Carbohydrate Research 338 (2003) 439–446
`
`www.elsevier.com/locate/carres
`
`Crystal structure of b-cyclodextrin–benzoic acid inclusion complex
`Thammarat Aree,a,* Narongsak Chaichitb
`aDepartment of Chemistry, Faculty of Science, Chulalongkorn Uni6ersity, Phyathai Road, Pathumwan, Bangkok 10330, Thailand
`bDepartment of Physics, Faculty of Science and Technology, Thammasat Uni6ersity, Rangsit, Pathum Thani 12121, Thailand
`
`Received 20 August 2002; accepted 27 October 2002
`
`Abstract
`
`The inclusion complex of b-cyclodextrin (b-CD) with benzoic acid (BA) has been characterized crystallographically. Two b-CDs
`cocrystallize with two BAs, 0.7 ethanol and 20.65 water molecules [2(C6H10O5)7·2(C7H6O2)·0.7(C2H6O)·20.65H2O] in the triclinic
`space group P1 with unit cell constants: a=15.210(1), b=15.678(1), c=15.687(1) A, , h=89.13(1), i=74.64(1), k=76.40(1)°.
`The anisotropic refinement of 1840 atomic parameters against 16,201 X-ray diffraction data converged at R=0.078. In the crystal
`lattice, b-CD forms dimers stabilized by direct O-2(m)–1/O-3(m)–1···O-2(n)–2/O-3(n)–2 hydrogen bonds (intradimer) and by
`indirect O-6(m)–1···O-6(n)–2 hydrogen bonds with one or two bridging water molecules joined in between (interdimer). These
`dimers are stacked like coins in a roll constructing endless channels where the guest molecules are included. The BA molecules
`protrude with their COOH groups at the b-CD O-6-sides and are maintained in positions by hydrogen bonding to the surrounding
`O-6 H groups and water molecules. Water molecules (20.65) are distributed over 30 positions in the interstices between b-CD
`molecules, except the water sites W-1, W-2 that are located in the channel of the b-CD dimer. Water site W-2 is hydrogen bonded
`to the disordered ethanol molecule (occupancy 0.7). © 2003 Elsevier Science Ltd. All rights reserved.
`
`Keywords: b-Cyclodextrin; Benzoic acid inclusion complexes; Crystal structures; X-ray analysis; Hydrogen bond
`
`Benzoic acid (BA) has been proven to form inclusion
`complexes with both a-CD and b-CD.5 – 8 Various tech-
`niques have been employed to investigate the com-
`plexes, e.g., in solution by NMR,5 by potentiometric
`titration;6 in the gas phase by FAB mass spectroscopy,7
`by theoretical calculations.8 The results predicted that
`the host–guest stoichiometry is 1:1, the BA aromatic
`
`1. Introduction
`
`b-Cyclodextrin (b-CD) is a macrocyclic oligosaccharide
`consisting of seven D-glucose units linked by a-(1“4)
`glycosidic bonds.1 It has the shape of a truncated cone
`and is amphiphilic with apolar cavity coated by C H
`groups and O-4, O-5 atoms, and hydrophilic rims with
`O-6 H groups on the narrower side, and O-2 H, O-
`3 H groups on the wider side (Fig. 1).
`CDs are well known for their ability to form inclu-
`sion complexes2 with various types of guest molecules
`fitting partially or completely into the host CD cavity
`as shown by crystallographic results.3 Such beneficial
`property of CDs has been applied in many industries,
`e.g., foods, pharmaceutics, agriculture.4 However, in-
`clusion geometry and stoichiometry of the complexes
`are different from guest to guest. Therefore, a general
`direction for predicting the authentic CD inclusion
`complexes is not accessible.
`
`* Corresponding author. Tel.: +66-2-2187584; fax: +66-
`2-2541309
`E-mail address: mam@atc.atccu.chula.ac.th (T. Aree).
`
`Fig. 1. Chemical structures and atomic numbering of b-CD
`and BA.
