Van der Waals versus hydrogen-bonding forces in a crystalline analog of cellotetraose: Cyclohexyl 4′-O-cyclohexyl β-D-cellobioside cyclohexane solvate

Article abstract of DOI:10.1021/ja805147t

Hydrogen bonding is important in cellulosic and other carbohydrate structures, but the role of interactions between nonpolar groups is less understood. Therefore, we synthesized cyclohexyl 4′-O-cyclohexyl β-D-cellobioside (8), a molecule that has two gluc

Full text of DOI:10.1021/ja805147t

Published on Web 11/14/2008
van der Waals versus Hydrogen-Bonding Forces in a
Crystalline Analog of Cellotetraose: Cyclohexyl
4′-O-Cyclohexyl ꢀ-D-Cellobioside Cyclohexane Solvate
Yuko Yoneda,† Kurt Mereiter,‡ Christian Jaeger,§ Lothar Brecker, Paul Kosma,†
Thomas Rosenau,*,† and Alfred French*,¶
Department of Chemistry, UniVersity of Natural Resources and Applied Life Sciences, Vienna
(BOKU) Muthgasse 18, A-1190 Vienna, Austria, Faculty of Chemistry, Vienna UniVersity of
Technology, Getreidemarkt 9/164 SC, A-1060 Vienna, Austria, BAM Federal Institute for
Materials Research and Testing, Richard-Willstaetter-Str. 11, D-12489 Berlin, Germany,
UniVersity of Vienna, Institute of Organic Chemistry, Wa¨hringer Str. 38, A-1090 Vienna,
Austria, and Southern Regional Research Center, U.S. Department of Agriculture,
1100 Robert E. Lee BouleVard, New Orleans, Louisiana 70124
Received July 3, 2008; E-mail: thomas.rosenau@boku.ac.at; al.french@ars.usda.gov
Abstract: Hydrogen bonding is important in cellulosic and other carbohydrate structures, but the role of
interactions between nonpolar groups is less understood. Therefore, we synthesized cyclohexyl 4′-O-
cyclohexyl ꢀ-D-cellobioside (8), a molecule that has two glucose rings and two nonpolar cyclohexyl rings.
Key to attaching the 4′-O-cyclohexyl group was making the 4′-O,6′-O-cyclohexylidene ketal. After
peracetylation, the cyclohexylidene ketal ring was opened regioselectively, providing 65% of 8 after final
deacetylation. Comparison of the crystal structure of 8, as the cyclohexane solvate, with those of cellulose
and its fragments, especially cellotetraose with four glucose rings, revealed extensive effects from the
cyclohexyl groups. Three conformationally unique molecules (A, B, and C) are in the triclinic unit cell of 8,
along with two solvent cyclohexanes. When viewed down the crystal’s a-axis, the array of C, A, and B
looks like the letter N, with A inclined so that its cyclohexyl groups can stack with those of the reducing
ends of the B and C molecules. The lower left and upper right points of the N are stacks of cyclohexyl rings
on the nonreducing ends of B and C, interspersed with solvent cyclohexanes. Whereas cellotetraose has
antiparallel (up-down) packing, A and B in 8 are oriented “down” in the unit cell while C is “up”. “Down-
down-up” (or, alternatively, “up-up-down”) packing is rare for carbohydrates. Other unusual details include
O6 in all three staggered orientations: one is tg, two are gg, and three are gt, confirmed with CP/MAS 13
C
NMR. The tg O6 donates a proton to an intramolecular hydrogen bond to O2′, opposite to the major schemes
in native cellulose I. A similar but novel O6B-H· · ·O2′B hydrogen bond is based on a slightly distorted gg
orientation. The hydrogen bonds between parallel molecules are unique, with linkages between O2′A and
O2′B, O3′A and O3′B, and O6A and O6B. Other details, such as the bifurcated O3 · · · O5′ and · · ·O6′
hydrogen bonds are similar to those of other cellulosic structures. C-H· · ·O hydrogen bonds are extensive
along the [110] line of quarter-staggering. The unusual features described here expand the range of structural
motifs to be considered for as-yet undetermined cellulose structures.
several important forms of cellulose: IR,1 Iꢀ,2 mercerized II,3,4
Introduction
and IIII.5 Despite these successes, attempts to better understand
Cellulose, the ꢀ-1,4-linked polymer of glucose, is the main
constituent of plant cell walls. As the predominant component
of cotton, rayon, and lyocell fibers, it is the major renewable
molecule in textiles. Likewise, the paper industry is based on
cellulose mostly from wood pulp. Consumption of cellulose
would expand greatly if its development as a source of biofuels
succeeds. Details of the structures of these materials at all levels
are needed for improvements in cellulose utilization. The past
decade has seen landmark reports of the crystal structures for
cellulose structure continue. Details for other crystalline forms,
e.g., cellulose IIIII, IVI,6 and IVII are unknown. Also, the
understanding of the transitions among the forms is still in its
(1) Nishiyama, Y.; Sugiyama, J.; Chanzy, H.; Langan, P. J. Am. Chem.
Soc. 2003, 125, 14300–14306.
(2) Nishiyama, Y.; Langan, P.; Chanzy, H. J. Am. Chem. Soc. 2002, 124,
9074–9082.
(3) Langan, P.; Nishiyama, Y.; Chanzy, H. J. Am. Chem. Soc. 1999, 121,
9940–9946.
(4) Langan, P.; Nishiyama, Y.; Chanzy, H. Biomacromolecules 2001, 2,
† University of Natural Resources and Applied Life Sciences Vienna.
‡ Vienna University of Technology.
410–416.
(5) Wada, M.; Chanzy, H.; Nishiyama, Y.; Langan, P. Macromolecules
§ BAM Federal Institute for Materials Research and Testing.
University of Vienna.
2004, 37, 8548–8555.
(6) Wada, M.; Heux, L.; Sugiyama, J. Biomacromolecules 2004, 5, 1385–
¶ U.S. Department of Agriculture.
1391.
9
16678 J. AM. CHEM. SOC. 2008, 130, 16678–16690
10.1021/ja805147t CCC: $40.75
2008 American Chemical Society

