Oxovanadium( IV) Complex Formation by Simple Sugars in Aqueous Solution Mario Branca, Giovanni Micera, Alessandro Des& and Daniele Sanna MB, GM, DS. Dipartimento di Chimica, Universitd di Sassari, Sassari, Italy.-AD. Zstituto C.N.R. per I’Applicazione delle Tecniche Chimiche Avanzate ai Problemi Agrobiologici, Sassari, Italy

ABSTRACT The binding of oxovanadium(IV) to simple sugars in neutral or basic aqueous solution, as studied by EPR and electronic absorption spectroscopy, is reported. The complexation is favored in basic media and involves the coordination of the metal ion to couples of adjacent deprotonated hydroxyls of the sugar molecule. However, only the ligands provided with cis couples can adopt this chelating ligand behavior. The ability of the cis hydroxyl couples to yield chelated complexes has been related to the structural rearrangement (decrease of the O-C-C-O torsion angle in the five-membered chelated ring) needed to permit the oxovanadium(IV) coordination by the sugar molecule.

INTRODUCTION Biological and environmental aspects of metal complexation by sugars have recently been reviewed [l , 21. Sugars interact with toxic and essential metal ions by acting as either reductants or chelators. Actually, they reduce, e.g., Fe(III), Cr(VI), and V(V), and complex the respective ions, Fe(Il), Cr(V), Cr(III), and VO(IV), originated by the reduction [3-lo]. Depending on the nature of the metal ion as well as on the pH of the solution, the complexing ability of sugars may involve deprotonated hydroxyl groups [ 1, 21. However, in most cases, extra substituents are needed to anchor the metal ion at low pH and they then favor the hydroxyl coordination in neutral or basic media. For instance,the NH, group of the amino sugars glucosamine, galactosamine, or mannosamine, favors the coordination of copper below pH 7 and yields stable N,O,

Address reprint requests to: Professor G. Micera, Dipartimento di Sassari, via Vienna 2-I-07100, Sassari, Italy.

Studi di Chimica, Universid

Journal of Inorganic Biochemistry, 45, 169-177 (1992) @ 1992 Elsevier Science Publishing Co., Inc., 655 Avenue of the Americas, NY, NY 10010

degli Studi

169 0162-0134/92/$5.00

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chelated complexes [5, 71. Furthermore, carboxylates can act as anchoring groups for copper(I1) in galacturonic and glucuronic acids [6]. Due to its strong hydrolytic tendency, the oxovanadium(lV) ion also needs the presence of additional donor groups (e.g.. carboxylates) in the sugar molecule but, once bound to the ligand, it can easily deprotonate the hydroxyl groups and strongly coordinate to up to four of them 16, 7, lo]. This suggests that simple sugars can directly bind VO(IV) in neutral or basic media without the assistance of extra donor groups. We report here experimental evidence to demonstrate that complexes whtch may be distinguished by EPR and electronic absorption spectroscoplrs are effectively formed by the interaction of oxovanadium(IV) with simple sugars. The following ligandw, D-glucose, D-galactose, D-marrnosr. D-rihose, D-xylose. D-lyxose, D-fructose. L-arabinose, L-sorbose, methyl ru--Dmannopyranoside, methyl methyl P-D-galactopyranoside. phenyi P-D-galactopyranoa-D-glucopyranoside, methyl ~-D-.arabinopyrrlnoside, [email protected], side, methyl galactose. 2-deoxy-D-glucose, and 2-deoxy- D-ribose {h,t‘eScheme 1) were examined. A back-titration method was used because an aqueous solution containing the metal ion VO’” and ligand was first added with NaOH. until it completelv dissolved ihe vanadium hydroxide precipitated. and then titrated ir;ith HCIO: EXPERIMENTAL The ligands were commercially .5H *O was used as the metal salt. 298 K on aqueous solutions (VO’ Absorption spectra were recorded

RESULTS

available chemicals (Aldrich or Sigma). VOSO, I X-band EPR spectra (9.1.5 GHz) uere recorded :tt ’ = 4 x 10~ 3 M) using a Varian E-9 spectrometer. on a Beckman Acta MIV spcctroptiotometer.

