Crystal and molecular structures of cyclomaltoheptaose inclusion complexes with HI and with methanol

Carbohydrate Research, 107 (1982) 7-16 Elsevier Scientific Publishing Company, Amsterdam

CRYSTAL AND OSE MCLUSION KLAUS

LINDXERAND

,tia.r-Planck-lnstif GGttingen

(West

MOLECULAR COMPLEXES

- Printed in The Netherlands

STRUCTURES WITH HI AND

OF CYCLOMALTOHEPTAWITH METHANOL*

WOLFRAMSAESGER ut fir

experirrenrelle

Medizin,

Abreihmg

Chemie,

Hermann-Rein-Sri-.

3. O-3400

Germany)

(Received July 6th, 1981; accepted for publication,

December

16th, 1981)

ABSl-RACT

P-Cyclodextrin (P-CD; cyclomaltoheptaose; cyclohepta-amylose; C,2H,,0,,) crystallises from aqueous solutions of HI and of MeOH in the form of stout prisms, which are isomorphous to each other with monoclinic space-group P2,; cell constants 7HI - S HzO: a = 21.25(3), b = 10_2S(2), c = 15.30(2) A, /.?= for C42H70035 - _ 113.25(g)“, and Z = 2; and for CS2H70035 - MeOH - 6.5 H,O: a = 21.03(3), b = 10.11(2), c = 15.33(2) A, /? = 111.02(9)“, and 2 = 2. X-Ray counter data were used to determine the structures of both crystals, which belong to the cage type, with /?-CD molecules in nearly identical, “round” shapes. In the HI complex, one I- is located inside, and one outside, the /?:CD cavity; in the MeOH complex, the MeOH is within the cavity_ The cavity is closed at the O-2,0-3 side by adjacent &CD molecules, and at the O-6 side by water molecules hydrogen-bonded to the guest and to surrounding P-CD molecules. Interstices between &CD molecules are filled by water of hydration mo!ecules in distorted co-ordination. INTRODUCTION

The doughnut-shaped cyclodextrin molecules, a family consisting of six (cx), seven (p), or eight (y) rr-D-glucopyranosyl residues, have been the subject of several studies during the past ten years, with the smallest, r-cyclodextrin (n-CD), being most intensively investigated l-‘_ We now report on two &CD inclusion complexes that are highly isomorphous to the recently described “empty” P-CD - dodecahydrate crystallised from pure water4 and with the B-CD - EtOH - 8 Hz0 obtained from aqueous ethano15. EXPERIMENTAL

The HI complex of @-CD was crystallised according to a published procedure6. HI was freshly purified by distillation

from hypophosphoric

*Topography of Cyclodextrin InclusionComplexes, Part XVIII. 000%6215!‘82/ OWO4000/5

02.75,

@

1982 -

acid, and the samples

For Part XVII,

see ref. 9.

Elsevier Scientific Publishing Company

,4788(4) ,4836(4) ,5351(4) .6028(4) ,6595(G) .6817(4) ,6040(4) ,5742(4) .6016(4) ,6788(4) .7167(5) .8584(4) ,7872(4) .7352(4) ,7544(4) .8266(4) .8526(5) ,9707(4) .9490(4)

Y _-_ ,1006(h) ,0261(6) -*.0527(5) -.0900(6) -,0113(6) -.0411(7) .4205(G) .3849(G) .2777(G) .2471(5) .2825(6) .2552(6) .4999((i) .4949(6) .4314(6) .4623(5) .4701(5) .5153(7) ,2593(5) .3178(G) 3.5(3) 3.8(3) 3.2(3) 3.1(3) 3.3(3) 5.3(4) 3,8(3) 3.7(3) 3.4(3) 3.3(3) 3,7(3) 5.1(3) 3.3(3) 3.7(3) 3,3(3) 3,1(2) 3.1(3) 4.5(3) 3.2(3) 3.3(3)

__.-

O-4(1) O-5(1) O-6(1) O-2(2) O-3(2) O-4(2) O-5(2) O-6(2)A O-6(2)B O-2(3) O-3(3) O-4(3) O-5(3) O-6(3) O-2(4) O-3(4) O-4(4) O-5(4) O-6(4) O-2(5)

AtonI . _.

