Solvent Effects on Protonation Constants of trimetoprim in Different Aqueous Solutions of ۱-propanol

The role and timing of physic chemical profiling in drug research has significantly changed during the last decade. Determination of fundamentally important physic chemical properties such as dissociation, solubility and lipophilicity has been shifted to the early stage of drug discovery in order to facilitate the screening of drug like candidates.The pKa value is a key parameter to predict the dissociation state of a molecule with respect to pH. Knowledge of this parameter is essential in estimation of ADME properties since absorption and distribution are highly affected by the dissociation of the compound. However, many drugs are sparingly soluble in water and any experimental pKa determination requires the use of an organic or hydro-organic solvent. Mixtures of water and organic solvent, mainly methanol, ethanol, or ۱-propanol, are usually employed. In the present work, the protonation constants of trimethoprim (an anti-bacterial compound) is determined in different aqueous solutions of ۱-propanol.

کلیدواژه ها:

Protonation constants ، trimetoprim ، propanol-water mixtures ، Kamlet-Taft solvatochromic parameters ، Solvent Effect