Complexation of Zn2+ ions by heparin

Abstract

Fig. 1 shows the binding of Zn2+ to heparin as measured by polarimetry (open symbols) and potentiometric titration (continuous plot). The results reinforce the notion that otentiometric titration affords a rapid and simple mettod by which cation-heparin interaction may be indirectly examined [l]. The plot in Fig. 1 is linear up to a [Zn2+]/[heparin disaccharide] ratio of about one. Linearity in analo ous plots derived from polarimetric examination of C a k and Cu2+ interaction with heparin, and occurrin at low [cationl/[heparin disaccharide] ratios, have i e e n observed [2,3]. The linearity suggests that the interactive process -presumed to be the formation of a species of cation-heparin complex -which gives rise to this part of the plot, occurs by a mechanism that does not conform to simple reversible equilibrium thermodynamics. The plot suggests that, a t higher [cation]/[heparin disaccharide] ratios, further cation interaction occurs. In the case of the Zn2+/heparin interaction this appears, under the conditions explored in Fig. 1, to approach completion at a [cation]/ [heparin disaccharide] ratio of about 3. It has been suggested that such observations may reveal the production, a t low [cation]/[heparin disaccharide] ratios, of a cationpolyanion complex that resembles a discrete, hydrated colloid, mineral-like state, that is therefore not subject to simple aqueous solution equilibrium processes, and that is stabilised by forces additional to electrostatic ones. A t higher [cation]/[heparin disaccharide] ratios, destabilization of the phase, generating the non-linear portion of the plot, may occur [2,3].-0 -0 -0. 0 . 0 -0. 0 -8 0 '0 Fig. 2 shows the near identity, a t low [Zn2+]/[heparin disaccharide] ratios, of potentiometrically derived plots obtained from experiments in which Zn2+ and heparin were mixed under conditions of widely differing 1.2 I I I I I 0 0. 0 4. 0.0 ' I I I I 0 1 2 3 4 [ZnV/lheparindhc&an 'del Fig. 1. Fractions equivalent to isothermal saturation fractions of binding sites on heparin occupied by Zn2+, d e r i v e d f r o m p o l a r i m e t r i c and p o t e n t i o m e t r i c measurements, as functions of [Zn2+]/[heparin disaccharide]A binding site was taken to be an average heparin disaccharide unit.Fractions equivalent to isothermal saturation fractions and derived from polarimetric ( 0 ) o r potentiometric measurements (4 were obtained, in the absence of NaCI, as described in references [l-31. 0 . 0 0 . 5 1.0 1.5 2.0 2 . 5 3.0 3.5 [ZG+l/l&eparindismhan 'del Fig. 2. Fractions equivalent to isothermal saturation fractions of binding sites on heparin occupied by Zn2+, derived from potentiometric measurements, as functions of [Z&+Ylheparin disa~ha15del: the effect of variation in m -I ZnSO4 was added to 20 cm3 of a solution containing the following concentrations of heparin (mmol.dm-3) in the absence of NaCI: (a) 0.011; (m) 0.042; (0) 0.15; ( 0 ) 0.29; ( 0 ) 0.59. Other details are as given in the legend to Fig. 1.[heparin]. Such similarity is also seen i n polarimetrically derived plo...

Heparins as essential antioxidants

“…Potentiometric titration and polarimetry have provided an insight into interaction that occurs between heparin and Fe(II) [10]. It remains for us to unequivocally confirm that heparin-bound Fe(II) is unable to participate in reactions involved in lipid peroxidation, or that once bound, Fe(II) is oxidised to Fe(III) in a manner similar to that occurring during the ferroxidase activity of caeruloplasmin.…”