AND DISCUSSION

Before examining the results, it must be taken into account that, in the absence of ligands, the only oxovanadium(IV) species which can be detected by EPR spectroscopy in aqueous solution are the aquaion [VO(H,O),j” @l-l < 3) and the full} hydrolyzed species [VO(OH), ] (pH > lo-- 1 I). On the contrary. the polynuclear species formed at intermediate pH values are EPR-silent 11I 1. .A rough examination of the VO(IV)-sugar systems in aqueous solution, as a function of pH. makes it possible to categorize the ligands into two classes. The first class is constituted b:, sugars where all the hydroxyl groups are in tram relative position to each other. These ligands are undoubtedly ineffective in the metal &elation. In facl. with the ligands methyl rw-D-glucopyranoside, methyl P-D-xylopyranusttle. and ?-deoxy-D glucose, which are not provided with couples of L*I.Shgdroxylx. no complex formation is actually substantiated by EPR spectroscopy with varying pH and ligand-to-metal molar ratio. The only EPR signals clearly detected in these systems are those of the [VO(OH),] hydrolyzed species above pH 10. Only at very high ligand molar excesses (e.g.. SO: 1) the presence of minor crlmplrxed species may be suggested by the broadening of the vanadyl hyperfine components ;rnd the slight decrease of the metal coupling constant. The second class is composed by the ligands having at least two hydroxyl groups in CLS position to each other. The behavior of this class is exemplified well by D-ribose. With this ligand. EPR spectra are observed at room temperature above pH 9 (Fig. I). and even at pH > 14 they are supportive of complexes different from the

OXOVANADIUM(IV)

AND SUGARS

171

R

c.2

CH2OH

OH

D-Glucose

CH20H

OMe

Methyl a-D-GlucopyranosMe

H

OMe

Methyl o-D-Xylopyranoside

H

OH

D-Xylose

CH20H

OH

0Galactose

CH20H

OMe

Methyl P-D-Galaciopyranoside

CH2OH

OPh

Phenyl p-D-Galactopyranoslde

H

OH

L-Arabimse

CH20H

OH

D-Mannose

CH20H

OMe

Methyl a-D-Mannopyranoside

H

OH

D-Lyxose

0

W’W

HO

OH

OH

D-Ribose

H

P-Deoxy-D-Ribose

R

H(OH)

OH(CH,OH)

OH

H

2-Deoxy-D-Galactose

H

OH

P-Deoxy-D-Glucose

H

OH

D-FNCtoSe

OH

H

L-So&me

Methyl (5D-Arabinopyranoside

SCHEME 1

hydrolyzed species [VO(OH),]-. This represents unambiguous evidence for the formation of mononuclear sugar-oxovanadium(IV) complexed species. In particular, two complexes (1 and 2) are distinguished. The complex 1 is the predominant species in solutions with the metal-to-ligand molar ration of 1: 1. Instead, at the molar ratio of 1:2 the species 2 also shows up. This complex is formed over the pH range 9-10, reaches a maximum of concentration at pH 12 and then is transformed,

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M. Branca et al.

FIGURE 1. X-Band EPR spectra recorded at room temperature on aqueous solutions of V02+(4 x IO-"M) and D-ribose at varying pH and metal-to-ligand molar ratio (M:L) (a) M:L = I:l, pH = 13.6; (b) M:L = 1:2, pH = 13.3: and (c) M:L. _ 1:s. pH = 10.5.

at least partly, into complex 1.The increase of the excess ligand strongly favors the formation of 2: suggesting that the species involves a I:2 metal-to-ligand stoichiometry. The same spectral trend is observed, at least qualitatively, with all the ligands having one or more couples of cis hydroxyl groups and this seem!, the necessary requisite to make possible the chelating coordinating behavior. Since Iwo anomeric forms (CYand /3), which are different for the position of the hydroxyl group at C-l ( are possible in unsubstituted sugars, most of the ligands examined here, beside D-ribose, exhibit a chelating behavior toward oxovanadium(IV), namely D-glucose, D-mannose, D-lyxose, D-xylose, D-galactose, D-fructose, l--arabinose. L-sorbose. 2-deoxy-D-galactose, 2-deoxy-D-ribose, methyl /3-D-galactopyranoside, phenyl & D-galactopyranoside. methyl /3-D-arabinopyranoside. and methyl Lu-D-mannopyranoside. The complex formation processes were followed also by electronic absorption