`
`0008-6215/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
`PII: S 0 0 0 8 - 6 2 1 5 ( 0 2 ) 0 0 4 8 5 - 8
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`
`Table 1
`crystallographic
`of
`Summary
`0.7C2H5OH·20.65H2O
`
`data
`
`for
`
`2b-CD·2BA·
`
`Chemical formula
`
`20
`… scans with 0.3° steps
`1.35–30.50
`−215h50, −225k519,
`−215l522
`0.7
`25,704
`16,201 [Rint=0.037]
`10,022
`
`2(C6H10O5)7·2(C7H6O2)·
`0.7(C2H6O)·20.65H2O
`2917.6
`Chemical formula weight
`rod, colorless
`Crystal habit, color
`Crystal size (mm3)
`0.5×0.6×0.7
`triclinic
`Crystal system
`P1
`Space group
`a (A, )
`15.210(1)
`b (A, )
`15.678(1)
`c (A, )
`15.687(1)
`89.13(1)
`h (°)
`74.64(1)
`i (°)
`76.40(1)
`k (°)
`V (A, 3)
`3501.4(1)
`1
`Z
`Dcalcd (g cm−3)
`1.364
`v (mm−1)
`0.12
`1515
`F(000)
`SMART CCD (Bruker)
`Diffractometer
`Radiation type, wavelength Mo Ka, 0.71073
`(A, )
`Temperature (°C)
`Data collection method
`q Range (°)
`Index ranges
`Resolution (A, )
`Reflections measured
`Independent reflections
`Reflections observed
`[I\2|(I)]
`Structure solution
`
`Molecular replacement
`(PATSEE)
`blocked-matrix least-squares
`on F 2
`2)+(0.0963P)2
`w=[S 2(F o
`+2.2578P]−1, where
`2)/3P=(F o2+2F c
`
`
`16,201/1840
`R a=0.078, wR b=0.177
`R a=0.134, wR b=0.216
`1.031
`0.52/−0.30
`
`Refinement method
`
`Weighting scheme
`
`Data/parameters
`R [F 2\2|(F 2)]
`R (all data)
`Goodness-of-fit
`Highest peak/deepest hole
`(e A, −3)
`a R=

Fo

−

Fc

/

Fo

.
`
`2)2/ w(F ob wR= {w(F o2−F c
`2)2}1/2.
`
`
`ring is parallel to the CD molecular axis and the
`COOH group points toward the narrower rim of the
`cone. A detailed structure of the inclusion complex is
`not yet reported so far. In this paper, we present insight
`into the three-dimensional structure of b-CD–BA in-
`clusion complex by means of X-ray crystallography.
`
`2. Experimental
`
`2.1. Crystallization and X-ray diffraction
`
`b-CD purchased from Cyclolab (Budapest/Hungary),
`BA and EtOH from Merck were used as received.
`b-CD (0.05 mol) and BA (0.10 mol) were dissolved in 2
`mL of 50:50 (% v/v) water–EtOH at room temperature
`(rt). The solution was warmed to 60 °C for 1 h and
`cooled down slowly. Rodlike, colorless crystals formed
`in 1 week by slow solvent evaporation.
`A single crystal of b-CD–BA complex with dimen-
`sions 0.4×0.5×0.7 mm3 was mounted in a glass capil-
`lary sealed at both ends with a trace of mother liquor.
`X-ray data collection was performed at rt using a
`SMART CCD diffractometer (Bruker) with Mo Ka
`radiation (u=0.71073 A, ) operating at 50 kV, 30 mA. A
`total of 25,704 reflections were measured in q range of
`1.35–30.50° (0.7 A, resolution). Data were corrected for
`Lorentz, polarization, and absorption effects and
`merged by SADABS9 and SHELXTL10 to yield 16,201
`unique reflections. The crystal belongs to triclinic space
`group P1 (for more details, see Table 1).
`
`2.2. Structure determination and refinement
`
`The crystal structure was determined by molecular re-
`placement with program PATSEE11 using the structure of
`b-CD–7-hydroxy-4-methylcoumarin complex12 as a
`phasing model (only the b-CD backbone was used for
`the calculations, O-6 atoms were omitted). b-CD O-6
`atoms, water oxygen atoms, BA, and EtOH molecules
`could be located by difference Fourier electron density
`maps aided by the graphic program XTALVIEW.13 All
`c
`O-6 atoms of the two b-CD molecules are fully occu-
`pied, except for O-66 of b-CD
`1 that is doubly
`disordered. Two BA molecules are found fully occupied
`within the b-CD cavities. Ethanol (occupancy 0.7) was
`the b-CD dimer. Water
`located in the channel of
`molecules (20.65) were distributed over 30 sites, located
`b-CD
`preferentially
`in
`the
`interstices
`between
`molecules. All hydrogen atoms were placed at theoreti-
`cal positions according to the ‘riding model’.14 The
`structure was refined by blocked-matrix least-squares
`on F 2 with program SHELXL-97.14 Anisotropic refine-
`ment of 1840 atomic parameters against 16,201 data
`with F 2\2|(F 2) converged at R=0.078 (except for
`EtOH that was refined isotropically). All atoms show
`normal thermal motion with Ueq in the range 0.03–0.14
`A, 2, except for EtOH and most water molecules that
`have higher Ueq, 0.10–0.31 A, 2 (see the thermal ellipsoid
`plots in Fig. 2).
