topography of cyclodextrin inclusion complexes : part i. classification of crystallographic data of...
TRANSCRIPT
Carbohydrate Research, 31 (1973) 37-46Q Elsevier Scientific Publishing Company, Amsterdam - Printed in Belgium
TOPOGRAPHY OF CYCLODEXTRIN INCLUSION COMPLEXESPART I CLASSIFICATION OF CRYSTALLOGRAPHIC DATA OFa-CYCLODEXTRIN INCLUSION COMPLEXES
R K MCMULLAN x, W SAENOER*`, J FAYOSt, AND D MoorzttAbtetlung Rdntgenstrukturanalyse, Gesellschafr fitr Molekutarbiologische Forschung mbH3301 Stockhew, itber Braunschweig (Deutschland)
(Received March 12th, 1973, accepted for publication, May 4th, 1973)
ABSTRACT
The crystallographic and stoichiometnc data obtained for 17 different inclusioncomplexes of a-cyclodextnn are reported The cell dimensions and space-groupsymmetries reflect the packing arrangement of the torus-shaped host molecules andare largely determined by the size and ionic character of the guest molecules
In the series acetic acid, propionic acid, butyric acid, valene acid, the firstthree complexes with a-cyclodextrm crystallize in a cage-type structure with spacegroup P2,2,2,, which is characteristic for small, non-ionic guest molecules Thevalerlc acid molecule seems to be too long to be accommodated in a cage structure,thus, the a-cyclodextrm molecules are arranged such that a structure consisting ofparallel channels is formed This packirg is typical for the inclusion of long, thin,or ionic guest molecules A third class of complexes with structures diffenng from thetwo described was also observed
A correlation exists between the type of inclusion complex and the volumerequired for a complex molecule 1200--1400 A' for molecular gt,ests, and 1400-1500A3 for ionic guests
INTRODUCTION
The degradation of starch by Bacillus tnacerans amylase yields' ' cyclic inter-mediates consisting of six to ten a-(1->4)-linked D-glucose residues A molecularmodel and overall dimensions of the smallest member of this family of compounds,a-cyclodextrm (cyclohexa-amylose) with the glucose residues in the Cl(D) chairconformation3 is depicted in Fig I
The cyclodextrins form a large number of inclusion complexes with suchdissimilar compounds as benzene derivatives, azo dyes, carboxyhe acids, alcohols,
Present addresses '"Department of Biochemistry, The University of Wisconsin, Madison, Wisconsin53706, U S A '*Max-Planck-Institut fu= experimentelle Medizin, 34 Gottingen, Hermann-Rein-Sir 3, Deutschland, to whom correspondence should be addressed tDepartamento de Rayos X,Instituto de Quimica-Fistca "Rocasolano", Madrid, Espana ttMax-Planck-Insutut fur Fest-korperforschung, 7000 Stuttgart 1, Deutschland
38
halogens, polyhahde ions, and the rare gases' 2 4 Potentiometnc, spectral, andreaction-kinetic data on various guest compounds have led to the conclusion thatadduct formation in solution is due to the annular structures of the cyclodextnnmolecules, which provide space in their interior for the binding of guest molecules ofappropriate sizes' s-'
R K MCMULLAN, W SAENGER, J FAYOS, D MOOTZ
Fig I The dimensions (A) of a-cyclodextnn
The earlier structural data on crystalline cyclodextrin inclusion compoundshave largely been summarized by Senti and Erlander', and studies of crystalline/i-cyclodextrin adducts have been reported' The structure of the a-cyclodextrin-iodine complex has been proposed on the basis of an incomplete X-ray study, thisstructure and the structure of the a-cyclodextrin-l-propanol adduct have beencompleted in detail by the authors of this paper and will be published elsewhereHybl et al ' and Manor and Saenger 1O have reported structural analyses of theadducts of a-cyclodextrin with potassium acetate and water, respectively
We now report on the crystallographic data of 17 inclusion complexes of a-cyclodextnn
EXPERIMENTAL
