Interaction of potassium fluoride with α-D-glucose

Article abstract of DOI:10.1016/S0022-1139(01)00359-1

Addition of KF to solutions of α-D-glucose (αDG) in DMSO-d₆ and D₂O alters the ¹H NMR spectra, which is attributed to an interaction of the hydrogen atoms of the -OH groups with the basic F^- anions of the salt. It is shown that K⁺ cations do not interact with the oxygen atoms of the -OH groups of the αDG. Mutarotation rates of αDG in D₂O in the presence of potassium halides and alkaline chlorides were measured from the integrated ¹³C NMR signal of the anomeric protons. The mutarotation rates were higher with KF than other potassium halides. In order to shed light on the interactions of KF with the αDG, the mutarotation of αDG in the presence of KF and KOH were also studied using polarimetric measurements. At similar pH values, the effect of KF on the mutarotation rate is about five times that observed for KOH, indicating a major affinity for the F^- anion by the anomeric proton as compared with OH^-. The acceleration of the mutarotation process of αDG is evidence for KF-αDG interactions, since NMR spectra of β conformer are also altered by the presence of KF.

Full text of DOI:10.1016/S0022-1139(01)00359-1

Journal of Fluorine Chemistry 110 ꢀ2001) 5±10
Interaction of potassium ¯uoride with a-D-glucose
a,b,*
Regino Gonz a lez , Pedro Ortiz , Edilso Reguera , Jos e F. Bertr a n
a,b
a,c
a,d
a
Centro de Investigaci o n en Ciencia Aplica y Tecnolog Âõ a Avanzada del Instituto, Polit e cnico Nacional ꢀCICATA-IPN),
Calzada Legaria, No. 694, Colonia Irrigaci o n, Delegaci o n Miguel Hidalgo, Mexico D.F., C.P. 11500, Mexico
b
Facultad de Qu Âõ mica-IMRE, Universidad de la Habana, Habana 10400, Cuba
c
IMRE, Universidad de La Habana, Habana 10400, Cuba
d
Centro de Qu Âõ mica Farmace u tica, Habana, Cuba
Received 25 September 2000; accepted 23 January 2001
Abstract
Addition of KF to solutions of a-D-glucose ꢀaDG) in DMSO-d
of the hydrogen atoms of the ±OH groups with the basic F anions of the salt. It is shown that K cations do not interact with the oxygen
1
6
and D
2
O alters the H NMR spectra, which is attributed to an interaction
À
‡
2
atoms of the ±OH groups of the aDG. Mutarotation rates of aDG in D O in the presence of potassium halides and alkaline chlorides were
measured from the integrated 13C NMR signal of the anomeric protons. The mutarotation rates were higher with KF than other potassium
halides. In order to shed light on the interactions of KF with the aDG, the mutarotation of aDG in the presence of KF and KOH were also
studied using polarimetric measurements. At similar pH values, the effect of KF on the mutarotation rate is about ®ve times that observed
À
À
for KOH, indicating a major af®nity for the F anion by the anomeric proton as compared with OH . The acceleration of the mutarotation
process of aDG is evidence for KF±aDG interactions, since NMR spectra of b conformer are also altered by the presence of KF.
#
2001 Elsevier Science B.V. All rights reserved.
Keywords: Potassium ¯uoride ꢀKF); a-D-Glucose; Proton NMR; Mutarotation
1
. Introduction
constant for a- and b-D-glucose over a wide temperature
range, from 0 to 408C [13]. Also, the reaction constant is
independent of the concentration of sugar over a wide range.
Later work revealed that catalysis of mutarotation is not an
exclusive property of hydrogen and hydroxyl ions [13]. It
has been reported [14] that the determination of the catalytic
activity of anions of weak acids requires adjustment of the
pH of the solution in order to keep the concentration of
hydroxyl ion low, because the catalytic activity of the
hydroxyl ions resulting from hydrolysis of the salt is so
great that it masks the smaller catalytic effect of the anion.
Evaluation of the catalytic activity of the hydroxyl ion is
dif®cult, because the mutarotation becomes too rapid to
allow an accurate measurement. Small variations in the
hydroxyl ion concentration cause large differences in the
reaction rates. It has been reported that the mutarotation
process of aDG follows kinetics of pseudo-®rst-order [13].
The aim of the present paper is to shed light on the nature of
aDG±KF interactions using NMR spectroscopy and polari-
metric measurements. According to the obtained evidence,
The interaction of metallic cations with carbohydrates is a
subject of growing interest in recent years due to the
importance of the complexes in chemistry [1±3] and biology
[
4±8]. Most of the work has been carried out in aqueous
solutions. The models used for the analysis of the interaction
are based in the structure of the sugars and the properties of
the cations ꢀcharge, size, polarizability) with practically no
reference to the role of the anions [9].
Recently, it has been reported on the interaction in the
solid state of alkali ¯uorides with acidic substances where
À
the stability of the acid ¯uoride anion, HF2 , determines the
course of the mechanochemical reactions [10]. A strong
interaction is also observed between KF and D-xylose, both
in solid state and from methanolic solutions, with formation
of a KF±xylose complex [11]. According to IR and NMR
spectra, the driving force of the complex formation is the
interaction of F with the ±OH protons.
Mutarotation of all reducing sugars are catalyzed by acids
and bases [12], with a same value of the mutarotation
À
À
‡
the main role is played by the F ion and not by the K ion. In
ordertodiscard the effectof the salt hydrolysis intheobserved
interactions, parallel polarimetric experiments were carried
out adding KOH to the aDG aqueous solution instead of KF.
*
Corresponding author.
E-mail address: reginog@yahoo.es ꢀR. Gonz a lez).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 3 5 9 - 1