.. ____.- - ~_-~. __

% 11 - ______ - . --. -. _ _.-_-- .-__

.5334(9) .5100(10) .4191(10) .4770(9) .4982(M) .5607(12) ,2871(11) ,2763(11) ,2875(10) .4116(10) .4OI5(10) .5149(12) -,1070(10) -.1462(11) -.0499(10) .0902(10) .1208(9) .2539(11) -.2734(10) -.3735(10)

__._ .-___ ----

,5492(4)

x

C-2(1) C-3(1) C-4(1) C-5(1) C-G(l) C-1(2) C-2(2) C-3(2) C-4(2) C-5(2) C-G(2) C-1(3) C-2(3) C-3(3) C-4(3) C-5(3) C-6(3) C-1(4) C-2(4)

.- --__ -__-

_ -_ _--_____ -____-__.

C-l(l)

_-.-

AtonI”

__-______

__ .- _ __

. .__.

.5432(3) .5927(3) ,6418(5) .5850(3) .5005(3) .5740(3) .7025(3) .7770(14) .6988(5) .7731(3) ,6690(3) ,7068(3) ,X727(3) ,8452(4) ,9229(3) .8789(3) ,8602(3) ,9957(3) 1.0062(5) .8004(3)

.3835(6) .5845(6) .6861(11) ,1543/7) .2901(g) .4123(6) .4006(7) .4932(43) .6430(I)) -.2789(7) -,0760(7) .1713(7) ,0259(7) ,2594(9) -,4918(7) -,4037(7) -.1215(7) -.1585(7) .1140(9) -.4310(7)

-

_

II

-._-__

4.3(2) 4.1(2) 3.3(2) 3.6(2) 5.5(3) 4.1(2) 4.2(2) 3,2(2) 3.5(2) 7,7(4) 4.9(2)

3.1(2) 3.6(2) 8.4(4) 4,3(2) 4,9(2) 3,1(2) 3.8(2) 10.9(15) 5.6(3)

.- __ __ ._ . .-.1558(3) .0579(4) -.0801(6) .4146(4) .2442(4) .1453(4) .3846(4) .2740(25) .2724(7) .4611(5) .4358(4) .3913(4) .5298(4) ,6059(5) .2641(4) ,4109(4) ,4080(3) .3126(4) .3441(6) -,1261(4)

X z Y __ _ . -- _- ._____. .._-___---_.-_---

_

h

ii u 3 m

2

F

__._

C-3(4) C-4(4) C-5(4) C-6(4) C-1(5) C-2(5) C-3(5) C-4(5) C-5(5) C-6(5) C-l(b) C-2(6) C-3(6) C-4(6) C-5(6) C-6(6) C-1(7) C-2(7) C-3(7) C-4(7) C-5(7) C-G(7) O-2(1) O-3(1)

_._-_----

.8958(4) .9187(4) .9465(4) .9839(5) .8642(4) .8586(4) .8555(4) .9177(4) .9175(4) .9783(5) .6625(4) .6510(4) .6921(4) .7656(4) .7738(4) .8445(5) .5242(4) .4832(4) .5266(4) .5910(4) .6277(4) .6817(5) .4347(3) .4199(3)

._____. -___

-.3125(10) -.1827(9) -.0896(10) .0276(12) -.2289(11) -.3604(10) -.3425(9) -.2638(10) -.1296(10) -.0436(12) .0471(9) -.1004(10) -.1506(9) -.1134(10) .0366(g) .0843(11) .4238(9) .3118(9) .1890(g) .2224(9) .3412(9) .3931(10) .4519(g) .4126(g)

-._-_--

.3490(G) .3994(5) .3414(6) .3975(g) -.1JOO(G) -.0658(5) .0309(5) .0898(5) .0428(6) .0958(7) -.3478(G) -.3428(G) -,2433(6) -.2210(5) -.2289(6) -.2113(7) -.2505(6) -.3117(5) -.2984(5) -.3160(5) -.2618(6) -.2981(6) .0703(4) --.1277(4)

