[03.06.2025] Content error, AnKing-MCAT/AnKingMed, ID 3070767

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However,

Yeah to me the card just doesnt make sense from the content in the books and other cards in our deck. Theres several questions online about it notably all stemming from this deck. I thought about it for a while and I think I might understand what happened/went wrong.

The error in stating “at the equivalence point, pH = pI” arises from a misinterpretation of the titration process for polyprotic molecules like amino acids. The original statement implies that when a proton is fully removed, reaching an equivalence point, the molecule’s net charge becomes zero and that this point is the pI. However, (ignoring the fact that this statement doesnt account for the multiple equivalence points displayed by amino acids) the real error made is that it doesnt account for the fact that deprotonation is a gradual process with overlapping equilibria. For example, at the second equivalence point for arginine, it may seem that the carboxyl group is fully deprotonated (–1 charge) and the α‐amino group is stoichiometrically deprotonated (neutral), while the guanidinium group remains protonated (+1 charge), which would suggest a net zero charge - aligning with our card. In reality, at the pH value corresponding to the second equivalence point, not every molecule has achieved this idealized state due to the gradual nature of the transition and the overlapping equilibrium with the protonated guanidinium group. Consequently, the overall net zero charge, the pI, is only reached when the equilibrium distribution of all protonation states averages to zero, which occurs at a higher pH then the second equivalence point (around 10.8 for arginine). pI is an equilibrium condition reflecting the overall charge distribution rather than a discrete stoichiometric endpoint. Mathematically, the isoelectric point (pI) for arginine is determined by balancing the acid–base equilibria of the ionizable groups that change charge in the pH range of interest. in this case, the α‑amino group (with pKa₂) and the guanidinium group (with pKa₃). Since the carboxyl group is already deprotonated (–1) at these pH values, the overall net charge is governed by the transition of the α‑amino group from its protonated (positive) to deprotonated (neutral) state and the gradual deprotonation of the guanidinium group (positive to neutral). At the pI, the effective positive charge from the guanidinium group is balanced by the loss of the positive charge from the α‑amino group.