Stability constants of D(−)-ribose complexes with calcium in diluted aqueous and methanolic solutions

MICROCHEMICAL

JOURNAL

27, 372-379

(1982)

Stability Constants of D(-)-Ribose Complexes with Calcium in Diluted Aqueous and Methanolic Solutions M. TOMASKOVIC,

Z.CIMERMAN,

AND Z.~TEFANAC

AND

E. PRETSCH AND J.BENDL Department

of Orgcrnic Chemistry, Ziirich, Received

SM’iss Federal Itwtittrtr S~vitzerland

of Technology,

August 3, 1981

INTRODUCTION

Convincing evidence that sugar complexes with alkali metals exist in alcoholic and aqueous media, based on polarographic and ebulliometric analyses, polarimetric measurements, and electrophoretic behaviour, has been presented by Rendleman (13, 14). Complex formation with alkaline earth cations has been also investigated and extensive information is now at disposal, owing in the first place to the contributions of Angyal and co-workers (I -5). The stability constants of the complexes formed by numerous carbohydrates with various cations in neutral aqueous solution have been determined. ‘H-NMR spectroscopy has been used as the method of choice, with rather high concentrations of both carbohydrate and metal ion. In some cases concurrent potentiometric measurements with ion-selective electrodes have also been performed (3, 6). The stability constants for D( -)-ribose complexes with calcium have been obtained by ‘H-NMR spectroscopy in 1.27 h4 calcium chloride solutions (I). The present paper refers to the stability constants of these complexes in diluted aqueous and methanolic solutions. EXPERIMENTAL

Appnrafus. Vapor pressure osmometric measurements were performed with a Hitachi Perkin-Elmer Model 115 for measuring molecular weight. The calibration constant for benzil was k = 8500 ohm kg g-mole-‘. A calcium selective electrode with a neutral carrier membrane kindly 372 0026-265X/82/030372-08$01.00/0 Copyright All riehts

0 1982 by Academic Press, Inc. of remoduction in any form reserved.

D(-)-RIBOSE

COMPLEXES

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CALCIUM

373

donated by professor W. Simon (ETH, Zurich, Switzerland) referred to a saturated calomel reference electrode (K 401 Radiometer) was used for measuring pCA. The pH was measured with a Radiometer G 202 C glass electrode. The EMF and pH measurements were performed with a Radiometer pHM 64 mV/pH meter at 20 2 0.5”C. Reagents. D(-)-Ribose was a Senn Chemicals product of 98% purity and calcium chloride p.a. was a product of Kemika (Zagreb, Yugoslavia). Methanol p.a. was absolutized by treatment with magnesium and molecular sieves. Quartz bidistilled water was used throughout. Procedures. Two approaches were pursued in vapor pressure osmometric measurements. The solutions containing continuously varying calcium to D( -)-ribose ratios were measured with respect to pure solvent (Hz0 or MeOH) on the reference thermistor. Resistance changes were separately recorded with pure calcium as well as with pure D(-)-ribose solutions of molality sequences corresponding to the series of mixed solutions (12). The method of differential vapor pressure osmometry was used for determining the average number of D( -)-ribose molecules per calcium ion and the stability constants in methanolic solutions (9). All measurements were performed at 40°C. Potentiometric titrations were carried out in aqueous media by successive addition of small increments of CaCl, solution to a fixed 20.0 m] volume of D( -)-ribose solution. Instead of calibrating the electrode with solutions of a known calcium concentration in the effective concentration region of the free cation in a solution containing salt, ligand, and complex at equilibrium, reference titrations of water samples (20.0 ml) with calcium chloride were performed before and after the ligand titration (8, 11). The free calcium corresponding to each increment of the titrant was obtained by interpolation from the reference titration curve. Even though the EMF differences between titration runs and reference titration curves were very small, analogous values were repeatedly recorded with excellent reproducibility. Dilution by titrant was taken into account and consistent stability constants were obtained over the whole range of calcium concentrations, not exceeding 0.1643 mole x l-l, the initial ligand concentrations being 0.099 mole x 1-l. The pH in the course of titration was within the range 6.1-5.9. RESULTS

AND DISCUSSION

Coordination to oxygen atoms without abstraction of hydroxylic protons is characteristic not only of sugar complexes with metal ions formed in neutral media but also of numerous complexes of crown ethers, cryp-

374

TOMASKOVIC

ET AL.

tates, and antibiotics. Analogy is further present when methods for studying complex formation and determining stability constants are considered (7-9, 11, 12). In the case of sugar complexes the main problem concerns the steric arrangement and restricted number of oxygen atoms (4). Accordingly, stability constants are significantly lower, i.e., the measured effects weaker, the more so as the solutions are more diluted. The results which follow should be considered with a view to the outlined circumstances. Vapor pressure osmometric studies of D(-)-ribose complexing with calcium in aqueous solutions 1 x lo-’ M with regard to both components had been discontinued for lack of a measurable effect. Subsequent measurements were performed in methanolic solutions as the complexing of sugars with metal ions is generally much stronger in alcoholic than in aqueous solutions (3). A wide scatter of data evident even from one series of experiments (Fig. 1) accompanying the small osmolality changes made the estimation of the stoichiometric proportion impossible. Therefore not

Am Osm

2.0-1 100%

1%

1x1G2M C&l2 in Methanol

80

1~10~~~ O-R&

inxMethan”DI

FIG. 1. Complex formation of D(-)-ribose with calcium in methanol (40°C). Osmolality change A (in milliosmoles, mOsm) in dependence of calcium and D( -)-ribose weight content of solutions measured by vapor pressure osmometry. The circles represent values calculated from the experimental data while the curves were calculated with the noted values of stability constants.

