DOI: 10.1002/chem.201504893
Communication
& Supramolecular Chemistry
Doubly Cavitand-Capped Porphyrin Capsule by Hydrogen Bonds Kazuki Kishimoto, Munechika Nakamura, and Kenji Kobayashi*[a] and ligand or electron donor and acceptor, can be encapsulated simultaneously and such guest encapsulation would endow this type of porphyrin capsule with potential as a functional material. It is known that cooperative quadriad phenol···pyridine (ArOH···Npy) hydrogen-bonding interactions are useful for stable capsular self-assembly if the molecular design is appropriate.[18] Herein, we report the quantitative self-assembly of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4-pyridylethynyl)cavitand (2) into a doubly cavitand-capped porphyrin capsule 2·1·2 by eight ArOH···Npy hydrogen bonds (Scheme 1). We also describe the remarkable solvent effect for guest encapsulation.
Abstract: The components of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4-pyridylethynyl)cavitand (2) in CDCl3 or C6D6 self-assemble quantitatively into the doubly cavitand-capped porphyrin capsule 2·1·2 through eight ArOH···Npy hydrogen bonds. Capsule 2·1·2 possesses two cavities divided by the porphyrin ring and encapsulates two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest to form G/G@(2·1·2). Remarkable solvent effect was observed, in which the apparent association constant of 2·1·2 with G in C6D6 was much greater than that in CDCl3.
Porphyrin derivatives have been widely used as building blocks for functional supramolecular architectures, such as a light-harvesting photosynthetic model, owing to their particular electronic and photophysical properties.[1] Porphyrin derivatives have also been studied as oxidation catalysts[2] as a mimic of cytochrome P-450, in which the apoprotein not only provides the binding pocket for a substrate but also protects the porphyrin as the reaction center. Covalently bound macrocyclic host-capped porphyrin capsules have been synthesized over the last few decades.[3–10] However, covalentbonded strategies for capsule formation often result in low chemical yields via many synthetic steps. Error correction through thermodynamic equilibration, minimization of synthetic effort by the use of modular subunits, and control of assembly processes through subunit design are characteristics of supramolecular approaches to capsular self-assembly.[11] Self-assembled porphyrin capsules or cages have been intensively studied.[12] However, in almost all cases, porphyrin subunits have been used as exterior walls of self-assembled capsules. Although a few examples of singly macrocyclic host-capped self-assembled porphyrin capsules have been reported,[13–15] a doubly macrocyclic host-capped self-assembled porphyrin capsule is unprecedented,[16, 17] probably because of a lack of an appropriate molecular design. The merits of a doubly macrocyclic host-capped porphyrin capsule are that two same guest molecules, such as electron donor or acceptor, or two different guest molecules, such as a combination of substrate [a] K. Kishimoto, M. Nakamura, Prof. K. Kobayashi Department of Chemistry, Faculty of Science Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201504893. Chem. Eur. J. 2016, 22, 2629 – 2633
Scheme 1. Self-assembly of a 1:2 mixture of 1 and 2 into capsule 2·1·2. In the molecular model of 2·1·2 calculated at PM3 level, the dodecyl side chains of the subunit 1 and the heptyl side chains of the subunit 2 are replaced by methyl groups.
Porphyrin 1[19] alone is not soluble in CDCl3 or C6D6. However, a 1:2 mixture of 1 and 2[20] becomes soluble in these solvents after heating the mixture at 50 8C for 12 hours. The 1 H NMR spectra of the mixture in CDCl3 or C6D6 showed a highly symmetrical single species (Figure 1), in which the signals of the Pya- and Pyb-protons and the outer and inner protons of the methylene-bridge rim (O-CHinHout-O) of the cavitand subunit 2 were shifted upfield by 0.17, 0.31, 0.32, and 0.41 ppm, respectively, in CDCl3 (Figure 1 b) and by 0.55, 0.65, 0.32, and 0.43 ppm, respectively, in C6D6 (Figures 1 d and S4 in the Supporting Information) relative to those of free 2, owing to the ring-current effect of the porphyrin subunit 1. Further-
2629
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Figure 1. 1H NMR spectra (400 MHz, 298 K) of a) 2 alone and b) 2·1·2 (after heating [1] = 2 mm if soluble and [2] = 4 mm at 50 8C for 12 h) in CDCl3 ; c) 2 alone and d) 2·1·2 (after heating [1] = 2 mm if soluble and [2] = 4 mm at 50 8C for 12 h) in C6D6. The signals marked “a–g” and “A–D” are assigned in Scheme 1.
