J . A m , Chem. SOC.1986, 108, 5738-5743
5738
Intramolecular Hydrogen Bonding in 1’-Sucrose Derivatives Determined by SIMPLE ‘H NMR Spectroscopy John C. Christofides,+David B. Davies,*+Julie A. Martin,*and Elner B. Rathbone’ Contribution from the Department of Chemistry, Birkbeck College, Malet Street, London W C l E 7HX, England, and Tate & Lyle Group Research and Development, Reading, Berkshire RG6 2BX. England. Received August 19, 1985
Abstract: Intramolecular hydrogen bonding in a series of 1’-sucrosederivatives having different numbers of hydroxyl groups has been investigated in Me2SO-d6solution by SIMPLE ‘H NMR measurements, Le., Secondary Isotope Multiplet NMR Spectroscopy of Partially Labeled Entities. Isotope effects, transmitted through intramolecular hydrogen bonds, are observed for the hydroxyl proton resonances; each separate hydrogen bond is manifested as a separate isotope shift. The existence of an intramolecular hydrogen bond in which OH3’ is the donor and OH2 is the acceptor hydroxyl group is revealed by isotope 4shift measurements of four 1’-chloro-1’-deoxysucrose derivatives: namely, 1,6-dichloro-1,6-dideoxy-~-~-fructofuranosyl chloro-4-deoxy-3-O-methyl-a-~-galactopyranoside (11; 1,6-dichloro-1,6-dideoxy-~-~-fructofuranosyl 4-chloro-4-deoxy-cu-~a-D-ghcopyranoside (3), and 1-chloro-1 -deoxy-P-Dgalactopyranoside (2), 1,6-dichloro-1,6-dideoxy-~-~-fructofuranosyl fructofuranosyl a-D-glucopyranoside(4). It is found that the OH3’-02 interresidue hydrogen bond in 1’-chloro-1’-deoxysucrose derivatives in solution is weaker than the analogous OH 1’.-02 hydrogen bond in 3’-substituted sucrose derivatives. ’H NMR measurements also show that the interresidue hydrogen bond stabilizes a weak hydrogen bond network between adjacent hydroxyl groups; the network extends to both sugar residues and the hydrogen bonds become progressively weaker at distances further from the relatively strong interresidue hydrogen bond, Le., OH6.OH4-OH3-OH2..-OH3’-.OH4’. For this series of molecules it is also shown that the interresidue hydrogen bonds become stronger as the hydrogen-bonding network extends to more of the molecule, Le., the process is cooperative.
Hydrogen bonding is an important interaction involved in deChart I termining the secondary structures of biomolecules such as proteins, nucleic acids, and carbohydrates. Evidence about the existence of hydrogen bonds in these systems comes from crystal structure determinations and, in particular, from neutron diffraction studies which provide the location of hydrogen atoms in the lattice. Hydrogen bonding in carbohydrate crystals has been studied extensively by Jeffrey and co-workersId and by Saenger compno R’ R2 R3 R4 no. of OHgroups and c o - w ~ r k e r s . ~Many ~ ~ examples of hydrogen bonding in carbohydrate crystals occur as part of networks of intermolecular Me H CI 4 1 CI ~~~ hydrogen bonds which may be chain-like’” or ~ i r c u l a r .Under H CI 5 2 CI H H OH H 6 these circumstances, it is found that bond distances are shorter 3 CI 4 OH H OH H 7 (and hence hydrogen bonds presumed stronger) for hydroxyl groups involved in both donor and acceptor interactions compared ecules with partially deuteriated hydroxyl groups observed under to those where the hydroxyl group is a donor only (cooperative of slow exchange, intramolecular hydrogen bonding ~ effect on hydrogen bonding). Quantum mechanical c