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Vibrational Raman optical activity of cyclodextrins
Tetrahedron:A~yme~ttryVol. 1, No. 8. pp. 513-516, 1990
0957-4166/90 $3.00+.00 Pe~gamort Presspie
Printed in Great Britain
Vibrational Rarnan Optical Activity of Cyclodextrins Laurence D. Barton e, Angelo P.. Gargaro, Zal Q. W e n David D. MacNlcol a n d C o l i n Butters
Chemistry Department, The University, Glasgow, G12 8QQ, U.K.
(Received 5 June 1990)
Abstract: Vibrational Raman optical activity spectra of aqueous solutions of ~-,
[3-
and ~,-D-cyclodextrin in the range 700-1500 cm -1 are reported. As well as showing features characteristic of D-glucose, the ROA spectra all show remarkably intense features between 890 and 960 cm -1 ori9inating in coupled C ( 1 ) - H deformations and glycosidic C-O stretches delocalized around the cyclodextrin rin 9 and which reflect the stereochemistry of the glycosidic links. Vibrational
optical
activity
measurements
stereochemical
information
every part of
the molecule. 1 V i b r a t i o n a l
on
because a vibrational
chiral
molecules
spectrum
can
contains
optical a c t i v i t y in
typical
provide much
bands chiral
associated molecules
new with
in
the
disordered phase was f i r s t observed using the Raman o p t i c a l a c t i v i t y (ROA) technique, which measures
a small
difference
in
the
polarized incident light. 2"3 U n t i l
Raman-scattered
recently,
lack of
intensity
sensitivity
in
right
and
has r e s t r i c t e d
left
circularly
ROA studies
to
favourable samples such as neat liquids; 4'$ b u t a major b r e a k t h r o u g h in ROA i n s t r u m e n t a t i o n based on the use of a backscattering g e o m e t r y 6'7 t o g e t h e r w i t h a cooled CCD d e t e c t o r 8 has now rendered a much wider range of samples accessible to such studies. This communication reports ROA spectra o f c y c l o d e x t r i n s in aqueous s o l u t i o n
which indicate that this technique
has great p o t e n t i a l f o r stereochemical studies o f these and o t h e r polysaccharides. Most carbohydrates (ECD)
measurements,
are
which
not
well
suited
are r e s t r i c t e d
to
to the
conventional
electronic
long-wavelength
bands; 9 nonetheless, some useful i n f o r m a t i o n a b o u t c o n f o r m a t i o n s
tails
circular of
the
dichroism first
ECD
o f c y c l o d e x t r i n s has been
obtained in this way. 10 Vibrational o p t i c a l a c t i v i t y spectra o f simple carbohydrates obtained using ROA's sibling technique o f vibrational circular dichroism (VCD) have been reported, tt b u t no VCD spectra of cyclodextrins have so far been published. The ROA spectra were recorded using the Glasgow multichannel for
backscattering 6'7 and CCD
Aldrich
and
Fluka
and
detection. 8 The c y c l o d e x t r i n
studied
as
near-saturated
samples
solutions,
in
i n s t r u m e n t 12 modified were
purchased
water
for
ct-
from and
T - D - c y c l o d e x t r i n , and in I N NaOH f o r [3-D-cyclodextrin in o r d e r to b o o s t the s o l u b i l i t y . The ROA measurements were made using a focused S00 m W a r g o n - i o n laser beam w i t h a spectral resolution (FWHH) of ~ 8 cm -I. A l l the ROA spectra were acquired f o r 2 hours. The ROA spectra of a-, [3- and ~ , - D - c y c l o d e x t r i n are shown in Figs. 1-3 respectively. The ROA spectra o f D-glucose, D - m a l t o s e and D - m a l t o t r i o s e , to be published elsewhere as part of 513
514
L . D . BARRONet al.
a preliminary survey of ROA spectra o f a range o f carbohydrates, 13 are o f central importance in discussing
the
cyctodextrin
results.