more, the OH signal of the subunit 1 appeared at d = 11.16 ppm in CDCl3 and 11.32 ppm in C6D6, these values being shifted downfield relative to that of free 1 (8.92 ppm) in [D6]DMSO. These results undoubtedly indicate the quantitative formation of the doubly cavitand-capped porphyrin capsule 2·1·2 via the eight ArOH···Npy hydrogen bonds (Scheme 1). The 1H NMR spectra of a 1:3 mixture of 1 and 2 in CDCl3 or C6D6 after heating at 50 8C for 12 hours showed a 1:1 mixture of 2·1·2 and free 2, in which the signals of 2·1·2 and free 2 were independently observed (Figures S5d and S6d in the Supporting Information). These results confirmed the 1:2 stoichiometry of 1 and 2 for capsule 2·1·2, and also indicated that the exchange between 2·1·2 and free 2 is slow on the NMR time scale. DOSY experiments also supported the formation of capsule 2·1·2 from the 1:2 or 1:3 mixtures of 1 and 2 (Figure S7 in the Supporting Information). On the other hand, a 1:1 mixture of 1 and 2 in CDCl3 gave a heterogeneous mixture, even after heating at 50 8C for 24 h, Chem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
in which only 2·1·2 was observed by 1H NMR spectroscopy and the insoluble material was free 1 (Figure S5 b, e in the Supporting Information). This result suggests that CDCl3 serves as a guest template for the formation of 2·1·2, as mentioned below. In contrast, a 1:1 mixture of 1 and 2 in C6D6 gave a homogeneous solution after heating at 50 8C for 24 h and produced a two- or three-component equilibrium mixture of 2·1·2 and another self-assembled species (Figure S6 b in the Supporting Information).[21] Capsule 2·1·2 possesses two cavities divided by the porphyrin ring and encapsulates two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest to form G/G@(2·1·2), in which each cavity accommodates one guest molecule. The formation of G/G@(2·1·2) was confirmed by 1H–1H COSY (Figure S8), 2D NOESY (Figure S9), and DOSY (Figure S10 in the Supporting Information) spectra. Upon addition of more than four equivalents of G to 2·1·2 (2 mm) in C6D6, the 1H NMR spectrum showed the complete disappearance of the signals of free
2630
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Figure 2. 1H NMR spectra (400 MHz, C6D6, 298 K) of a) [2·1·2] = 2 mm, b) [2·1·2] = 2 mm and [G] = 8 mm (G/G@(2·1·2) + free G), and c) G alone. d) Molecular model of G/G@(2·1·2) calculated at the PM3 level, in which the dodecyl side chains of the subunit 1 and the heptyl side chains of the subunit 2 are replaced by methyl groups.
2·1·2 and the appearance of new signals corresponding to G/ G@(2·1·2) (Figure 2 b). The signals of G/G@(2·1·2) and free G were independently observed, because the exchange of G in and out of 2·1·2 was slow on the NMR time scale. The signals of ArHortho, ArHpara, OMe, and OAc protons of the encapsulated G were shifted upfield by 1.37, 3.61, 2.32, and 3.59 ppm, respectively, relative to those of free G, owing to the shielding effects of 2·1·2. These chemical-shift changes (Dd) and a molecular model indicate that the methyl groups of the OMe groups at the meta-positions and the methyl group of the OAc group of the encapsulated G are oriented to the porphyrin ring of the subunit 1 and the aromatic cavity end of the bowl-shaped subunit 2, respectively, so as to maximize CH-p (van der Waals) interactions (Figure 2 d). Acetoxybenzene and 1,3-dimethoxybenzene were not encapsulated in 2·1·2. In G/G@(2·1·2), the inner proton signal of the methylene-bridge rim of the subunit 2 was shifted downfield by 0.36 ppm relative to that of free 2·1·2, because of the CHin···O=C(CH3)O interaction with the OAc group of G.[18b] The NH signal of the subunit 1 was shifted downfield by 0.60 ppm relative to that of free 2·1·2, probably because of the deshielding effect of the encapsulated G with the edge-to-face orientation (Figure 2 d and see below). The OH signal of the subunit 1 was shifted downfield by 0.36 ppm relative to that of free 2·1·2, because of the enhancement of thermodynamic stability of 2·1·2 assisted by capsule-guest interactions (see below). The Dd = ¢2.32 ppm of the OMe signal was much smaller than Dd = ¢3.61 ppm of ArHpara in G/ G@(2·1·2). As shown in Figure 2 d, the ArHpara is closer to the center of the porphyrin ring (in the xy plane) of the subunit 1 but at a larger distance above this plane, whereas the two OMe groups are more remote from the xy porphyrin plane but closer above this plane. As a result, the ArHpara is subject to more shielding effect of the porphyrin ring than the OMe groups. Chem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
Upon addition of one equivalent of G to capsule 2·1·2 (2 mm) in C6D6, one molecular G-encapsulated capsule G@(2·1·2) was observed together with G/G@(2·1·2) and free 2·1·2 in a 54:28:18 ratio, in which the 1H NMR NH and OH signals of the three species were independently observed (Figure 3). In compound G@(2·1·2), two OH signals were observed because of structural desymmetrization of G@(2·1·2) and/or the difference in stability between the G@(1·2) part and the 1·2 part. The NH and OH signals of G@(2·1·2) appeared between those of G/G@(2·1·2) and free 2·1·2 (Figure 3 g, h), the orders of chemical shifts being in agreement with the idea mentioned above. Upon addition of four equivalents of G to 2·1·2 (2 mm) in C6D6, only G/G@(2·1·2) was observed. Figure 4 shows the plots of the formation ratio of the three species as a function of [G]. When it is assumed that a mixture of 2·1·2 (2 mm) and G (8 mm) does not contain G@(2·1·2), the apparent association constant (Kapp) of 2·1·2 with G to form G/G@(2·1·2) can be estimated. The solvent effect for Kapp was remarkable. The Kapp values in various solvents increased in the order CDCl3 (Kapp = 9.1 Õ 102 m¢2 at 298 K) ! C6D6 (Kapp = > 1.0 Õ 107 m¢2 at 298 K and Kapp = 2.8 Õ 105 m¢2 at 313 K) < [D10]p-xylene (Kapp = > 1.0 Õ 107 m¢2 at 298 K and Kapp = 9.6 Õ 105 m¢2 at 313 K). The unusually small Kapp value in CDCl3 (Figure S11 in the Supporting Information) could be caused by the character of CDCl3 as a competitor guest molecule for 2·1·2.[22] An enormously large excess amount of CDCl3 as solvent increases the formation ratio of (CDCl3)n/(CDCl3)n@(2·1·2) (n = 1 or 2) compared with G/ G@(2·1·2), even if the Kapp of 2·1·2 with CDCl3 is much smaller than the Kapp of 2·1·2 with G. The thermodynamic parameters for the encapsulation of G into 2·1·2 in C6D6 and [D10]p-xylene are as follows: DH = ¢21.6 kcal mol¢1 and DS = ¢1 ¢1 ¢44.1 cal mol K in C6D6 (Figures S12 and S13 in the Supporting Information), and DH = ¢23.1 kcal mol¢1 and DS =
2631
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Figure 3. 1H NMR spectra of a mixture of 2·1·2 (2 mm) and G (0–8 mm) in various ratios in C6D6 at 298 K: a) [G] = 0 mm, b) [G] = 1 mm, c) [G] = 2 mm, d) [G] = 4 mm, e) [G] = 6 mm, and f) [G] = 8 mm. Expansion spectra in the regions of g) OH groups and h) NH groups in Figure 3 b, in which the solid circle, open circle, and solid square indicate the signals of G/G@(2·1·2), G@(2·1·2), and 2·1·2, respectively.