Bonding Forces in a Crystalline Analog of Cellotetraose
A R T I C L E S
early stages,7,8 and relatively little is known about the noncrys-
talline regions where many reactions and other interactions are
thought to occur. A particular issue is the role of polar and
nonpolar groups in crystal formation9 that immediately follows
biosynthesis. The crystals of cellulose are thought to make
enzymatic degradation difficult, so understanding the forces that
hold the crystals together may help in finding ways to reduce
“biomass recalcitrance”10 during processing to make biofuel.
scheme all have unusual features in response to the presence of
cyclohexane.
Experimental Section
General. Commercial chemicals were of the highest grade
available and were used without further purification. Reagent-grade
solvents were used for all extractions and workup procedures.
Distilled water was used for all aqueous extractions and for all
aqueous solutions. n-Hexane, diethyl ether, ethyl acetate, and
petroleum ether used in chromatography were distilled before use.
All reactions involving nonaqueous conditions were conducted in
oven-dried (140 °C, overnight) or flame-dried glassware under an
argon or nitrogen atmosphere. Thin layer chromatography (TLC)
was performed using Merck silica gel 60 F254 precoated plates.
Flash chromatography was performed using Baker silica gel (40
µm particle size). The use of brine refers to saturated aqueous NaCl.
Melting points, determined on a Kofler-type micro hot stage with
Reichert-Biovar microscope, are uncorrected. Elemental analyses
were performed at the Microanalytical Laboratory of the Institute
of Physical Chemistry at the University of Vienna.
Another approach to understanding cellulose structure is to
study the structures of related small molecules. Cellobiose, the
dimeric fragment of cellulose, was the second disaccharide
structure to be determined by X-ray diffraction.11,12 Now, results
from studies of numerous related small molecules can be
combined to synthesize additional information about the pos-
sibilities for cellulose in the as-yet unknown structures.13
Previous studies of analogs usually depended on the avail-
ability of suitable crystalline samples. The present paper reports
the second molecule that we synthesized expressly to provide
a cellulose analog for structural study. It follows work on the
first small relative of cellulose to crystallize in two different
forms, 1,4′-dimethyl cellobioside,14 as well as efforts of
Vasella’s group.15-17 Here we report the synthesis and structural
study of cyclohexyl 4′-O-cyclohexyl-ꢀ-D-glucopyranosyl-(1f4)-
ꢀ-D-glucopyranoside (8) or, alternatively, 1,4′-dicyclohexyl
cellobioside. (We have used 8 to represent both the molecule
itself and the crystalline cyclohexane solvate form.) This
molecule was targeted because of its similarity to cellotetraose,18,19
with the cyclohexyl rings replacing the two terminal glucose
rings of the tetraose. It can also be thought of as a derivative of
cellobiose to which two nonpolar caps are added. Because
cyclohexanes in 8 replace the O1 and O4′ hydroxyl hydrogen
atoms of cellobiose, the latter will not be involved in hydrogen
bond donation, a situation more like that in midchain cellulose.
Solution NMR. 1H NMR spectra were recorded at 600.13,
400.13 or 300.13 MHz for 1H and at 150.86, 100.03 or 75.47 MHz
for 13C NMR in CDCl3 as the solvent if not otherwise stated.
Chemical shifts, relative to TMS as internal standard, are given in
δ values, and coupling constants in Hz. 13C peaks were assigned
by means of APT, HMQC, and HMBC spectra.
Solid-State NMR. 13C solid-state NMR measurements were
performed using an AVANCE 600 (14.1 T, Bruker Biospin GmbH,
Rheinstetten, Germany). Magic angle sample spinning (MAS) was
applied using 4 mm zirconia rotors at a rotation frequency of 15.5
kHz. 13C NMR spectra were recorded using cross-polarization20
with magic angle sample spinning (CPMAS) at a Larmor frequency
of 150.9 MHz. The 1H 90° pulse length was 2.5 µs, and a CP
contact time of 2 ms was used with repetition times of 3 s. During
the contact time, the carbon spin lock field strength was held
constant, while the proton spin-lock field was ramped linearly
(ramped-CP)21 down to 50% of the initial value. Proton decoupling
was carried out with a 15° two pulse phase modulation (TPPM)
sequence.22 13C chemical shifts (δ) have been calibrated using the
glycine COOH signal set to δ ) 176.4 ppm as a secondary standard.
Crystallography. X-ray crystallography utilized a Bruker Smart
APEX CCD 3-axis diffractometer with sealed X-ray tube, Mo KR
radiation, a graphite monochromator, and a crystal-to-detector
distance of 50 mm. 0.3° ω-scan frames covered a complete sphere
of the reciprocal space (5 × 600 frames). After data integration,
corrections for absorption and λ/2-effects were applied to the data
using program SADABS.23 Structure solution was by direct
methods using SHELXS97,24 and the structure was refined using
full-matrix least-squares on F2 (SHELXL97).25 Carbon-bonded
hydrogen atoms were inserted in idealized positions, oxygen-bonded
hydrogen atoms were at first located in a difference Fourier map
and were then refined with AFIX 147 constraints. The orientation
disorder of two out of the six independent cyclohexyl termini was
taken into account with stabilizing 1-2 and 1-3 distance restraints.
Moreover, a DELU 0.003 restraint was applied to the Uij of all
non-hydrogen atoms.
Added cyclohexyl groups, along with the existing C-H
groups of the glucose rings, should increase the influence of
nonpolar group attractions on the overall structure. Looking
ahead to the results, this “self-assembly of sub-nano particles”,
also called crystallization, has resulted in a molecular array that
is influenced to a surprising extent by the cyclohexyl moieties.
O-H· · ·O and C-H· · ·O hydrogen bonding are also extensive,
but the crystal packing, O6 orientation, and hydrogen bonding
(7) Shibazaki, H.; Kuga, S.; Okano, T. Cellulose 1997, 4, 75–87.
(8) Dinand, E.; Vignon, M.; Chanzy, H.; Heux, L. Cellulose 2002, 9, 7–
18.
(9) Cousins, S. K.; Brown, R. M. Polymer 1995, 36, 3885–3888.
(10) Himmel, M. E.; Ding, S.-Y.; Johnson, D. K.; Adney, W. S.; Nimlos,
M. R.; Brady, J. W.; Foust, T. D. Science 2007, 315, 804–807.
(11) Jacobson, R. A.; Wunderlich, J. A.; Lipscomb, W. N. Acta Crystallogr.
1961, 14, 598–607.
Chemical Synthesis. All products were purified to homogeneity
by TLC/GCMS analysis. All given yields refer to isolated, pure
(12) Chu, S. S. C.; Jeffrey, G. A. Acta Crystallogr., Sect. B: Struct.
Crystallogr. Cryst. Chem. 1968, 24, 830–838.
(13) French, A. D.; Johnson, G. P. Cellulose 2004, 11, 5–22.
(14) Rencurosi, A.; Ro¨hrling, J.; Pauli, J.; Potthast, A.; Ja¨ger, C.; Pe´rez,
S.; Kosma, P.; Imberty, A. Angew. Chem., Int. Ed. 2002, 41, 4277–
4281.
(20) Hartmann, S. R.; Hahn, E. L. Phys. ReV. 1962, 128, 2042–2053.
(21) Metz, G.; Wu, X. L.; Smith, S. O. J. Magn. Reson., Ser. A 1994, 110,
219–227.
(15) Murty, K.V.S.N.; Xie, T.; Bernet, B.; Vasella, A. HelV. Chim. Acta
2006, 89, 675–730.
(22) Bennett, A. E.; Rienstra, C. M.; Auger, M.; Lakshmi, K. V.; Griffin,
R. G. J. Chem. Phys. 1995, 103, 6951–6958.
(16) Murty, K. V. S. N.; Vasella, A. HelV. Chim. Acta 2001, 84, 939–963.
(17) Bernet, B.; Xu, J.; Vasella, A. HelV. Chim. Acta 2000, 83, 2072–
2114.
(23) Sheldrick, G. M. SADABS, Program for Empirical Absorption Cor-
rection of Area Detector Data; University of Gottingen: Germany,
1996.
(18) Gessler, K.; Krauss, N.; Steiner, T.; Betzel, C.; Sandmann, C.; Saenger,
W. Science 1994, 266, 1027–1029.
(24) Sheldrick, G. M. SHELXS97, Program for the Solution of Crystal
Structures; University of Gottingen: Germany, 1996.
(25) Sheldrick, G. M. SHELXL97, Program for Crystal Structure Refine-
ment; University of Gottingen: Germany, 1997.
(19) Gessler, K.; Krauss, N.; Steiner, T.; Betzel, C.; Sarko, A.; Saenger,
W. J. Am. Chem. Soc. 1995, 117, 11397–11406.
9
J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008 16679

A R T I C L E S
Yoneda et al.
Scheme 1. Synthesis Summary. Seven-Step Sequence Leading to Cyclohexyl
4′-O-Cyclohexyl-ꢀ-D-glucopyranosyl-(1f4)-ꢀ-D-glucopyranoside (Cyclohexyl 4′-O-Cyclohexyl ꢀ-D-Cellobioside, 8) in 16% Overall Yield; Note
the Novel Regioselective Opening of the 4′-O,6′-O-Cyclohexylidene Ketal
products. Seven intermediate compounds were synthesized (Scheme
1), of which the first three compounds (1-3) are standard in
oligosaccharide chemistry. Therefore, their preparation and con-
firmatory data are not listed in the following.
170.29 (7 × CO in acetate). Anal. Calcd for C32H46O18: C, 53.48;
H, 6.45. Found: C, 53.37; H, 6.39.
Cyclohexyl ꢀ-D-Glucopyranosyl-(1f4)-ꢀ-D-glucopyranoside
(5). To a solution of 4 (782 mg, 1.09 mmol) in CH2Cl2/MeOH
(v/v ) 1:1, 21 mL) was added NaOMe in MeOH (0.1 M, 1.1 mL)
at 0 °C. The solution was stirred at room temperature for 4 h, and
then NaOMe was neutralized with acidic ion-exchange resin
DOWEX 50W X8. The resin was filtered off, and the filtrate was
evaporated. The residue was purified by flash column chromatog-
raphy (MeOH/CH2Cl2, v/v ) 1:4) to give compound 5 (460 mg,
Cyclohexyl 2′,3′,4′,6′-Tetra-O-acetyl-ꢀ-D-glucopyranosyl-(1f4)-
2,3,6-tri-O-acetyl-ꢀ-D-glucopyranoside (4). To a solution of
2′,3′,4′,6′-tetra-O-acetyl-ꢀ-D-glucopyranosyl-(1f4)-2,3,6-tri-O-
acetyl- R-D-glucopyranosyl trichloroacetimidate (3, 4.947 g, 6.335
mmol) in anhydrous CH2Cl2 in the presence of molecular sieve
(4Å, powder) was added cyclohexanol (3.3 mL, 32 mmol) at room
temperature. BF3 ·Et2O (80 µL, 0.633 mmol) was added at -18
°C, and the solution was stirred for 1 h. Stirring was continued for
3 h, and a new portion of BF3 ·Et2O (80 µL, 0.633 mmol) was
added every hour at -18 °C. The reaction mixture was neutralized
with trimethylamine (500 µL) at -18 °C, and the molecular sieve
was filtered off. The filtrate was evaporated, diluted with EtOAc
(200 mL), washed with 0.01 N aqueous HCl, neutralized with
saturated aqueous NaHCO3, washed with water and brine, and dried
over MgSO4. After evaporation to dryness, the residue was purified
by flash column chromatography (EtOAc/toluene, v/v ) 1:1) to
give a colorless solid, which was crystallized from CH2Cl2/EtOH
as colorless plates (1.959 g, 43%). Additional material was
contained in the filtrate (1.356 g, 30%). Rf ) 0.63 (EtOAc/toluene,
99%) as colorless glass-like solid. Rf ) 0.45 (MeOH/CH2Cl2, v/v
1
) 3:7); mp ) 209-211 °C; [R]20 ) -22.5 (c 1.00, water); H
D
NMR (D2O): δ 1.19-2.03 (m, 10H, cyclohexyl), 3.31 (dd, J1,2
8.0 Hz, J2,3 ) 9.2 Hz, 1H, H-2), 3.36 (dd, J1′,2′ ) 7.9 Hz, J2′,3′
)
)
9.0 Hz, 1H, H-2′), 3.46 (dd, J3′,4′ ) 8.9 Hz, J4′,5′ ) 9.7 Hz, 1H,
H-4′), 3.54 (ddd, J4′,5′ ) 9.7 Hz, J5′,6′a ) 5.6 Hz, J5′,6′b ) 2.1 Hz,
1H, H-5′), 3.56 (br, dd, J2′,3′ ) 9.0 Hz, J3′,4′ ) 8.9 Hz, 1H, H-3′),
3.60-3.69 (m, 3H, H-5, H-3, H-4), 3.77 (dd, J5′,6′a ) 5.6 Hz, J6′a,6′b
) 12.0 Hz, 1H, H-6′a), 3.82 (m, 1H, O-CH in cyclohexyl), 3.84
(dd, J5,6a ) 4.6 Hz, J6a,6b ) 12.2 Hz, 1H, H-6a), 3.96 (dd, J5′,6′b
)
2.1 Hz, J6′a,6′b ) 12.0 Hz, 1H, H-6′b), 4.00 (dd, J5,6b ) 2.1 Hz,
J6a,6b ) 12.2 Hz, 1H, H-6b), 4.55 (d, J1′,2′ ) 7.9 Hz, 1H, H-1′),
4.63 (d, J1,2 ) 8.0 Hz, 1H, H-1); 13C NMR (D2O): δ 24.13, 24.31,
25.50, 31.92, 33.47 (5 × CH2 in cyclohexyl), 60.66 (C-6), 61.09
(C-6′), 69.95 (C-4′), 73.39 (C-2), 73.64 (C-2′), 74.89 (C-3), 75.11
(C-5), 76.01 (C-3′), 76.42 (C-5′), 79.26 (O-CH in cyclohexyl), 79.31
(C-4), 100.50 (C-1), 102.94 (C-1′). Anal. Calcd for C18H32O11: C,
50.94; H, 7.60. Found: C, 50.90; H, 7.55.
v/v ) 2:1); mp ) 207-208 °C; [R]20 ) -25.5 (c 1.00, CHCl3).
D
1H NMR: δ 1.18-1.87 (m, 10H, cyclohexyl), 2.12, 2.09, 2.03, 2.02,
2.014, 2.008, 1.98 (7s, 7 × 3H, CH3 in acetate), 3.57 (ddd, J4,5
)
9.9 Hz, J5,6a ) 5.1 Hz, J5,6b ) 2.0 Hz, 1H, H-5), 3.60 (m, 1H,
O-CH in cyclohexyl), 3.66 (ddd, J4′,5′ ) 9.6 Hz, J5′,6′a ) 2.3 Hz,
J5′,6′b ) 4.5 Hz, 1H, H-5′), 3.75 (dd, J3,4 ) 9.1 Hz, J4,5 ) 9.9 Hz,
1H, H-4), 4.04 (dd, J5′,6′a ) 2.3 Hz, J6′a,6′b ) 12.5 Hz, 1H, H-6′a),
Cyclohexyl 4′,6′-O-Cyclohexylidene-ꢀ-D-glucopyranosyl-(1f4)-
ꢀ-D-glucopyranoside (6). To a solution of 5 (425 mg, 1.00 mmol)
in DMF (10 mL) were added cyclohexanone dimethyl ketal (305
µL, 2.00 mmol) and p-toluenesulfonic acid monohydrate (10 mg,
0.050 mmol) at room temperature. The solution was stirred under
decreased pressure (4 kPa) at 30 °C for 4 h. Another portion of
cyclohexanone dimethyl ketal (152 µL, 1.00 mmol) and p-
toluenesulfonic acid monohydrate (10 mg, 0.050 mmol) was added,
and stirring was continued for another 4 h. After addition of a third
portion of cyclohexanone dimethyl ketal (152 µL, 1.00 mmol) and
p-toluenesulfonic acid monohydrate (10 mg, 0.050 mmol) and
stirring of the solution for 1 h, the reaction mixture was neutralized
with solid NaHCO3 by stirring overnight. Solids were removed by
filtration, and the filtrate was coevaporated with toluene to dryness.
The residue was purified by flash column chromatography (MeOH/
4.09 (dd, J5,6a ) 5.1 Hz, J
) 11.9 Hz, 1H, H-6a), 4.36 (dd,
6a,6b
J5′,6′b ) 4.5 Hz, J6′a,6′b ) 12.5 Hz, 1H, H-6′b), 4.48 (dd, J5,6b ) 2.0
Hz, J6a,6b ) 11.9 Hz, 1H, H-6b), 4.50 (d, J1′,2′ ) 8.1 Hz, 1H, H-1′),
4.53 (d, J1,2 ) 8.1 Hz, 1H, H-1), 4.87 (dd, J1,2 ) 8.1 Hz, J2,3 ) 9.7
Hz, 1H, H-2), 4.92 (dd, J1′,2′ ) 8.1 Hz, J2′,3′ ) 9.1 Hz, 1H, H-2′),
5.05 (dd, J3′,4′ ) 9.4 Hz, J4′,5′ ) 9.6 Hz, 1H, H-4′), 5.14 (dd, J2′,3′
) 9.1 Hz, J3′,4′ ) 9.4 Hz, 1H, H-3′), 5.17 (dd, J2,3 ) 9.7 Hz, J3,4
) 9.1 Hz, 1H, H-3). 13C NMR: δ 20.61, 20.61, 20.61, 20.66, 20.71,
20.76, 20.92 (7 × CH3 in acetate), 23.62, 36.75, 25.52, 31.67, 33.25
(5 × CH2 in cycohexyl), 61.61 (C-6′), 62.03 (C-6), 67.85 (C-4′),
71.64 (C-2′), 71.76 (C-2), 71.93 (C-5′), 72.54 (C-5), 72.61 (C-3),
72.94 (C-3′), 76.63 (C-4), 78.02 (O-CH in cyclohexyl), 99.18 (C-
1), 100.68 (C-1′), 168.84, 169.10, 169.31, 169.66, 170.01, 170.12,
9
16680 J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008