6
R. Gonz a lez et al. / Journal of Fluorine Chemistry 110 ꢀ2001) 5±10
2
2
. Experimental
signals was based on the work of Perlin [18]. When KF is
1
added to a solution of aDG in DMSO-d , the H NMR
6
.1. Reagents
spectrum shows signi®cant changes ꢀsee Fig. 2). All the OH
proton signals are broadened. The signals of the anomeric
protons H1a and H1b can now be clearly seen. The coupling
The KF, KOH and aDG used in this study were analytical
grade commercial products ꢀMerck, Sigma). Water was
doubly distilled.
3J
excludes the possibility that these protons could be
H1ÀH2
involved in some dynamic process due to conformational
change in the sugar molecule. Therefore, the broadening of
the signals is not due to the in¯uence of the other proton
linked to the same carbon atom. We interpreted the observed
2
2
.2. Measurements
À
.2.1. Spectroscopic data
The KF±aDG interactions both in DMSO-d and D O
broadening as a result of the interactions of the basic F
6
2
anions with protons of OH groups of the aDG. To test the
validity of this hypothesis, experiments with other potassium
salts including KCl, KBr and KI instead of KF added to aDG
were measured in a JEOL ECLIPSE 270 FT NMR pulse
spectrometer, using 270 MHz for the 1H NMR and
6
7.5 MHz for the 13C NMR spectra. For NMR kinetic
solutions in DMSO-d instead of KF were carried out. The
1
6
experiments, solutions of KF and aDG in D O were prepared
corresponding H NMR spectra do not show signi®cant
modi®cations when compared with that of pure aDG
ꢀFig. 1). Also, this proves that K cations do not interact
2
ꢀ
at T ˆ 20 C and the spectra were taken at different times up
‡
to 48 h ꢀtaken as in®nite time). The ratio of aDG to bDG in
the solution was determined by means of anomeric signal
integration in each 13C NMR spectrum. The salts were
dissolved until saturation.
with the oxygen atoms of the OH groups of the aDG, and
therefore, the observed changes in the NMR signals when
À
KF is added to aDG solutions must be only due to F and
OH groups interactions.
À
2
.2.2. Optical rotation
Given amounts of KF or KOH and aDG were dissolved in
3.2. Mutarotation kinetic from NMR spectra in D O
2
water, quickly poured into a 20-cm cell, and the optical
rotation measured at 188C at certain time intervals with a
polarimeter Polax Atago Kagaku Co. instrument. In order to
minimize the time required for dissolution, the aDG should
be ground.
The mutarotation kinetics from NMR spectra were deter-
mined in D O because the water is one of the most common
2
solvents used in the study of interactions of carbohydrates
with other species. The results of the kinetic study are shown
in Table 1. In all runs, the regression coef®cient was
>0.9980. Mutarotation of aDG in the presence of KF is very
fast, so it is impossible to obtain reliable data on the percent
conversion of aDG versus time. The calculated values of the
2
.2.3. Kinetic
In all cases ꢀfrom NMR and optical rotation data), mutar-
otation rate was determined by the expression
ꢀ
ꢁ
0
pseudo-®rst-order constant k for the mutarotation of aDG
1
b À f
1
k ˆ
log
in the presence of KCl, KBr and KI or in absence of these
salts were similar ꢀsee Table 1). It seems that only KF
shows a pronounced interaction with aDG. In order to study
t2 À t1
b À f
2
where b and b are the values at the end of the correspond-
1
2
ing times t and t , and f the constant final and was
the cation effect on the mutarotation rate of aDG in D O,
2
1
2
measured at 48 h. From the slope of each straight line
obtained in the first-order plot of the data, a pseudo-first-
order rate constant, k , was estimated. The mutarotation
constant is expressed by use of logarithmic base 10 and the
time in minutes, because this custom has been largely
maintained by carbohydrate chemists [15].
NMR spectra were recorded adding LiCl, NaCl and CsCl.
No signi®cant role of the cation on the mutarotation rate of
0
0
aDG was observed since the calculated k values were
similar in the presence of these last salts and also similar
0
to the k value in water without a catalyst ꢀsee Table 1). The
observed increase in the mutarotation rate when KF is
added to a aDG solution in D O is assumed to be due to
2
À
an interaction between aDG and the F ion. These results
are in accordance with the above-discussed experiments
3
. Results and discussion
0
in DMSO-d . When compared in water, the obtained k
6
3
.1. Interactions of KF with a-D-glucose in DMSO-d6
In order to study the mechanism of KF±aDG interactions,
values in D O was slightly smaller because of an isotopic
2
effect [12].
DMSO-d was selected because in this solvent, the equili-
brium processes for monosaccharides are slow on the NMR
time scale ꢀion sugar equilibrium, mutarotation) [16,17].
3.3. Mutarotation rate of a-D-glucose in water in the
presence of KF
6
1
The H NMR spectra of aDG in DMSO-d in the 4.10±
Mutarotation of aDG in the presence of KF was too fast
and it was not possible to obtain the mutarotation rate data in
6
6
.80 ppm region are shown in Fig. 1. The assignment of the