OXOVANADIUM(IV)

AND SUGARS

173

spectroscopy. In this case, the formation of the polymeric hydrolytic species may be revealed by broad absorptions in the UV visible region and the monomeric complex [VO(OH),]by an intense band around 410 run. On the contrary, the spectra of the complexes of the l- and a-types, which closely follow the EPR spectral trend (see Fig. 2(b), 2(c)), are normal for oxovanadium species with O-donor ligands [ll]. However, electronic absorption spectroscopy substantiates that a further species 3, which is not observed by EPR, is formed at pH values (7-9) lower than for 1 and 2 and only with the ligands having couples of cis hydroxyls (Fig. 2(a)). The comparative examination of the EPR data (Table 1) indicates that the parameters of the complex 2 compare favorably with those of sugar complexes involving two couples of deprotonated hydroxyl functions from two sugar molecules [6], see Scheme 2. Instead, the complex 1, which is formed by 2 after addition of base and is remarkably different from the fully hydrolyzed species [VO(OH),]-, is a mixed complex involving a chelating sugar molecule and two hydroxo groups. All the experimental evidence supports that the EPR-silent complex 3, which is found at pH lower than for 2 and 1, is the 1: 1 species where the metal ion is bound to a chelating sugar molecule and to a single hydroxo group. As is well known, e.g., see

I

1

400

Wavelength

I

800

600 (m-4

FIGURE 2. Electronic spectra of aqueous solutions of V02+(2 x 10e2 M) and D-ribose at varying pH and metal-to-ligand molar ratio (M:L) (a) M:L = l:l, pH = 8.7; (b) M:L = 1:2, pH = 12.2; and (c) M:L = l:l, pH = 13.8.

174

hf. Branca et al.

TABLE 1. Spectral Data for the Oxovanadium (IV) Complexes of Ribose _~_..__.__ .-__- -.--___.___-_-.-_ __--_I_ ESR Absorption Maxima” --_--&,,, jnm). f (M ’ cm ‘) A,, (IO ~Acm--‘, Species i!T,,

----

1 2

________~,~~._~___~_~~~~.-~-~-~~~-~~~__.x5 105~239. I 971 76 420(26). it.47: 110(?6),

3

[VO(H20)$+ P”XoW 1I

---.___

/ .967 i .970

“The values of t are referred

106 87

:o total metal concentratmn

_._____

510(9).

705(1”)

505( IO), 6X0(3:, 535(18).

6hSt?7i

63019) sh. 7X)( 181 4101

__._

1141.‘i.‘.CEX,! sh .._.__~_.

._ ___.._ _-._

for wlut~on~ uhcre

ttw .:;xnpiex

sptwe~

i\

predominantly formed.

[ 121, such kinds of hydrolyzed species undergo dimerization and give rise to dihydroxo-bridged species which, being strongly magnetically coupled, do not exhibit EPR signals. In more basic solution these complexes are transformed into the monomeric dihydroxo species 1” The intensity of the EPR signals, the pH threshold for the formation of the complexed species. and the amount of complex 2 relative to complex 1 in the different systems can be used to get an insight into the relative stability of the complexed species. A comparative examination show that. within the class of the ligands adopting a chelating behavior. the stability of the complexes varies as a function of the ligand structure, e.g., the number of ci,\ hydroxyls. the preferred conformations, and the position of bulky substituents, etc. For cxamplc, by considering the sugars exhibiting the galacto conformation, the ability to form b&-chelated complexes follows the order D-galactose ?r’ methyl ~-D-gala~topyran~)sid~ > phenyl @-D-galactopyranoside. Analogously, compared to methyl S-D-arabinopyrannsjde. I,-arabinose is more effective in the chelation of’ oxovanadium(lV Jo To find a suitable explanation, some structural considerations must be preliminarily taken into account, The examination of molecular models shows that in a sugar molecule, while the dihedral angle between adjacent ~‘is hydroxyi groups can range from 0 to + 60” (in the eclipsed and staggered conformations. respectively), between the tram groups it cannot be less than 60”. The observation that only the cis groups