Bonding Forces in a Crystalline Analog of Cellotetraose
A R T I C L E S
Figure 1. Thermal ellipsoid plot (50% probability) for 8 showing, from left to right, the three molecules of 8 (A, B, and C), and two cyclohexane molecules
(S and T). Carbon and oxygen atoms are labeled. The molecules are projected onto the (210) plane. The minor components of the disordered B and C
molecules are labeled E and F, respectively.
CH2Cl2, v/v ) 1:19) to give a colorless solid, which was crystallized
from EtOAc to afford 6 as colorless crystals (106 mg 21%), the
filtrate containing an additional portion of the product (150 mg,
30%). Rf ) 0.32 (MeOH/CH2Cl2, v/v ) 1:9); mp ) 219-221 °C,
[R]20D ) -41.7 (c 1.0, MeOH). 1H NMR (CD3OD): δ 1.19-2.05
(m, 20H, cyclohexyl and cyclohexylidene), 3.19 (br, dd, J1,2 ) 7.9
Hz, J2,3 ) 8.7 Hz, 1H, H-2 or H-2′), 3.28 (br, dd, J1,2 ) 7.8 Hz,
J2,3 ) 8.9 Hz, 1H, H-2 or H-2′), 3.31-3.38 (m, 2H, H-5, H-5′),
3.47-3.48 (m, 2H, H-3, H-3′), 3.54-3.55 (m, 2H, H-4, H-4′), 3.68
(m, 1H, cyclohexyl), 3.74-3.90 (m, 4H, H-6a, H-6b, H-6′a, H-6′b),
4.39 (d, J1,2 ) 7.9 Hz, 1H, H-1 or H-1′), 4.48 (d, J1,2 ) 7.8 Hz,
1H, H-1 or H-1′). 13C NMR (CD3OD) δ 23.56, 23.78, 25.08, 25.27,
26.78, 26.83, 28.78, 32.83, 34.72, 39.01 (5 × CH2 in cyclohexyl,
5 × CH2 in cyclohexylidene), 61.86, 62.18 (C-6, C-6′), 68.86 (C-5
or C-5′), 73.67 (C-4′), 74.83, 74.96, 75.81, 76.09 (C-2, C-2′, C-3,
C-3′), 76.19 (C-5 or C-5′), 78.38 (O-CH in cyclohexyl), 80.85 (C-
4), 100.81 (O-C-O in cyclohexylidene), 102.15, 105.08 (C-1, C-1′).
Anal. Calcd for C24H40O11: C, 55.16; H, 8.10. Found: C, 55.28; H,
8.07.
H-4′), 3.73 (br, dd, J5′,6′a ) 9.9 Hz, J6′a,6′b ) 10.6 Hz, 1H, H-6′a),
3.75 (br, dd, J3,4 ) 8.9 Hz, J4,5 ) 9.6 Hz, 1H, H-4), 3.92 (dd, J5′,6′b
) 5.3 Hz, J6′a,6′b ) 10.6 Hz, 1H, H-6′b), 4.07 (dd, J5,6a ) 5.0 Hz,
J6a,6b ) 11.9 Hz, 1H, H-6a), 4.45 (dd, J5,6b ) 2.0 Hz, J6a,6b ) 11.9
Hz, 1H, H-6b), 4.50 (d, J1′,2′ ) 7.6 Hz, 1H, H-1′), 4.53 (d, J1,2
7.9 Hz, 1H, H-1), 4.84 (dd, J1,2 ) 7.9 Hz, J2,3 ) 9.6 Hz, 1H, H-2),
4.88 (dd, J1′,2′ ) 7.6 Hz, J2′,3′ ) 9.2 Hz, 1H, H-2′), 5.07 (t, J2′,3′
)
)
J3′,4′ ) 9.2 Hz, 1H, H-3′), 5.15 (dd, J2,3 ) 9.6 Hz, J3,4 ) 8.9 Hz,
1H, H-3). 13C NMR: δ 20.68, 20.76, 20.76, 20.93, 21.13 (5 × CH3
in acetate), 22.53, 22.78, 23.64, 23.77, 25.52, 25.52, 27.52, 31.67,
33.24, 37.67 (5 × CH2 in cyclohexyl, 5 × CH2 cyclohexylidene),
61.32 (C-6′), 62.08 (C-6), 67.47 (C-5′), 70.15 (C-4′), 71.79 (C-2),
72.39 (C-5), 72.44 (C-3′), 72.53 (C-2′), 73.23 (C-3), 77.21 (C-4),
78.02 (O-CH in cyclohexyl), 99.05 (C-1), 99.84 (O-C-O in
cyclohexylidene), 101.55 (C-1′), 169.26, 169.36, 169.42, 169.95,
170.19 (5 × CO in acetate). Anal. Calcd for C34H50O16: C, 57.13;
H, 7.05. Found: C, 56.89; H, 7.20.
Cyclohexyl 4′-O-Cyclohexyl-ꢀ-D-glucopyranosyl-(1f4)-ꢀ-D-
glucopyranoside (8). To a solution of 7 (109 mg, 0.153 mmol), in
anhydrous CH2Cl2 (10 mL) were added borane trimethylamine
complex (56 mg, 0.763 mmol), molecular sieve (4 Å, powder), and
AlCl3 (102 mg, 0.763 mmol) at -72 °C. The solution was stirred
for 1 h at this temperature, and then a second portion of borane
trimethylamine complex (56 mg, 0.763 mmol) and AlCl3 (102 mg,
0.763 mmol) was added. The solution was stirred for another h,
and ion-exchange resin DOWEX 50W X8 and MeOH were added
at -72 °C. Solids were filtered off, and the filtrate was evaporated.
The residue was purified by flash column chromatography (EtOAc/
toluene (v/v ) 1:2), then EtOH/EtOAc/toluene, v/v/v ) 1:2:2). To
a solution of the product in MeOH/CH2Cl2 (v/v ) 1:1, 10 mL)
NaOMe in MeOH (0.1 M, 152 µL) was added. The solution was
stirred at room temperature overnight. NaOMe was neutralized with
DOWEX 50W X8 ion-exchange resin. The solid was filtered off,
and the filtrate was evaporated. The residue was purified by flash
Cyclohexyl 2′,3′-Di-O-acetyl-4′,6′-O-cyclohexylidene-ꢀ-D-glu-
copyranosyl-(1f4)-2,3,6-tri-O-acetyl-ꢀ-D-glucopyranoside (7).
Ketal 6 (80 mg, 0.159 mmol) was stirred in pyridine (2 mL) and
acetic acid anhydride (8 mL) in the presence of 4-(dimethylami-
no)pyridine (1 mg) at room temperature overnight. The reaction
mixture was coevaporated with EtOH to dryness. The residue was
purified by flash column chromatography (EtOAc/toluene, v/v )
1:4) to afford 7 (109 mg, 96%) as colorless syrup. The syrup was
crystallized from CH2Cl2/n-hexane. Rf ) 0.48 (EtOAc/toluene, v/v
) 1:2); mp 189-191 °C; [R]20 ) -30.9 (c 1.00, CHCl3). 1H
D
NMR: δ 1.20-1.87 (m, 20H, cyclohexyl, cyclohexylidene), 2.00,
2.02, 2.03, 2.04, 2.11 (5s, 5 × 3H, CH3 in acetate), 3.29 (dt, J4′,5′
) J5′,6′a ) 9.9 Hz, J5′,6′b ) 5.3 Hz, 1H, H-5′), 3.54 (ddd, J4,5 ) 9.6
Hz, J5,6a ) 5.0 Hz, J5,6b ) 2.0 Hz, 1H, H-5), 3.57 (m, 1H, O-CH
in cyclohexyl), 3.68 (br, dd, J3′,4′ ) 9.2 Hz, J4′,5′ ) 9.9 Hz, 1H,
9
J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008 16681