.-__ -- ---__

3-l(3) 3,1(2) 3.2(3) 5.1(4) 3.5(3) 3.5(3) 3.1(3) 3.0(2) 3,8(3) 4.8(3) 3.3(3) 3.5(3) 3,4(3) 3.0(2) 3.2(3) 4.4(3) 3.1(3) 3,1(3) 3.0(2) 2.7(2) 3-l(3) 3.8(3) 4.4(2) 4.6(2)

_.- _--_

O-3(5) O-4(5) O-5(5) O-G(S) O-2(6) O-3(6) O-4(6) O-5(6) O-6(6) O-2(7) O-3(7) O-4(7) O-5(7) O-6(7) o-w-1 o-w-2 o-w-3 o-w-4 O-MC C-MC o-w-7 o-w-5 O-W-6

____

_

,8530(3) ,9131(3) .9202(3) 1.0414(3) ,5795(3) .6843(4) .8024(3) .7324(3) .8737(3) .4231(3) .4906(3) .6349(3) .5819(3) .6502(3) .5399(3) .9791(4) .7590(5) .8838(5) .2996(5) .2528(7) l-0725(5) .8621(12) .7763(10) -.4654(7) -.2424(7) -.1559(7) -.1133(9) --.1235(7) -.2897(7) -.1573(6) .0774(7) *0290(9) .2876(7) ,0862(7) .1094(6) .4524(6) .4375(g) -.3640(7) -.1469(10) .5890(14) .5027(13) .3132(12) .4096(21) -.1822(11) .2421(19) -.6971(21)

,0728(4) .1794(3) -.0503(4) ,1188(5) -.3678(4) -.2389(5) --.1271(3) -,3226(4) -,2729(5) -,2907(4) -,3611(4) -,2845(3) -.2729(4) -,3954(4) -,4466(4) ,7640(6) ,6012(7) ,7094(7) -.1172(9) -.1496(13) -,0379(7) .2629(22) -,0539(18)

4.4(2) 3.2(2) 4.0(Z) 6.0(3) 4,2(2) 5.0(2) 3.2(2) 3.4(2) 5.6(3) 4.0(2) 3.7(2) 2.7(2) 3.0(2) 4.4(2) 4.5(2) 7.5(3) 11,6(5) 9.1(4) 10,9(5) 10.6(7) 8.6(4) 18.0(16) 12.2(10)

C-l(l) C-2(1) C-3( 1) C-4(1) C-5(1) C-G(l) C-1(2) C-2(2) C-3(2) C-4(2) C-5(2) C-G(2) C-l (3) C-2(3) C-3(3) C-4(3) C-5(3) C-6(3) C-1(4)

.8577(G) .9637(5)

.5501(5) ,4797(5) .4855(5) .5361(5) .6047(6) ,6595(5) .6869(6) ,6089(5) ,5742(6) .6041(5) .6809(5) .7187(G) .8503(6) .7769(5) .7292(5) .7540(5) .5490(13) ,5259(11) ,4349(12) dR54(11) ,5078(12) .5706(17) .2970(13) .2940(12) .3111(12) .4259(1I) .4070(12) .5120(13) -.112X(11) -.1387(12) -.0401(12) .0965(I I) .1138(ll) .2406(13) - .2757(11)

1

,08I7(7) ,0034(7) - .0688(7) - ,1037(7) -,0226(8) -,0.529(8) .4095(8) ,3716(g) .2642(R) .2313(7) .2690(8) .2404(8) .4973(7) .4861(7) .4212(7) .4537(7) .4661(7) .5149(10) .2651(7)

___ -- _._.

_

2.7(4) 2.4(j) 2.3(4) 2.1(4) 2.5(4) 3.3(4) 2.6(4) 2,3(4) 2.4(4) 2810) 2.5(4) 2,8(4) 2.2(4) 2.1(3) I .7(3) 1.9(3) I .9(3) 3-O(5) 2.0(3)

u O-4(1) O-5(1) 0.6(l) O-2(2) O-3(2) O-4(2) O-5(2) O-G(2) O-2(3) O-3(3) O-4(3) O-5(3) O-6(3) O-2(4) O-3(4) 0*4(4) O-5(4) O-6(4) O-2(5)