`A summary of crystallographic data and the geomet-
`rical parameters for the b-CD–BA inclusion complex
`are given in Tables 1 and 2, respectively. The final
`fractional atomic coordinates and equivalent isotropic
`
`Page 2 of 8
`
`

`
`T. Aree, N. Chaichit /Carbohydrate Research 338 (2003) 439–446
`
`441
`
`thermal displacement factors are given as supplemen-
`tary material.
`The atomic numbering scheme is that used conven-
`tionally for carbohydrates, i.e., the first number denotes
`
`c
`c
`c
`c
`1 (thin line) on b-CD
`Fig. 3. Superposition of b-CD
`2
`(thick line). BA
`1 and
`2 shown with white and black
`ball-and-stick, respectively (small balls are C and bigger O).
`Top view on the left and side view on the right.
`
`the position in the glucose and the second number the
`glucose number in the CD macrocycle. Additionally,
`c
`extra numbers 1 and 2 are used to indicate the b-CD
`c
`c
`molecules
`1 and 2, respectively. For example C-32–1
`2 ofb-CD molecule
`denotes C-3 of glucose unit
`1
`(see Fig. 1). The letters A, B indicate disordered atoms.
`For the guest molecules, similar atomic numbering is
`adopted and the letter Z indicates
`the two BA
`c
`molecules, e.g., C-4Z–2 stands for C-4 of BA molecule
`2 (see Fig. 1).
`
`3. Results and discussion
`
`3.1. Structural description of b-CD macrocycles
`
`The asymmetric unit consists of two b-CDs, two BAs,
`0.7 ethanol, and 20.65 water molecules. The two b-CD
`molecules are almost identical as indicated by small rms
`deviation of superposition 0.13 A,
`(O-6 and H-atoms
`were excluded from the calculations), see Fig. 3. All
`glucose residues adopt a slightly distorted 4C1 chair
`conformation as shown by the Cremer–Pople pucker-
`ing parameters, Q and q 15 in the range 0.54–0.58 A, ,
`3–10°, respectively, Table 2. The orientation of the
`glucose about the O-4 glycosidic bond is described by
`the torsion angles „, ƒ in the ranges 108.7–128.1°,
`119.1–132.1°, showing that all glucoses are oriented syn
`(i.e., all O-2 H, O-3 H groups are on the same side of
`the cone), Table 2. This can be seen also by the narrow
`span of tilt angle 1.9–12.6°. The annular shape of b-CD
`is stabilized by intramolecular, interglucose O-3(n)···O-
`2(n+1) hydrogen bonds with O···O distances 2.69–
`2.85 A, . In addition, the O-4(n+1) O-4(n) O-4(n−1)
`angles 124.8–132.2° and the small deviations of O-4
`atoms from their common least-squares plane (B0.11
`A, ) are evidences for the well defined heptagon formed
`by the lines connecting the O-4 atoms in the b-CD
`macrocycles.
`The orientation of the C-6 O-6 bond is described by
`torsion angles C-4 C-5 C-6 O-6 and O-5 C-5 C-6 O-6
`
`2b-CD·2BA·
`2. ORTEP-III22
`Fig.
`the
`stereo plot of
`0.7C2H5OH·20.65H2O inclusion complex drawn with thermal
`ellipsoid (30%) representation. Ellipsoids with and without
`octant shading are OCD, OW and CCD, respectively; b-CD
`bonds are represented by white sticks and BA bonds black
`sticks. Dashed lines indicate possible O H···O hydrogen
`bonds with O···O separation within 3.5 A, .
`
`Page 3 of 8
`
`

`
`iBoldnumbersarethevaluesofb-CD
`hValuesfortwofolddisorderedO-66–1withtheoccupancyfactors0.5forbothsitesAandB.