A R T I C L E S
Yoneda et al.
Table 1. Crystal Data and Structure Refinement for Cyclohexyl
4′-O-Cyclohexyl ꢀ-Cellobioside
column chromatography (EtOH/EtOAc/toluene, v/v/v ) 3:10:10)
to give target 8 (50 mg, 65%) as colorless solid. Recrystallization
was performed from cyclohexane/MeOH (v/v ) 3:1). Rf ) 0.30
empirical formula
moiety formula
formula weight
temp (K)
C84H150O33
3(C24H42O11), 2(C6H12
1688.04
(EtOH/EtOAc/toluene, v/v/v ) 3:10:10), mp 220-280 °C, [R]20
)
D
1
) -14.9 (c 0.490, MeOH). H NMR (CD3OD): δ 1.15-2.04 (m,
100(2)
20H, 2 × cyclohexyl), 3.21 (dd, J1,2 ) 7.9 Hz, J2,3 ) 8.9 Hz, 1H,
H-2), 3.21 (dd, J1′,2′ ) 7.9 Hz, J2′,3′ ) 9.0 Hz, 1H, H-2′), 3.29 (ddd,
J4′,5′ ) 8.5 Hz, J5′,6′a ) 5.0 Hz, J5′,6′b ) 2.3 Hz, 1H, H-5′), 3.33 (t,
wavelength (Å)
crystal system, space
group
0.71073
triclinic, P1
j
J3′,4′ ) J4′,5′ ) 8.5 Hz, 1H, H-4′), 3.38 (ddd, J4,5 ) 9.1 Hz, J5,6a
4.0 Hz, J5,6b ) 2.9 Hz, 1H, H-5), 3.40 (dd, J2′,3′ ) 9.0 Hz, J3′,4′
)
)
unit cell dimensions
a (Å)
b (Å)
preferred
reduced
10.7024(7)
10.7024(7)
10.9502(7)
23.4669(15)
80.043(1)
52.828(1)
89.314(1)
2143.4(2)
1, 1.308
10.9502(7)
19.0194(12)
78.077(1)
79.467(1)
89.314(1)
8.5 Hz, 1H, H-3′), 3.50 (t, J2,3 ) J3,4 ) 8.9 Hz, 1H, H-3), 3.54 (br,
dd, J3,4 ) 8.9 Hz, J4,5 ) 9.1 Hz, 1H, H-4), 3.61 (tt, Jaa ) 9.4 Hz,
Jae ) 3.9 Hz, 1H, 4′-O-CH in cyclohexyl), 3.65 (dd, J5′,6′a ) 5.0
Hz, J6′a,6′b ) 11.8 Hz, 1H, H-6′a), 3.69 (tt, Jaa ) 9.4 Hz, Jae ) 3.8
c (Å)
R (deg)
ꢀ (deg)
γ (deg)
volume (Å3)
Z, calcd density
(g/cm3)
Hz, 1H, 1-O-CH in cyclohexyl), 3.84 (dd, J5′,6′b ) 2.3 Hz, J6′a,6′b
)
11.8 Hz, 1H, H-6′b), 3.85 (dd, J5,6a ) 4.0 Hz, J6a,6b ) 12.1 Hz,
1H, H-6a), 3.86 (dd, J5,6b ) 2.9 Hz, J6a,6b ) 12.1 Hz, 1H, H-6b),
4.39 (d, J1′,2′ ) 7.9 Hz, 1H, H-1′), 4.40 (d, J1,2 ) 7.9 Hz, 1H, H-1).
13C NMR: δ 25.40, 25.52, 25.83, 25.85, 27.13, 27.20, 33.19, 34.27,
34.73, 35.06 (5 × CH2 in 1-O-cyclohexyl, 5 × CH2 in 4′-O-
cyclohexyl), 62.32 (C-6), 62.38 (C-6′), 75.20 (C-2), 75.45 (C-2′),
76.74, 76.83, 76.94 (C-3, C-5, C-4′), 77.83 (C-5′), 78.40 (C-3′),
78.78 (O-CH in 1-O-cyclohexyl), 80.56 (O-CH in 4′-O-cyclohexyl),
81.14 (C-4), 102.61 (C-1), 104.93 (C-1′). Anal. Calcd for C24H42O11:
C, 56.90; H, 8.36. Found: C, 56.56; H, 8.36.
absorption coefficient
0.099
(mm-1
)
F(000)
918
crystal size (mm3)
θ range for data
collection (deg)
index ranges
0.60 × 0.60 × 0.20
2.40 to 30.07
-15 e h e 14,
-15 e k e 15,
-26 e l e 26
38659/12443 [Rint
0.0257]
reflections collected/
unique
)
completeness to θ )
98.9%
Results and Discussion
30.07°
absorption correction
multiscan (program
SADABS)
0.98 and 0.92
Synthesis. Target compound 8 was synthesized in 16% overall
yield, starting from cellobiose octaacetate (1) according to the
seven-step sequence shown above in Scheme 1. After selective
deprotection of the reducing end to give cellobiose heptaacetate
(2), glycosidation with cyclohexanol was performed under
“Schmidt conditions”,26 i.e., via the corresponding trichloro-
acetimidate (3), which afforded 73% of the ꢀ-configured product
(4) when working in anhydrous CH2Cl2 in the presence of
powdered molecular sieve (4Å) and BF3 ·Et2O catalyst at -18
°C. The resulting cyclohexyl ꢀ-D-cellobioside peracetate (4) was
deprotected into cyclohexyl ꢀ-D-cellobioside (5), and a 4′-O,6′-
O-cyclohexylidene ketal27 was introduced (6). This approach
was chosen after all alternative attempts to introduce the 4′-O-
cyclohexyl group by etherification failed. After peracetylation
(7), this cyclohexylidene ketal ring was opened regioselectively,
which was the key step in the sequence, providing 65% of the
final compound (8) after deacetylation. The regioselective
opening of the cyclohexylidene ketal was comprehensively
studied and optimized, and more than 20 reductant/Lewis acid
combinations under different solvent and temperature conditions
were tested, starting from conditions used for the opening of
the common benzylidene acetals. The reagent pair boran
trimethylamine complex/aluminum chloride in dichloromethane
at -72 °C gave the best results, providing 75% of the desired
4′-O-cyclohexyl derivative, with only 10% of the 6′-O-cyclo-
hexyl side product. Crystals for diffraction were grown from
cyclohexane/MeOH (v/v ) 3:1) by slow evaporation.
max and min
transmission
refinement method
full-matrix
least-squares on F2
12443/336/1112
data/restraints/
parameters
goodness-of-fit on F2
final R indices [I >
2σ(I)]
1.041
R1 ) 0.0451, wR2
)
)
0.1121
R indices (all data)
R1 ) 0.0492, wR2
0.1161
absolute structure
parameter
0.1(4)
largest diff peak and
0.77 and -0.36
hole (e Å-3
)
molecules,19 and methyl cellotrioside has four crystallographi-
cally unique but structurally similar molecules per unit cell.28
For triclinic crystal structures, a reduced cell is conventionally
used. Our “preferred” cell differs from the reduced cell, also
reported in Table 1, that was automatically derived during
analysis of the X-ray data. Both cells have the same volumes
and a- and b-dimensions, but their c-axes and R- and ꢀ-angles
differ.
We chose the less-conventional cell because the molecular
alignment deviates less from its c-axis. In cellulose the c-axis
and the molecular axes coincide. In the tetraose19 structure, the
alignment is closer than in 8 but not quite coincident.
Figure 1 shows the thermal ellipsoids from the structure
determination as well as the disordered cyclohexyl moieties on
the nonreducing ends of the B and C molecules. Most ellipsoids
are satisfactorily small except for atoms of one cyclohexyl
residue (nonreducing end of A) and one cyclohexane solvent
molecule (S). A closer view of the disordered ends is given in
Figure S1, Supporting Information. The B and C labels also
apply to the major components of the disordered cyclohexyl
rings (62.4% and 61.0%, respectively). The minor components
Basic Crystal Structure. Table 1 presents the key crystal-
j
lographic information. The triclinic P1 unit cell contains three
molecules (A, B, and C) of 8, each with its own geometric
features, as well as two separate cyclohexane solvent molecules
(S and T). The finding of three crystallographically unique
substrate molecules in the unit cell is rare, and novel for small
cellulose analogs. Most have one or two (symmetry-related)
molecules in the unit cell. Cellotetraose has two similar
(26) Hoffmann, M. G.; Schmidt, R. R. Liebigs Ann. Chem. 1985, 12, 2403.
(27) Bissett, F. H.; Evans, M. E.; Parrish, F. W. Carbohydr. Res. 1967, 5,
184.
(28) Raymond, S.; Henrissat, B.; Qui, D. T.; Kvick, Å.; Chanzy, H.
Carbohydr. Res. 1995, 277, 209–229.
9
16682 J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008

