In this work, we show that the apparent pKa measured by standard titration experiments is an insufficient measure of acidity or basicity of organic functional groups in multiprotic compounds─a frequent aspect of lead optimization in pharmaceutical research. We show that the use of the apparent pKa in this context may result in costly mistakes. To properly represent the group's true acidity/basicity, we propose pK50─a single-proton midpoint measure derived from a statistical thermodynamics treatment of multiprotic ionization. We show that pK50, which may be directly measured in specialized NMR titration experiments, is superior in tracking the functional group's acidity/basicity across congeneric series of related compounds and converges to the well familiar ionization constant in the monoprotic case.