R. Gonz a lez et al. / Journal of Fluorine Chemistry 110 ꢀ2001) 5±10
7
Fig. 1. 1H NMR spectrum of a-D-glucose in DMSO-d
. Indicated are the assignments of the observed signals.
6
the time from 13C NMR spectra, so it was necessary to make
polarimetric measurements.
its conformers in the solution. The effect of a base, like
KOH, on the mutarotation is well-known [12]. KF is a salt,
which undergoes hydrolysis in aqueous solution. One could
think that the observed effect of KF on the mutarotation of
aDG is associated to hydrolysis of this salt. However, at
similar pH value, the effect of KF ꢀmeasured through the
Mutarotation rate of aDG in the presence of KF was
measured and compared with those obtained in water with
and without addition of KOH as catalyst. Fig. 3 shows how
the mutarotation of aDG evolves in water when KF or KOH
is added. In Table 2 are collected the pseudo-®rst-order rate
constants calculated for different concentrations of KF or
KOH. The equilibrium values in water and KF were similar
and smaller than that observed with KOH, which was
attributed to the formation of gluconate ion when KOH is
added. As expected, any of these two substances ꢀKFor KOH)
accelerates the evolution of the sugar to the equilibrium of
0
value of k ) is about ®ve times that observed for KOH
À
ꢀTable 2), indicating a major interaction of F anion with
the protons, when compared with KOH. However, the
interaction of KF with aDG is not limited to an increase
in the mutarotation rate to reach equilibrium of conformers.
1
The H NMR signals of the OH protons of the b conformer
also show a pronounced broadening when KF is present
Table 1
0
Values of pseudo-first-order constant ꢀk ) derived from NMR spectra for the mutarotation of the a-D-glucose, in deuterium oxide, in the presence of potassium
halides and alkaline chloride
Salt
Only D
2.62
2
O
Only D
2.60
2
O
KF
KCl
3.0
KBr
2.10
KI
LiCl
1.97
NaCl
2.31
CsCl
2.00
0
3
À1 a
b
±
k ꢀÂ 10 min
)
2.00
a
ꢀ
All measurements were carried out at T ˆ 20 C.
b
The mutarotation was too fast to allow the acquisition of a representative NMR spectrum.