Crystals of the inclusion compounds were grown, following the procedure ofCramer and Henglein", from aqueous solutions of a-cyclodextrin mixed withamounts of guest substances in excess of 1 1 molar ratios Attemps to obtain adductsof bromotoluene, nitrotoluene, and pentachlorophenol from preparations containingthese materials dissolved in supernatant ether layers produced crystals having dif-fraction patterns and densities that were almost identical with those of the etheradduct It was therefore concluded that the inclusion of these substances, if it occurredat all, was of the nature of random substitutions, in the predominantly ether-con-taining adduct On the other hand, crystals of the iodine and 1-butanol adductscould be grown by this procedure In order to prevent decomposition, it was foundexpedient to store the crystals in their mother liquors
CYCLODEXTRIN COMPLEXES 39
Thu crystal densities were measured by flotation of the crystals in hexane-methyl iodide mixtures, using relatively large, transparent samples freed from surfaceliquid by absorbent paper There were no perceptible changes in the crystal densitiesdue to loss of the guest components into the organic mixtures during these measure-ments The crystals for the X-ray measurements were encased in polystyrene filmsand thus stabilized Crystals of the iodine adduct underwent radiation damage, butnot to a degree that would affect the results of the preliminary X-ray study The space-group symmetries were determined from Weissenberg and precession photographsData for unit-cell dimensions were either measured by using a diffractometer orobtained from Weissenberg photographs calibrated with aluminium pore der diffrac-tion lines
RESULTS
The crystallographic and stoichiometnc data for the 16 inclusion complexeswhich have been examined, and one data set obtained from literature, are given inTable I, where the structures are subdivided into groups, according to their diffrac-tion symmetry (or pseudosymmetry) and unit-cell dimensions The values of the latticeconstants are, in most instances, the results from least-squares refinements on setsof 20 data for which the observation to parameter ratios exceed 6 1 In parenthesesare listed the standard deviations obtained by this procedure 12 The uncertaintylimits on the density values are probable errors as estimated from severe! independentmeasurements The entries of column 6 (volume per inclusion complex unit) wereobtained by dividing the unit-cell volume by the number of complex molecules perunit cell, column 5 The experimental molecular weights listed in column 7 applyto the formula units of the hydrated x-cyclodextrm or its adduct The hydrationnumbers of column 8 are determines by dif erence from these values and molecularweights of the 1 1 adducts (or the 1 2/2 adduct for Methyl Orange)
DISCUSSION
Class I cage structuresThe structures of Class I with orthorhombic space-group P2 12 i2, have complex
frameworks for which models have been postulated" from the guest distributiondetermined in the adduct of reported composition (CI,H,0O5)6 12 14H2O In thispacking arrangement, now resolved in detail for the 1-propanol, iodine, and wateradducts" 14 listed in Table I, the cylindrical openings within the x-cyclodextrinmolecules are blocked on open ends by contiguous molecules, thereby formingcylindrical enclosures or cages in the host structure (Fig 2a), which is held togetherby an intricate hydrogen-bonding scheme As seen from Table I, and especially inthe series acetic acid, propionic acid, butyric acid, valeric acid, this host structurebecomes unstable, to structures of Class 1, for guest molecules exceeding a criticallength consistent with the expectation' that the axial dimension of the cage limits
TABLE I
CRYSTALLOGRAPHIC
DAT
A OF
a-C
YCLO
DEXT
RIN
INCL
USION COMPLPXES, CLASSIFIED ACCORDING TO CRYSTAL SYMMETRIES AND UN
IT-C
ELL
DIME
NSIO
NS8
Gues
t mo
lecu
leSp
ace
grou
psCe
ll C
onst
ants
Observed
density
(g'mn-1
)
Numb
er o
far
olec
ulec
per
unit cell
Volu
me p
erIn
clus
ion
complex rant
Mol rot of the
complex from
X-ray data
Hydr
atio
nnumber for
I I
Comp
lex
(4)
(A')
Clas
s 11
Water (1)
P2,2,2,
a14846(3)
1492(1)
41200
1078
58b
3400 (1)
c
951 (4)
Iodine (2)
P212,2
,a
1424
0(4)
1 70
4(ca
le)
41220
1309
406
360'4(6)
c
9.558(6)
1-Pr
opan
ol (
3)P2
1212
1a
14292(4)
1468(2)
41257
1113
4.5(
48)
b37
515
(7)
c
9393(3)
Acetic acid (4)
P2,2,2
1a
14.3
4 (1
)14
83(2
)4
1272
1136
5 7
b3762 (1)
c9427(5)
Prop,onic acid (5)
P2,2,2,
a1437 (1)
41288
6 37 91 (2)
c946 (1)
Buty
ric
acid
(6)
P2,2,2,
a14
.29
(I)
1470(2)
41287
1139
4 3
b38
11
(1)
c9 45 (1)
1-Butanol(7)
P212,2
,a
14 3