Thus
all
negative-positive c o u p l e t centred at ~ 1340 cm -!
three
cyclodextrin
ROA
spectra
show
a
t h a t also appears in D-glucose (at s l i g h t l y
l o w e r frequency) where i t has been associated w i t h d e f o r m a t i o n s o f the C H 2 O H group; and all three show an ROA "fingerprint" between ~ 980 and 1170 cm -! s i m i l a r to t h a t in glucose and associated w i t h ring C - O and C - C stretching t o g e t h e r with C - O - H
and C - C - H bending which
is characteristic o f the p a t t e r n o f OH ring substituents. The most s t r i k i n g cycloclextrin ROA features are the enormous p o s i t i v e - n e g a t i v e c o u p l e t s between ~ 890 and 960 c m - l : no similar features appear in D-glucose,
but
they appear w i t h
D - m a l t o t r i o s e where they have been associated w i t h
D-maltose
and
modes i n v o l v i n g c o n t r i b u t i o n s f r o m
much
less i n t e n s i t y
in
the
anomeric C ( I ) - H d e f o r m a t i o n s and the glycosidic C - O - C stretch. The general appearance o f the three c y c l o d e x t r i n ROA spectra is i t s e l f quite revealing. Thus the ROA features of
13-D-cyclodextrin
(as p r e d o m i n a n t l y
monoanion
sharp structure, especially in the c o u p l e t centred at ~ 1340 c m - l : seen
in
the
ROA
conformational T-D-cyclodextrin
spectrum
possibilities are
of
D-maltose, 13
in
{3-cyclodextrin
generally
broader
and
[3-D-cyclodextrin (anion), and are remarkably
and
may
and much
reflect
maltose. less
in base 14) show
the same characteristics are a
similar
The
restriction
of
features
of
those
of
ROA
structured
than
similar to those of D-maltotriose, 13 indicating
that y-cyclodextrin might have a similar increase in conformational possibilities to maltotriose on account of the larger ring.
I
a
O.$
V 8OO
t 1200
tO0O
Figure 1. The backscattered Raman
(I R +
IL)
and ROA
1400
(I R -
era"
IL)
spectra
of
c~-D-cyclodextrin in water. The enormous glycosidic c o u p l e t s seen in all three c y c l o d e x t r i n ROA spectra between ~ 890 and 960 cm -1 have dimensionless ROA intensities A -- ( l R - I L ) / ( I R + I L) of several parts in 102 , which is an o r d e r o f magnitude larger than the largest A-values usually encountered. The fact t h a t the A-values of the similar g l y c o s i d i c ROA feature in m a l t o s e and m a l t o t r i o s e have more typical magnitudes, w i t h those o f m a l t o t r i o s e r o u g h l y double those of maltose, is
Vibrational Rarnan optical activity
515
evidence that these large cyclodextrin ROA couplets originate in coupled vibrational modes of the glycosidic
links delocalized around the cyclodextrin
ring. In fact
Raman bands in this
region have been assigned previously to skeletal ring modes involving the glycosidic bonds: 15'16 but only the bands at 949 cm -1 in a-cyclodextrin and 945 cm -1 in 13-cyclodextrin (and by
analogy
that
at
945 cm -1
in
I~-I~a-Cayclodextrln.
y-cyclodextrin)
~
were
explicitly
associated
with a
~
~" 0 f OIS~IOS h.z, L,.~ "" s 1
I
800
1200 . . I
. . . . .
[
. . . . . .
14.00 I
. . . .
J
Cm 4
Figure 2. The backscattered Raman and R O A spectra of 13-D-cyciodextrin in IN NaOH.
y-I~.-Cyctode~trin
i[o5....
/ OOO
O t OQ
t2OO I
.
1
1400
Cm"
Figure 3. The backscattered Raman and R O A spectra of y-D-cyclodextrin in water. delocalizecl ring mode; 15 yet close inspection of our ROA spectra reveals
that the negative
parts of the glycosidic ROA couplets are not in fact associated with these particular bands
L . D . BARRONet al.