capsulation in 2·1·2. The Kapp of 2·1·2 with G in C6D6 was much greater than that in CDCl3, in which CDCl3 would serve as a competitor guest to G for 2·1·2. Studies on 1) the elucidation of another self-assembled species formed from a 1:1 mixture of 1 and 2 in C6D6 ;[21] and 2) self-assembly of Zn-porphyrin 1Zn and 2 into 2·1-Zn·2 directed to simultaneous encapsulation of two different guest molecules are currently under way in our laboratory.
Acknowledgements Figure 4. Plots of the formation ratio of G/G@(2·1·2), G@(2·1·2), and 2·1·2 as a function of [G], based on the 1H NMR data of Figure 3.
¢46.7 cal mol¢1 K¢1 in [D10]p-xylene (Figures S16 and S17 in the Supporting Information). In both solvents, the encapsulation of G in 2·1·2 was enthalpically driven (DH < 0 and DS < 0). However, the DH and DS contributions for the encapsulation of G in 2·1·2 in C6D6 are somewhat decreased and increased, respectively, compared with those in [D10]p-xylene. In conclusion, we have demonstrated the quantitative selfassembly of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4pyridylethynyl)cavitand (2) into the doubly cavitand-capped porphyrin capsule 2·1·2 through eight ArOH···Npy hydrogen bonds. Capsule 2·1·2 possesses two cavities divided by the porphyrin ring, in which two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest were encapsulated to form G/ G@(2·1·2). Remarkable solvent effect was found for guest enChem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
This work was supported in part by Grant-in-Aid from JSPS (no. 25288034). Keywords: cavitands · host–guest systems · porphyrins · selfassembly · supramolecular chemistry
2632
[1] a) A. Satake, Y. Kobuke, Tetrahedron 2005, 61, 13 – 41; b) C. M. Drain, A. Varotto, I. Radivojevic, Chem. Rev. 2009, 109, 1630 – 1658; c) I. Beletskaya, V. S. Tyurin, A. Y. Tsivadze, R. Guilard, C. Stern, Chem. Rev. 2009, 109, 1659 – 1713; d) N. Aratani, D. Kim, A. Osuka, Acc. Chem. Res. 2009, 42, 1922 – 1934. [2] K. Gopalaiah, Chem. Rev. 2013, 113, 3248 – 3296. [3] For cyclodextrin-capped porphyrin, see: a) Y. Kuroda, T. Hiroshige, T. Sera, Y. Shiroiwa, H. Tanaka, H. Ogoshi, J. Am. Chem. Soc. 1989, 111, 1912 – 1913; b) Y. Kuroda, Y. Egawa, H. Seshio, H. Ogoshi, Chem. Lett. 1994, 2361 – 2364. [4] For binaphthol-strapped porphyrin, see: J. T. Groves, P. Viski, J. Org. Chem. 1990, 55, 3628 – 3634. [5] For cyclophane-capped porphyrin, see: D. R. Benson, R. Valentekovich, F. Diederich, Angew. Chem. Int. Ed. Engl. 1990, 29, 191 – 193; Angew. Chem. 1990, 102, 213 – 216. Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication [6] For steroid-capped porphyrin, see: a) R. P. Bonar-Law, J. K. M. Sanders, J. Am. Chem. Soc. 1995, 117, 259 – 271; b) R. P. Bonar-Law, J. Am. Chem. Soc. 1995, 117, 12397 – 12407. [7] For crown ether-capped porphyrin, see: M. J. Gunter, T. P. Jeynes, M. R. Johnston, P. Turner, Z. Chen, J. Chem. Soc. Perkin Trans. 1 1998, 1945 – 1957. [8] For calixarene-capped porphyrin, see: a) T. Nagasaki, H. Fujishima, M. Takeuchi, S. Shinkai, J. Chem. Soc. Perkin Trans. 1 1995, 1883 – 1888; b) D. M. Rudkevich, W. Verboom, D. N. Reinhoudt, J. Org. Chem. 1995, 60, 6585 – 6587. [9] For calix[4]resorcinarene-cavitand-capped porphyrin, see: a) O. Middel, W. Verboom, D. N. Reinhoudt, J. Org. Chem. 2001, 66, 3998 – 4005; b) J. Nakazawa, J. Hagiwara, M. Mizuki, Y. Shimazaki, F. Tani, Y. Naruta, Angew. Chem. Int. Ed. 2005, 44, 3744 – 3746; Angew. Chem. 2005, 117, 3810 – 3812; c) J. Nakazawa, J. Hagiwara, Y. Shimazaki, F. Tani, Y. Naruta, Bull. Chem. Soc. Jpn. 2012, 85, 912 – 919. [10] For diphenylglycoluril-capped porphyrin, see: a) P. Thordarson, E. J. A. Bijsterveld, A. E. Rowan, R. J. M. Nolte, Nature 2003, 424, 915 – 918; b) P. Thordarson, E. J. A. Bijsterveld, J. A. A. W. Elemans, P. Kask, R. J. M. Nolte, A. E. Rowan, J. Am. Chem. Soc. 