a l c ~ l a t i o n s ~ ~ ~conditions between hydroxyl groups is manifested by isotopically shifted confirm that chain-like hydrogen bonds in the crystal structure hydroxyl proton resonances. The phenomenon has been termed are energetically favored above individual ones. By comparison with crystallographic studies such detailed information about the strength and direction of hydrogen bonding ( I ) Jeffrey, G. A,; Takagi, S . Acc. Chem. Res. 1978, 11, 264. is generally not available for molecules in solution, though a (2) Jeffrey, G. A.; Lewis, L. Carbohydr. Res. 1978, 60, 179-182. number of N M R methods have been used to provide information (3) Jeffrey, G. A. Carbohydr. Res. 1973, 28, 233-241. (4) Jeffrey, G. A,; Gress, M. E.; Takagi, S. J. Am. Chem. SOC.1977, 99, on the presence of both inter- and intramolecular hydrogen bonds, 609-6 1 I . e.g., chemical shifts, solvent and temperature dependence of (5) Jeffrey, G. A,; Mitra, J. J. Am. Chem. SOC.1984, 106, 5546-5553. chemical shifts, solvent exchange studies, NOE effects, and (6) Ceccarelli, C.; Jeffrey, G. A,; Taylor, R. J. Mol. Struct. 1981, 7 , magnitudes of appropriate spin coupling constants.” In an early 255-271. (7) Lindner, K.; Saenger, W. Acta Crysfallogr. 1982, 838, 203-210. study of intramolecular hydrogen bonding in solution Lemieux (8) Seanger, W. Angew. Chem., Int. Ed. Engl. 1980, 19, 398-399. and Paviai2 showed that hydrogen bonding of a strong acceptor (9) Tse, T.-C.; Newton, M. D. J . Am. Chem. SOC.1977, 99, 611-613. such as M e 2 S 0 to a hydroxyl group increased the ability of that (10) Newton, M. D. Acta Crystallogr. 1983, 839, 104-113. hydroxyl to participate in intramolecular hydrogen bonding. (1 1) (a) Vinogradov, S. N.; Linnell, R. H. In Hydrogen Bonding; Van Nostrand Reinhold Co.: New York, 1971. (b) %.-Jacques, M.; Sundarajan, Although N M R methods are used to indicate the presence of P. R.; Taylor, K. J.; Marchessault, R. H. J. Am. Chem. SOC.1976, 98, hydrogen bonding in carbohydrates, they are usually unable to 4386-4391. (c) Taravel, F. R.; Vignon, M. R. Polym. Bull. 1982, 7, 153-157. discriminate between the donor and acceptor hydroxyl groups or (d) Gagnaire. D.; Saint-Germain, J.; Vincendon, M. J. Appl. Polym. Sci.: to provide a basis for comparison of the relative strengths of Appl. Polym. Spmp. 1983, 37, 261-275. (e) Niccolai, N.; Rossi, C.; Brizzi, V.; Gibbons, W. A. J. Am. Chem. SOC.1984, 106, 5732-5733. hydrogen bonds in these molecules. This is particularly difficult (12) Lemieux, R. U.; Pavia, A. A. Can. J . Chem. 1969,47, 4441-4446. in solvents like Me2S0, which are strong hydrogen bond acceptors (13) Lemieux, R. U.; Bock, K. Jpn. J. Antibiot. Suppl. XXXII 1979, and where intermolecular (solvent) hydrogen bonding is preS163-SI77. dominant. On the other hand, recent ’ H N M R studies of car(14) Bock, K.; Lemieux, R. U. Carbohydr. Res. 1982, 100, 63-74. (15) Christofides, J. C.; Davies, D. B. J. Chem. SOC.,Chem. Commun. bohydrates in Me2SO-d6solution (sucrose,’3i5 cyclodextrin,’6 and 1985, 1533-1534. 3,3’,4’,6’-tetra-0-acetylsucrose(5)17) have shown that, for mol-
’Birkbeck College.
(16) Christofides, J. C.; Davies, D. B. J. Chem. SOC.,Chem. Commun. 1982, 560-562. (17) Davies, D. B.; Christofides, J. C. In Natural Products Chemistry;
‘Tate & Lyle Group Research and Development,
Zalewski, R. I., Sholik, J . J., Eds.; Elsevier: Amsterdam, 1985; pp 305-317.