516
b u t are at s l i g h t l y lower f r e q u e n c y . We t h e r e f o r e c o n c l u d e t h a t ,
t h r e e cyclodextrins,
in all
there are a t l e a s t t w o o v e r l a p p i n g b a n d s on t h e l o w - f r e q u e n c y side o f t h e p r e v i o u s l y - a s s i g n e d delocalized ring m o d e t h a t are a l s o delocalized a r o u n d t h e c y c l o d e x t r i n ring. We have a l s o m e a s u r e d ROA s p e c t r a o f a q u e o u s s o l u t i o n s o f ~ - D - c y c l o d e x t r i n c o n t a i n i n g the g u e s t m o l e c u l e s s o d i u m b e n z o a t e and t h e t w o e n a n t i o m e r s o f p h e n y l a l a n i n e . While they are g e n e r a l l y very s i m i l a r to t h e s p e c t r a s h o w n here, t h e r e are s o m e s m a l l b u t
significant
local d i f f e r e n c e s which may r e f l e c t a t r a n s f o r m a t i o n f r o m a "tense' to a m o r e s y m m e t r i c a l "relaxed" c o n f o r m a t i o n c o r r e s p o n d i n g to t h e model o f S a e n g e r e t al. 17 I n s t r u m e n t a l i m p r o v e m e n t s are now in hand which s h o u l d provide an o r d e r of m a g n i t u d e increase in s p e e d features
to
be
of
the
measured
m e a s u r e m e n t s . This when
different
will
guests
enable are
quantitative
incorporated,
differences thereby
in
ROA
providing
a
c o m p l e t e l y new s o u r c e of i n f o r m a t i o n on t h e d e t a i l s of c o n f o r m a t i o n a l c h a n g e s associated with the a c c o m m o d a t i o n o f d i f f e r e n t g u e s t s in c y c l o d e x t r i n s in a q u e o u s s o l u t i o n .
Acknowledgments: We t h a n k t h e S.E.R.C and t h e W o l f s o n F o u n d a t i o n f o r r e s e a r c h g r a n t s , the S.E.R.C. f o r a r e s e a r c h s t u d e n t s h i p for A.R.G., and Prof. P. L. Polavarapu a n d Drs. A. F. Drake and (3. E. T r a n t e r f o r discussions.
References I. L. D. Barron, ' M o l e c u l a r Light Scattering and Optical Activity', Cambridge University Press, Cambridge, 1982. 2. L. D. Barton, M. P. Bogaard and A. D. Buckingham, j. Am. Chem. Soc., 1972, 9S, 603.
3. W. Hug, S. Kint, G. F. Bailey and J. R. Scherer, J. Am. Chem. Soe., 1975, 97, 5589. 4. L. D. Barron, in 'Vibrational Spectra and Structure',
H.
D. Bist, J.
R. Durig
and J. F.
Sullivan, Eds., Elsevier, Amsterdam, 1989, Vol. 17B, p. 343. 5. L. A. Nafie and C. G. Zimba, in 'Biological Applications of Raman Spectroscopy', T. G. Spiro, Ed., Wiley, New York, 1987, Vol. 1, p. 307. 6. L Hecht, L. D. Barron and W. Hug, Chem. Phys. Lett., 1989, 1S8, 341. 7. W.
Hug,
in "Raman Spectroscopy', J. Lascombe and P. V.
Huong,
Eds.,
Wiley-Heyden,
Chichester, 1082, p. 3. 8. L. D. Barron, L. Hecht, W. Hug and M. J. Maclntosh, J. Am. Chem. Sot., 1989, I l l ,
873{.
9. C. W. Johnson, j r . , Advances in Carbohydrate Chemistry and Biochemistry, 1987, 45, 73. lO. D. G. Lewis and W. C. Johnson, Jr., Biopolymers, 1978, 11, 1439. 11. C. M. Tummalapal{i, D. M. Back and P. L
Polavarapu, J. Chem. Sot.,
Faraday Trans. 1,
1988, 84, 2585, and references therein. 12. L. D. Barron, D. J. C u t l e r and J. F. Torrance, J. Raman Spectros¢., 1987, {8, 281. 13. L. D. Barton, A. R. Gargaro and Z. Q. Wen, Carbohydr. Res., s u b m i t t e d f o r publication. 14. R. I. Gelb, L. M. Schwartz, j . j . Bradshaw and D. A. Laufer, Bioorg. Chem., 1980, 9, 299. 15. J. J. Cael, J. L. Koenig and J. Blackwell, Carbohydr. Res., 1973, 29, 123. 16. A. T. Tu, J. Lee and F. P. Milanovich, Carbohydr. Res., 1979, 76, 239. 17. W. Saenger, M. Noltemeyer, P. C. Manor, B. Hingerty and B. Klar, Bioorg. Chem., 1976, S, 187.
