J. Am. Chem. Soc. 1997, 119, 8991-9001
8991
Molecular Recognition of Carbohydrates by Zinc Porphyrins: Lewis Acid/Lewis Base Combinations as a Dominant Factor for Their Selectivity Tadashi Mizutani,* Takuya Kurahashi, Takeshi Murakami, Noriyoshi Matsumi, and Hisanobu Ogoshi* Contribution from the Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity, Sakyo-ku, Kyoto 606-01, Japan ReceiVed April 25, 1997. ReVised Manuscript ReceiVed July 8, 1997X Abstract: A systematic study of the binding of carbohydrates by functionalized zinc porphyrins indicated that [5, 15-bis(8-quinolyl)porphyrinato]zinc(II) (1) showed marked affinity for octyl glucoside and mannoside in CHCl3 (-∆G° ) 4.5-6.3 kcal mol-1). Analysis of the complexation-induced shifts of the carbohydrate OH protons in the 1H NMR revealed that receptor 1 bound the 4-OH group of mannoside and glucoside by coordination to the zinc and the 6-OH and 3-OH groups by hydrogen bonding to the quinolyl nitrogen atoms. These NMR results and comparison of binding affinity with reference receptors and ligands indicated that receptor 1 recognized the trans,trans-1,2dihydroxy-3-(hydroxymethyl) moiety of carbohydrates by the combination of Lewis acid (zinc) and Lewis bases (quinolyl nitrogens). Poor affinities of 1 to octyl galactosides and octyl 2-O-methyl-R-mannoside were ascribed to neighboring group effects, where a neighboring group in ligands not directly involved in the receptor-ligand interactions had considerable influence on the affinity through destabilizing the hydrogen-bonding-network(s) in the receptor-ligand complex. The circular dichroism induced in the porphyrin Soret band by complexation with the carbohydrates displayed characteristic patterns, which parallel the patterns of the complexation-induced shifts in the 1H NMR. The CD patterns sensitively reflected the receptor-ligand interaction modes, particularly ligand orientation and fluctuation in the complex. Variable-temperature CD revealed that glucoside was fluctuating on 1 while mannoside was rigidly fixed on 1 at room temperature. Addition of alcohols to CHCl3 suppressed the binding by 1, while addition of polar additives such as water, alcohols, phenols, and ethers assisted the binding by 3 and 4 (-∆∆G° ) 0.2-0.4 kcal mol-1) in a low concentration range (0-1.5 mol %).
Among a number of carbohydrates, glucose, galactose, mannose, fucose, N-acetylglucosamine, N-acetylgalactosamine, and sialic acids are known to play key roles in the cell recognition. Precise molecular recognition of these carbohydrates by a synthetic receptor is a challenging goal in artificial receptor chemistry. Considerable efforts have been done to construct model receptors of sugars, including resorcinolaldehyde cyclotetramer,1 tetrahydroxycholaphane,2 C3 macrocyclic receptor,3 boronic-acid-based receptors,4 polyaza cleft,5 aminocyclodextrins,6 phosphonates,7 capped porphyrin,8 glycophane,9 and polypyridine macrocycle.10 These studies focused on diverse aspects of carbohydrate recognition such as diastereoselectivity, enantioselectivity, binding in polar solvents, and facile detection of the binding events, particularly by taking Abstract published in AdVance ACS Abstracts, September 15, 1997. (1) (a) Aoyama, Y.; Tanaka, Y.; Sugahara, S. J. Am. Chem. Soc. 1989, 111, 5397. (b) Kurihara, K.; Ohto, K.; Tanaka, Y.; Aoyama, Y.; Kunitake, T. J. Am. Chem. Soc. 1991, 113, 444. (2) Bhattarai, K. M.; Bonar-Law, R. P.; Davis, A. P.; Murray, B. A. J. Chem. Soc., Chem. Commun. 