Bonding Forces in a Crystalline Analog of Cellotetraose
A R T I C L E S
Figure 3. View from the top of the crystal structure with the carbohydrate
portion replaced by straight, red lines. The molecules are aligned so that
the carbohydrate lines of the B and C molecules are almost perpendicular
to the page (red dots), whereas the A molecule is tilted, as indicated by its
“carbohydrate line” that stretches from one row of molecules parallel to
the a-axis to its adjacent row. Green lines are at the top of the layer, and
black are at the bottom.
Figure 2. Projection down the b-axis of the unit cell, showing the a- and
c-axes and two of the layers of 8. Carbon atoms are green and oxygen
atoms are red; hydrogen atoms are not shown. Letters denote the five
different molecules shown in Figure 1, and the disordered ends of B and C
are shown.
of the disordered cyclohexyl groups are given letters E (37.6%
occupancy, alternative part of the B molecule) and F (39.0%,
part of the C molecule). Bonds from the disordered C and F
cyclohexyl rings to O4′ are axial, while linkages from all other
cyclohexyl groups are equatorial.
Crystal Packing; Chain Orientation. Aspects of the crystal
packing are shown in Figures 2-6. Figure 2, a view down the
b-axis, shows that the constituents of the crystal structure are
arranged in layers that are tilted with respect to the c-axis. The
bonded and solvent cyclohexanes comprise the top and bottom,
relatively nonpolar surfaces of each layer, with the central
cellobiose residues being able to form both O-H· · ·O and
C-H· · ·O hydrogen bonds and less polar van der Waals
interactions. Unlike a lipid bilayer, single molecules of 8 span
the entire thickness of the layer, and the “head groups” are
nonpolar. The disordered cyclohexyl group on the B molecule
is on the top of each layer, and the disordered group on the C
molecule is on the bottom. As also shown in Figure 1, the A
and B molecules have “down” orientations in the unit cell, that
is, the z-coordinates of their O5 atoms are greater than the
z-coordinates of the O1 atoms. On the other hand, the C
molecule is oriented “up.” Therefore, the unit cell contains twice
as many down-pointing molecules as up, giving a down-down-
up packing. Such packing is rare but has been found for the
3-fold double helices of welan29 and calcium ι-carrageenan,30
structures that have trigonal unit cells. Another molecule, poly-
L-lactide, can pack in a north-south-south (up-down-down)
Figure 4. View of stacking of the cyclohexyl moieties, projected down
the a-axis of a single layer, with the carbohydrate replaced by a straight
line. The view is slightly rotated so that four repeats of each molecule can
be seen. Three “N”-shaped groupings are shown, along with the A and B
partners on the left side and C molecules without the A and B partners on
the right.
scheme.31 Although not a double helix, it is a 3-fold helix that
also packs in a trigonal unit cell. More relevant to cellulose,
Lotz has speculated32 that the correct packing of 3-fold triethyl
cellulose helices could be similar to poly-L-lactide instead of
the six-chain cell proposed by Zugenmaier.33 The molecules of
8 do not correspond to 3-fold helices. Finally, γ-chitin, which
has a cellulosic backbone, has been proposed to contain three
chains per cell based on early work, with two up and the other
down or vice versa.34
In Figure 2, counterpart cyclohexane molecules interact at
the interface between the top of the lower layer and the bottom
of the upper layer. Thus, the S cyclohexane molecule is closest
to the T solvent molecule. Also, the reducing-end groups of
(31) Puiggali, J.; Ikada, Y.; Tsuji, H.; Cartier, L.; Okihara, T.; Lotz, B.
Polymer 2000, 41, 8921–8930.
(32) Cartier, L.; Spassky, N.; Lotz, B. C. R. Acad. Sci. Paris 1996, 322,
429–435.
(29) Chandrasekaran, R.; Radha, A.; Lee, E. J. Carbohydr. Res. 1994, 252,
183–207.
(33) Zugenmaier, P. J. Appl. Polym. Sci, Appl. Polym. Symp. 1983, 37,
223–238.
(30) Janaswamy, S.; Chandrasekaran, R. Carbohydr. Res. 2001, 335, 181–
194.
(34) Rudall, K. M. AdV. Insect Physiol. 1963, 1, 257–313.
9
J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008 16683

A R T I C L E S
Yoneda et al.
contacts between layers that were shorter than 2.6 Å, whereas
B-F and E-F had contacts of 2.21 and 2.28 Å, respectively
(Figure S1)
Cyclohexane. The solvent molecules fill in gaps on the upper
and lower surfaces of the individual layers, presumably com-
pensating for the lesser bulk of a cyclohexyl group compared
to a glucopyranosyl residue. Further understanding of the role
of the cyclohexyl groups was attained by drawing the carbo-
hydrate portion of each molecule of 8 as a straight line in Figures
3 and 4. In Figure 3, tilted slightly away from a view down the
c-axis, the projected carbohydrate line for the A structures is
fairly long, indicating that A is tilted relative to B and C, which
have very short projected lines. The S molecule is above the
lower end of the A molecule and the T molecule is below the
upper end of the A molecule. The disordered end of each B
molecule appears in this view to have a propeller shape arising
from the major and minor components, and the two components
of the disordered ends of the C molecules are seen as hexagons
that are rotationally offset from each other but otherwise
superimposed.
In Figure 4, a view along the a-axis, the disordered cyclohexyl
parts of the C molecules are stacked with the T solvent
molecules. The ordered cyclohexyl moieties on the reducing
ends of the C molecules are interspersed with the ordered
cyclohexyl groups on the nonreducing ends of the A molecules,
and the ordered cyclohexyl groups on the reducing ends of A
are interspersed with ordered cyclohexyls on the reducing ends
of the B molecules. The N-shaped sequence of C-A-B ends with
the disordered cyclohexyl moieties on the nonreducing end of
B interspersed with S molecules, an arrangement very similar
to the nonreducing end of the C molecules at the beginning of
the sequence. The importance of the interactions of the nonpolar
groups is underscored by the alignments of the cyclohexyl
moieties in this a-axis projection and the differing tilts for the
lines from the different cellobiose portions. Additional views
of the cyclohexane stacking are in Figure S2, Supporting
Information.
Figure 5. Packing of the carbohydrate moieties of the A, B, and C
molecules, projected down the c-axis. The unit cell, the [110] line, and the
(210) and (120) planes are indicated. Dashed lines surround the six
molecules nearest to the A and C molecules.
Carbohydrate. To best view the features of the carbohydrate
portion, the cyclohexyl moieties have been eliminated from
Figure 5, which shows the packing of the cellobiose residues.
The view is down the c-axis and is similar to a view down the
chain axis of cellulose II or cellotetraose. The six neighbors
around the A and C residues are each enclosed by dashed lines.
To reduce clutter, an enclosure for B residues is not shown.
Each kind (A, B, or C) is surrounded entirely by the two other
kinds of residue. A consequence is that the “up” C molecules
are surrounded only by “down” A and B molecules, whereas
the As and Bs are surrounded by both up and down molecules.
A molecules are not in contact with other As, and Bs are not in
contact with other Bs. Despite the visual similarity with the
packing in cellulose II and cellotetraose, the details for 8 are
different because some of the contacts in those other structures
are between identical molecules that are related by translational
symmetry.
Also shown in Figure 5 are the a and b unit cell axes and the
three alignments of molecules that make intermolecular hydrogen-
bonding contacts. The [110] lines pass through a stack of
residues with their relatively nonpolar sides facing each other.
On the other hand, the (210) planes contain sheets of molecules
that are all linked by hydrogen bonds, each residue to both of
its in-sheet neighbors. The (120) planes also contain sheets, but
as will be seen below, only three molecules are linked with
hydrogen bonds before there is an interruption.
Figure 6. A, B, and C molecules, arranged along the [110] line (see Figure
5) that connects the o and a,b points of the base of the unit cell. Arrows
indicate the “up” or “down” orientation of the chains. The minor fractions
of the disordered cyclohexyl substituents are not shown. The heavy
horizontal line passes through the O4′ of the left-most A molecule and
underneath the C7 atom (circled) of the fifth molecule from the left. If the
line passed through O1 instead, that would show perfect “quarter stagger”
of the chains. The dashed line and 8.36 Å distance show the advance along
the c-axis for three chains, or 2.79 Å for each.
the C and A molecules are close, as are the reducing B and
nonreducing A ends.
The disordered B and E cyclohexyl groups interact with the
disordered C and F groups. B-C and E-C combinations had no
9
16684 J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008