82(3
)1 476(2)
41289
1146
5 5
b37
,99
(1)
C
944 (I)
ClassIIA
Methyl Orange (8
)P2,2,2,
a2210 (3)
1499(2)
21500
1356
122
b16
39
(3)
c
8 29 (3)
Potassium acetate (9)
P212,2
a21 89
1 434
2150D
1298
97(1
54 g
uest
per
acy
clo-
b16
54
dext
rin)
vc
3 30
Sodi
um h
exan
oate (10)
Class 1113
Diet
hyl
ethe
r
I-Octanol (11)
Lauc
Vale
rie
acid
(12
)Lauc
3-Me
thyl
. I-
buta
nol
(13)
Bari
um i
odid
e-io
dine
(14
)
Clas
s Il
lPo
tass
ium
iodi
de-i
odin
e (1
5)
Sodium perchlora
te (
16)
P2,2,2
1
Pl Hexagonal
(6/mm)
Hexa
gona
l(6/mm)
P2,
P622
P6222
C2
a21
94
(2)
b16
53
(1)
c16
56
(5)
a13 949(5)
a91 3
(3)
b13 870(5)
fl85 5
(1)
c15 669(8)
y 120
29 (
2)
a13 86 (3)
c15 63 (3)
a13 85 (3)
c15 62 (3)
1446(2)
1 430
1409(2)
1.40
9(2)
1 445(2)
1675(5)
1 686(4)
1515(2)
4 2 2 2 4 2 6 12
1503
1303
1300
1298
1368
1387
1457
1483
1308
1121
1102
1101
1189
1400
1477
1355
109
4 1
1 4
7 1
144
a b f1 c a c
23 6
4 (5
)13 95 (3)
950
(2)
1664 (t)
13 71
17 0
4
a15
89
c39 94
a1987 (I)
b33
71
(3)
910
6 86
(4)
c27
79
(2)
aFur
ther
dat
a we
re p
rese
nted
in
Ref
13'These data were taken from Ref 3
a
bc
ab
c
Iodi
ne14
38A
3607A
943A
1-Pr
opan
ol14
2437
30943
Etha
nol
1431
3746
943
Methanol
13 94A
36 8
3 A
947A
Wate
r1from two
151
338
96
Wate
r1
different batches
14 7
833
.96
951
42
R K MCMULLAN, W SAENGER, J FAYOS, D MOOTZ
the straight-chain guests to C4 or lower members The salt adducts with anionssmall enough to fit into these cages, viz, potassium acetate and sodium perchlorateadducts, also form structures of other types, probably because of the more-favourablesites for cation coordination existing in those frameworks
The frameworks of Class I are not strictly isomorphous, as has been previouslynoted in the series comprising the iodine, methanol, ethanol and 1-propanol adducts 13
These small differences in packing of a-cyclodextrin molecules are accompaniedby changes in the number of water molecules engaged in the host structures Thus,in the iodine adduct, there are four water molecules per cyclodextrin molecule,whereas the 1-propanol adduct contains five water sites, of which two are statis-tically occupied, giving the hydration number of 4 8 (Table I) On the other hand,the enclosures appear to be fully occupied, each with one guest molecule Likewise,for other complexes of this class, one might expect I I adducts with 4-6 water mol-ecules per cyclodextrin molecule, with the simple hydrate being a special case inwhich two water molecules fill the enclosure" The hydration number of 14 pre-viously formulated" for the iodine adduct greatly exceeds tht expectation valuesimposed on the stoichiometry by the structure and accordingly is probably erroneous
Class II channel structuresThe adducts of Class IIA are isostructural in their host frameworks with the
a-cyclodextrin-potassium acetate complex' In this framework, the cyclodextrinrings pack coaxially to form continuous channels which run along the c direction(Figs 2b and 2d), the anions are distributed through the channels in complex patternsof disorder, while the cations are located in external cavities formed by oxygen atoms
Statistical disorder of the amome guest must also occur in the Methyl Orangeadduct, as the diffraction patterns show no evidence of a superlattice although themaximum dimension of the anion is approximately twice the expected periodiclength of the channel In the sodium hexanoate adduct, on the other hand, the anionsappear to be ordered, as the channel arrays have a periodicity twice that of themolecular dimensions of a-cyclodextrin
That the frameworks of Class IIA depart significantly from hexagonal closestpacking of colinear cylinders appears to be due to the accommodation of tonic guestsbetween channels of the structures, inasmuch as the crystals of adducts of molecularguests (Class IIB) have lattices of dimensions and symmetry consistent with thehigh intrinsic regularity and simplicity of this arrangement (Figs 2c and 2d)