2003, 125, 1186 – 1187; c) A. B. C. Deutman, J. M. M. Smits, R. de Gelder, J. A. A. W. Elemans, R. J. M. Nolte, A. E. Rowan, Chem. Eur. J. 2014, 20, 11574 – 11583; d) S. Cantekin, A. J. Markvoort, J. A. A. W. Elemans, A. E. Rowan, R. J. M. Nolte, J. Am. Chem. Soc. 2015, 137, 3915 – 3923. [11] a) J. Rebek Jr., Acc. Chem. Res. 2009, 42, 1660 – 1668; b) N. M. Rue, J. Sun, R. Warmuth, Isr. J. Chem. 2011, 51, 743 – 768; c) R. Chakrabarty, P. S. Mukherjee, P. J. Stang, Chem. Rev. 2011, 111, 6810 – 6918; d) K. Harris, D. Fujita, M. Fujita, Chem. Commun. 2013, 49, 6703 – 6712; e) A. M. Castilla, W. J. Ramsay, J. R. Nitschke, Acc. Chem. Res. 2014, 47, 2063 – 2073; f) K. Kobayashi, M. Yamanaka, Chem. Soc. Rev. 2015, 44, 449 – 466; g) C. J. Brown, F. D. Toste, R. G. Bergman, K. N. Raymond, Chem. Rev. 2015, 115, 3012 – 3035. [12] S. Durot, J. Taesch, V. Heitz, Chem. Rev. 2014, 114, 8542 – 8578, and references therein. [13] For a singly calixarene-capped porphyrin based on ionic interactions, see: a) R. Fiammengo, P. Timmerman, F. de Jong, D. N. Reinhoudt, Chem. Commun. 2000, 2313 – 2314; b) R. Fiammengo, P. Timmerman, J. Huskens, K. Versluis, A. J. R. Heck, D. N. Reinhoudt, Tetrahedron 2002, 58, 757 – 764. [14] For a singly calixarene-capped porphyrin based on hydrogen bonds, see: a) H. Ohkawa, S. Arai, S. Takeoka, T. Shibue, H. Nishide, Chem. Lett.
Chem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
2003, 32, 1052 – 1053; b) S. Arai, H. Ohkawa, S. Ishihara, T. Shibue, S. Takeoka, H. Nishide, Bull. Chem. Soc. Jpn. 2005, 78, 2007 – 2013. For a singly cavitand-capped porphyrin based on hydrogen bonds, see: J. Nakazawa, M. Mizuki, Y. Shimazaki, F. Tani, Y. Naruta, Org. Lett. 2006, 8, 4275 – 4278. For inclusion of aryl groups of tetraarylporphyrins by cyclodextrin, see: a) K. Sasaki, H. Nakagawa, X. Zhang, S. Sakurai, K. Kano, Y. Kuroda, Chem. Commun. 2004, 408 – 409; b) K. Kano, H. Kitagishi, M. Kodera, S. Hirota, Angew. Chem. Int. Ed. 2005, 44, 435 – 438; Angew. Chem. 2005, 117, 439 – 442; c) K. Watanabe, H. Kitagishi, K. Kano, Angew. Chem. Int. Ed. 2013, 52, 6894 – 6897; Angew. Chem. 2013, 125, 7032 – 7035. For inclusion of tetraarylporphyrin as a guest by cucurbit[10]uril, see: S. Liu, A. D. Shukla, S. Gadde, B. D. Wagner, A. E. Kaifer, L. Isaacs, Angew. Chem. Int. Ed. 2008, 47, 2657 – 2660; Angew. Chem. 2008, 120, 2697 – 2700. For self-assembly of tetrakis(4-hydroxyphenyl)cavitand and tetra(4-pyridyl)cavitand into a hydrogen-bonded capsule, see: a) K. Kobayashi, R. Kitagawa, Y. Yamada, M. Yamanaka, T. Suematsu, Y. Sei, K. Yamaguchi, J. Org. Chem. 2007, 72, 3242 – 3246; b) H. Kitagawa, Y. Kobori, M. Yamanaka, K. Yoza, K. Kobayashi, Proc. Natl. Acad. Sci. USA 2009, 106, 10444 – 10448; c) K. Ichihara, H. Kawai, Y. Togari, E. Kikuta, H. Kitagawa, S. Tsuzuki, K. Yoza, M. Yamanaka, K. Kobayashi, Chem. Eur. J. 2013, 19, 3685 – 3692. For the synthesis of 4-alkyl-3,5-dimethoxybenzaldehyde, see: U. Azzena, G. Melloni, A. M. Piroddi, J. Org. Chem. 1992, 57, 3101 – 3106. For the synthesis of 1, see the Supporting Information. a) K. Kobayashi, Y. Yamada, M. Yamanaka, Y. Sei, K. Yamaguchi, J. Am. Chem. Soc. 2004, 126, 13896 – 13897; b) M. Yamanaka, Y. Yamada, Y. Sei, K. Yamaguchi, K. Kobayashi, J. Am. Chem. Soc. 2006, 128, 1531 – 1539. Another self-assembled species could be a doubly cavitand-capped triply porphyrin-sandwich capsule 2·1·1·1·2 and/or a doubly cavitandcapped doubly porphyrin-sandwich capsule 2·1·1·2. However, at this stage, we have no concrete evidence for these species, and we need to wait for further studies. For an example of CDCl3 as a competitor guest for guest encapsulation in a capsule, see: N. Nishimura, K. Yoza, K. Kobayashi, J. Am. Chem. Soc. 2010, 132, 777 – 790.