`gIntradimerichydrogenbondsbetweenO-2,O-3ofglucoseunitn(b-CD
`fDeviationofO-4atomsfromtheleast-squaresplanethroughthesevenO-4atoms.
`eAngleateachglycosidicO-4:O-4(n+1) O-4(n) O-4(n−1).
`dTiltangles,definedastheanglesbetweentheO-4planeandtheplanesthroughC-1(n),C-4(n),O-4(n)andO-4(n−1).
`cTorsionanglesƒand„atglycosidicO-4,definedasO-5(n) C-1(n) O-4(n−1) C-4(n−1)andC-1(n) O-4(n−1) C-4(n−1) C-3(n−1),respectively.
`bIndicatesthedeviationfromthetheoreticalchairconformation(idealvalue:q=0).
`aCremer–Poplepuckeringamplitude.15
`
`2).
`
`c
`
`1)andofglucoseunitm(b-CD
`
`c
`
`2.
`
`c
`
`442
`
`T. Aree, N. Chaichit /Carbohydrate Research 338 (2003) 439–446
`
`−65.1(8)
`
`−66.0(8)
`56.1(8)
`54.8(9)
`
`−65.5(7)
`−69.8(11)h
`59.0(10)h,
`57.9(8)
`179.0(8)h,50.3(12)h
`
`−62.8(9)
`
`−65.2(7)
`61.7(10)
`56.5(8)
`
`3.02(1)
`
`3.11(1)
`
`2.85(1)
`
`3.11(1)
`2.82(1)
`2.69(1)
`−0.06
`0.09
`
`3.05(1)
`
`3.08(1)
`
`2.89(1)
`
`3.11(1)
`2.70(1)
`2.76(1)
`0.06
`−0.01
`
`2.96(1)
`
`2.96(1)
`
`2.79(1)
`
`3.00(1)
`2.73(1)
`2.82(1)
`−0.01
`−0.03
`
`−61.6(7)
`
`−67.7(8)
`57.3(8)
`54.0(8)
`
`3.11(1)
`
`3.04(1)
`
`2.81(1)
`
`3.05(1)
`2.76(1)
`2.84(1)
`−0.01
`0.01
`
`−67.3(9)
`
`−69.4(8)
`55.3(10)
`50.5(10)
`
`3.11(1)
`
`3.27(1)
`
`2.88(1)
`
`2.99(1)
`2.79(1)
`2.79(1)
`−0.01
`−0.01
`
`−60.0(7)
`
`−71.3(9)
`61.2(7)
`50.3(9)
`
`3.31(1)
`
`3.42(1)
`
`3.10(1)
`
`3.15(1)
`2.83(1)
`2.85(1)
`0.03
`0.06
`
`130.3(1)
`130.2(1)
`3.6(3)
`6.4(2)
`122.6(6),123.4(6)
`115.6(6),123.8(6)
`0.57,9
`0.57,5
`
`125.6(1)
`130.9(1)
`1.9(1)
`9.9(2)
`116.7(6),119.1(7)
`112.8(6),127.6(6)
`0.55,8
`0.57,4
`
`127.8(1)
`126.6(1)
`6.9(2)
`10.0(1)
`115.2(7),126.2(7)
`108.7(6),127.8(6)
`0.54,4
`0.55,3
`
`132.4(1)
`126.3(1)
`6.7(2)
`12.6(3)
`113.2(6),125.4(6)
`113.2(6),128.3(6)
`0.58,3
`0.57,4
`
`127.0(1)
`132.2(1)
`8.9(1)
`10.9(5)
`113.4(6),129.4(6)
`112.2(7),132.1(7)
`0.57,8
`0.57,4
`
`126.3(1)
`128.5(2)
`10.1(3)
`5.8(5)
`116.0(6),129.3(6)
`128.1(7),126.1(8)
`0.58,7
`0.56,6
`
`130.5(1)
`124.8(2)
`7.2(4)
`3.7(2)
`115.8(6),131.2(6)
`112.4(7),119.5(7)
`0.55,4i
`0.58,10
`
`7
`
`6
`
`5
`
`4
`
`3
`
`2
`
`1
`
`O-4anglee
`
`Tiltangled
`
`ƒc,„c
`
`Qa,qb
`
`Residue
`
`Geometricalparametersof2b-CD·2BA·0.7C2H5OH·20.65H2O(distancesinA,andanglesin°)
`Table2
`
`−62.9(7)
`
`−61.9(8)
`57.6(8)
`61.0(9)
`
`2.90(1)
`
`3.16(1)
`
`3.12(1)
`
`O-5 C-5 C-6 O-6
`
`C-4 C-5 C-6 O-6
`Torsionangle
`
`O-2(n)–1···O-
`
`O-2(n)–1···O-
`
`3(m)–2g
`
`2(m)–2g
`
`3(m)–2g
`
`O-3(n)–l···O-
`
`2(m)–2g
`
`2.94(1)
`2.77(1)
`O-3(n)···O-2(n+1)2.76(1)
`
`O-3(n)–1···O-
`
`0.01
`−0.11
`
`O-4deviationf
`Distances
`
`Page 4 of 8
`
`

`
`T. Aree, N. Chaichit /Carbohydrate Research 338 (2003) 439–446
`
`443
`
`in Table 2. All C-6 O-6 bonds are directed ‘away’ from