SCHEME 2

OXOVANADIUM(IV)

AND SUGARS

175

are able to yield (O-, O- ) complexes indicates that the value of the torsion angle in the sugar O-C-C-O moiety is determinant for the closure of the five-membered chelated ring. A rearrangement of the ligand structure leading to torsion angles less than 60” has always been observed in the ethylene bridge of chelated complexes, e.g., 33” in VO(acen) [ 131, as a result of a compromise between the steric requirements of the metal coordination and ligand conformation. Therefore it may be concluded that also in sugars an angle smaller than 60” is needed to favor the five-membered cyclic complex and only the cis couples, which can adopt conformations intermediate between the staggered and eclipsed ones, are suitable for metal chelation. In terms of entropic factors, in the case of cis couples the torsion angle can change continuously from + 60 to - 60” even after metal binding, originating a series of conformations which are compatible with reasonably good metal-donor distances. In comparison, the conformational freedom of the sugar molecule is much more restricted in the case of metal-bound Puns hydroxyl groups. A very limited number of ligand conformations, with torsion angles very near to 60”) are expected to contribute to these chelated species leading to a rigid structure and a loss of internal entropy which, as it is well known [14], are unfavorable factors in chelation reactions. After such considerations have been made, the experimental results may be better interpreted by comparing the behavior of similar ligands. Table 2 lists the conformational data of some of the sugars examined here, e.g., the relative amount of (Y- and fl-anomers in the free molecules and the number and type of cis hydroxyls. It can be seen that D-galactose can chelate through both the [O(l), O(2)] and [O(3), O(4)] couples in the o-form, but only through the [O(3), O(4)] couple in the &form. Instead, the methyl and phenyl galactopyranosides in the &conformation can use

TABLE 2. Conformation of Some Sugar Ligands in Aqueous Solutiona Ligand D-&lactose

OL %

cis OH

21-36

P(l), W)l

Methyl @-D-galactopyranoside Phenyl P-D-galactopyranoside L-Arabinose

-

[O(3), 0(4)1 -

Methyl 13-D-arabinopyranoside D-Mannose

68

tw9>

0(3)1

Methyl a-D-mannopyranoside D-Glucose Methyl a-D-glucopyranoside D-Xylose Methyl fl-D-xylopyranoside D-Ribose

100 36 100 31 -

Pc9, P(l),

0(3)1 W)l

20

to(~), P(2), P(3), P(3), PC09

2-Deoxy-D-ribose D-Lyxose

a Taken from Ref 15. b Not reported.

34

b b

Ku), WN [O(3), 0(4)1 -

Kx 0, wu w-)1 O(3)] 0(4)1 0(4)1 0(3)1

0%

cis OH

64-73

[O(3), O(4)]

loo 100 63

[O(3)> 0(4)1 P(3), 0(4)1 [O(3), 0(4)1

100 32

[O(3), (x4)1 Ku)> om [O(2), 0(3)1 -

64 63 100 56

b b

Km P(3),

0(3)1 0(4)1

P(3), 0(4)1 [O(1), W)l Kw, 0(3)1

176 M. Branca et al.

only the [O(3), O(4)] couple. This structural difference makes the latter ligands less effective in chelation, e.g., the bis-complex 2 is less favored compared to the hydrolyzed species 1, as can be deduced by comparative analysis of spectra in Figure 3. On the other hand, in the same figure it can be observed that. compared to methyl @-D-arabinopyranoside (provided with a single cis couple), L.-arabinose which in the a-form has two couples of cis hydroxyls, is more efficient in complexation. The same arguments are valid to explain the different chelating single cis couple) compared to methyl /3-D-xylopyranoside

ability

of D-xylose

(a

(no & couple), and a-D-glucopyranoside and 2-deoxy-D-

D-glucose and D-ribose compared to methyl ribose, respectively. Obviously, the rearrangements following metal coordination can lead to conformations less stable than the usual chair form, e.g., bulky substituents could interact between each other or be moved into pseudo axial positions. Therefore even subtle changes in the structure could be important in determining the stability of the formed complexes.