Bonding Forces in a Crystalline Analog of Cellotetraose
A R T I C L E S
Table 2. Intramolecular O-H· · ·O Hydrogen Bonding Geometriesa
donor
acceptor
H· · ·O (Å)
O· · ·O (Å)
O-H· · ·O (deg)
O3A-H3A
O3A-H3A
O3B-H3B
O3B-H3B
O3C-H3C
O3C-H3C
O3C-H3C
O6B-H6B
O6B-H6B
O6C-H6C
O6C-H6C
O3′C-H3′C
O5′A
O6′A
O5′B
O6′B
O5′C
O6′C
O4C
O4B
O2′B
O4C
1.82
2.37
2.03
2.53
1.84
2.41
2.72b
2.62b
1.83
2.32
2.06
2.57
2.719(2)
2.984(2)
2.847(2)
3.276(2)
2.755(2)
3.061(2)
3.049(2)
3.066(2)
2.800(2)
2.864(2)
3.014(2)
2.995(2)
153
120
141
134
157
124
100
108
175
115
166
107
O2′C
O2′C
a d(D· · ·A) < R(D) + R(A) + 0.50 Å ) 3.54 Å (O-H· · ·O), 3.72 Å
(C-H· · ·O); d(H· · ·A) < R(H) + R(A) - 0.12 Å ) 2.60 Å; D-H· · ·A
> 100.0°. Covalent radii (Å) for C: 1.70; H: 1.20; O: 1.52.39 b This
distance exceeds the distance criteria for hydrogen bonding in the
PLATON program39 but fits the angular criteria well. As part of a
3-center bond, the O2′C· · ·O3′A’s 144° angle, the 149° angle for the
O2′C· · ·O2A bond, and the 65° O3A-H2′C-O2A angle of 65.5° add up
to 358°, close to the ideal value of 360° for a 3-center hydrogen bond.
assignments.35 In 8, all O6 orientations (Table 5) are within
23° of the ideal O5-C5-C6-O6 torsion angles of +60°, -60°
and 180°, respectively. It is unusual to find examples with the
tg orientation for molecules having the gluco configuration at
O4, although the tg orientation is found in both native forms of
cellulose, IR1 and Iꢀ.2 Structures having all three forms in the
same crystal are truly rare. Only two crystals in the Cambridge
Structural Database36 have CH2OH orientations that are within
30° of the ideal values for each of the three orientations. Both
are ꢀ-cyclodextrins.37,38 The O6 gg, O6′ gt motif was found in
both crystal structures of the 1,4′-dimethyl cellobioside, while
cellotetraose has all O6 in the gt orientation.
One way to appreciate the impact of the hydrogen bonding
is in terms of the sheets and stacks of molecules that they appear
to organize. Another consideration is the network of cooperative
hydrogen bonds. For this discussion, all O-H and C-H
covalent bond lengths were set to the neutron diffraction values
of 0.97 and 1.10 Å,39 respectively, and the geometric data were
recalculated. Geometric features are in Tables 2-4, along with
the criteria for defining hydrogen bonds from the PLATON
program.40 We also scanned the structures with a more-inclusive
H· · ·O criterion of 2.85 Å (for the O-H· · ·O bonds only) and
found four additional interactions that are included in Tables 2
and 3, as well as Figures 8 and 9.
Figure 7. Solid-state (13C CPMAS, CP ) 1 ms, 150.9 MHz) NMR of
compound 8. Inset: C-6 region showing all three preferred conformations,
gt/gg/tg ) 3:2:1.
Approximate Quarter Staggering in the [110] Stack. An
important feature of the [110] stack is indicated in Figure 6 by
a horizontal line. This line intersects the O4′ of the first molecule
on the left, and is just under the C7 on the second B molecule
to its right. That B molecule is the fourth molecule after the
left-most A molecule. If the upward shift, or stagger, for each
molecule were an advance of one-fourth of the length of a
cellobiose residue, the horizontal line would intersect O1 on
the fourth molecule, but the advance is slightly greater. Working
with the unit cell geometry, the a,b point is 8.36 Å higher than
the origin point (o) for a distance that spans three molecules.
This corresponds to a shift of 2.79 Å for one molecule or 11.15
Å for four molecules, a number that can be compared with
dO1-O4′ values of 10.21 Å, 10.35 Å and 10.13 Å for the A, B
and C residues. Similarly continuous “quarter stagger” (2.81
Å) is found in parallel-packed, triclinic cellulose IR. In parallel
cellulose Iꢀ,2 antiparallel II,4 and cellotetraose,19 alternating
chains of the unit cell are also elevated by about one-fourth
(2.72, 2.40, and 2.44 Å, respectively) of the cellobiose unit,
compared to the other chains. In cellulose IIII,5 there is no
stagger of the chains.
Hydrogen Bonding and O6 Orientation. All 18 are donors,
15 are hydroxyl acceptors, and three are C-H acceptors.
Altogether, there are 28 different O-H· · ·O hydrogen bonds,
all networked. We have also identified 14 different C-H· · ·O
hydrogen bonds. Because C-H groups cannot be acceptors, they
only participate in networks as branches. Three of the C-H· · ·O
hydrogen bonds are not networked because their acceptors are
ether oxygens that do not happen to also accept other protons.
Of the 15 ether oxygens, nine are either O-H or C-H acceptors.
No reducing ring O5 atoms are involved, nor are O1B, O4A or
O4′C.
Two of those additional bonds are critical to the discussion
of the networking in 8, below. One is an intramolecular link
involving O3C, H3C, and O4C, with an H · · ·O distance of 2.72
Å, an O· · ·O distance of 3.049 Å, and an O-H· · ·O angle of
100°; the other is intermolecular with O2B, H2B, and O2A,
with values of 2.73 Å, 3.248 Å and 114°. The PLATON
software reports two independent networks, and we have
retained that result. However, either of these two long and
angular bonds would link the two networks, leaving only one
(35) Horii, F.; Hirai, A.; Kitamaru, R. Polym. Bull. (Berlin) 1983, 10, 357–
61.
(36) Allen, F. H. Acta Crystallogr., Sect. B: Struct. Sci. 2002, 58, 380–
388.
These hydrogen bonding systems stabilize the O6 groups in
all three of the staggered orientations, namely gt, gg and tg.
13C cross-polarization magic angle spinning (CP-MAS) NMR
(Figure 7) confirmed the presence of all three C6-OH orienta-
tions in one crystal structure. The six distinct peaks from the
different O6 groups are indicated in the inset along with their
(37) Hamilton, J. A.; Sabesan, M. N. Carbohydr. Res. 1982, 102, 31–46.
(38) Pop, M. M.; Goubitz, K.; Borodi, G.; Bogdan, M.; De Ridder, D. J. A.;
Peschar, R.; Schenk, H. Acta Crystallogr., Sect. B: Struct. Sci. 2002,
58, 1036–1043.
(39) Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological Structures;
Springer-Verlag: Berlin, 1991.
(40) Spek, A. L. J. Appl. Crystallogr. 2003, 36, 7–13.
9
J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008 16685

A R T I C L E S
Yoneda et al.
Table 3. Intermolecular O-H· · ·O hydrogen bonds
donor
acceptor
ARUa
H· · ·O (Å) O· · ·O (Å) O-H· · ·O (deg)
O2A-H2A
O6A-H6A
O2′A-H2′A O6′C
O3′A-H3′A O2C
O6′A-H6′A O6C
O2B-H2B
O2B-H2B
O3B
O6B
1465
within
1565
1565
1475
1645
1645
within
within
1645
1645
within
1635
1635
1635
within
1.67
1.88
1.79
1.78
1.81
1.83
2.73b
1.77
1.75
2.60
1.94
1.76
2.16
2.77b
1.82
1.75
2.633(2)
2.816(2)
2.748(2)
2.725(2)
2.747(2)
2.740(2)
3.248(2)
2.692(2)
2.713(2)
3.069(2)
2.857(2)
2.710(2)
3.006(2)
3.633(2)
2.717(2)
2.715(2)
170
162
168
163
161
156
114
158
170
110
156
165
144
149
152
170
O1A
O2A
O2′B-H2′B O2′A
O3′B-H3′B O3′A
O6′B-H6′B O3A
O6′B-H6′B O6′A
O2C-H2C
O6′B
O2′C-H2′C O2A
O2′C-H2′C O3A
O3′C-H3′C O2A
O6′C-H6′C O2B
a ARU ) asymmetric residue unit. [ 1645 ] ) 1 + x, -1 + y, z; [
1545 ] ) x, -1 + y, z; [ 1635 ] ) 1 + x, -2 + y, z; [ 1565 ] ) x, 1 +
y, z; [ 1465 ] ) -1 + x, 1 + y, z; [ 1475 ] ) -1 + x, 2 + y, z. b This
distance exceeds the PLATON criterion.40
Table 4. C-H· · ·O Hydrogen Bonds
Figure 8. Hydrogen bonding and O6 orientation (gt, gg, or tg) in the three
molecules connected by hydrogen bonds in the (120) sheets, as well as S
(cyclohexane). Four C-H· · ·O hydrogen bonds are shown.
donor
acceptor
ARUa
H· · ·O (Å) C· · ·O (Å) C-H· · ·O (deg)
C2S-H22S
O3′B
within
2.60
2.46
2.40
2.44
2.47
2.43
2.58
2.53
2.43
2.48
2.42
2.56
2.50
2.59
3.435(4)
3.044(2)
2.968(4)
3.543(3)
3.532(3)
3.476(3)
3.583(3)
3.594(3)
3.506(2)
3.571(3)
3.059(3)
3.438(3)
3.473(3)
3.674(4)
132
112
110
178
162
159
151
162
165
170
170
136
147
170
C13A-H13A O3′A
C13C-H13C O3′C
C2A-H2AA O3C
C6A-H61A O6′C
C5′A-H5′A O1C
C6′A-H62A O4B
C2B-H2BB O3′C
C5′B-H5′B O4C
C2C-H2CC O3A
C5C-H5CC O4′B
C1’C-H1’C O6A
C2′C-H2”C O3B
C8C-H81C O4′A
intramolecular
intramolecular
1465
1565
1465
1565
1565
1565
1645
1545
1645
1545
1645
link, but its O6 is only 22° from the ideal gg orientation and
98° from the ideal tg orientation. The O6· · ·O2′ link based on
O6 gg has not been observed previously. O6B and O6C also
have secondary, three-centered hydrogen bonds to the inter-
residue glycosidic oxygen atom, O4. Only one hydroxyl
orientation remotely resembles the “clockwise” or “counter-
clockwise” hydrogen bonds favored for isolated-molecule
molecular modeling studies. On C, an approximately counter-
clockwise O3′-H donates to O2′, but O2′ is a double acceptor
and its hydrogen is involved in a three-centered, intermolecular
arrangement in the (210) sheet.
a See Table 3 for ARU definitions.
(120) Sheet O-H· · ·O Bonds. Although the glucose rings are
evenly spaced and their planes are well aligned with the (120)
plane (Figure 5), the intermolecular hydrogen bonding does not
link the molecules continuously. As shown in Figure 8, the sheet
segments in the (120) plane contain only three molecules, with
the A molecule in the center. Two donor hydroxyls in bonds
between B and A are on B, and A reciprocates with one.
Although O6′A and O6′B are linked together on the nonre-
ducing ends, the molecules are offset and O2A donates to O3B
and O2B donates to O1A as well as to O2A (a very weak,
bifurcated link). Both O-H· · ·O hydrogen bonds between A
and C have A atoms as donors.
(210) Sheet O-H· · ·O Bonds. Unlike the (120) sheet, all
molecules in the (210) sheet in Figure 9 are hydrogen-bonded
to their neighbors, continuously throughout the crystal. A novel
arrangement exists in this sheet, namely, that like atoms in A
and B are linked. Thus, O2′B donates to O2′A, O3′B donates
to O3′A, and O6′A donates to O6C. As in the (120) sheet, the
A and B molecules are turned toward each other. This is in
contrast to other known structures of cellulose and its analogs.
Therein, when there are adjacent parallel molecules within a
given sheet, the molecules are related by translational symmetry
and each has the same rotational orientation. Therefore, O6
atoms on one molecule can interact with O3 or O2 atoms on
adjacent molecules.
Table 5. O6 Orientations
residue
nominal ꢀ(O5-C5-C6-O6) (deg) ꢀ(C4-C5-C6-O6) (deg)
A (reducing)
A′ (nonreducing)
B (reducing)
B′ (nonreducing)
C (reducing)
C′ (nonreducing)
gg
gt
gg
gt
tg
gt
-63.3
66.7
-82.3
55.8
165.9
50.9
59.1
-174.1
37.6
174.6
-75.6
170.0
network. Thus, two of the extra-long hydrogen bonds are
included in the depiction of the networks in Figure 11 (below),
but the two network-combining bonds are not shown there. We
did not combine the networks, partly because that would depend
on the somewhat dubious long bonds, but also because it greatly
complicated the graphical depiction of already complicated
networks.
Intramolecular. As shown in Figures 8 and 9, all O5′ atoms
are acceptors for the O3 hydroxyl hydrogens, an arrangement
found in all cellulose forms so far and frequently in small
analogs. The O3-H is also donated to O6′ in a three-centered
or bifurcated arrangement. The liaison with O6′ is less frequently
discussed because of its longer length, 2.37 Å to 2.53 Å in 8,
but it appears to stabilize the O6′ atoms in the gt orientation.
The reducing-end O6 atoms, on the other hand, take either gg
or tg orientations. In our C molecule, O6 has a tg orientation
and donates its hydrogen to O2′, as in the minor disordered
schemes in cellulose I.1,2 The B molecule also has an O6 · · ·O2′
Because B and C are antiparallel, they can have reciprocal
heterogeneous pairings: O2B receives from O6′C and O2C
9
16686 J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008

