tert-butyl groups are significantly different among the molecules due to bending caused by the isomerization. The bending angle of the ideal conformation of 4CPD was 47.9°, while that of molecule A in (S,S)-4BDHP-2-Vis-7h remained at 22.4°. Although the molecule A was also solved by a disordering model with superimposed 4CPD and 4BDHP (Figure S40, Table S10), the conformation of 4CPD remains the intermediate form. The differences between the theoretical and observed conformation of 4CPD could be attributed to the fact that molecule A was disrupted to accommodate the most stable conformation of 4CPD due to steric hindrance in the framework.

Other crystals irradiated by visible light for 4 h [(S,S)-4BDHP-2-Vis-4h] and for 14 h [(S,S)-4BDHP-2-Vis-14h] were also analyzed. (S,S)-4BDHP-2-Vis-4h has lower crystallinity than (S,S)-4BDHP-2-Vis-7h, and has the shorter C(17)⋅⋅⋅C(18) distance of 1.935 Å, indicating that the crystal has not reached the steady state yet (Figure S41). On the other hand, (S,S)-4BDHP-2-Vis-14h has a structure similar to (S,S)-4BDHP-2-Vis-7h, where the C(17)⋅⋅⋅C(18) distance is 2.231 Å, implying that the isomerization was once saturated (Figure S42). Further irradiation resulted in a yellow-colored crystal, which showed significantly weak diffraction intensity due to loss of crystallinity. The photo-isomerization, however, strongly depends on size and shape of single crystals due to relatively low quantum yield of the photo-isomerization reaction. Therefore, even single crystals are subjected to the same irradiation time, crystallographic analysis of the resultant crystals shows different degree of photo-isomerization depending on the crystals, preventing quantitative analysis for bulk crystals.

Finally, the thermal ring-closing reaction that occurred in a crystalline state was investigated. Heating of a photoisomerized crystal of (S,S)-4BDHP-2 resulted in color changes of the crystal from brown to dark brown (Figure S43). Crystallographic analysis of the heated crystal showed decrease of the C(3a¹)−C(5a¹) distance (Figure S44, Table S11). These results indicate the isomerization reaction from 4CPD to 4BDHP also occurred.