8
R. Gonz a lez et al. / Journal of Fluorine Chemistry 110 ꢀ2001) 5±10
Fig. 2. 1H NMR spectrum of a-D-glucose in DMSO-d
anomeric protons in a-D-glucose are well resolved.
when KF is added. The broadening of the OH proton signals can be observed. Now the signals of
6
ꢀ
see Fig. 2). The increase in the mutarotation rate is only a
of KF follows a pseudo-®rst-order behavior ꢀsee Fig. 4). The
0
way to reveal the KF±aDG interactions.
From the kinetical point of view, there are some points
that deserve comment. The mutarotation rate in the presence
calculated pseudo-®rst-order constant k , shows a linear
dependence of the KF concentration ꢀsee Fig. 5). From
the slope of Fig. 5, the following pseudo-second-order
0
À1
À1
constant was derived: k ˆ 0:00735 l mol min . There-
0
fore, k can be expressed as
k0 ˆ kH2O‰FÀŠ
where the term kH O represents the contribution of the water
2
molecules. Since [H O] varies only slightly in aqueous
2
systems, its effect is usually included in the kH2O term.
Thus, the mutarotation rate of aDG in the presence of KF
is given by
Àd‰adGŠ
À
ˆ
kH O‰adGŠ‰F Š
2
dt
The most acidic protons of the sugar are those of the
À
anomeric OH groups. The major KF±aDG interactions
must proceed through these protons, catalyzing the opening
of the sugar ring at that site to favor the mutarotation
process. The mutarotation begins with the ionization of
Fig. 3. Rotation power of a-D-glucose in water with and without KF and
KOH added as catalyst.