Alottt .__.-. -

,5436(4) .5952(4) ,6359(5) ,5X98(4) .5029(4) ,5727(4) .7089(4) .7040(4) *7579(4) .6629(4) .7098(3) .8699(3) .8585(4) .9174(4) .X733(4) .8514(3) .9879(3) .9875(5) .X058(4)

---

X

-

__. _-

----

,3872(7) .5959(X) .6858(1I) ,1730(9) .3221(10) ,4277(g) ,4051(8) .6405(g) -,2679(8) ---,0570(8) .1788(8) ,0147(7) .2449(9) -.4848(B) .- .4094(8) -.1327(S) --.1633(g) . I Isa(s) --.4102(8)

Y

._-. __

z

- -.1687(5) .0445(5) -.1055(7) .4012(5) .2357(6) , I296(5) .3729(5) ,2643(G) .4484(5) ,4209(5) .3812(4) .5304(5) ,6079(5) ,2600(5) .4093(5) ,4057(5) .3223(5) ,3517(7) --.I 395(5)

-

2.1(2) 2.6(3) 5*2(4) 3.1(3) 4.4(3) 2.2(2) 2.2(2) 3-O(3) 2.7(3) 2.6(3) I d(2) I .9(2) 3.4(3) 2.5(3) 2.8(3) 2.1(2) 2.X2) 4.3(4) 2,6(2)

u

fi u 3 gY 9 6 9

F

STRUCTURE

OF CYCLOMALTOHEPTAOSE

COMPLEXES

11

K. LIFTDETER,

12

W. SAENGER

were prepared in a cold room in order to avoid decomposition of P-CD. The MeOH complex was obtained by allowin,= a 60% aqueous MeOH solution saturated at boiling temperature with F-CD to cool slowly. Because crystals of B-CD tend to dry out under ambient conditions, they were mounted in quartz capillaries together with some mother liquor. X-Ray diffraction data were collected with an automated STOE four-circle diffractometer employing graphite-monochromatised MoKz radiation for the Hi adduct and Ni-filtered CuKa radiation for the MeOH complex. Data were corrected empirically for absorption effects: and converted into normalised structure amplitudes E,,. The structure of the B-CD - HI - S H,O complex was determined by both Patterson and direct methods’, and refined by full-matrix, least-squares cycles to a final R-factor of 6.5 o/0for all the 5036 measured data weighted according to countin g statistics and employing anisotropic thermal parameters. The known positions of C and 0 atoms were then used to solve the structure of the isomorphous MeOH adduct which, after location of Lvater and MeOH atoms by difference Fourier techniques, refined to an R-factor of 79; for all 4643 measured data. Hydrogen atoms for water and B-CD hydroxyl groups could not be positioned with certainty and were therefore omitted from the refinement, whereas C-H hydrogen atoms were put at calculated positions and used in refinements with isotropic thermal parameters. Final atomic co-ordinates and isotropic temperature factors (caIcu!ated from anisotropic ones) are given in Tabies I and II; lists of structure amplitudes and comprehensive atomic parameters have been deposited with the data file*. In the P-CD - 2 HI - S Hz0 complex, a11 atoms are fully ordered, whereas, in &CD - MeOH - 6.5 H,O, HO-6 of D-glucose 2 and two water molecules, O-W-5 and O-W-6, are only partially occupied as follows: O-6(2A), O-31(2); O-6(2B), O-79(3); O-W-5, O-66(3); and O-W-6, O-50(2); all other occupancies are 1.0. DISCUSSION

