The challenges of modern medicinal chemistry increase with the complexity of the chemical compounds studied. Often these compounds are multiprotic with both acidic and basic functional groups. Since ionization patterns of such compounds are overly complex, the traditional concepts applied to apparent ionization constants (pKa) such as group "assignment", "acid", and "base" are woefully inadequate and may hamper drug discovery and development. We highlight this inadequacy and its consequences so that the medicinal chemistry community fully understands the critical issues at stake.
Robert Fraczkiewicz (2025) studied this question.