1992, 752. (3) Liu, R.; Still, W. C. Tetrahedron Lett. 1993, 34, 2573. (4) (a) Murakami, H.; Nagasaki, T.; Hamachi, I.; Shinkai, S. Tetrahedron Lett. 1993, 34, 6273. (b) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. Nature 1995, 374, 345. (c) James, T. D.; Sandanayake, K. R. A. S.; Iguchi, R.; Shinkai, S. J. Am. Chem. Soc. 1995, 117, 8982. (d) Takeuchi, M.; Imada, T.; Shinkai, S. J. Am. Chem. Soc. 1996, 118, 10658. (5) Huang, C.-Y.; Cabell, L. A.; Anslyn, E. V. J. Am. Chem. Soc. 1994, 116, 2778. (6) Eliseev, A. V.; Schneider, H.-J. J. Am. Chem. Soc. 1994, 116, 6081. (7) Das, G.; Hamilton, A. D. J. Am. Chem. Soc. 1994, 116, 11139. (8) Bonar-Law, R. P.; Sanders, J. K. M. J. Am. Chem. Soc. 1995, 117, 259. (9) Jimenez-Barbero, J.; Junquera, E.; Martin-Pastor, M.; Sharma, S.; Vicent, C.; Penades, S. J. Am. Chem. Soc. 1995, 117, 11198. (10) Inouye, M.; Miyake, T.; Furusyo, M.; Nakazumi, H. J. Am. Chem. Soc. 1995, 117, 12416. X
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advantage of the chirality of carbohydrates. Owing to the structural similarity of carbohydrates and their highly polar nature, we are still far from the goal, particularly specific carbohydrate recognition in water via noncovalent interactions. Another important aspect of carbohydrate recognition chemistry is that carbohydrates are poor substrates for spectroscopic investigations. Therefore, it is desired to develop a sensitive spectroscopic method to probe the carbohydrate binding. The X-ray crystallographic structure of the mannose-binding protein-mannose complex showed that calcium and carboxylates of the amino acid side chains form hydrogen-bondingnetworks with mannose.11 To mimic such hydrogen-bondingnetworks, we designed receptors bearing two hydrogen-bonding sites and one Lewis acid site fixed on porphyrins.12 We aim to address the following two issues: (1) the structural motif of receptors required for carbohydrate recognition and structural features of carbohydrates to be recognized by the receptors and (2) roles of polar additives in energetics and selectivity of carbohydrate recognition, based on the comparative studies of binding affinity, 1H NMR, and induced circular dichroism studies of the relative orientation of ligands in the receptorligand complexes. Results Five zinc porphyrins were prepared, and their affinities for carbohydrate derivatives were investigated. Receptor 1 has two (11) Weis, W. I.; Drickamer, K.; Hendrickson, W. A. Nature 1992, 360, 127. (12) For preliminary accounts of this work, see: Mizutani, T.; Murakami, T.; Matsumi, N.; Kurahashi, T.; Ogoshi, H. J. Chem. Soc., Chem. Commun. 1995, 1257.
© 1997 American Chemical Society
8992 J. Am. Chem. Soc., Vol. 119, No. 38, 1997
Mizutani et al.
Table 1. Binding Constants (K) and Free Energy Changes (∆G°) of Receptor-Carbohydrate Complex Formation in Chloroform at 15 °Ca K/M-1 (-∆G°/(kcal mol-1))
a
ligand
receptor 1
receptor 2
receptor 3
receptor 4
receptor 5
R-Glc β-Glc R-Gal β-Gal R-Man β-Man 2-O-Me-R-Man 6-O-Ac-β-Glc 6-O-Bz-β-Glc
7 570 (5.11) 41 400 (6.09) 1 870 (4.31) 3 840 (4.73) 15 500 (5.52) 61 700 (6.31) 380 (3.40) 6800 (5.05) 7300 (5.09)
2 530 (4.49) 6 360 (5.01) 1 030 (3.97) 1 620 (4.23) 8 220 (5.16) 23 300 (5.76) 250 (3.16) 2060 (4.37) b
320 (3.30) 570 (3.63) 650 (3.70) 690 (3.74) 810 (3.83) 250 (3.16) 400 (3.43) 530 (3.59) 600 (3.66)
3 670 (4.70) 2 090 (4.38) 2 240 (4.42) 1 710 (4.26) 3 860 (4.73) 2 970 (4.58) 2 550 (4.49) b b