D(-)-RIBOSE

COMPLEXES

WITH

CALCIUM

375

more than a positive evidence of the existence of complex species and an approximate impression of the extent of complexing resulted. Differential vapor pressure osmometric measurements definitely show the existence not only of 1:l but also of 1:2 complex species by a steep increase of ii, the average number of D(-)-ribose molecules per calcium (Fig. 2). The stability constant values K1 = 28 kg x mole-’ (RSD = 82%) and K1 x K, = 96.5 kg* x mole-* (RSD = 6.6%) should be interpreted with care (Fig. 3). The large error (50%) pointed out in the original paper (9) is in our case even larger and the value of K, becomes unreasonable. From potentiometric experimental data in aqueous solutions less than 1.6 x 10-l M with regard to calcium chloride and 0.99 x 10-l M to D(-)-ribose (Fig. 4), K1 = 1.70 liters x moleP1 (SD = 1.05 x 10-3) was obtained considering only the 1: 1 stoichiometric proportion. By taking into account the 1:2 proportion K, = 1.13 liters x mole-’ (SD = 0.95 x 10m3)and K2 = 8.47 liters x mole-’ (SD = 0.95 x 10m3)also resulted. A direct proof of the presence of a complex with 1:2 calcium to D( -)-ribose ratio is lacking but a smaller deviation of experimental data from the calculated points (Table 1) justifies considering both proportions. The comparison of the stability constants obtained under identical conditions in both media failed because of the limitations inherent in the systems of measurement. Namely, the sensitivity of the vapor pressure R 1.5-

l.O-

FIG. 2. Formation curves of D(-kribose complexes with calcium in methanol obtained by differential vapor pressure osmometric measurements.

(40°C)

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ET AL.

6-

so= 0.228 s,:ao&l

s,-0.201

0 ~ ‘. II-

-2

102x(ii-2) x[LI Iii-11

.

-4’

-2

I

! b

I

2

4

6

0

J

10

FIG. 3. Calculation of stability constants K, and K, of D(-)-ribose complexes with calcium in methanol (40°C) based on differential vapor pressure osmometric data.

osmometer was inadequate in aqueous medium while the behaviour of the calcium selective electrode was anomalous in methanolic solutions. The stability constants were computed with concentrations without further conversion into the thermodynamic equilibrium constants. The activities of the calcium cation are well known for the ionic strength range

Titrant FIG. 4. Potentiometric

volume, ml

titration with a calcium selective electrode of A: 20.0 ml sample of pure water, and B: 20.0 ml sample of I x 10-l M D(-)-ribose aqueous solution: titrant: 0.986 M CaCI, aqueous solution.

D(-)-RIBOSE

COMPLEXES TABLE

WITH

377

CALCIUM

I

SENSITIVITYOFTHE MODEL APPLIED FORCOMPUTATIONOF STABILITY CONSTANTSPROMPOTENTIOMETRICDATA Sensitivity with regard to K, K, = 8.47 constant, K, variable K,

SD 2.54 1.80 1.21 0.95 1.18 1.67 2.22 2.77

0.7 K, opt = 0.79 0.8 K, opt = 0.90 0.9 K, opt = 1.02 K, opt = 1.13 1.1 K, opt = 1.24 1.2 K, opt = 1.36 1.3 K, opt = 1.47 1.4 K, opt = 1.58 Sensitivity with regard to K, K, = 1.13 constant, K, variable L

x x x x x x x x

lo-” lo-” 10-z lo-” IO-” IO-:’ 10m” IO-”

SD

0.7 K, opt = 5.93 0.8 K, opt = 6.78 0.9 K, opt = 7.62 K, opt = 8.47 1.1 K, opt = 9.32 1.2 K, opt = 10.16 1.3 K2 opt = 11.03 1.4 K, opt = 11.86

1.22 1.07 0.98 0.95 0.98 1.06 1.17 1.30

x x x x x x x x

lo-” lo-” IO-:’ lo-:1 lO-:l lo-” 10-3 lo-”

covered, but for the complex cation the relevant data are missing. Only a vague assumption of the ionic diameter comprised in the Debye-Htickel formula could be made based on crystallographic data for 1:2 complexes of calcium with sugars other than D(-)-ribose (10). CONCLUSION

In neutral aqueous solutions (pH 6.0 + 0.1) with a calcium chloride concentration increasing from 0.098 x 10-i M to 1.64 x 10-l M and with 0.99 x 10-l M D(-)-ribose by potentiometric measurements with a calcium selective electrode the stability constant K, = 1.70 liters x mole-’ was determined. Excellent reproducibility of the EMF measurements is reflected in SD = 1.05 x 10M3for 30 experimental points around the calculated ones. The deviation is smaller if both 1: 1 and 1:2 calcium to D(-)-ribose ratios are taken into account: K1 = 1.13 liters x mole-’ (SD = 0.95 x 10P3)and Kz = 8.47 liters x mole-’ (SD as for K,). The model applied for calculations is more sensitive with regard to K, than it is for K, (Table 1).