Received: December 5, 2015 Published online on January 20, 2016
2633
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
& Supramolecular Chemistry
Doubly Cavitand-Capped Porphyrin Capsule by Hydrogen Bonds Kazuki Kishimoto, Munechika Nakamura, and Kenji Kobayashi*[a] and ligand or electron donor and acceptor, can be encapsulated simultaneously and such guest encapsulation would endow this type of porphyrin capsule with potential as a functional material. It is known that cooperative quadriad phenol···pyridine (ArOH···Npy) hydrogen-bonding interactions are useful for stable capsular self-assembly if the molecular design is appropriate.[18] Herein, we report the quantitative self-assembly of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4-pyridylethynyl)cavitand (2) into a doubly cavitand-capped porphyrin capsule 2·1·2 by eight ArOH···Npy hydrogen bonds (Scheme 1). We also describe the remarkable solvent effect for guest encapsulation.
Abstract: The components of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4-pyridylethynyl)cavitand (2) in CDCl3 or C6D6 self-assemble quantitatively into the doubly cavitand-capped porphyrin capsule 2·1·2 through eight ArOH···Npy hydrogen bonds. Capsule 2·1·2 possesses two cavities divided by the porphyrin ring and encapsulates two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest to form G/G@(2·1·2). Remarkable solvent effect was observed, in which the apparent association constant of 2·1·2 with G in C6D6 was much greater than that in CDCl3.
Porphyrin derivatives have been widely used as building blocks for functional supramolecular architectures, such as a light-harvesting photosynthetic model, owing to their particular electronic and photophysical properties.[1] Porphyrin derivatives have also been studied as oxidation catalysts[2] as a mimic of cytochrome P-450, in which the apoprotein not only provides the binding pocket for a substrate but also protects the porphyrin as the reaction center. Covalently bound macrocyclic host-capped porphyrin capsules have been synthesized over the last few decades.[3–10] However, covalentbonded strategies for capsule formation often result in low chemical yields via many synthetic steps. Error correction through thermodynamic equilibration, minimization of synthetic effort by the use of modular subunits, and control of assembly processes through subunit design are characteristics of supramolecular approaches to capsular self-assembly.[11] Self-assembled porphyrin capsules or cages have been intensively studied.[12] However, in almost all cases, porphyrin subunits have been used as exterior walls of self-assembled capsules. Although a few examples of singly macrocyclic host-capped self-assembled porphyrin capsules have been reported,[13–15] a doubly macrocyclic host-capped self-assembled porphyrin capsule is unprecedented,[16, 17] probably because of a lack of an appropriate molecular design. The merits of a doubly macrocyclic host-capped porphyrin capsule are that two same guest molecules, such as electron donor or acceptor, or two different guest molecules, such as a combination of substrate [a] K. Kishimoto, M. Nakamura, Prof. K. Kobayashi Department of Chemistry, Faculty of Science Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529 (Japan) E-mail: [email protected] Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201504893. Chem. Eur. J. 2016, 22, 2629 – 2633
Scheme 1. Self-assembly of a 1:2 mixture of 1 and 2 into capsule 2·1·2. In the molecular model of 2·1·2 calculated at PM3 level, the dodecyl side chains of the subunit 1 and the heptyl side chains of the subunit 2 are replaced by methyl groups.
Porphyrin 1[19] alone is not soluble in CDCl3 or C6D6. However, a 1:2 mixture of 1 and 2[20] becomes soluble in these solvents after heating the mixture at 50 8C for 12 hours. The 1 H NMR spectra of the mixture in CDCl3 or C6D6 showed a highly symmetrical single species (Figure 1), in which the signals of the Pya- and Pyb-protons and the outer and inner protons of the methylene-bridge rim (O-CHinHout-O) of the cavitand subunit 2 were shifted upfield by 0.17, 0.31, 0.32, and 0.41 ppm, respectively, in CDCl3 (Figure 1 b) and by 0.55, 0.65, 0.32, and 0.43 ppm, respectively, in C6D6 (Figures 1 d and S4 in the Supporting Information) relative to those of free 2, owing to the ring-current effect of the porphyrin subunit 1. Further-
2629
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Figure 1. 1H NMR spectra (400 MHz, 298 K) of a) 2 alone and b) 2·1·2 (after heating [1] = 2 mm if soluble and [2] = 4 mm at 50 8C for 12 h) in CDCl3 ; c) 2 alone and d) 2·1·2 (after heating [1] = 2 mm if soluble and [2] = 4 mm at 50 8C for 12 h) in C6D6. The signals marked “a–g” and “A–D” are assigned in Scheme 1.
more, the OH signal of the subunit 1 appeared at d = 11.16 ppm in CDCl3 and 11.32 ppm in C6D6, these values being shifted downfield relative to that of free 1 (8.92 ppm) in [D6]DMSO. These results undoubtedly indicate the quantitative formation of the doubly cavitand-capped porphyrin capsule 2·1·2 via the eight ArOH···Npy hydrogen bonds (Scheme 1). The 1H NMR spectra of a 1:3 mixture of 1 and 2 in CDCl3 or C6D6 after heating at 50 8C for 12 hours showed a 1:1 mixture of 2·1·2 and free 2, in which the signals of 2·1·2 and free 2 were independently observed (Figures S5d and S6d in the Supporting Information). These results confirmed the 1:2 stoichiometry of 1 and 2 for capsule 2·1·2, and also indicated that the exchange between 2·1·2 and free 2 is slow on the NMR time scale. DOSY experiments also supported the formation of capsule 2·1·2 from the 1:2 or 1:3 mixtures of 1 and 2 (Figure S7 in the Supporting Information). On the other hand, a 1:1 mixture of 1 and 2 in CDCl3 gave a heterogeneous mixture, even after heating at 50 8C for 24 h, Chem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
in which only 2·1·2 was observed by 1H NMR spectroscopy and the insoluble material was free 1 (Figure S5 b, e in the Supporting Information). This result suggests that CDCl3 serves as a guest template for the formation of 2·1·2, as mentioned below. In contrast, a 1:1 mixture of 1 and 2 in C6D6 gave a homogeneous solution after heating at 50 8C for 24 h and produced a two- or three-component equilibrium mixture of 2·1·2 and another self-assembled species (Figure S6 b in the Supporting Information).[21] Capsule 2·1·2 possesses two cavities divided by the porphyrin ring and encapsulates two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest to form G/G@(2·1·2), in which each cavity accommodates one guest molecule. The formation of G/G@(2·1·2) was confirmed by 1H–1H COSY (Figure S8), 2D NOESY (Figure S9), and DOSY (Figure S10 in the Supporting Information) spectra. Upon addition of more than four equivalents of G to 2·1·2 (2 mm) in C6D6, the 1H NMR spectrum showed the complete disappearance of the signals of free
2630
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Figure 2. 1H NMR spectra (400 MHz, C6D6, 298 K) of a) [2·1·2] = 2 mm, b) [2·1·2] = 2 mm and [G] = 8 mm (G/G@(2·1·2) + free G), and c) G alone. d) Molecular model of G/G@(2·1·2) calculated at the PM3 level, in which the dodecyl side chains of the subunit 1 and the heptyl side chains of the subunit 2 are replaced by methyl groups.
