Asymmetric induction of supramolecular helicity in calix[4]arene-based triple-stranded helicate

Abstract

Calix[4]arene-based triple helicates take up an achiral part of chiral guests; the chiral center outside the cavity causes the asymmetric induction of their supramolecular helicity.

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Coordination-driven self-assembly has received great attention over recent decades due to its potential application in host–guest chemistry. A number of structural motifs have been developed by coordination-driven self-assembly.¹ Metallohelicates are a class of motifs which attract special interest because of their unique structural features. The first double-stranded helicate composed of tris(bipyridine) ligands and Cu^I ions was reported by Lehn.² Metallohelicates have since been intensively studied. A series of dicatechol ligands was reported by Raymond,^3,4 Stack,⁵ and Albrecht⁶ to create dinuclear triple-stranded helicates. Most triple-stranded helicates do not have enough room to encapsulate a sizable guest; thus, some of them isomerize the tetrahedral complexes upon the addition of a sizable guest.⁷

The chirality of the triple-stranded helicates can take the form of the handedness of a helical structure. In the absence of a chiral source, helical assemblies composed of achiral components possess both possible helical conformations (P and M), having equal intermolecular interaction energies, and they exist as racemic mixtures. The chiral induction of triple-stranded helicates in the presence of a chiral aromatic cation has been reported in the literature.⁸ The helicates are negatively charged; therefore, the salts stay around the aromatic rings of the metal center of the helicates, which biases the population of the P and M helical conformations. However, there are limited examples of the chiral induction of triple-stranded helicates having a cavity for chiral guest encapsulation.

Calix[4]arene is one of the most versatile molecular building blocks suitable for developing a functionalized host that encapsulates a guest within its cavity.^9,10 Incorporation of the calix[4]arene unit into a triple-stranded helicate can create a self-assembled molecular host possessing a large cavity suitable for guest encapsulation. We designed a new class of calix[4]arene-based metallohelicates 1 that have a large guest binding space surrounded by twelve aromatic rings in which a chiral guest can be accommodated to give rise to the asymmetric induction of the helical assembly without the isomerization of the tetrahedral structure (Fig. 1). This study reports the synthesis of triple-stranded helicates via the metal-assisted self-assembly of a calix[4]arene, and its asymmetric induction by chiral guest complexation within the space composed of the three calix[4]arene cavities.

Fig. 1 Triple-stranded helicates 1 based on calix[4]arene 2.

The synthesis of compound 2 started from 5,11-diamino-25,26,27,28-tetrapropoxycalix[4]arene.¹¹ The condensation reaction of the diaminocalix[4]arene and 2,3-dibenzyloxybenzoic acid¹² produced the protected calix[4]arene. The subsequent deprotection of the benzyl groups furnished calix[4]arene 2.

Treatment of 2 with two equivalents of KOH produced the dianion, which was titrated with Ga(acac)₃ or Fe(acac)₃. The dianion gave an absorption maximum at 290 nm, which gradually decreased upon the addition of Ga(acac)₃, and new bands emerged at 270 and 350 nm (Fig. 2). Isosbestic points at 284 and 339 nm were observed during the titration until the amount of Ga(acac)₃ reached 0.67 equivalents of the dianion. The further addition of Ga(acac)₃ did not lead to any isosbestic points . The Job plot gave a peak in the 3 : 2 ratio of the dianion to Ga(acac)₃. These results suggest the formation of the triple-stranded helicate 1a. The ¹H NMR spectrum of 1a displayed six sets of magnetically nonequivalent aromatic signals, indicating that the complex formed retains the C₂ symmetric axis (see ESI‡ ). Comparison of diffusion coefficients between 1a and 2 provides the ratio of their radii. The diffusion coefficients of 1a and 2 were determined by the PFG-NMR technique using the BPPSTE pulse sequence at 293 K in methanol-d₄ (D_1a = 4.018 ± 0.004 × 10⁻¹⁰ m² s⁻¹ and D₂ = 6.030 ± 0.006 × 10⁻¹⁰ m² s⁻¹). The resulting ratio D_1a/D₂ = 0.66 is in reasonable agreement with the theoretical ratio of 0.66–0.62 expected for a trimer.¹³ Judging from the ratio, the formation of higher order assemblies is ruled out. Accordingly, it is clear that the triple-stranded helicate 1a forms in solution. The formation of the iron(III)-based triple-stranded helicate 1b is also confirmed because the absorption titration profile is similar to that observed in 1a (see ESI‡ ).

Fig. 2 Absorption spectra of the dianion of 2 (3.3 × 10⁻⁵ mol L⁻¹) in the presence of Ga(acac)₃ in MeOH at 298 K. The concentrations of Ga(acac)₃ are (a–g from the bottom) 0.0, 0.7, 1.3, 2.0, 2.2, 3.3, 4.9 (× 10⁻⁵ mol L⁻¹).