,.
0957-4166/90 $3.00+.00 Pe~gamort Presspie
Printed in Great Britain
Vibrational Rarnan Optical Activity of Cyclodextrins Laurence D. Barton e, Angelo P.. Gargaro, Zal Q. W e n David D. MacNlcol a n d C o l i n Butters
Chemistry Department, The University, Glasgow, G12 8QQ, U.K.
(Received 5 June 1990)
Abstract: Vibrational Raman optical activity spectra of aqueous solutions of ~-,
[3-
and ~,-D-cyclodextrin in the range 700-1500 cm -1 are reported. As well as showing features characteristic of D-glucose, the ROA spectra all show remarkably intense features between 890 and 960 cm -1 ori9inating in coupled C ( 1 ) - H deformations and glycosidic C-O stretches delocalized around the cyclodextrin rin 9 and which reflect the stereochemistry of the glycosidic links. Vibrational
optical
activity
measurements
stereochemical
information
every part of
the molecule. 1 V i b r a t i o n a l
on
because a vibrational
chiral
molecules
spectrum
can
contains
optical a c t i v i t y in
typical
provide much
bands chiral
associated molecules
new with
in
the
disordered phase was f i r s t observed using the Raman o p t i c a l a c t i v i t y (ROA) technique, which measures
a small
difference
in
the
polarized incident light. 2"3 U n t i l
Raman-scattered
recently,
lack of
intensity
sensitivity
in
right
and
has r e s t r i c t e d
left
circularly
ROA studies
to
favourable samples such as neat liquids; 4'$ b u t a major b r e a k t h r o u g h in ROA i n s t r u m e n t a t i o n based on the use of a backscattering g e o m e t r y 6'7 t o g e t h e r w i t h a cooled CCD d e t e c t o r 8 has now rendered a much wider range of samples accessible to such studies. This communication reports ROA spectra o f c y c l o d e x t r i n s in aqueous s o l u t i o n
which indicate that this technique
has great p o t e n t i a l f o r stereochemical studies o f these and o t h e r polysaccharides. Most carbohydrates (ECD)
measurements,
are
which
not
well
suited
are r e s t r i c t e d
to
to the
conventional
electronic
long-wavelength
bands; 9 nonetheless, some useful i n f o r m a t i o n a b o u t c o n f o r m a t i o n s
tails
circular of
the
dichroism first
ECD
o f c y c l o d e x t r i n s has been
obtained in this way. 10 Vibrational o p t i c a l a c t i v i t y spectra o f simple carbohydrates obtained using ROA's sibling technique o f vibrational circular dichroism (VCD) have been reported, tt b u t no VCD spectra of cyclodextrins have so far been published. The ROA spectra were recorded using the Glasgow multichannel for
backscattering 6'7 and CCD
Aldrich
and
Fluka
and
detection. 8 The c y c l o d e x t r i n
studied
as
near-saturated
samples
solutions,
in
i n s t r u m e n t 12 modified were
purchased
water
for
ct-
from and
T - D - c y c l o d e x t r i n , and in I N NaOH f o r [3-D-cyclodextrin in o r d e r to b o o s t the s o l u b i l i t y . The ROA measurements were made using a focused S00 m W a r g o n - i o n laser beam w i t h a spectral resolution (FWHH) of ~ 8 cm -I. A l l the ROA spectra were acquired f o r 2 hours. The ROA spectra of a-, [3- and ~ , - D - c y c l o d e x t r i n are shown in Figs. 1-3 respectively. The ROA spectra o f D-glucose, D - m a l t o s e and D - m a l t o t r i o s e , to be published elsewhere as part of 513
514
L . D . BARRONet al.
a preliminary survey of ROA spectra o f a range o f carbohydrates, 13 are o f central importance in discussing
the
cyctodextrin
results.