2·1·2 and the appearance of new signals corresponding to G/ G@(2·1·2) (Figure 2 b). The signals of G/G@(2·1·2) and free G were independently observed, because the exchange of G in and out of 2·1·2 was slow on the NMR time scale. The signals of ArHortho, ArHpara, OMe, and OAc protons of the encapsulated G were shifted upfield by 1.37, 3.61, 2.32, and 3.59 ppm, respectively, relative to those of free G, owing to the shielding effects of 2·1·2. These chemical-shift changes (Dd) and a molecular model indicate that the methyl groups of the OMe groups at the meta-positions and the methyl group of the OAc group of the encapsulated G are oriented to the porphyrin ring of the subunit 1 and the aromatic cavity end of the bowl-shaped subunit 2, respectively, so as to maximize CH-p (van der Waals) interactions (Figure 2 d). Acetoxybenzene and 1,3-dimethoxybenzene were not encapsulated in 2·1·2. In G/G@(2·1·2), the inner proton signal of the methylene-bridge rim of the subunit 2 was shifted downfield by 0.36 ppm relative to that of free 2·1·2, because of the CHin···O=C(CH3)O interaction with the OAc group of G.[18b] The NH signal of the subunit 1 was shifted downfield by 0.60 ppm relative to that of free 2·1·2, probably because of the deshielding effect of the encapsulated G with the edge-to-face orientation (Figure 2 d and see below). The OH signal of the subunit 1 was shifted downfield by 0.36 ppm relative to that of free 2·1·2, because of the enhancement of thermodynamic stability of 2·1·2 assisted by capsule-guest interactions (see below). The Dd = ¢2.32 ppm of the OMe signal was much smaller than Dd = ¢3.61 ppm of ArHpara in G/ G@(2·1·2). As shown in Figure 2 d, the ArHpara is closer to the center of the porphyrin ring (in the xy plane) of the subunit 1 but at a larger distance above this plane, whereas the two OMe groups are more remote from the xy porphyrin plane but closer above this plane. As a result, the ArHpara is subject to more shielding effect of the porphyrin ring than the OMe groups. Chem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
Upon addition of one equivalent of G to capsule 2·1·2 (2 mm) in C6D6, one molecular G-encapsulated capsule G@(2·1·2) was observed together with G/G@(2·1·2) and free 2·1·2 in a 54:28:18 ratio, in which the 1H NMR NH and OH signals of the three species were independently observed (Figure 3). In compound G@(2·1·2), two OH signals were observed because of structural desymmetrization of G@(2·1·2) and/or the difference in stability between the G@(1·2) part and the 1·2 part. The NH and OH signals of G@(2·1·2) appeared between those of G/G@(2·1·2) and free 2·1·2 (Figure 3 g, h), the orders of chemical shifts being in agreement with the idea mentioned above. Upon addition of four equivalents of G to 2·1·2 (2 mm) in C6D6, only G/G@(2·1·2) was observed. Figure 4 shows the plots of the formation ratio of the three species as a function of [G]. When it is assumed that a mixture of 2·1·2 (2 mm) and G (8 mm) does not contain G@(2·1·2), the apparent association constant (Kapp) of 2·1·2 with G to form G/G@(2·1·2) can be estimated. The solvent effect for Kapp was remarkable. The Kapp values in various solvents increased in the order CDCl3 (Kapp = 9.1 Õ 102 m¢2 at 298 K) ! C6D6 (Kapp = > 1.0 Õ 107 m¢2 at 298 K and Kapp = 2.8 Õ 105 m¢2 at 313 K) < [D10]p-xylene (Kapp = > 1.0 Õ 107 m¢2 at 298 K and Kapp = 9.6 Õ 105 m¢2 at 313 K). The unusually small Kapp value in CDCl3 (Figure S11 in the Supporting Information) could be caused by the character of CDCl3 as a competitor guest molecule for 2·1·2.[22] An enormously large excess amount of CDCl3 as solvent increases the formation ratio of (CDCl3)n/(CDCl3)n@(2·1·2) (n = 1 or 2) compared with G/ G@(2·1·2), even if the Kapp of 2·1·2 with CDCl3 is much smaller than the Kapp of 2·1·2 with G. The thermodynamic parameters for the encapsulation of G into 2·1·2 in C6D6 and [D10]p-xylene are as follows: DH = ¢21.6 kcal mol¢1 and DS = ¢1 ¢1 ¢44.1 cal mol K in C6D6 (Figures S12 and S13 in the Supporting Information), and DH = ¢23.1 kcal mol¢1 and DS =
2631
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication
Figure 3. 1H NMR spectra of a mixture of 2·1·2 (2 mm) and G (0–8 mm) in various ratios in C6D6 at 298 K: a) [G] = 0 mm, b) [G] = 1 mm, c) [G] = 2 mm, d) [G] = 4 mm, e) [G] = 6 mm, and f) [G] = 8 mm. Expansion spectra in the regions of g) OH groups and h) NH groups in Figure 3 b, in which the solid circle, open circle, and solid square indicate the signals of G/G@(2·1·2), G@(2·1·2), and 2·1·2, respectively.