`the b-CD cavities and are hydrogen bonded with neigh-
`boring water sites and O-6 H groups (Figs. 3, 5 and 6),
`as shown by torsion angles C-4 C-5 C-6 O-6 and O-
`5 C-5 C-6 O-6 in the ranges 50.3–61.7° and −60.0 to
`−71.3°, respectively (Table 2). Except for O-66A–1
`that points ‘toward’ the cavity and hydrogen bonds to
`water sites W-9, W-21, W-23 and O-2Z–1, Fig. 6. The
`corresponding torsion angles are 179.0 and 59.0°, Table
`2.
`
`Two b-CD molecules form a dimer where their O-
`2 H, O-3 H groups are engaged in intermolecular O-
`hydrogen
`2(n)–1/O-3(n)–1···O-2(m)–2/O-3(m)–2
`bonds with O···O distances 2.79–3.16 A, , except O22–
`1···O26–2 (3.42 A, ), O-22–1···O-35–2 (3.31 A, ), and
`O-23–1···O-25–2 (3.27 A, ), Table 2. Such feature has
`been observed frequently in crystal structures of b-CD.3
`Since the X-ray data at room temperature of
`the
`present structure did not permit the H-atom positions
`to be determined, the detailed hydrogen bonding in the
`b-CD dimer could not be obtained. However, the recent
`study of b-CD–1,12-dodecanedioic acid inclusion com-
`plex using synchrotron high-resolution data (0.65 A, ) at
`100 K16 allowed the accurate location of H-atoms of
`
`the b-CD O H groups to be verified. The results
`showed that only O-3 H groups of a b-CD monomer
`are involved in the intermolecular hydrogen bonds at
`the O-2-, O-3-sides of the b-CD dimer.
`
`3.2. Inclusion geometry of BA molecules
`
`Fig. 4 shows that both BA molecules are placed in the
`central cavities of b-CD molecules. The two aromatic
`ring centers of BA are shifted from the O-4-plane
`centers to the O-6-sides of b-CD by approx 1.0 A,
`(distance d), see Figs. 2 and 3. The two aromatic ring
`planes are inclined 52° with respect to the O-4 plane
`(angle ~) and make an angle of 13° with respect to each
`other. The BA molecules protrude with their COOH
`groups at the b-CD O-6-sides and are maintained in
`positions by hydrogen bonding to the surrounding O-
`6 H groups and water molecules, Figs. 2–4. They are
`almost in the same environment as their COOH groups
`are coordinated via six O H···O hydrogen bonds (O···O
`distances 2.58–3.35 A, ), except for O-2Z–1 that is addi-
`tionally hydrogen bonded to O-66A–1, Fig. 4. The
`inclusion geometry of BA in the present structure
`agrees with those proposed by previous studies5,8 as the
`
`Fig. 4. Schematic presentation of the inclusion geometry of the BA molecules in the b-CD cavities. Aromatic rings of the two BA
`molecules are represented with gray hexagons. d defined as the center-to-center distance of the BA aromatic ring to b-CD O-4
`plane. Angle ~ showing inclination of the BA molecular axis (dotted line) with respect to the glycosidic O-4 plane (double line).
