Hexasulfonated calix[6]arene derivatives: a new class of catalysts, surfactants, and host molecules.

TLDR: It was found that these calix[6]arene derivatives efficiently accelerate acid-catalyzed hydration of I-benzyl1,4-dihydronicotinamide and the reaction proceeds according to the Michaelis-Menten kinetics, indicating that hexasulfonated calixarenes serve as a new class of catalysts, surfactants, and host molecules.

Abstract: Water-soluble hexasulfonated calix[6]arenes with various substituents (I-R) have been synthesized for the first time and applied as host molecules in an aqueous system. Dynamic ‘H NMR studies established that calb[6]arene-p-hexasulfonate (1-H) adopts a “winged” or “hinged” conformation in D20-Me2SO-d6 (2:l v/v) owing to hydrogen bonding among the OH groups, while 5,11,17,23,29,35-hexasulfonato-37,38,39,40,41,42-hexakis(hexyloxy)calix[6]arene (l-C6) adopts a similar conformation in D20 owing to hydrophobic bonding among the hexyl groups. The aggregation behavior in water was examined about I-C6 and I-C12. Physical (light-scattering, surface tension, and conductance) and spectral (fluorescence and absorption spectroscopies) studies established that 1-C, has a cmc at ca. 6 X IO4 M, as does sodium dodecyl sulfate (SDS), while I C l 2 has no detectable cmc and rather acts as a “unimolecular” micelle. In fact, l-C6 associated with small molecules (pyrene, 2-anilinonaphthalene, and Orange OT) according to the micelle-like biphasic concentration dependence, while 1-C12 formed host-guest-type 1: 1 complexes with these molecules. It was found that these calix[6]arene derivatives efficiently accelerate acid-catalyzed hydration of I-benzyl1,4-dihydronicotinamide and the reaction proceeds according to the Michaelis-Menten kinetics. In particular, the rate constants for 1-H and 1-CH2COOH, which both have acidic protons to catalyze the reaction and anionic sulfonates to stabilize the cationic intermediate at the two edges of the cavity, were greater by 426-1220-fold than those for noncyclic analogues. These findings indicate that hexasulfonated calix[6]arenes serve as a new class of catalysts, surfactants, and host molecules. This is the first example for the host-guest-type behavior of calixarenes observed in an aqueous system. The chemistry of cyclodextrins and cyclophanes has occupied a central interest in host-guest chemistry for the last two decades, and many functionalized host molecules which can mimic the in vivo action of enzymes by means of simple in vitro chemical systems have been exploited.2d Recently, Gutsche and coworker~’,~ have reported on a series of new cyclic molecules called “calixarenes” which are cyclic oligomers made up of benzene units as cyclodextrins are made up of glucose units. Since calixarenes possess a cylindrical architecture similar to cyclodextrins, they are expected to be useful to design enzyme mimics in totally synthetic systems.’.* Several groups have reported on the ionophoric properties of calixarenes which were obtained by introducing ether and/or ester groups into the edge of the cylindrical a rch i te~ture .~’~ In contrast, almost nothing is known with certainty as to the inclusion properties of calixarenes in solution, which should be more important in the design of the enzyme mimics. The data reported so far have been limited to only the solid and in fact, Gutsche stated in his recent review (1) Preliminary communications: (a) Shinkai, S.; Mori, S.; Tsubaki, T.; Sone, T.; Manabe, 0. Tetrahedron L e f f . 1984, 25, 5315. (b) Shinkai, S.; Koreishi, H.; Mori, S.; Sone, T.; Manabe, 0. Chem. Letf. 1985, 1033. (2) Breslow, R. Acc. Chem. Res. 1980, 13, 170. (3) Tabushi, I. Acc. Chem. Res. 1982, 15, 66. (4) Komiyama, M.; Hirai, H. J . Am. Chem. SOC. 1983, 105, 2018. (5) Bender, M. L.; Komiyama, M. In ‘Cyclodextrin Chemistry”; Spring(6) Murakami, Y. ‘Cyclophanes 11”; Springer-Verlag: Berlin, 1983; p 107. (7) Gutsche, C. D. Arc. Chem. Res. 1983, 16, 161. (8) Gutsche, C. D. In “Host Guest Complex Chemistry/Macrocycles”; (9) Chang, S.-K.; Cho, I. Chem. Lett. 1984, 477. (10) Ungaro, R.; Pochini, A.; Andreetti, G. D. J. Inclusion Phenom. 1984, er-Verlag: New York, 1977. Springer-Verlag: Berlin, 1985, p 375. 2. 199. -, . (1 1) Bocchi, V.; Foina, D.; Pochini, A,; Ungaro, R.; Andreetti, G. D. (12) McKervey, M. A.; Seward, E. M.; Ferguson, G.; Ruhl, B.; Harris, S. Tetrahedron 1982, 38, 373. J. J . Chem. SOC., Chem. Commun. 1985, 388. (1 3) Calixarenes can extract certain metal cations into the organic phase as their counterions: (a) Izatt, R. M.; Lamb, J. D.; Hawkins, R. T.; Brown, P. R.; Izatt, S. R.; Christensen, J. J. J. Am. Chem. Soc. 1983, 105, 1782. (b) Izatt, S. R.; Hawkins, R. T.; Christensen, J. J.; Zatt, R. M. Ibid. 1985, 107, 63. (14) Andreetti, G. D.; Ungaro, R.; Pochini, A. J. Chem. Soc., Chem. Commun. 1979, 1005. (15) (a) Coruzzi, M.; Andreetti, G. D.; Bocchi, V.; Pochini, A,; Ungaro, R. J . Chem. Soc., Perkin Trans. 2 1982, 1133. (b) Ungaro, R.; Pochini, A,; Andreetti, G. D.; Domiano, P. Ibid. 1985, 197. 0002-7863/86/ 1508-2409$01.50/0 article that there are no published data in support of solution complexes of calixarenes.8*16 This is in sharp contrast to cyclodextrins, which can form a variety of host-guest-type solution complexes. We noticed that the difference would stem mainly from the poor solubility of calixarenes; they are sparingly soluble in several organic solvents but insoluble in aqueous solutions. Therefore, the experimental efforts should be directed toward solubilization of calixarenes, which would eventually lead to tHe exploitation of calixarene-based host molecules and enzyme mimics. Here, we wish to report the synthesis and the solution properties of new water-soluble hexasulfonated calix[6]arenes (1-R). We have found that they serve not only as host molecules in an aqueous system but also as a new class of surfactants and acid catalysts.