Low Field NMR Determination of pKa Values for Hydrophilic Drugs for Students in Medicinal Chemistry

For an interdisciplinary approach on different topics of medicinal and analytical chemistry, we applied a known experimental pKa value determination method on the field of the bench top nuclear magnetic resonance (NMR) spectrometry of some known biologically active pyridine-based drugs, i.e., pyridoxine hydrochloride, isoniazid, and nicotine amide. The chemical shifts of the aromatic ring protons in the 1H NMR spectrum change depending on the protonation status. The data were analyzed on dependence of the chemical shifts by different pH (pD) environments and then the pKa values were calculated. The pKa values obtained were in agreement with the literature data for the compounds, searched by the students on web programs available at our university. The importance of the pKa values in protein-ligand interactions and distribution etc. of drugs was brought up to the students’ attention. In addition, by the use of a free web application for pKa values prediction, students calculated the predicted modeled pKa value. The experimental and in-silico approaches enhance the tool box for undergraduate students in medicinal chemistry.