Potentiometric investigation of the complexation of divalent metal ions by a sugar α-amino acid

Potentiometric Investigation of the Complexation of Divalent Metal Ions by a Sugar a-Amino Acid M. Angeles Diaz Diez, Fernando J. Garcia Barros and Crist6bal Valenzuela Calahorro iWWD. Departamento de Quimica Analitica y Electroquimica, Facultad de Ciencias, Universidad de Ehtremadura, 04071 Badajoz, Spain.-FJGB, CVC. Departamento de Q&mica Inorgrinica, Facultad de Ciencias, Universidad de Extremadura, 06071 Badajoz, Spain

ABSTRACT The stability constants for the equilibrium of complexation between a sugar a-amino acid and the divalent metal ions cobalt(H), nickel(II), coppeI(II), zindII), and cadmium(U) have been determined by potentiometry at 298 K and ionic strength I = 0.1 M in aqueous solution. The complexes observed as well as their stability constants are discussed in terms of the characteristics of the amino acid.

INTRODUCTION Carbohydrates immunogenic pharmaceutical

are often

highly

soluble

in water

and are usually

only weakly

and of low toxicity. These properties are veIy useful in developing agents.

Thus, carbohydrate

derivatives

are useful

for the design

of new drugs. One such possibility is the development of chelates for the removal of toxic metals or the uptake of essential metals. The interactions of carbohydrates with metal have been of interest in recent years, above all in the field of industry and biochemistry in connection with metal-containing enzymes. Thus, the complexation behavior of carbohydrates has been reviewed recently [l I. However, the coordination chemistry of carbohydrates presents some difficulties regarding the isolation of discrete compounds,

to: professor M. Angeles Diaz Diez, Departamento Facuitad de Ciencias, Universidad de Extremadura, 06071

Address reprint requeAs and correspondence de Quimica AnaWca y Ehxtmquimka,

Badejo& Spain. Joumul~hw~~~M~Bkkr&y, X,243-247W!M) Q 1994 Ekvier Ysience inc, 655 Avenue oFtbe Americaq NY, NY 10010

243 0162-0134/94/$7.00

244 M. A. DiizzDiez

and if the hydroxyl groups are involved in the binding of metal ions, results indicate that the relative position of the hydroxyl group may have a critical influence not only on the structure but also on the stability of the species formed [2,3]. The abundance of functional groups on carbohydrates allows for the manipulation of sites away from the binding sites so that other useful properties may be imparted to the molecules. Thus, the manipulation of the aldehyde group on carbohydrates allowed us to obtain carbohydrate a-amino acid derivatives [41 and recently, we have studied the interactions of some carbohydrate cy-amino acids with transition-metal ions in aqueous medium [s-7]. In order to obtain more information on the complex formation behavior of such Iigands, we have prepared 2-benxylamino-2-deoxy-D-glycero-L-gluco-heptonic acid (ZBnaminoI&co) (Figure 11, studied its acid-base equilibrium, and investigated its coordination with Co(B), Ni(II), Cu(II), Zn(II), and Cd(B) ions. The results are compared with those obtained with other analogous cr-amino acids [&lo] in order to observe the differences in acid-base and complexing properties.

EXPERIMENTAL Reagents 2-Benzylamino-2-deoxy-D-glycero&gluco-heptonic acid (2-Bnamino-Ggluco) [4] was obtained as described and it was recrystallized twice from water. Stock solutions of Co(n), NXII), C&I), Z&I>, and cd(B) ions were prepared from the corresponding nitrate salts. The concentration of the solutions were determined by titration against EDTA [ll]. Sodium hydroxide stock solutions were prepared by dilution of a concentrated solution of sodium hydroxide, according to Kolthoff et al. [12]. Alkali titre and absence of carbonate were periodically checked by means of the appropriate Gram plots [13] using potassium phthalate. Sodium perchlorate was used to keep the ionic strength constant at 0.1 M. All solutions were thoroughly flushed with high-quality nitrogen (purity = 99.99% v.v.) before use. Doubly freshly distilled water was used throughout. AU the remaining chemicals proved to be sufficiently reliable to be used without further purification.

7” FHhH2B.

H-roH HO-CI

H

Ho-Y-H H-roH CH20H

FIGURE

1. Structuralformulae

of the ligand 2-Bnamino-Lgluco.