Thus, the dimensions of a and c (--13 9 and -16 A) given in Table I (class 1113)correspond to the expected diameter and double height of a-cyclodextrin toruses(Fig 1) in van der Waals contact in hexagonal frameworks The hypersymmetry ofthis arrangement is remarkably pronounced on diffraction patterns of the tnchmcether adduct and to a lesser extent on patterns of the 3-methylbutan-l-ol adductWhile the 1-octanol, valenc acid, and barium iodide-iodine adducts achieve hexagonalsymmetry, their diffraction patterns show diffuse streaking in the c direction super-imposed on sharp reflections which define subcells having the dimensions given
CYCLODEXTRIN COMPLEXES
(a)
(c) (d)
(b)
43
Fig 2 The packing scheme of a-cyclodextrm adducts (a) Class I with small molecular guests,looking along the crystallographic a-axis, a-cyclodextnn molecules are seen from the side, similar toFig 1, right hand (b) Class IIA with ionic guests, looking along the channel axis (c) Class 118 withlarge molecular guests, looking along the channel axis (d) Side view of class IIA, B channel structures
44
R K MCMULLAN, W SAENGER, J. FAYOS, D MOOTZ
in Table I In view of this streaking and the existence of the apparently ordered etherstructure of lower symmetry, it seems probable that, in these structures, the guestsare disordered along channels, while the symmetric, cyclodextnn host-moleculesare ordered in the main framework The crystal structure of the barium iodide-iodine adduct has been determined from the Patterson function The orientation ofthe two a-cyclodextrin toruses could not be derived with certainty as the iodine atomsappear disordered along the hexagonal axis's
Class III, other structuresThe a-cyclodextnn-potassium iodide-iodine complex crystallizes in a hexagonal
space-group but, as is obvious from the cell constants, the packing must be differentfrom that observed for Class II structures It was established's from a Pattersonsynthesis that the a-cyclodextrin molecules are again arranged co-linearly in a channel-type structure However, the channels do not run parallel to each other and to thehexagonal crystallographic axis but are perpendicular to this axis This type ofpacking is also indicated by streak formation in the hkO equator due to a disorderof the iodine atoms along the a-cyclodextrin channels
The crystallographic data of the sodium perchlorate adduct seem to indicate astructure different from any host framework hitherto studied, but bear some relationto the data observed for the a-cyclodextnn-potassium acetate complex The unit-cell axial dimensions of the sodium perchlorate adduct a = 19 87, b = 33 71, c =27 79 A, can be considered to be multiples of the cell constants obtained for thea-cyclodextrin-potassium acetate complex, 1 x 21 89, 2 x 16 54, 3 x 8 30 A
The volume per inclusion complex unitThe volumes per inclusion complex unit given in column 6 of Table I and in
Fig 3 represent a measure for the volume required by one a-cyclodextrin moleculeplus the surrounding molecules of water of hydration It is interesting to note thatthese figures vary from one crystal class to another and thus reflect the differentpacking patterns
In class I structures, the volume per inclusion complex unit increases from1200 A', the lowest entry in column 6, Table I, until it reaches a plateau at -1290 A 3That the water inclusion complex requires the smallest volume also becomes obviousfrom its detailed X-ray structural analysis 10 , the a-cyclodextrin molecule is nolonger toroidal, but distorted such that the void becomes smaller in order to achievevan der Waal's contact with the enclosed two water molecules When however,the guest molecule, due to its dimensions or due to its ionic character, requires anadduct volume exceeding -1290 A3, the crystal structure changes to class 1. or III
The volume per inclusion complex unit is constant (1500 A 3) for class IIAadducts This indicates that the host framework for these adducts is very similar,probably more strictly isomorphous than in the other structure classes of Table I,the accommodation of the ionic guests of different dimensions within the a-cyclo-dextrm channel and of the different monovalent cations outside the channels'
CYCLODEXTRIN COMPLEXES
WE
A3
Class HA -I
-*4 Class II BClass
uva-
0
in
O
•
c 1300-
1200-
10 9 B 16 15
~ • Ionic guests
-~-.-- Molecvlor guests
14
e
Sr class i
s • 0
•
•
13 12 11 / 6 5 4 3 2 1
45
Fig 3 Representation of the "volumes per inclusion complex unit" for the a-cyclodextnn adductslisted in Table I