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ET AL.

The K, value conceivably goes along with the stability constants calculated on the ground of integrated ‘H-NMR spectra. In 1.27 M calcium chloride solution the values were found to be 1.2 liters x mole-’ for fi-pyranose, 4.6 liters x mole-’ for cY-pyranose, and 5 liters x mole-’ for cw-furanosewhile the composition of D(-)-ribose was 42% /3-pyranose, 40% cr-pyranose, 5% p-furanose and 13% a-furanose (I). Differential vapor pressure osmometric measurements in methanolic solutions 1.24 x 10e2A4 with regard to calcium chloride and 0.2 x 10M2- 3 x 1O-2M to D(-)-ribose resulted in the evidence of the simultaneous presence of complex species with 1: 1 and 1:2 calcium to D( -)-ribose ratios. Although the stability constants are burdened with too big errors and cannot be considered as reliable a rough assessment, that K, MeOH15 x K1 H,O confirms previous qualitative information (3). SUMMARY The study of D(-)-ribose complexing with calcium in aqueous solutions less than 1.64 x 10-i M by potentiometric measurements with a calcium selective electrode afforded the value of K, = 1.70 liters x mole-’ (SD = 1.05 X 10m3). Numerical analysis indicated that complex species with 1: 1 and 1:2 calcium to I)(-)-ribose ratios are present simultaneously: K, = 1.13 liters x mole-’ and K2 = 8.47 liters x mole-’ (SD = 0.95 x lo-“). In methanolic medium 1.24 x lo-* M with regard to calcium chloride both stoichiometric proportions were evidenced. A large error accompanying the stability constant K, = 28 kg x mole-’ (RSD = 82%) renders unreasonable the K, value obtained from the product K, x K2 = 96.5 kg2 x mole-*. The results are discussed with respect to the data published for more concentrated (1.27 M) aqueous solutions obtained on the basis of ‘H-NMR spectroscopic investigations.

REFERENCES I. Angyal, S. .I., Complexes of carbohydrates with metal cations. I. Determination of the extent of complexing by N.M.R. spectroscopy. Aust. J. Chem. 25, 1957- 1966 (1972). 2. Angyal, S. J., Complexes of sugars with cations.Adij. Chem. Ser. 117, 106- 120 (1973). 3. Angyal, S. J., Complex formation between sugars and metal ions. Pure Appl. Chem. 35, 131-146 (1973). 4. Angyal, S. J., Complexing of polyols with cations. Tetrahedron 30, 1695-1702 (1974). 5. Angyal, S. J., and Davies, K. P., Complexing of sugars with metal ions. Chem. Commun. 1971, 500-501. 6. Angyal, S. J., and Hickman, R. J., Complexes of carbohydrates with metal cations. IV. Cyclitols. Austr. J. Chem. 28, 1279-1287 (1975). 7. Bissig, R., Pretsch, E., Morf, W. E., and Simon, W., Makrocyclische und acyclische neutrale Ionophore. Einfluss des Ringschlusses auf die Kationenselektivitat. Helv. Chim. Acta 61, 1520-1538 (1978). 8. Frensdorff, H. K., Stability constants of cyclic polyether complexes with univalent cations. J. Am. Chem. Sot. 93, 600-606 (1971). 9. Kirsch, N. N. L., and Simon, W., Ermittlung von Bildungskurven nach J. Bjerrum mittels differenzieller Dampfdruckosmometrie. Helv. Chim. Acfa 59, 235-242 (1976). 10. Kretsinger, R. H., and Nelson, D. J., Calcium in biological systems. Coord. C/rem. Rev. 18, 29-124 (1976).

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Lehn, J. M., and Sauvage, J. P., [2]-Cryptates: Stability and selectivity of alkali and alkaline-earth macrobicyclic complexes. J. Am. Chem. Sot. 97, 6700-6707 (1975). 12. Pioda, L. A. R., Wachter, H. A., Dohner, R. E., and Simon, W.. Komplexe von Nonactin und Monactin mit Natrium-. Kalium- und Ammonium-Ionen. He/v. Chim. Acttr 50, 1373-1375 (1967). 13. Rendleman, J. A., Jr., Alkali metal complexes of carbohydrates. 1. Interaction of alkali metal salts with carbohydrates in alcoholic media. J. Org. Chrm. 31, 1839-1845 (19661. 14. Rendleman, J. A., Jr., Complexes ofalkali metals with carbohydrates in aqueous media. Am. Chrm. SM. WI,. Writer Air Wmste Chrm. Gen. Pop. 1970, 158- 164: cf. Chrm. Ahstr. 76, 127282t (1972).