POTENTIOMETRIC

INVESTIGATION

OF METAL IONS

245

Apparatus and Titration Procedures Formation constants were determined by performing potentiometric titrations in a double-walled vessel kept ,at 25 f O.l”C by circulating water and stirred magnetically under a continuous flow of nitrogen. The free hydrogen ion concentration was measured with a Radiometer pHM82 pH meter equipped with a wide-range glass electrode (Radiometer G2040C) and a calomel reference electrode (Radiometer K4040). The electrode system was calibrated in terms of hydrogen ion concentration by performing strong acid versus strong base titrations [14]. All solutions were prepared with 5 x 10e3 mol drnm3 ligand, and 1: 1, 1: 2, and 1: 3 ratios of metal to ligand. Data Treatment Formation constants of the complexes formed were calculated using the computer program MINIQUAD [151. Initial tentative indentification of the species present was based on the shapes of the experimental formation curves. The shape of the formation curves was used to deduce the possible stoichiometries of the complex species present in each system as well as to obtain rough estimates for their formation constants. These estimates were consequently introduced into the computer program MINIQUAD as input data and relined. All the calculations were performed on a Sperry Computer S.O.-1771 (Computer Center, University of Extremadura). RESULTS AND DISCUSSION The calculation of reliable values for stability constants of the complexes requires the knowledge of accurate and precise value of the ionization constant for the ligand at the same working conditions. This constant is given in Table 1, together with those of analogous a-amino acids for the purpose of comparison. Metal, ligand, and H+ ions were chosen as components in evaluating the stability constants. The general three-component equilibria can be written as pM+qL

+rH-M,L,H,.

(1)

Charges are omitted for the sake of clarity. The associated overall formation constant is denoted by Pwr.

TABLE 1. Ionization Constants of 2-Bnamino-Lgluco mol dme3 (NaClOJ, T = 298 K) cu-Amino Acid

PI%

Threonine Valine Ahnine 2-Amino-D-gluconic 2-Bnamino-D-gulo 2-BllauliuQ-w-tale ZBnamino-L-gluco

8.96 9.49 9.70 9.08 8.20 8.22 8.12

and Other a-Amino Acids (I = 0.1

Reference 8 8 8 10 5 7 This work

246

M. A. Dhz Diez

The numerical analysis of all the experimental e.m.f. data has been carried out with the computer program MINIQUAD [15], which was used both to determine the equilibrium model and to calculate the stability constants. The titration curves for a system were treated either as a single set or as separate entities without significant variation in the stability constants. Only experimental points in which variations in the degree of formation of the complexes occurred were processed in the last refinement. Calculations including the metal hydrolysis formation constant values cited in the literature [16] for the main hydrolysis products of metal ions were used. Besides, the inclusions of polynuclear species in the calculation implied that they were rejected by the computer or they led to a considerable increase in the R values. It may be concluded that the only complexes present were those listed in Table 2. All of the systems studied were found to contain complexes of the forms ML and ML,, which agree with the behavior of analogous cu-amino acids as N-unprotected and N-protected. In addition to these species, the existing experimental evidence was sufficient to determine with accuracy that ML(OH), ML(OH),, M(LH),, and ML(LH) complexes are formed at least in some moment of the titrations. From Table 1 it is apparent that the values of pwr found suggest that the probability of complexes being formed where the ligand 2-Bnamino-L-gluco is coordinated in its zwitterion form through the carboxylate group is very high, a fact that is usual in other amino acids complexes [17]. However, the species distribution computed from the constants reported in the aforementioned table show that as the pH increases, the proportion of the metal, ligand, and species that contains the coordinated zwitterion decreases, and that of the species ML, ML,, MUOH), and ML(OH1, increases. This seems to be in agreement with TABLE 2. Stability Data (log p) for Complexes Present in the M(II)/2-Bnamino-L-gluco Systems at 298 K and I = 0.1 mol dme3 (NaClOJ MUI)

,i

q

r

Complex

GJ&

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

1 2 1 2 1 2 1 2 2 1 2 1 1 1 2 1 1

0 0 0 0

ML

Ni(I1)

c&I)

Z&I)

cd(II)

-1 2 0 0 1 0 0 -1 -2 0 0 -1 -2

ML2

ML ML2

ML(OHY MCLH), ML %LH) ML ML2

MUOH) ML(OH), ML ML2

MUOH) MUOH),

aR = Hamilton R-factor calculated by MINIQUAD. bFigures in parentheses are the computed standard deviations. ‘When r = - 1, this refers to proton rem&al from the complex.