Cationic guests 3–7 were selected for the binding study of 1a, since the guest binding space of 1a is surrounded by the twelve π-basic aromatic rings (Fig. 3). The binding studies of 1a were carried out using the ¹H NMRtitration technique. The proton signal of S–CH₃ of guest 3 was characteristically shifted upfield. The Job plot showed the formation of a 1 : 1 host–guest complex between 1a and 3 in methanol-d₄. Non-linear curve fitting analysis gave a binding constant (K_a = 1200 ± 100 L mol⁻¹).¹⁴ The complexation-induced chemical shift changes (CIS) of the guest protons were estimated by curve-fitting analysis (S–CH₃: –1.02, C(O)–CH: 0.00, C(O)–CH₃: −0.01, COOCH₃: −0.06 ppm). A significant upfield shift was only observed for the methyl groups adjacent to the sulfonium, while the CIS values of the protons of 3 were less than −0.10 ppm upon the addition of excess potassium tris(pyrocatecholato)gallate K₆Ga(cat)₃ instead of 1a. The same characteristics were observed for the CIS values of the protons of 4; the protons of the aromatic ring and the methyl group connected to the pyridinium ring only showed an upfield shift when a small amount of 1a was added (see ESI‡ ). The association constants of 4–7 were determined by UV–vis titration (K_as = 460 ± 20, 290 ± 20, 310 ± 20, and 2700 ± 200 L mol⁻¹ for 4, 5, 6, and 7, respectively). It is obvious that the cationic parts of the guests are partially encapsulated within the cavity made up of the three cavities of the calix[4]arenes, and the chiral moieties remain outside it.

Fig. 3 Chiral guest molecules 3–7.

Chiral induction of triple-stranded helicates 1a,b was studied using circular dichroism spectroscopy. The absorption bands appeared around 340 and 500 nm; the former results from electronic communication of the metal centers and the catechol ligand of 1a,b, and the latter arises from ligand-to-metal charge transfer (LMCT) (Fig. 4).¹⁵ These are sensitive to the chirality at the metal center. The addition of chiral guest 3 in 1a,b did not produce induced circular dichroism (ICD) in the bands. In contrast, the addition of chiral guest 4 in 1a,b gave rise to strong ICD signals, especially the CD spectra of 1b with D- and L-4, which provided the bisignate curves in the LMCT band (Fig. 4). Tris(pyrocatecholato)ferrate K₆Fe(cat)₃ did not show any ICD in the LMCT band upon the addition of 100 equivalents of 4. These results clearly indicate that the helical nature of the triple-stranded helicate 1b is affected by the partial encapsulation of the chiral guest even though the chiral center of the guest remains outside the host cavity. The absolute configuration of the major helicate can be deduced via comparison with the LMCT-CD bands of the structurally characterized tris(pyrocatecholato)ferrate.³ The LMCT band of 1b with D-4 at approximately 540 nm was positive, suggesting that the major isomer has the Λ,Λ-absolute configuration.

Fig. 4 Absorption and circular dichroism spectra of 1a (black), 1b (green), 1a (10.2 μmol L⁻¹) with 100 equiv. of D-4 (blue solid) and with 100 equiv. of L-4 (blue dash), 1b (16.7 μmol L⁻¹) with 100 equiv. of D-4 (red solid) and with 100 equiv. of L-4 (red dash), and K₆Fe(cat)₃ (16.6 μmol L⁻¹) with 100 equiv. of D-4 (brown solid) and with 100 equiv. of L-4 (brown dash) in methanol at 273 K.

To gain insight into the asymmetric induction of the triple-stranded helicates, the steric effect of the guest side chains in the asymmetric induction of the triple-stranded helicate was studied. The ICD spectra of 1b were measured in the presence of D-guests 4–7 at 273 K. The ICD of 1b with D-5 is strongest in the series of guests (Fig. 5). Accordingly, the phenyl group plays a key role in controlling the helical configuration of the triple-stranded helicate 1b in one direction.

Fig. 5 Circular dichroism spectra of 1b (16.7 μmol L⁻¹) with (a): D-5 (0.50 mmol L⁻¹), (b): D-6 (1.60 mmol L⁻¹), (c): D-4 (3.30 mmol L⁻¹), (d): D-7 (0.50 mmol L⁻¹) in methanol at 273 K.¹⁶

While a precise structure of the supramolecular complex remains to be determined, a molecular mechanics calculation of the complex is informative. The supramolecular complex of Λ,Λ-1 with D-5 was calculated by Macromodel V 9.1 using the AMBER* force field.¹⁷ In the calculated structure, the two methyl groups stay inside the calix[4]arene cavities, creating the attractive CH–π interactions that result in the partial encapsulation of the aromatic unit of the guest (Fig. 6). The chiral unit is outside the cavity; the phenyl group directly communicates with the chiral center of the assembly via an aromatic stacking interaction, which is probably responsible for the asymmetric induction.

Fig. 6 Stereo plot of the calculated structure of the complex D-5@1b.

In summary, we have demonstrated that a calix[4]arene possessing two ligation units assembles to form triple-stranded helicates with the Ga(III) and Fe(III) cations, and the assemblies encapsulate the cationic guests into the cavity surrounded by the three calix[4]arene cavities; the chiral center of the guest creates a steric interaction with the exterior of the triple-stranded helicate that asymmetrically influences its helical configuration. We are currently developing studies of extended supramolecular triple-stranded helicates to further expand the supramolecular approach towards chiral information transfer.

This work was supported by Grants-in-Aid for Scientific Research (No. 18350065) of JSPS, and a Grant-in-Aid for Science Research (No. 19022024) in the Priority Area “Super-Hierarchical Structures” from the MEXT, Japan. We acknowledge financial support from the Murata, Ogasawara, Iketani, and Inamori Foundations.

Notes and references

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Footnotes

† Dedicated to Professor Seiji Shinkai on the occasion of his 65th birthday.

‡ Electronic supplementary information (ESI) available: Synthesis of 1 and 2, absorption titration profiles, Job plots and ¹H NMR spectra during the complex formation of 1, ¹H NMR spectra and Job plot of 3 and 4 upon the addition of 1a. See DOI: 10.1039/b900599d

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