Determination of spectrophotometric protonation constant of cholinesterase inhibitors

Abstract

The protonation constant (pK_a) of rivastigmine, galantamine and donepezil which are cholinesterase inhibitors used in cure of Alzheimer's disease in acetonitrile-water binary mixtures were determined at 25 ^oC in ionic strength by spectrophotometric method. Spectra of the drugs were recorded with 1 nm resolution over the 200 to 400 nm interval. Data assessment was carried out with the STAR software program to calculate molar absorbances and stability constants of the compounds studied. Aqueous protonation constant of these compounds were calculated from determined through linear  relationship between the mole fraction of acetonitrile and the pK_a values and the Yasuda-Shedlovsky equality. The pK_a values of inhibitors at 25°C were converted to values at 37°C, without extra estimation. The predicted and calculated pK_a values were compared with literature values.

Keywords

• Cholinesterase Inhibitors,Protonation Constant,UV-VIS Spectrophotometry,Solute Descriptors

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