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Thermodynamic dissociation constants of risedronate using spectrophotometric and potentiometric pH-titration

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Central European Journal of Chemistry

Abstract

Risedronate inhibits bone resorption in diseases like osteoporosis, Paget’s disease, tumor bone diseases or the malfunction of phosphocalcium metabolism. The acid-base properties of risedronate in an aqueous solution have been studied in a pH range from 2 to 12 and can be described in terms of four dissociation steps: pK a,2, pK a,4, pK a,5 (related to the dissociation of POH groups) and pK a,3 related to the dissociation of protonated amino group NH3 +. The mixed dissociation constants were determined at different ionic strengths I = 0.02 to 0.20 mol dm−3 KCl and of 25°C and 37°C using pH-spectrophotometric and pH-potentiometric titration methods. Determination of group parameters L 0, H T might lead to false estimates of common parameters p K a;therefore, the computational strategy employed is important. A comparison between the two programs ESAB and HYPERQUAD demonstrated that the ESAB program provides a better fit of potentiometric titration curve. The thermodynamic dissociation constants pK Ta were estimated by a nonlinear regression of (pK a, I) data and a Debye-Hückel equation at 25°C and 37°C, pK Ta,2 = 2.37(1) and 2.44(1), pK Ta,3 = 6.29(3) and 6.26(1), pK Ta,4 = 7.48(1) and 7.46(2) and pK Ta,5 = 9.31(7) and 8.70(3) at 25°C and 37°C using pH-spectroscopic data and pK Ta,2 = 2.48(3) and 2.43(1), pK Ta,3 = 6.12(2) and 6.10(2), pK Ta,4 = 7.25(2) and 7.23(1) and pK Ta,5 = 12.04(5) and 11.81(2) at 25°C and 37°C. The ascertained estimates of three dissociation constants pK a,3, pK a,4, pK a,5 are in agreement with the predicted values obtained using PALLAS

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Authors and Affiliations

  1. Department of Analytical Chemistry, University of Pardubice, CZ 532 10, Pardubice, Czech Republic

    Milan Meloun, Zuzana Ferenčíková & Hana Málková

  2. Zentiva k.s., CZ 102 37, Prague, Czech Republic

    Tomáš Pekárek

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  1. Milan Meloun
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  2. Zuzana Ferenčíková
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  3. Hana Málková
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  4. Tomáš Pekárek
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Correspondence to Milan Meloun.

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Meloun, M., Ferenčíková, Z., Málková, H. et al. Thermodynamic dissociation constants of risedronate using spectrophotometric and potentiometric pH-titration. cent.eur.j.chem. 10, 338–353 (2012). https://doi.org/10.2478/s11532-011-0150-3

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