Spectrophotometric and pH-Metric Studies of Ce(III), Dy(III), Gd(III),Yb(III) and Pr(III) Metal Complexes with Rifampicin

The metal-ligand and proton-ligand stability constant of Ce(III), Dy(III), Gd(III),Yb(III) and Pr(III) metals with substituted heterocyclic drug (Rifampicin) were determined at various ionic strength by pH metric titration. NaClO4 was used to maintain ionic strength of solution. The results obtained were extrapolated to the zero ionic strength using an equation with one individual parameter. The thermodynamic stability constant of the complexes were also calculated. The formation of complexes has been studied by Job’s method. The results obtained were of stability constants by pH metric method is confirmed by Job’s method. .

Tekade 10 et al. have studied the apparent metal-ligand stability constant and confirmation of complexes .The compositions of complexes were confirmed by Job's method as modified by Vasburgh and Gold 11 . In the present work, the values of pK, metalligand stability constant at different ionic strength have been determined in the 70% dioxane-water mixture. We attempted to study the effect of ionic strength on thermodynamic parameters of complexes of rifampicin with Ce(III), Dy(III), Gd(III),Yb(III) and Pr(III) metals in 70% dioxane-water mixture by pH metrically and spectrophotometrically.

Experimental
The pH measurements were carried out with equip-tronic EQ-610 pH meter (accuracy ± 0.01 units) using combine glass electrode at 208 K. All the rare earth nitrates were used of 99.9% pure. All metal nitrates used were purchased from Sigma Aldrich Chem. Co., U.S.A. Metal nitrate solutions were prepared in triply distilled water and concentration was estimated by standard method. The drug solutions were prepared in 70% 1,4 dioxane solution. The 1, 4 dioxane was purified by the method described by Vogel 12 . The pH metric readings were taken in 70% 1, 4 dioxane-water mixture and were converted to [H + ] value by applying the correction. The overall ionic strength of solution was maintained constant by adding NaClO 4 . All the solutions were titrated with standard carbonate free NaOH (0.2 N) solution at different ionic strengths using NaClO 4 (0.02, 0.04, 0.06, 0.08 M). The solutions involved in the experimental procedure for pH metric titrations are: 1) Free HClO 4 (A); 2) Free HClO 4 + Ligand (A+L), Free HClO 4 + Ligand +Metal ion (A+L+M) The volume of NaOH added in each titration was plotted against pH and the corresponding volume at successive pH for each set was determined and calculated. The metal-ligand stability constant of lanthanide metal complexes with rifampicin were investigated spectrophotometrically. The absorbance measurements were carried out with Shimadzu UV-1800 ENG 240V, Japan spectrophotometer. The solutions of metal nitrates and rifampicin were prepared in 70% dioxanewater mixture. NaClO 4 was used for maintaining the constant ionic strength. The different composition of metal ion (1x10 -4 M) and ligand ion (1x10 -4 M) were prepared in ten series. For determination of λ max , 50% metal ion solution was used, at which maximum absorbance observed The absorption of all composition was measured at constant wave length (λ max ) and at constant pH.

Results and Discussion
In the present investigation the dependence of proton-ligand stability constant (pK) and metalligand stability constant (log K) on ionic strength of medium was examined by keeping fixed concentration of metal nitrates and ligand solution during pH metric titration. The system has been studied at 0.02, 0.04, 0.06 and 0.08 M ionic strength by varying the concentration of sodium per chlorate. The total ionic strength of medium was calculated The values of proton-ligand and metal-ligand constant of lanthanide metal complexes at different ionic strength 0.02, 0.04, 0.06 and 0.08 M were determined. These values were determined by using Irving-Rossotties method 13 . From Table 1, it shows that the values of proton-ligand stability constant (pK) decreases with increasing ionic strength of medium. The metal-ligand stability constant (log K) also decrease with increasing ionic strength. For determination of stability constant at zero ionic strength the Bronsted equation was used.
pK Log K1 √µ √µ log K = log K 0 + A Σ ∆ Ζ 2 µ pK = pK 0 -A ∆ Ζ 2 µ 10 Where, K 0 is the formation constant at zero ionic strength. pK 0 is proton-ligand stability constant at zero ionic strength. 'A' is the Debye-Huckel constant. ∆Z 2 is the difference in square of the changes of product and reactant ion. The pK 0 and logK 0 values were calculated by plotting the graph of pK, log K 1 , log K 2 versus µ (Figures 1-3).  Table 2, it is seen that the good agreement among thermodynamic constant obtained from different plots. The plots of pK, log K 1 , log K 2 versus µ gives straight line over the entire range of ionic strength for both systems. It shows that the Bronsted relationship is valid for dissociation equilibrium. Fazlur Rahman et al. 13 have determined similar results of stability constant of different metal complexes with substituted acetophenone oxime at 0.1, 0.05 and 0.01 M ionic strength in 70% dioxane-water mixture. Table 2. Thermodynamic stability constant (pK 0 and log K 0 ) values for Ce(III), Dy(III), Gd(III),Yb(III) and Pr(III) metal ions with rifampicin pK vs. The values of ∆Z 2 were calculated from the slope of plots pK vs.√µ, log K 1 vs. √µ, log K 2 √µ. The value of 'A' was taken 14 equal to 0.5161. The value of ∆ Ζ 2 shown in Table 3. The observed value of ∆Ζ 2 is different from the expected value. These values do not give conclusive evidence regarding the magnitude of the charge of reacting species. This discrepancy may be due to the limited applicability of Bronsted equation. The conditional stability constant of rifampicin-lanthanide metals complexes were determined for all systems by using the following equation.
Where, K= conditional stability constant, x = concentration of complex, a 1 and b 1 were concentration of metal ion and ligand before dilution. a 2 and b 2 were concentration of metal ion and ligand after dilution. The values of 'x' were calculated from the graph plotted between optical density and % composition of metal ions in solution (Figure 4-7). From Table 4, it is seen that there is good agreement among thermodynamic constant obtained from pH metry and spectrophotometrically.

Conclusion
The calculated values of stability constant at various ionic strength are high. From the results obtained in this experiment, the complexes of rifampicin with Ce(III), Dy(III), Gd(III),Yb(III) and Pr(III) metal ions were quite stable at over all range of ionic strength.
The values of thermodynamic parameters are nearly same from all plots, were good agreement of results. The values of conditional metal-ligand stability constant shows good agreement with the values determined by pH-metrically.