Both adducts described here belong to the cage type, with P-CD rings arranged in herring-bone fashion due to the twofold screw axis. This organisation leads to closure of P-CD cavities by adjacent &CD molesules on both sides, in contrast with the “open” channel structures. Ali gIucosy1 residues are in the “C, conformation, and the ring of intramolecular hydrogen-bonds between HO-2 and HO-3 of adjacent glucosyl residues is always fully established, with mean O-2, - - - O-3,,1 distances of 2.86(7) A for B-CD - MeOH 6.5 Hz0 and 2.90(15) A for &CD - 2 HI - 8 H20. In the Iatter case, the standard deviation is higher than in the former and reflects more variation in O-2 **a O-3 distances, probably brought about by protonation of water molecules by HI. The *Listsof structure factors and anisotropicthermaiparametershave been deposited with the British LibraryLendingDivisionas Suppiementaxy PublicationNo. SUP 33872 (13 pp.). Copies may be obtainedthroughThe FxecutiveSecretary,International Unionof Crystallography, 5 Abbey Square, Chester CHl

WV,

Great Britain.

STRUCTURE

OF CYCLOMALTOHEPTAOSE

13

COMPLEXES

Fig. 1. Stereodiagram of B-CD - HI - 8H-10, showing water molecules and I- as ellipsoids, and &CD C aid 0 atoms as spheres. Hydrogen-bonding contacts are indicated by open IineG. Figures in bold face refer to glucosyl residues, other figures are for water molecules as listed in Table II, and L stsnds for iodide ion.

FioJ. 2. Packing diagram of &CD Fig. 1.

- HI

- 8H20,

looking

down

the b-auk. Graphid

details a~ in

only major difference between the two B-CD moIecuIes described here Iies in the orientation of the C-6-O-6 bonds. In genera& these are turned “away” from the center of the moiecuie, corresponding to the (-)1garrc1re conformation of the 0-5C-5-C-6-O-6 group. In the MeOH complex, one of these bonds is in the (f )gartche range, whereas, in the HI complex, two of these bonds are turned towards the center of the molecule in order to form hydrogen bonds with enclosed water molecules (Figs.

1 and

3).

Bond angles and distances are not given expiicitly, because they are in overall agreement with those described in greater detail for the crystal structure of B-CD -

14

R. LINDNER,

W. SAENGER

Fig. 3. Stereodiagram of B-CD - MeOH - 6SHc0, looking onto the plane defined by O-4 atoms and nearly along the axis of the MeOH molecule (*)_ Note that MeOH is pushed towards the “righthand” side of the cavity; the MeOH hydroxyl faces the viewer and is hydrogen-bonded to hydroxyls of adjacent B-CD molecuies whereas the methyl group is located within the cavity and opposes two water molecules that display excessive thermal vibration and!or disorder. Graphical details as in Fig. 1; the MeOH hydroxyl located outside the cavity is indicated by OMe.

Fig_ 4. Packing asinFig. 1.

diagram of j3-CD - MeOH - 6SHs0,

looking down the b-axis. Graphical

details

dodecahydrate’. Besides these , geometrical details concerning the shape of the macrocycle are comparable and suggest that the circular structure of &CD is rather “rigid”, due to the well-established ring of hydrogen bonds between HO-2 and HO-3 of adjacent glucosyl residues. The packing schemes of the HI - 8 H,O and MeOH - 6.5 H,O complexes of /?-CD are comparable not only for the B-CD hosts but also for some water of hydration

STRt?CTURE OF CYCLOMALTOHEPTAOSE

molecules

located

15

CO>ZPLEXES

near the O-6 side of P-CD

molecules

and in the interstices

behveen

/?-CD molecules. Major differences are seen around guest molecules, within the cavity, and around the I- located behveen /?-CD molecules. This is also evident from the co-ordination scheme for the two I-, the one inside the b-CD cavity being 5-fold A, whereas the one co-ordinated with I- --- 0 distances in the range 3.37-4.02 accommodated in interstices is g-fold co-ordinated with oxygen atoms at distances 3.42-4.19 A. Assuming van der Waals contact

hydrogen-bonding distance computes”

interactions of the type I- - - - H-O, the to 4.35 A, suggesting that all of these short distances are probably hydrogen bonds. In the P-CD - MeOH - 6.5 HZ0 complex, the MeOH molecuie is iocated within the b-CD cavity and oriented along the axis of the annulus, but shifted sideways such that it is in van der Waals contact