1OmT

%h

FIGURE 3. X-Band EPR spectra recorded at room temperature on aqueous solutions of V02’(4 x 1O-~3 M) and sugars at ligand-to-metal molar ration of 2: I and pH values corresponding to the maximum formation of complex 2: (a) D-galactose, pH 10.5; (b) methyl ,!-D-galactopyranoside, pH =z 11.3; (c) L-arabinose, pH 10.4; and (d) methyl B-Darabinopyranoside, pH = I 1.3. The low-field resonances of complexes I and 2 are shown.

OXOVANADIUM(IV) AND SUGARS

177

CONCLUDING REMARKS In conclusion,

the work supports that, provided that couples groups are available for metal binding, simple sugars may agents in biological and environmental systems, especially media. It also appears that the number of available cis couples sugar structure as distorted by metal coordination are important the chelated complexes.

of adjacent hydroxyl be effective chelating in neutral and basic and the stability of the in the stabilization of

REFERENCES 1. K. Burger and L. Nagy, in Biocoordination Chemistry: Coordination Equilibria in Biologically Active Systems, K. Burger, Ed. Ellis Horward, Chichester, U.K., 1990, Chap. 3. 2. C. F. G. C. Geraldes and M. M. C. A. Castro, in Metal Speciation in the Environment, J. A. C. Broekaert, S. Giicer, and F. Adams, Eds. Springer-Verlag, Berlin, 1990, p. 105. 3. G. Micera, S. Deiana, C. Gessa, and M. Petrera, Znorg. Chim. Acta 56, 109 (1981). 4. C. Gessa, M. L. De Cherchi, A. De&, S. Deiana, and G. Micera, Znorg. Chim. Acta

80, L53 (1983). 5. G. Micera,

S. Deiana,

A. Des&, P. Decock,

B. Dubois,

and H. Kozlowski,

Znorg.

Chim. Acta 107, 45 (1985). 6. G. Micera, A. Dess;, H. Kozlowski, B. Radomska, J. Urbanska, P. Decock, B. Dubois, and I. Oliver, Carbohydr. Res. 188, 25 (1989). 7. M. Branca, G. Micera, A. Des& and H. Kozlowski, J. Chem. Sot. (Dalton), 1283

(1989). 8. H. Kozlowski, P. Decock,

I. Olivier, G. Micera, A. Pusino, and L. D. Pettit, Carbo-

hydr. Res. 197, 109 (1990). 9. M. Branca, A. De&, H. Kozlowski, G. Micera, and J. Swiatek, J. Znorg. Biochem. 39, 217 (1990). 10. M. Branca, G. Micera, D. Sanna, A. Des&, and H. Kozlowski, J. Chem. Sot. (Dalton), 1997 (1990). 11. N. D. Chasteen, in Biological Magnetic Resonance, L. J. Berliner and J. Reuben, Eds. Plenum Press, New York, 1981, Vol. 3, Chap. 2. A. Zubor, T. Kiss, M. Branca, A. Des&, H. Kozlowski, and G. 12. M. Jezowska-Bojczuk, Micera, J. Chem. Sot. (Dalton), 2903 (1990). 13. D. Bruins and D. L. Weaver, Znorg. Chem. 9, 130 (1970). 14. C.-S. Chung, J. Chem. Ed. 61, 1062 (1984). Reading, MA, 1983, Chap. 29. 15. G. M. Loudon, Organic Chemistry, Addison-Wesley,

Received July 9, 1991; accepted August 20, 1991