`Filled circles indicate oxygen atoms and dashed lines intermolecular O H···O hydrogen bonds. Dashed lines linked between the
`b-CD monomer show O-2(m)–1/O-3(m)–1···O-2(n)–2/O-3(n)–2 hydrogen bonds in the b-CD dimer. Connection of water sites
`W-1, W-2, and ethanol molecule is depicted in the framed area. Symmetry operations: (i) x, y, z−1; (ii) x+1, y, z−1; (iii)
`x+1, y−1, z−1; (iv) x, y, z+1; (v) x−1, y, z+1.
`
`Page 5 of 8
`
`

`
`444
`
`T. Aree, N. Chaichit /Carbohydrate Research 338 (2003) 439–446
`
`and 5. Water site W-1 is too close to the ethanol OH
`group (1.97 A, ) and water site W-2 (1.82 A, ), i.e., they
`are not in hydrogen bonding distance indicating that
`water site W-1 cannot be occupied simultaneously with
`water site W-2 and ethanol (their occupancies sum up
`to one). The W-2 ethanol distance 2.40 A, accounts for
`hydrogen bond interaction showing that water site W-2
`and ethanol may coexist (Fig. 4). In addition, short
`interatomic distances among water sites W-9 W-10
`(1.22 A, ), W-14 W-15 (1.63 A, ), W-24 W-26 (1.57–1.74
`A, ), and W-27 W-29 (1.07–1.64 A, ) suggest that the
`water sites in each cluster are not coexistent. Water
`sites play an important role in stabilizing the crystal
`structure as they contribute to hydrogen bonding as
`bridges, e.g., at O-2-, O-3-side: O-21–1···W-19···O-36–
`2, O-22–1···W-16···O-35–2, O-32–1···W-26···O-25–2,
`O-23–1···W-3···O-25–2;
`at O-6-side: O-61–1···W-
`18···O66–2,
`O-61–1···W-7···O-64–2,
`O-62–1···W-
`11···W-23···O-62–2, O-65–1···W-21···O-65–2, O-66A–
`1···W-9···O-65–2 (Fig. 6). The hydrogen-bonding net-
`work in the present structure is complicated since there
`are many partially occupied water sites (Fig. 6).
`
`3.4. Crystal packing
`
`The b-CD molecules are stacked along the crystallo-
`graphic c-axis, in the alternative head-to-head and tail-
`to-tail channel mode20 as frequently observed in the
`c
`b-CD crystal structures3 (Fig. 5). The glycosidic O-4
`planes of the b-CD
`1, 2 are almost parallel. They are
`slightly inclined approx 11.1, 9.8° to the ab-plane, and
`c
`c
`make an angle of 2.8° with respect to each other. The
`distance from O-4-plane center of b-CD
`1 to
`2 is
`7.17 A, . Both O-4-plane centers are not lined vertically
`but are shifted 2.89 and 1.33 A,
`in a- and b-directions,
`respectively. The molecular arrangement is stabilized at
`one end of b-CD (in the same column) by intermolecu-
`lar O-2(m)–1/O-3(m)–1···O-2(n)–2/O-3(n)–2 hydrogen
`bonds (O···O distances 2.79–3.42 A, ), Figs. 2 and 5,
`Table 2. At the other end, the O-6 H groups are not
`directly hydrogen bonded to the O-6 H groups of
`adjacent b-CD but linked by one or two bridging water
`molecules, e.g., O-61–1···W-18···O-66–2, O-62–1···W-
`11···W-23···O-62–2, O-65–1···W-21···W-7···O-64–2. In
`addition, a number of OCD···OCD, OCD···OW···OCD,
`OCD···OW···OW···OCD hydrogen bonds found between
`neighboring b-CD columns contribute to the stability
`of the crystal structure (Figs. 5 and 6).
`In comparison with the complexes of BA derivatives,
`the complex of 4-t-butylbenzoic acid17 and of 3,5-
`dimethylbenzoic acid18 show similar packing patterns as
`the present crystal structure. This contrasts with the
`complex of acetylsalicylic acid–salicylic acid19 in which
`b-CD dimers are stacked in layers like bricks in a wall.
`After the b-CD–BA inclusion complex has been
`characterized both in solution and gas phase by various
`
`the 2b-CD·2BA·0.7C2H5OH·
`Fig. 5. Crystal packing of
`20.65H2O inclusion complex in channel mode that is stabi-
`lized by O-2(m)–1/O-3(m)–1···O-2(n)–2/O-3(n)–2 (tail-to-
`c
`c
`tail), O-6(m)–1···OW···O-6(n)–2 (head-to-head) hydrogen
`bonds (dashed lines) between b-CD
`1 and
`2. O-2CD,
`O-3CD, O-6CD and OW. are represented with gray and black
`spheres, respectively. The BA molecules are black and H-
`atoms not shown. Drawn with program MOLSCRIPT.23
`
`BA COOH group is directed to the narrower rim of the
`cone.