0002-7863/86/1508-5738$01.50/00 1986 American Chemical Society
J . Am. Chem. SOC.,Vol. 108, No. 19, 1986
Intramolecular H Bonding i n 1 ’-Sucrose Deriwrices Table I. ‘H N M R Chemical Shifts for Compounds 1-4“
Table 11. ‘ H N M R Coupling Constants (Hz) for Compounds 1-4Q
compound proton
1
2
3
4
5.18 3.16 3.41 3.1 1 3.63 3.52-3.60’ 3.52-3.60’
H- 1 H-2 H-3 H-4 H-5 H-6a H-6b
5.16 3.15’ 3.156 4.67 4.29 3.51 3.47
5.15 3.59 3.93 4.33 4.30 3.48 3.44
5.11 3.18 3.42 3.01 3.63 3.63 3.41
H-l’a
3.66 3.58 4.03 3.81 3.74 3.94 3.75
3.66 3.57 4.02 3.80 3.74 3.94 3.74
3.67 3.62 4.05 3.81 3.73 4.02 3.73
3.67 3.63 4.01 3.76 3.52-3.60‘ 3.52-3.60‘ 3.48
5.05
4.95 5.22
4.94
4.88
4.83 4.75 4.80 4.49
4.77 4.76 4.77 4.38
5.16 5.57
5.17 5.55
5.17 5.52
4.94 5.30 4.45
H-l’b H-3’ H-4’ H-5‘ H-6‘a H-6’b OH-2 OH-3 OH-4 OH-6 OH-3’ OH-4’ OH-6‘
5739
“ 6 scale, relative to internal Me2SO-d, at 2.49 ppm. bDue to overlap of signals, chemical shifts could not be determined accurately.
SIMPLE N M R because it entails the observation of Secondary Isotope Multiplets of Partially Labeled Entities.ls From a combination of ‘H and I3C N M R studies of hydrogen-bonding effects in cyclodextrin,16.isit was shown that the ‘ H N M R observations in this molecule are consistent with the hypothesis that the hydroxyl group acting as donor exhibits a negative (to low frequency) isotope shift, when the acceptor hydroxyl group hydrogen atom is replaced by deuterium and, vice versa, for the hydroxyl group acting as hydrogen bond acceptor which exhibits an unusual positive (to high frequency) shift on replacement of the donor hydroxyl group hydrogen atom with the heavier isotope. A similar explanation was used to describe analogous ‘ H NMR isotope shifts observed for s u c r ~ s e ~and ~ - 3,3’,4’,6’-tetra-0~~ acetylsu~rose,’~ consistent with the existence of an interresidue hydrogen bond between OH1’ (donor, negative isotope shift) and OH2 (acceptor, positive isotope shift). Similar measurements of methyl maltoside in M e 2 S 0 s o l ~ t i o n ’revealed ~ not only the presence of the OH2’/OH3 interresidue hydrogen bond in this molecule but also evidence for OH2’/OH3’ intraresidue hydrogen bonding. SIMPLE ’H N M R measurements on 3’,6’-di-0benzoylsucrose (6)*Orevealed the presence of a hydrogen bond network in which weak hydrogen-bonding interactions occur between all neighboring hydroxyl groups of the glucose residue; the network is stabilized by the relatively strong interresidue hydrogen bond between the OH1’ and the O H 2 groups. In contrast to the intramolecular hydrogen bond network observed in solution, neutron diffraction studies of sucrosezi in the solid state show that most hydroxyl groups are involved in intermolecular hydrogen bonds either with water molecules or with hydroxyl groups on neighboring sucrose molecules; in addition, two intramolecular hydrogen bonds (OH]’ 0 2 and OH6’ 0 5 ) are observed for sucrose in the crystal. In the present work, the hydrogen-bonding properties of four 1’-chloro-1’-deoxysucrose derivatives (Chart I) in Me2SO-d, solution were studied by the SIMPLE IH N M R method: l ,6-dichloro-l,6-dideoxy-~-~-fructofuranosyl 4-chloro-4-deoxy-3-0-
compound
coupling constant
1
2
3
4
1.2 2.3 3.4 4,5 5,6a 5,6b 6a,6b
3.2‘ 8.5’ 2.7 1.5 5.9 6.6 10.5‘
3.7 9.9 3.5 1.4 6.0 6.5 10.7‘
3.7 9.7 8.8 10.1 2.0b 5.46 11.8h,‘
3.7 9.8 8.9 10.0 2.2 4.6
l’a,l’b 3‘,4’ 4’5’ 5’,6’a 5’,6‘b 6’a,6’b
12.2‘ 8.3 8.1 9.5 2.7 13.2‘
12.3“
12.3‘ 8.4 8.0 9.5 2.8 12.1c
12.2‘ 8.6 7.8 b 4.8 10.9