log Ppqr 3.75(4)b 6.75(3) 4.67(7) 8.346) - 3.642) 21.96(5) 7.10(3) 13.47(6) 17.470) 3.78(2) 5.840) - 5.65(2) - 14.12(3) 3.99(2) 7.87(3) - 7.25(5) - 16.63(6)

R= 0.0038 0.0040

0.0033

0.0029

0.0034

P O T E N T I O M E T R I C INVESTIGATION OF M E T A L IONS

247

the fact that a protonated amino group is expected to be essentially nonexistent at high pH values, by which the coordination of the ligand in anionic form is most-favored, and thus the anion could form a five-membered chelate ring that should give additional stabilization to the system. However, the fact that M(II)/2-Bnamino-L-gluco systems contain a greater proportion of hydroxylated species than other sugar a-amino acids [5-7] allows us to suggest that there must be a certain influence of the sugar chain [2, 3]. In this case, the loss of proton(s) from the coi'responding ML complex seems to be favored. Because of the steric complexity of sugar, there is no reliable technique, except for x-ray crystallography or N M R spectroscopy, to darify the details of the structures of these complexes, even when the complex has been successfully isolated.

REFERENCES 1. D. M. Whitfield, S. Stojkovsld, and B. Sarkar, Coord. Chem. Rev. 122, 171 (1993). 2. H. Kozlowski, P. Decock, I. Olivier, G. Micera, A. Pusino, and L. D. Pettit, Carbohyd. Res. 197, 109 (1990). 3. M. Jezowska-Bojczuk, H. Kozlowski, P. Decock, M. Cerny, and T. Trnka, Carbohyd. Res. 216, 453 (1991). 4. J. A. Galbis, J. C. Palacios, and E. Roman, Carbohyd. Res. 114, 158 (1983). 5. C. Valenzuela Calahorro, M. A. Diaz Diez, E. Sabio Rey, F. J. Garcfa Barros, and E. Roman Gal~in, Polyhedron 11(5), 563 (1992). 6. M. A. Diaz Diez, F. J. Garcfa Barros, E. Sabio Rey, and C. Valelmuela Calahorro, J. Inorg. Biochem. 48, 129 (1992). 7. M. A. Diaz Diez, F.J. Garcfa Barros, E. Sabio Rey, and C. Valenzuela Calahorro, J. Inorg. Biochem., 53, 109 (1994). 8. T. Kiss, in Biocoordination Chemistry: Coordination Equilibrium in Biologically Active Systems, K. Burger, Ed., Ellis Horwood Limited, London, 1990, Chap. 3. 9. S. H. Laurie, in Comprehensive Coordination Chemistry, Sir G. Wilkinson, Ed., Pergamon Press, Oxford, 1987, Vol. 2, pp. 742-743. 10. A. E. Martell and R. M. Smith, Critical Stability Constants, Plenum Press, New York, 1982, Vol. 5. 11. F. Bermejo and A. Prieto, Aplicaciones Anallticas del A E D T y AnCdogos, Ser. Publ. Univ., Santiago de Compostela, 1960. 12. I. M. Kolthoff, E. B. Sandell, E. J. Meehan, and S. Bruckenstein, Quantitative Chemical Analysis, The Macmillan Company, Collier-Macmillan Canada Ltd., Toronto, 1969. 13. D. Dryssen, D. Jagner, and F. Wengelin, Computer of Ionic Equilibria and Titration Procedures with Specific Reference to Analytical Chemistry, Almqvist and Wiksell, Stockholm, 1968. 14. P. W. Linder, R. G. Torrington, and D. R. Williams, Analysis using Glass Electrodes, Open University Press, Milton Keynes, 1984. 15. A. Sabatini, A. Vacca, and P. GaiTs, Talanta 21, 53 (1974). 16. C. F. Baes, Jr. and R. E. Mesmer, The Hydrolysis of Cations, John Wiley, New York, 1976. 17. L. P. Battaglia, A. Bonamartini Corradi, G. Mareotrigiano, L. Menabue, and G. C. PeUacani, J. Chem. Soc. Dalton Trans. 102, 2663 (1980), and references cited therein.

Received November 11, 1993; accepted January 12, 1994