seems to bear little influence on the packing of the a-cyclodextrin molecules in theorthorhombic umt-cells of P2 1212, or P21212 symmetry
g
In class IIB, the volume per inclusion complex for the molecular guests rangesfrom 1300-1387 A' In this structural class, the molecular guests are arrangedinside the a-cyclodextrin channels, the a-cyclodextrin molecules are packed in asimilar scheme but in different (tnchmc, monochnic, and hexagonal) space groups,iving a natural explanation for the variance 1n the volumes per inclusion-complex
unit .The crystal packing patterns observed for class III with ionic guests are different
from the patterns observed for class IIA structures However, the volumes perinclusion complex unit (1457 and 1483 A3) are comparable to that (1500 A') recordedfor class IIA structures This might indicate that, in the class 111 adducts, the cationsare located "outside" the a-cyclodextrin molecules, as was found' for the class IIApotassium acetate complex
It appears to be a structural law that a-cyclodextnn adducts with small mo-ecular guests crystallize in class I structures with 1200-1290 A' per inclusion complexunit, with larger molecular guests, class IIB structures with up to about 1400 A' perinclusion complex unit are obtained The adducts with ionic guests crystallize inclass III and class IIA structure types requiring - 1400-1500A' per inclusion complexunit
46
R K. MCMULLAN, W SAENGER, J FAYOS, D MOOTZ
CONCLUSIONS
The structure-determining factor in the crystalline materials listed in Table Iis the association between guest and a-cyclodextnn molecules with the requirementsofinclusion playing the dominant role, the host frameworks comprising a-cyclodextnnmolecules and water molecules associated by hydrogen-bonding account for thegross dimensions and intrinsic symmetry properties of the lattices, as do theframe-
works in other inclusion or clathrate compounds' 6.17 The adducts of molecular
compounds, depending on the maximum dimension of the guests, fall into two
structural classes crystals of orthorhombic space-groups P2,2121 formed by mol-
ecules of dimensions smaller or equal to a C4 chain (Class I, cage structures) and
crystals of hexagonal or pseudohexagonal space-groups formed by guest molecules
of greater dimensions (Class IIB ; channel structures) The structures of ionic (salt)adducts likewise form two structures the channel structures of orthorhombic P2,2,2or P212r21 symmetry (Class IIA) are related to those of the larger molecular non-
ionic guests (Class IIB) ; the structures ofClass III are different from those ofClasses Iand H, although the channel structure is preserved m the potassium iodide-iodineadduct and might be present in the sodium perchlorate complex if cell dimensions
are taken as sole criterion .
ACKNOWLEDGMENT
One of us (R M) thanks the Alexander von Humboldt-Stifung for financial
support.
REFERENCES
1 F. CRAMER, Einschlufverbindungen, Spnnger-Verlag, Heidelberg, 19542 D. FRENCH, Adrian. Carbohyd Chem, 12 (1957) 2503 A. Hvm., R E RUNDLE, AND D E WrimiAm, J Amer Chem Sac, 87 (1965) 27794 F M HENGLEiN, Ph D Thesis, Techmsche Hochschule, Darmstadt, 19575 F CRAMER, W SAENGER, AND H CH SPATZ, J Amer Chem Sac, 89 (1967) 146 N HENNRICH AND F CRAMER, J Amer Chem Sac, 87 (1965) 11217 F C_RAMER AND W KAMPE, J Amer Chem Soc, 87 (1965) 1115 .8 F. SENrr AND S ERLANDER, in L MANDELCORN (Ed), Non-Stoichiometrrc Compounds, Academic
Press, New York, 1964, p 5689 1 A HAMILTON, L K. STEINRAUF, AND R L VAN ErrEN, Acta Crystallogr, Sect B, 24 (1968)
156010 P. C MANOR AND W. SAENGER, Nature (London), 237 (1972) 38211 F CRAMER AND F M HENGLEIN, Chem Ber, 90 (1957) 257212 1 M STEWART AND D Hicm, X-ray 63 Program System for X-ray Crystallography, The Depart-
ment ofChemistry at the Universities ofWashington (Seattle) and Maryland (College Park), 196513 W 7 JAMES, D FRENCH, AND R E RuNDiE, Acta Crystallogr, Sect. B, 12 (1959) 38514 R K MCMULLAN, W SAENGER, J FAYOS, AND D Moorz, unpublished data .15 P C MANOR AND W. SAENGER, unpublished data16 H. M PowELL, in L MANDELcogr (Ed), Non-Stoichrametnc Compounds, Academic Press,
New York, 1964, p 43817 G A JEFFREY AND R K MCMULLAN, Progr Inorg Chem, 8 (1967) 43.