Thus
all
negative-positive c o u p l e t centred at ~ 1340 cm -!
three
cyclodextrin
ROA
spectra
show
a
t h a t also appears in D-glucose (at s l i g h t l y
l o w e r frequency) where i t has been associated w i t h d e f o r m a t i o n s o f the C H 2 O H group; and all three show an ROA "fingerprint" between ~ 980 and 1170 cm -! s i m i l a r to t h a t in glucose and associated w i t h ring C - O and C - C stretching t o g e t h e r with C - O - H
and C - C - H bending which
is characteristic o f the p a t t e r n o f OH ring substituents. The most s t r i k i n g cycloclextrin ROA features are the enormous p o s i t i v e - n e g a t i v e c o u p l e t s between ~ 890 and 960 c m - l : no similar features appear in D-glucose,
but
they appear w i t h
D - m a l t o t r i o s e where they have been associated w i t h
D-maltose
and
modes i n v o l v i n g c o n t r i b u t i o n s f r o m
much
less i n t e n s i t y
in
the
anomeric C ( I ) - H d e f o r m a t i o n s and the glycosidic C - O - C stretch. The general appearance o f the three c y c l o d e x t r i n ROA spectra is i t s e l f quite revealing. Thus the ROA features of
13-D-cyclodextrin
(as p r e d o m i n a n t l y
monoanion
sharp structure, especially in the c o u p l e t centred at ~ 1340 c m - l : seen
in
the
ROA
conformational T-D-cyclodextrin
spectrum
possibilities are
of
D-maltose, 13
in
{3-cyclodextrin
generally
broader
and
[3-D-cyclodextrin (anion), and are remarkably
and
may
and much
reflect
maltose. less
in base 14) show
the same characteristics are a
similar
The
restriction
of
features
of
those
of
ROA
structured
than
similar to those of D-maltotriose, 13 indicating
that y-cyclodextrin might have a similar increase in conformational possibilities to maltotriose on account of the larger ring.
I
a
O.$
V 8OO
t 1200
tO0O
Figure 1. The backscattered Raman
(I R +
IL)
and ROA
1400
(I R -
era"
IL)
spectra
of
c~-D-cyclodextrin in water. The enormous glycosidic c o u p l e t s seen in all three c y c l o d e x t r i n ROA spectra between ~ 890 and 960 cm -1 have dimensionless ROA intensities A -- ( l R - I L ) / ( I R + I L) of several parts in 102 , which is an o r d e r o f magnitude larger than the largest A-values usually encountered. The fact t h a t the A-values of the similar g l y c o s i d i c ROA feature in m a l t o s e and m a l t o t r i o s e have more typical magnitudes, w i t h those o f m a l t o t r i o s e r o u g h l y double those of maltose, is
Vibrational Rarnan optical activity
515
evidence that these large cyclodextrin ROA couplets originate in coupled vibrational modes of the glycosidic
links delocalized around the cyclodextrin
ring. In fact
Raman bands in this
region have been assigned previously to skeletal ring modes involving the glycosidic bonds: 15'16 but only the bands at 949 cm -1 in a-cyclodextrin and 945 cm -1 in 13-cyclodextrin (and by
analogy
that
at
945 cm -1
in
I~-I~a-Cayclodextrln.
y-cyclodextrin)
~
were
explicitly
associated
with a
~
~" 0 f OIS~IOS h.z, L,.~ "" s 1
I
800
1200 . . I
. . . . .
[
. . . . . .
14.00 I
. . . .
J
Cm 4
Figure 2. The backscattered Raman and R O A spectra of 13-D-cyciodextrin in IN NaOH.
y-I~.-Cyctode~trin
i[o5....
/ OOO
O t OQ
t2OO I
.