Bonding Forces in a Crystalline Analog of Cellotetraose
A R T I C L E S
Figure 9. Four molecules of 8 in the (210) plane, in which all neighboring molecules are hydrogen bonded to each other. The second C molecule is shown
so that the B-C hydrogen bonds are included. The S and T molecules are not shown, nor are E and F. Intramolecular hydrogen bonds are repetitions from
Figure 7.
C-H· · ·O bonds, seven involve O3 or O3′ as acceptors, with
other acceptors being O4 and O4′ (four instances), O6 and O6′
(one each), and O1. In cellotetraose, only the glycosidic oxygen
atoms are acceptors for C-H donors. Besides C2 on S, C2 and
C2′ atoms donate four times, with others being C5′ (three
instances), C13 (twice), C1′, C6, C6′ and C8.
Networks. The finite networks are illustrated in Figure 11.
Network 1 consists of nine O-H· · ·O and four C-H· · ·O
hydrogen bonds that involve five different cellobiosyl residues.
Its intermolecular hydrogen bonds connect molecules in adjacent
[110] stacks. Network 2 connects six different cellobiose
residues and involves 17 different O-H· · ·O hydrogen bonds
and seven C-H· · ·O links. While Network 2 has a linear
component, it also has a large homodromic cycle consisting of
O6′B, O6′A, O6C, O2′C, O2A, and O3B which completes the
link to O6′B. Another homodromic cycle adds O3A to the O6′A,
O6C and O2′C atoms of the larger cycle (see also Figure 9).
Molecular Conformation. Ring Shapes. All 16 of the ring
structures have normal chair conformations, listed in Table 6.
The glucose rings have somewhat larger puckering amplitudes
(Q) than the cyclohexyl rings on average, and the values of θ,
the extent of deviation from a perfect chair form, are also larger.
Glycosidic Linkages and Geometries of Extrapolated Helices.
Figure 10. Ten intermolecular C-H· · ·O hydrogen bonds in the [110]
Geometries for the linkages between the various rings are given
in Table 7. Both heavy-atom and hydrogen-based definitions
are given for the same torsion angles. They are generally in
line with an assumption of tetrahedral geometry requiring that
φH ) φO5 + 120° and ψH ) ψC5 + 120°. The conformations
for the glucose-glucose linkages are quite similar to linkages
in cellulose itself and in some of the other small molecules
including dimethyl cellobioside. Figure 12 shows the linkage
geometries from 8 plotted on a conformational energy surface
for cellobiose.41 Energies were calculated for 181 different
combinations of exocyclic group orientations or some other,
smaller variations, using energy minimization with HF/6-31G(d)
electronic structure theory. Besides values of φ and ψ from 8,
stack; intramolecular hydrogen bonds are not shown, nor are hydrogen atoms
that are not involved in hydrogen bonds.
donates to O6′B. Between antiparallel C and A, O6′A donates
to O6C, and O2′C donates to both O2A and O3A (minor
component). The latter bond does not meet the PLATON H · · ·O
distance criterion but would complete a homodromic cycle.
O3′C also donates to O2A.
C-H· · ·O Hydrogen Bonds. Ten intermolecular C-H· · ·O
bonds are among molecules in the [110] stack, as shown in
Figure 10, and the other four are indicated in Figure 8. One
intermolecular bond in Figure 8 is from the S cyclohexyl solvent
molecule to the B molecule, and another links C6A to O6′C.
Two intramolecular bonds in Figure 8 involve the A and C
cyclohexyl groups on nonreducing ends. Considering all the
(41) French, A. D.; Johnson, G. P. Can. J. Chem. 2006, 84, 603–612.
9
J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008 16687

A R T I C L E S
Yoneda et al.
Figure 11. Hydrogen bond networks in 8. An intramolecular hydrogen bond from O3C to O4C (see Figures 8 and 9) that exceeds the distance criterion
would, given appropriate symmetry operations, connect these two networks. The same is true for a very weak bond between O2B and O2A. C-H· · ·O
hydrogen bonds are indicated by their green carbon atoms as well as the C atom labels.
Table 6. Puckering Parameters for the Rings
cellotetraose ) 9° × 1.414 /2 or about 6.4°, with the other
deviations being 0.6° to 3.6°. Distances for 8 are 1.4°, 9.4°,
and 3.3°, for A, B, and C. The linkages to the cyclohexyl rings
of 8 have a minimum deviation of 13.1° (CR in Figure 12) and
a maximum of 46.5° (BR). The two maximum deviations are
for the reducing-end linkages of the A and B molecules. They
can have less-negative values of ψC12 because of the lack of a
primary alcohol group on the cyclohexyl substituent. The
xylobiosyl moiety in crystalline O-(4-O-methyl-R-D-glucopy-
ranosyluronic acid)-(1f2)-O-ꢀ-D-xylopyranosyl-(1f4)-D-xy-
lopyranose trihydrate, which also lacks hydroxymethyl groups,
has a comparable conformation (-79.6°, -81.9°).42 Quantum
mechanical energy surfaces for the dimer of tetrahydropyran
show these two conformations within the 1 kcal/mol contour,
whereas the surface for an analogous dimer of 5-methyl
tetrahydropyran shows such conformations as having energies
of 2-4 kcal/mol, depending on the quantum method and
whether molecule A or B of the xylobiose is specified.43
The linkages at the nonreducing ends of the A and B
molecules (AN and BN in Figure 12) differ substantially from
inter-residue linkages in crystals of small analogs of cellulose.
They also correspond to slightly elevated energies on energy
maps for either cellobiose or the tetrahydropyran analogs
presumably because there is no exoanomeric effect to guide
the φ(C18-C13-O4′-C4′) torsion angle.
In the case of the nonreducing end of molecule C, the axial
linkage to the cyclohexyl group makes comparisons with
maltose geometry more appropriate. Because of the disorder of
the cyclohexyl group at this position, the coordinates may not
be well-determined, as indicated by the suspiciously high and
low values of the glycosidic bond angle, major component value
of 127°, minor component 98°. Their torsion angles are most
similar to the nonflipping linkages in permethylated γ-cyclode-
xtrin.44,45 No inter-residue hydrogen bonding is present in that
molecule.
ring label molecule
note
Φ (deg) θ (deg) Q (Å)
A
A′
B
B′
C
C′
glucosyl
glucosyl
glucosyl
glucosyl
glucosyl
glucosyl
reducing
nonreducing
reducing
nonreducing
reducing
nonreducing
49
50
312
338
2
2.6 0.583
6.8 0.602
10.1 0.592
3.3 0.598
6.9 0.573
11.6 0.606
51
average for glucose rings
6.9 0.592
a
A
A′
B
B′
C
C′
E
F
S
T
cyclohexyl C7A-C12A
cyclohexyl C13A-C18A
cyclohexyl C7B-C12B
cyclohexyl C13B-C18B, disordered
cyclohexyl C7C-C12C
cyclohexyl C13C-C18C, disordered, axial 140
cyclohexyl C13E-C18E, minor
cyclohexyl C13F-C18F, minor, axial
cyclohexyl C1S-C6S separate molecule
cyclohexyl C1T-C6T separate molecule
average for cyclohexanes
157
260
199
320
234
0.581
0.561
0.584
0.572
0.579
178.7
179.0
178.0
178.9
179.0
a
a
a
a
2.3 0.569
a
219
151
252
259
0.563
179.0
2.6 0.574
1.7 0.561
a
0.562
0.571
178.7
1.5
b
a Values for θ of 0° and 180° for cyclohexane are equivalent. The
reported values are from the PLATON software for the structure of 8.
b If θ was >90°, the value used for the average was 180° - θ.
Figure 12 also shows points for other cellulose analogs. The
A, B, and C conformations of the central cellobiose residues of
8 are intermingled with the conformations from cellotetraose
and methyl cellotrioside, close to the dashed diagonal line
representing approximate 2-fold screw-axis pseudo symmetry.
One way to utilize conformational information from small
molecules is to extrapolate from their linkage and residue
geometries to obtain the parameters for helical polymers.13 Helix
parameters for cellulose molecules from that procedure are given
in Table 8. The linkage in the B molecule corresponds to a
slightly right-handed (2.11 residues per turn) helix, while
linkages in the A and C molecules correspond to almost perfect
models of 2-fold screw axis symmetry in cellulose chains.
While the central cellobiose linkages have nearly 2-fold screw
symmetry, similar to those in cellotetraose, the conformations
of the linkages to the cyclohexyl groups deviate substantially
from pseudo 2-fold screw symmetry. The closeness to 2-fold
symmetry can be roughly estimated by first adding the φ and ψ
values for a given linkage and subtracting -240° (if defined
by O5′ and C5 atoms) or 0° (if H1′ and H4 are in the
definitions). The distance of any point to that line is the re-
mainder divided by 2 and multiplied times ꢀ2. Thus, the
distance in φ,ψ space for the most distorted linkage in
Bond Lengths. Table 9 shows the data for the backbone C-O
bonds from this reasonably high-quality determination. As
expected based on the anomeric effect, the C1-O1 bond lengths
(42) Moran, R. A.; Richards, G. F. Acta Crystallogr., Sect. B: Struct.
Crystallogr. Cryst. Chem. 1973, 29, 2770–2783.
(43) French, A. D.; Johnson, G. P. Cellulose 2004, 11, 449–462.
(44) Aree, T.; Uson, I.; Schulz, B.; Reck, G.; Hoier, H.; Sheldrick, G. M.;
Saenger, W. J. Am. Chem. Soc. 1999, 121, 3321–3327.
(45) French, A. D.; Johnson, G. P. Carbohydr. Res. 2007, 342, 1223–1237.
9
16688 J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008