capsulation in 2·1·2. The Kapp of 2·1·2 with G in C6D6 was much greater than that in CDCl3, in which CDCl3 would serve as a competitor guest to G for 2·1·2. Studies on 1) the elucidation of another self-assembled species formed from a 1:1 mixture of 1 and 2 in C6D6 ;[21] and 2) self-assembly of Zn-porphyrin 1Zn and 2 into 2·1-Zn·2 directed to simultaneous encapsulation of two different guest molecules are currently under way in our laboratory.
Acknowledgements Figure 4. Plots of the formation ratio of G/G@(2·1·2), G@(2·1·2), and 2·1·2 as a function of [G], based on the 1H NMR data of Figure 3.
¢46.7 cal mol¢1 K¢1 in [D10]p-xylene (Figures S16 and S17 in the Supporting Information). In both solvents, the encapsulation of G in 2·1·2 was enthalpically driven (DH < 0 and DS < 0). However, the DH and DS contributions for the encapsulation of G in 2·1·2 in C6D6 are somewhat decreased and increased, respectively, compared with those in [D10]p-xylene. In conclusion, we have demonstrated the quantitative selfassembly of a 1:2 mixture of meso-tetrakis(4-dodecyl-3,5-dihydroxyphenyl)porphyrin (1) and a bowl-shaped tetrakis(4pyridylethynyl)cavitand (2) into the doubly cavitand-capped porphyrin capsule 2·1·2 through eight ArOH···Npy hydrogen bonds. Capsule 2·1·2 possesses two cavities divided by the porphyrin ring, in which two molecules of 1-acetoxy-3,5-dimethoxybenzene (G) as a guest were encapsulated to form G/ G@(2·1·2). Remarkable solvent effect was found for guest enChem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
This work was supported in part by Grant-in-Aid from JSPS (no. 25288034). Keywords: cavitands · host–guest systems · porphyrins · selfassembly · supramolecular chemistry
2632
[1] a) A. Satake, Y. Kobuke, Tetrahedron 2005, 61, 13 – 41; b) C. M. Drain, A. Varotto, I. Radivojevic, Chem. Rev. 2009, 109, 1630 – 1658; c) I. Beletskaya, V. S. Tyurin, A. Y. Tsivadze, R. Guilard, C. Stern, Chem. Rev. 2009, 109, 1659 – 1713; d) N. Aratani, D. Kim, A. Osuka, Acc. Chem. Res. 2009, 42, 1922 – 1934. [2] K. Gopalaiah, Chem. Rev. 2013, 113, 3248 – 3296. [3] For cyclodextrin-capped porphyrin, see: a) Y. Kuroda, T. Hiroshige, T. Sera, Y. Shiroiwa, H. Tanaka, H. Ogoshi, J. Am. Chem. Soc. 1989, 111, 1912 – 1913; b) Y. Kuroda, Y. Egawa, H. Seshio, H. Ogoshi, Chem. Lett. 1994, 2361 – 2364. [4] For binaphthol-strapped porphyrin, see: J. T. Groves, P. Viski, J. Org. Chem. 1990, 55, 3628 – 3634. [5] For cyclophane-capped porphyrin, see: D. R. Benson, R. Valentekovich, F. Diederich, Angew. Chem. Int. Ed. Engl. 1990, 29, 191 – 193; Angew. Chem. 1990, 102, 213 – 216. Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Communication [6] For steroid-capped porphyrin, see: a) R. P. Bonar-Law, J. K. M. Sanders, J. Am. Chem. Soc. 1995, 117, 259 – 271; b) R. P. Bonar-Law, J. Am. Chem. Soc. 1995, 117, 12397 – 12407. [7] For crown ether-capped porphyrin, see: M. J. Gunter, T. P. Jeynes, M. R. Johnston, P. Turner, Z. Chen, J. Chem. Soc. Perkin Trans. 1 1998, 1945 – 1957. [8] For calixarene-capped porphyrin, see: a) T. Nagasaki, H. Fujishima, M. Takeuchi, S. Shinkai, J. Chem. Soc. Perkin Trans. 1 1995, 1883 – 1888; b) D. M. Rudkevich, W. Verboom, D. N. Reinhoudt, J. Org. Chem. 1995, 60, 6585 – 6587. [9] For calix[4]resorcinarene-cavitand-capped porphyrin, see: a) O. Middel, W. Verboom, D. N. Reinhoudt, J. Org. Chem. 2001, 66, 3998 – 4005; b) J. Nakazawa, J. Hagiwara, M. Mizuki, Y. Shimazaki, F. Tani, Y. Naruta, Angew. Chem. Int. Ed. 2005, 44, 3744 – 3746; Angew. Chem. 2005, 117, 3810 – 3812; c) J. Nakazawa, J. Hagiwara, Y. Shimazaki, F. Tani, Y. Naruta, Bull. Chem. Soc. Jpn. 2012, 85, 912 – 919. [10] For diphenylglycoluril-capped porphyrin, see: a) P. Thordarson, E. J. A. Bijsterveld, A. E. Rowan, R. J. M. Nolte, Nature 2003, 424, 915 – 918; b) P. Thordarson, E. J. A. Bijsterveld, J. A. A. W. Elemans, P. Kask, R. J. M. Nolte, A. E. Rowan, J. Am. Chem. Soc. 2003, 125, 1186 – 1187; c) A. B. C. Deutman, J. M. M. Smits, R. de Gelder, J. A. A. W. Elemans, R. J. M. Nolte, A. E. Rowan, Chem. Eur. J. 2014, 20, 11574 – 11583; d) S. Cantekin, A. J. Markvoort, J. A. A. W. Elemans, A. E. Rowan, R. J. M. Nolte, J. Am. Chem. Soc. 2015, 137, 3915 – 3923. [11] a) J. Rebek Jr., Acc. Chem. Res. 2009, 42, 1660 – 1668; b) N. M. Rue, J. Sun, R. Warmuth, Isr. J. Chem. 2011, 51, 743 – 768; c) R. Chakrabarty, P. S. Mukherjee, P. J. Stang, Chem. Rev. 2011, 111, 6810 – 6918; d) K. Harris, D. Fujita, M. Fujita, Chem. Commun. 