1
1400
Cm"
Figure 3. The backscattered Raman and R O A spectra of y-D-cyclodextrin in water. delocalizecl ring mode; 15 yet close inspection of our ROA spectra reveals
that the negative
parts of the glycosidic ROA couplets are not in fact associated with these particular bands
L . D . BARRONet al.
516
b u t are at s l i g h t l y lower f r e q u e n c y . We t h e r e f o r e c o n c l u d e t h a t ,
t h r e e cyclodextrins,
in all
there are a t l e a s t t w o o v e r l a p p i n g b a n d s on t h e l o w - f r e q u e n c y side o f t h e p r e v i o u s l y - a s s i g n e d delocalized ring m o d e t h a t are a l s o delocalized a r o u n d t h e c y c l o d e x t r i n ring. We have a l s o m e a s u r e d ROA s p e c t r a o f a q u e o u s s o l u t i o n s o f ~ - D - c y c l o d e x t r i n c o n t a i n i n g the g u e s t m o l e c u l e s s o d i u m b e n z o a t e and t h e t w o e n a n t i o m e r s o f p h e n y l a l a n i n e . While they are g e n e r a l l y very s i m i l a r to t h e s p e c t r a s h o w n here, t h e r e are s o m e s m a l l b u t
significant
local d i f f e r e n c e s which may r e f l e c t a t r a n s f o r m a t i o n f r o m a "tense' to a m o r e s y m m e t r i c a l "relaxed" c o n f o r m a t i o n c o r r e s p o n d i n g to t h e model o f S a e n g e r e t al. 17 I n s t r u m e n t a l i m p r o v e m e n t s are now in hand which s h o u l d provide an o r d e r of m a g n i t u d e increase in s p e e d features
to
be
of
the
measured
m e a s u r e m e n t s . This when
different
will
guests
enable are
quantitative
incorporated,
differences thereby
in
ROA
providing
a
c o m p l e t e l y new s o u r c e of i n f o r m a t i o n on t h e d e t a i l s of c o n f o r m a t i o n a l c h a n g e s associated with the a c c o m m o d a t i o n o f d i f f e r e n t g u e s t s in c y c l o d e x t r i n s in a q u e o u s s o l u t i o n .
Acknowledgments: We t h a n k t h e S.E.R.C and t h e W o l f s o n F o u n d a t i o n f o r r e s e a r c h g r a n t s , the S.E.R.C. f o r a r e s e a r c h s t u d e n t s h i p for A.R.G., and Prof. P. L. Polavarapu a n d Drs. A. F. Drake and (3. E. T r a n t e r f o r discussions.
References I. L. D. Barron, ' M o l e c u l a r Light Scattering and Optical Activity', Cambridge University Press, Cambridge, 1982. 2. L. D. Barton, M. P. Bogaard and A. D. Buckingham, j. Am. Chem. Soc., 1972, 9S, 603.
3. W. Hug, S. Kint, G. F. Bailey and J. R. Scherer, J. Am. Chem. Soe., 1975, 97, 5589. 4. L. D. Barron, in 'Vibrational Spectra and Structure',
H.
D. Bist, J.
R. Durig
and J. F.
Sullivan, Eds., Elsevier, Amsterdam, 1989, Vol. 17B, p. 343. 5. L. A. Nafie and C. G. Zimba, in 'Biological Applications of Raman Spectroscopy', T. G. Spiro, Ed., Wiley, New York, 1987, Vol. 1, p. 307. 6. L Hecht, L. D. Barron and W. Hug, Chem. Phys. Lett., 1989, 1S8, 341. 7. W.
Hug,
in "Raman Spectroscopy', J. Lascombe and P. V.
Huong,
Eds.,
Wiley-Heyden,
Chichester, 1082, p. 3. 8. L. D. Barron, L. Hecht, W. Hug and M. J. Maclntosh, J. Am. Chem. Sot., 1989, I l l ,
873{.
9. C. W. Johnson, j r . , Advances in Carbohydrate Chemistry and Biochemistry, 1987, 45, 73. lO. D. G. Lewis and W. C. Johnson, Jr., Biopolymers, 1978, 11, 1439. 11. C. M. Tummalapal{i, D. M. Back and P. L
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