with the atoms of the cavity. The MeOH

hydroxyl

is hydrogen-bonded to a disordered HO-6 of an adjacent P-CD molecule and to HO-3 of another &CD molecule, all hydroxyls being located near the O-2,0-3 rim of the enclosing &CD molecule_ The methyl group of MeOH points into the F-CD cavity, facing two water molecules that display excessive thermal motion or even disorder, probably in order to fill empty space within the P-CD cavity (Figs. 3 and 4). The inclusion geometry of P-CD - MeOH - 6 .S I-I,0 is largely different from that of the /l-CD - EtOH - S H,O complex. In the latter, the enclosed EtOH is distributed over two sites in nearly antiparallel orientation, with ethyl groups and one water molecule positioned in the cavity, whereas EtOH hydroxyls are hydrogenbonded to B-CD hydroxyls and to water on both the O-2, O-3, and O-6 sides of the cavity. Common to both MeOH and EtOH complexes with /?-CD, however, is the close contact of guest molecules with atoms lining the P-CD cavity. Comparing

the /LCD - MeOH

- 6.5 H,O

complex

with

the

(r-CD. MeOH *

it is found that the situation is different again, with the smaller 5 Hz0 analogue”, dis(5.2 A verszzs 7 A in B-CD) cavity filled by one MeOH molecule statistically ordered over two sites; one is hydrogen-bonded with two HO-6 groups of the host CY-CD, whereas the other is located within the X-CD cavity and in no obvious hydrogenbonding contact with hydroxyl groups or with water. In addition, we should add that, in the “empty” &CD - 12 H,O complex, the enclosed

6.5 water

molecules

are statistically

disordered

over

9 sites and display

rather large thermal motion. On inclusion of a guest molecule, it appears that the disorder is greatly reduced, and replaced by more well-defined locations of enclosed guest and water molecules. Comparison of the HI and MeOH adducts with P-CD described here with the “empty” P-CD - 12 Ii,0 reveals that, in contrast to the smaller X-CD uncomplexed, molecule’, B-CD is more rigid, maintaining its “round’ shape under a variety of conditions. This finding suggests that, for /LCD, release of strain energy cannot be a major driving-force for adduct formation, but rather, hydrophobic forces and expulsion of “activated water” from the cavity have to be invoked3.

K. LINDNER,

I6

W. S.4ENGER

REFERENCES 1 2 3 4 5 6 7 8

9 10 11 12

W. SAEXGER,Jerusalem Symp. Qaantztm Chem. Biochem., 8 (1976) 265-405. W. SXRGER, ,&rge,v_ Chem. Izzt. Ed. Engl., 19 (1980) 343-362. M. L. BENDERAND M. KobllY~hl4, Cyclodextrizz Chemtstry, Springer-Verlag, Berlin, 1978. K. L~SDXER AND W. !%EXGER. Anger. CIzem. Int. Ed. EngI., 17 (1978) 694695. R. Tozcuorc+ M. ABE, T. FUJIWARA, K.-I. TOXIITA,em W. SAENGER,C/tern. Lett., (1980) 491-494. J. Sznu ASD 2. S. BUDAI, Acta Chim. Acad. Sri. Hzazg., 94 (1977) 383-391. A. C. T. NORTH, D. C. Pups, AND F. S. MXIHEWS, Acta Crystallogr., Sect. A., 24 (1968) 351-359. P. M.-ux, L. LESSIMGER,M. M. Woorrsox, G. GERXUN, AXD J. P. DECLERCQ,MULTAN, aSystem of Computer Programs for the Automatic Solution of Noncentrosymmetric CrystaI Strzrctzrres, Universities of York (Great Britain) and Louvain (Belgium), 1977. K. LINDXER ASD W. SAENGER, Carbohydr- Res., 99 (1982) 103-I 15. R. C_ Wrxrr, CRC Handbook of Chemistry azzd Physics, CRC Press, Cleveland, Ohio, 1977, p. D-178. B. HISCERTY AXP W. SAGER, J. Am. Chem. Sot., 95 (1976) 3357-3365. C. K. JOHSSON, Report ORNL-3794, Oak Ridge National Laboratory, Tennessee, 1965.