`It is worth comparing the present structure with the
`b-CD complexes with BA derivatives crystallized in the
`triclinic space group P1.17 – 19 Although the host b-CD
`molecules have the same dimeric structures as found in
`the present structure, the inclusion geometries are dif-
`ferent. In the complex of 4-t-butylbenzoic acid,17 the
`host–guest ratio is 2:2 and the two guest molecules are
`in different environments in the b-CD cavities. The
`aromatic ring of one guest molecule is included in the
`b-CD cavity while that of the other one is in the
`channel of the b-CD dimer. In the complex of 3,5-
`dimethylbenzoic acid,18 the guest molecules are exten-
`sively disordered. For the guest sites in the b-CD
`cavities, their COOH groups point to the O-2-, O-3-side
`while some are in the channel of the b-CD dimer. In the
`complex of acetylsalicylic acid–salicylic acid,19 the aro-
`matic rings of two acetylsalicylic acid molecules are
`embedded in each b-CD cavity and the salicylic acid is
`in the channel of the b-CD dimer.
`
`3.3. Disordered water molecules
`
`Water molecules (20.65) are distributed over 30 posi-
`tions (W-3 W-7, W-12, W-18 W-20, W-22, W-23, W-
`30 are fully occupied while the others have occupancies
`in the ranges 0.25–0.75)
`in the interstices between
`b-CD macrocycles, except for the water sites W-1, W-2
`that are in the channel of the b-CD dimer, Figs. 2, 4
`
`Page 6 of 8
`
`

`
`T. Aree, N. Chaichit /Carbohydrate Research 338 (2003) 439–446
`
`445
`
`Fig. 6. O H···O hydrogen bonds (dashed lines) in the 2b-CD·2BA·0.7C2H5OH·20.65H2O inclusion complex with O···O distance
`within 3.5 A, . Underlined atomic names indicate atoms in the general position x, y, z; the others are in symmetry related positions.
`Arrows show connection of glucose units in b-CD.
`
`techniques since 25 years ago,21 its structural evidence
`in crystalline state is finally reported in the present
`paper. The previous results forecasted a 1:1 host–guest
`stoichiometry and orientation of BA with its aromatic
`ring parallel to the CD molecular axis and the COOH
`group points to the CD O-6-side. This agrees well with
`the crystallographic results. However, X-ray analysis
`reveals deeper details of BA inclusion geometry. The
`stoichiometry is 2:2 and the BA aromatic ring is in fact,
`not parallel but slanted to the b-CD molecular axis. BA
`is maintained in position by hydrogen bonds to the
`surrounding O-6 H groups and water molecules.
`The present finding is not consistent with the inclu-
`sion complexes of b-CD with other BA derivatives both
`in terms of stoichiometry and inclusion geometry as
`mentioned above. Since the functional groups attached
`to the aromatic ring have different hydrogen bonding
`donor/acceptor functionality and bulkiness, they are
`oriented differently in the b-CD cavity to be energeti-
`cally stable. Therefore, a general direction for predict-
`ing the authentic CD inclusion complexes
`is not
`possible and these complexes needed to be investigated
`case by case.
`
`Supplementary material
`
`Crystallographic data (excluding structure factors)
`
`have been deposited with the Cambridge Crystallo-
`graphic Data Center as supplementary publication No.
`CSD-191347. These data can be obtained free of charge
`via www.ccdc.cam.ac.uk/conts/retrieving.html or from
`The Director, CCDC, 12 Union Road, Cambridge,
`CB2 1EZ, UK (Tel.: +44-1223-336-408; fax: +44-
`1223-336-033; e-mail: deposit@ccdc.cam.ac.uk).
`
`Acknowledgements
`
`This work was supported by grants for development
`of new faculty staff of Chulalongkorn University and
`by the Thailand Research Fund. We thank the Aus-
`trian-Thai Center (ATC) for Computer-Assisted Chem-
`ical Education and Research, in Bangkok for providing
`computer time in data analysis.
`
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