R. Gonz a lez et al. / Journal of Fluorine Chemistry 110 ꢀ2001) 5±10
9
Table 2
Experimental conditions and the values of pseudo-first-order constant for the mutarotation of a-D-glucose in water, in the presence of KF and KOH
a
À1
À1
À1
0
3
À1 a
b
b
Experiment
[a-D-Glucose] ꢀmol l
)
[KF] ꢀmol l
)
[KOH] ꢀmol l
)
k ꢀÂ 10 min
)
pH1
pH2
c
G1
0.2001
±
±
6.4
7.5
7.01
7.80
6.85
6.90
7.00
7.25
7.14
7.20
7.65
7.70
5.71
6.78
8.85
9.20
9.35
11.50
d
G2
G3
0.2003
0.2262
0.2262
0.2438
0.2330
0.2614
0.2335
0.2334
0.2455
0.2453
0.2450
0.2457
0.2310
0.0356
0.2363
0.4750
0.4774
0.6166
0.7155
1.0361
±
d
±
24.5
28.0
27.9
39.0
55.0
67.0
8.7
8.01
d
G4
±
8.32
d
G5
±
8.31
d
G6
G7
±
8.35
8.42
d
±
d
G8
±
8.53
e
G9
±
0.000001
0.000013
0.000150
0.000240
0.000370
0.003500
7.98
9.12
e
G10
G11
G12
G13
G14
±
8.7
e
±
31.5
58.1
93.0
10.10
10.38
10.57
11.54
e
±
e
±
e
f
±
±
a
ꢀ
All measurements were carried out at T ˆ 18 C.
b
c
d
e
f
pH1 and pH2 are the pH values at t ˆ 0 min and at the end of the mutarotation process, respectively.
Mutarotation of a-D-glucose in absence of a catalyst.
With KF as catalyst.
With KOH as catalyst.
The mutarotation was very fast to allow a reliable measurement.
0
Fig. 5. Dependence of the pseudo-first-order rate constant, k , on the initial
concentration of KF.
Fig. 4. Pseudo-first-order plots of the mutarotation process of a-D-glucose
in water in the presence of KF.
1
the sugar. The mutarotation mechanism involves mobile and
reversible addition of a catalyst to the sugar anion, followed
by slow rupture of the ring, as in the base-catalyzed mechan-
ism suggested in [12].
suf®cient to explain the observed broadening in the H NMR
signals of the OH groups of the sugar when KF is added. In
addition, they are also suf®cient to accelerate the mutarota-
tion process.
KF is a salt, which shows a pronounced interaction with
acidic protons [11]. In solid state reactions with acidic
À
substances, F anions collect protons to form the acidic
salt KHF [11]. For weakly acidic substances, the presence
4. Conclusions
2
of water can hinder the occurrence of the proton transfer
reactions due to the solvation effect of water [19]. The
protons of sugar are not too acidic to be removed by
interaction with KF, however, at least in the solid state that
interaction is very pronounced shifting the O±H stretching
bands ꢀin the IR spectra) toward the lower frequency. The
interaction in solution ꢀDMSO, D O or H O) are weaker, but
When KF is added to solutions of aDG in DMSO-d , the
H NMR signals of the OH groups of the sugar are sig-
ni®cantly broadened. When the NMR experiments are car-
6
1
ried out in D O, a pronounced increase in the mutarotation
2
rate of the sugar is observed. The observed changes can be
À
ascribed to the F anion since no effects are observed for
other potassium halides or alkali chlorides. When the mutar-
2
2

10
R. Gonz a lez et al. / Journal of Fluorine Chemistry 110 ꢀ2001) 5±10
[
[
[
2] J.F. Verchere, J.P. Sanvage, G.R. Rapaumbya, Analyst 115
1990) 637.
otation process is studied by a polarimetric method in
parallel experiments by adding KF or KOH to the aDG
aqueous solutions at similar OH concentration, KF shows an
activity ®ve times that observed for KOH suggesting that the
observed effect of KF is not directly related with its hydro-
lysis in water. From these observations, then appears to be a
direct interaction of KF with aDG.
ꢀ
3] J.M. Harrowfield, M. Mocerino, B.W. Skeltin, W. Wei, A.H. White, J.
Chem. Soc., Dalton Trans. ꢀ1995) 783.
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5] S. Yano, T. Otsuka, Metal Ions Biol. Syst. 32 ꢀ1996) 27.
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Acknowledgements
[
9] J.A. Rendleman, Food Chemistry, Vol. 3, Applied Science Publishers,
UK, 1978, p. 47.
The authors gratefully acknowledge the support of the
sponsor of this research: Centro de Investigaci o n en Ciencia
Aplicada y Tecnolog Âõ a Avanzada del Instituto Polit e cnico
Nacional ꢀM e xico). The interest of Dr. Feliciano S a nchez-
Sinencio for our research in this ®eld is also gratefully
appreciated.
[
10] J. Fern aÁ ndez-Bertr aÁ n, E. Reguera, Solid State Ion. 93 ꢀ1997) 139.
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[
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14] H.S. Isbell, W. Pigman, Adv. Carbohyd. Chem. 24 ꢀ1969) 18.
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New York, 1940, p. 100.
[
[
[
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