Bonding Forces in a Crystalline Analog of Cellotetraose
A R T I C L E S
Table 7. Linkage Geometries (Major Components Only) (deg)
linkage
central
A
B
C
reducing end
A
B
C
φ (O5′-C1′-O4-C4)
-89.1
ψ (C5-C4-O4-C1′)
-152.9
φ (H1′-C1′-O4-C4)
ψ (H4-C4-O4-C1′)
τ (C1′-O4-C4)
115.2
116.1
115.5
τ (C1-O1-C7)
114.8
113.2
116.3
τ (C13-O4′-C4′)
116.7
113.6
127.4
31.3
-34.4
-101.7
-151.6
18.4
29.3
-32.7
-35.1
ψ (H7-C7-O1-C1)
34.4
28
-39.5
ψ (H4′-C4′-O4′-C13)
-35.8
-12.1
-59.3
-92.0
φ (O5-C1-O1-C7)
-92.5
-82.4
-101.6
-152.7
ψ (C12-C7-O1-C1)
-85.5
-91.8
-156.9
ψ (C5′-C4′-O4′-C13)
-154.6
φ (H1-C1-O1-C7)
27.2
36.9
19.3
nonreducing
φ (C18-C13-O4′-4′)
-132.7
φ (H13-C13-O4′-C4′)
A
B
C
-13.8
-30.1
-57.7a
-146.6
-131.9
-176.3
(C14-C13-O4′-C4′) 61.1a
a Axial linkage.
Table 9. C-O Lengths in Ring and Interring Bonds, C5-C6
Lengths (Å)
molecule
C5-O5
O5-C1
C1-O1(4)
O1(4)-C7
C5-C6
A (reducing)
1.4309 1.4193
1.3929
1.3958
1.3890
1.3975
1.3883
1.3918
1.3926
1.4494
1.4411
1.4396
1.4322
1.4432
1.4441
1.4416
1.5125
1.5119
1.5220
1.5100
1.5286
1.5206
1.5176
A′ (nonreducing) 1.4374 1.4275
B (reducing) 1.4338 1.4275
B′ (nonreducing) 1.4406 1.4217
C (reducing) 1.4362 1.4303
C′ (nonreducing) 1.4325 1.4348
average 1.4352 1.4269
a material that has a broad and fairly high melting point and
planar, nonpolar surfaces is as yet unknown. Our first response
was that it has a reverse amphipathic structure, with the polar
groups buried in the middle of the individual layers and with
nonpolar head groups. Unlike lipid bilayers, however, the layer
is spanned by complete molecules, depending on the nonbonded
forces only for cohesion in directions perpendicular to the
molecular long axes.
Figure 12. Partial HF/6-31G(d) energy surface for cellobiose with
experimental structures indicated by markers.40 Gray dots correspond to
other small analogs of cellulose such as lactose or cellobiose. The 14 ×
marks, many overlapped and hidden, correspond to linkages from methyl
cellotrioside28 and cellotetraose.19 Magenta [ with A, B, and C labels are
for the interglucose linkages in 8. The magenta + with AR, BR, and CR
represent linkages in 8 to the cyclohexyl groups on the reducing ends of A,
B, and C, respectively, and AN and BN are for linkages to the cyclohexyl
groups on the nonreducing ends. The axial-equatorial CN linkage is not
shown. The diagonal, dashed line shows the approximate location of
structures having 2-fold screw-axis pseudo symmetry, and the circular
dashed line is for 0.25 kcal/mol. Solid contour lines are at intervals of 1
kcal/mol. The contours are not necessarily relevant for the linkages to the
cyclohexyl groups.
One way to judge the relative degree of influence of the
hydrogen-bonding and nonpolar interactions is to examine which
aspects of cellulosic materials are retained and which are
fundamentally altered by the presence of the nonpolar cyclo-
hexyl moieties. The arrangement of the molecules in N-shaped
groups is a major indicator of the influence of the nonpolar
groups on the structure. The four corners of the N correspond
to stacks of cyclohexyl rings from alternating sources. Relative
to the mutually antiparallel, flanking C and B molecules, the A
molecule is inclined so that its reducing end cyclohexanes can
stack with the cyclohexanes of B, and A’s nonreducing end
cyclohexane can stack with the reducing end cyclohexane of
C. These molecules have found it advantageous to pack with
all three of the reducing end cyclohexanes interacting with each
other, while two of the three nonreducing end groups are instead
stacked with solvent. This leads to the unusual “down-down-
up” molecular orientation.
Table 8. O1-O4 Distances and Extrapolated Helix Geometries
O1-O4
distance (Å) (residues/turn) (rise/residue) (Å) (based on O4 atoms) (Å)
n
h
helix radius
residue
A (reducing)
5.474
2.02
-2.01
2.11
2.11
2.02
5.15
5.11
5.18
5.18
5.16
5.11
0.93
0.95
0.86
0.89
0.91
0.94
A′ (nonreducing) 5.454
B (reducing) 5.454
B′ (nonreducing) 5.468
C (reducing) 5.474
C′ (nonreducing) 5.440
2.02
Despite the presence of the nonpolar groups, there is no major
loss of hydrogen bonding compared to other carbohydrates.
Besides the 28 conventional O-H· · ·O hydrogen bonds, 14
C-H· · ·O attractions were identified. However, some of the
intermolecular hydrogen bonds are different from those seen
before, with a good example being the O3′B· · ·O3′A, O2′B· · ·
O2′A, and O6A · · ·O6B interactions. Also, a novel intramo-
lecular link was identified between a gg O6 and O2′, as well as
the first sighting of a tg O6 in a cellulose analog.
are considerably shorter than the other C-O bonds in this
sequence. The O5-C1 bonds are just a little shorter on average
than the C5-O5 and aglycon distances. We also have included
the C5-C6 bond lengths that are somewhat shorter, on average,
than other C-C distances in 8 or the cyclohexanes.
Conclusions
The synthetic addition of nonpolar cyclohexyl groups to
cellobiose resulted in a crystallizable compound that has
numerous unusual features. Whether there is a practical use for
Some of the normal features of cellulose and its analogs were
preserved. We found the retention of the slightly altered quarter
stagger to be most remarkable, stabilized by 10 of the C-H· · ·O
9
J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008 16689

A R T I C L E S
Yoneda et al.
Janaswamy for helpful input on up-up-down structures. Dr. Paul
Langan and Professor Ed Stevens offered comments at an early
point in this study. Comments on a near-final draft were received
from Professors Don Kiely and Charles Lake. This work was
supported by the Austrian Science Fund (FWF, P-17426) and by
normal research funding from the Agricultural Research Service,
U.S. Department of Agriculture.
hydrogen bonds. The often-found, 2-fold screw-axis pseudo
symmetry was also present, along with the O3 · · ·O5′ and · · ·O6′
hydrogen bonds. The ability to accommodate both the cyclo-
hexane packing and a general organization of the carbohydrate
in an array that is similar in broad detail to cellulose II was
also remarkable.
The replacement of the two terminal glucose groups of
cellotetraose with cyclohexane resulted in a molecule that had
a core very much like the disaccharide core of cellotetraose,
but the outer linkages were very different in their geometries
from those of cellotetraose.
Supporting Information Available: Crystallographic data of
8 in CIF format; Figures S1 and S2 showing the disorder and
1
cyclohexane packing, respectively; H and 13C NMR spectra
The crystallographic data have been deposited with the
Cambridge Crystallographic Data Centre, CCDC Nos. 707928
and 707929.
of 8 in solution included as Figure S3. This material is available
free of charge via the Internet at http://pubs.acs.org.
Acknowledgment. The authors thank Professor Henri Chanzy,
and Professor Rengaswami Chandrasekaran and Dr. Srinivas
JA805147T
9
16690 J. AM. CHEM. SOC. VOL. 130, NO. 49, 2008