2013, 49, 6703 – 6712; e) A. M. Castilla, W. J. Ramsay, J. R. Nitschke, Acc. Chem. Res. 2014, 47, 2063 – 2073; f) K. Kobayashi, M. Yamanaka, Chem. Soc. Rev. 2015, 44, 449 – 466; g) C. J. Brown, F. D. Toste, R. G. Bergman, K. N. Raymond, Chem. Rev. 2015, 115, 3012 – 3035. [12] S. Durot, J. Taesch, V. Heitz, Chem. Rev. 2014, 114, 8542 – 8578, and references therein. [13] For a singly calixarene-capped porphyrin based on ionic interactions, see: a) R. Fiammengo, P. Timmerman, F. de Jong, D. N. Reinhoudt, Chem. Commun. 2000, 2313 – 2314; b) R. Fiammengo, P. Timmerman, J. Huskens, K. Versluis, A. J. R. Heck, D. N. Reinhoudt, Tetrahedron 2002, 58, 757 – 764. [14] For a singly calixarene-capped porphyrin based on hydrogen bonds, see: a) H. Ohkawa, S. Arai, S. Takeoka, T. Shibue, H. Nishide, Chem. Lett.
Chem. Eur. J. 2016, 22, 2629 – 2633
www.chemeurj.org
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
2003, 32, 1052 – 1053; b) S. Arai, H. Ohkawa, S. Ishihara, T. Shibue, S. Takeoka, H. Nishide, Bull. Chem. Soc. Jpn. 2005, 78, 2007 – 2013. For a singly cavitand-capped porphyrin based on hydrogen bonds, see: J. Nakazawa, M. Mizuki, Y. Shimazaki, F. Tani, Y. Naruta, Org. Lett. 2006, 8, 4275 – 4278. For inclusion of aryl groups of tetraarylporphyrins by cyclodextrin, see: a) K. Sasaki, H. Nakagawa, X. Zhang, S. Sakurai, K. Kano, Y. Kuroda, Chem. Commun. 2004, 408 – 409; b) K. Kano, H. Kitagishi, M. Kodera, S. Hirota, Angew. Chem. Int. Ed. 2005, 44, 435 – 438; Angew. Chem. 2005, 117, 439 – 442; c) K. Watanabe, H. Kitagishi, K. Kano, Angew. Chem. Int. Ed. 2013, 52, 6894 – 6897; Angew. Chem. 2013, 125, 7032 – 7035. For inclusion of tetraarylporphyrin as a guest by cucurbit[10]uril, see: S. Liu, A. D. Shukla, S. Gadde, B. D. Wagner, A. E. Kaifer, L. Isaacs, Angew. Chem. Int. Ed. 2008, 47, 2657 – 2660; Angew. Chem. 2008, 120, 2697 – 2700. For self-assembly of tetrakis(4-hydroxyphenyl)cavitand and tetra(4-pyridyl)cavitand into a hydrogen-bonded capsule, see: a) K. Kobayashi, R. Kitagawa, Y. Yamada, M. Yamanaka, T. Suematsu, Y. Sei, K. Yamaguchi, J. Org. Chem. 2007, 72, 3242 – 3246; b) H. Kitagawa, Y. Kobori, M. Yamanaka, K. Yoza, K. Kobayashi, Proc. Natl. Acad. Sci. USA 2009, 106, 10444 – 10448; c) K. Ichihara, H. Kawai, Y. Togari, E. Kikuta, H. Kitagawa, S. Tsuzuki, K. Yoza, M. Yamanaka, K. Kobayashi, Chem. Eur. J. 2013, 19, 3685 – 3692. For the synthesis of 4-alkyl-3,5-dimethoxybenzaldehyde, see: U. Azzena, G. Melloni, A. M. Piroddi, J. Org. Chem. 1992, 57, 3101 – 3106. For the synthesis of 1, see the Supporting Information. a) K. Kobayashi, Y. Yamada, M. Yamanaka, Y. Sei, K. Yamaguchi, J. Am. Chem. Soc. 2004, 126, 13896 – 13897; b) M. Yamanaka, Y. Yamada, Y. Sei, K. Yamaguchi, K. Kobayashi, J. Am. Chem. Soc. 2006, 128, 1531 – 1539. Another self-assembled species could be a doubly cavitand-capped triply porphyrin-sandwich capsule 2·1·1·1·2 and/or a doubly cavitandcapped doubly porphyrin-sandwich capsule 2·1·1·2. However, at this stage, we have no concrete evidence for these species, and we need to wait for further studies. For an example of CDCl3 as a competitor guest for guest encapsulation in a capsule, see: N. Nishimura, K. Yoza, K. Kobayashi, J. Am. Chem. Soc. 2010, 132, 777 – 790.
Received: December 5, 2015 Published online on January 20, 2016
2633
Ó 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
