Hi @jacewowen. We require MCAT specific source citations with all suggestions (Kaplan, Khan Academy, UWorld etc.) More details here for suggestion guidelines: AnKing MCAT Deck Submission Guidelines
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.
@pkaps01 where, if anywhere, did we land on this? I remember having a few back-and-forths, though I don’t immediately recall where those conversations were
There’s a new suggestion open on the same thing, so wanted to circle back to what we had determined previously
IIRC:
- Card isn’t great.
- Really it’s intending to reference amino acids.
- Even then, it really only applies to zwitterion amino acids, specifically.
If memory serves, we had agreed on all that but never landed on a non-clunky way to phrase it, I think
Haha yeah this one is a headache. Basic gist of my rationale above:
The statement “at the equivalence point, pH = pI” is incorrect because it conflates a stoichiometric equivalence point, which is a discrete moment when an acid or base is fully neutralized (based on the idealized view that the reaction proceeds completely and irreversibly), with the isoelectric point (pI), which is defined by the equilibrium distribution of multiple protonation states as it is a average net charge.
I don’t think this statement as written in the card is ever correct.
I guess the magical question is, then: how, if at all, can we phrase this to dodge all the bullets
Is it enough to just be stupid simple and say something like:
- At the equivalence point of a titration for a zwitterion, pH = pI
Seems a bit clumsy, but I’m not sure I immediately see another handy way to sidestep all the other potential issues with it
The statement “At the equivalence point of a titration, pH = pI” is fundamentally incorrect for two key reasons:
- Conceptual :
The equivalence point is purely stoichiometric: it marks the completion of neutralizing a specific ionizable group (e.g., α-amino), without considering equilibrium distributions of other groups (such as the guanidinium).
In contrast, the isoelectric point (pI) is defined by an equilibrium condition, specifically the pH at which the average net charge across all protonation states is zero. It inherently considers equilibrium distributions of every ionizable group simultaneously.
- Numerical ambiguity
Even if one attempts to use an equivalence point as a rough proxy for pI, the statement “equivalence point = pI” does not specify which equivalence point (1st, 2nd, 3rd, etc.) is meant, making the claim unclear.
Using arginine as an example to illustrate all points:
At arginine’s 2nd equivalence point, the stoichiometric neutralization of the α-amino group does not account for the equilibrium protonation state of the guanidinium group. Thus, the equivalence point does not precisely reflect the actual equilibrium conditions needed to yield zero net charge.
In short, this statement is problematic because it incorrectly equates an idealized stoichiometric concept (equivalence point) taking into account a single group with an equilibrium-based definition (pI) which is the average net charge of multiple protonation states, and it fails to specify clearly which equivalence point is even intended.
I wonder if this card even has merit given the caveats would have to look like:
At the specific {{c2::equivalence point}} which would seemingly make the molecule have a net charge of 0 based purely on stoichiometry, the pH approximates the {{c1::pI}}.
lol
I definitely don’t think we’re going to be able to throw in enough caveats to make this sentence hold generally true across the board for all potentially relevant scenarios. If that’s our only option, it would be better to just trash it
But:
Correct me if I’m wrong, but if you take the isoelectric point for a zwitterion as a whole, the statement would hold true, no?
Granted, I get that it is comprised of two individual isoelectric points, but the isoelectric point of the molecule (pI) should equal the pH at the equivalence point
If we build up, to try to snag all possible scenarios, this card is going to be a mess.
Conversely, if we just dumb it down so it’s only talking about a zwitterion, it’s not actually that far off base (and, I suspect, this is what was intended in the original writing)
Granted, I get that it is comprised of two individual isoelectric points, but the isoelectric point of the molecule (pI) should equal the pH at the equivalence point
There’s a single isoelectric point but multiple equivalence points. I think you mean if you take the equivalence point of the molecule as a whole.
I think that frame of reference doesn’t exist. Stoichiometric equivalence points, by definition, involve the complete neutralization (full protonation or deprotonation) of individual ionizable groups and represent discrete steps on a titration curve. In contrast, the pI reflects an equilibrium condition, characterized by a balance of partially protonated and partially deprotonated states across multiple functional groups simultaneously, resulting in an average net charge of exactly zero.
Thus, although the pI identifies an exact pH value at which the molecule is electrically neutral overall, this condition cannot arise from a single stoichiometric event. Consequently, there cant be a whole-molecule equivalence point coinciding exactly with the pI as that would account for the continuous equilibrium distributions of multiple protonation states which equivalence points do not.
I’m neither sure if that’s always true, nor if it could even be applicable to the way we discuss neutralization in basically any biological system ever, really. Short of a 1:1 mixture in a Petri dish, you’re always dealing in multiples
I’m not sure there’s a pedagogical need for it to have arisen from a single event, really. Almost by definition, lots of events going on in any solution ever.
But, neither does this get us any closer to a determination or solution
Thats the exact definition of an equivalence point though and the point I’m trying to make. The equivalence point is strictly stoichiometric: it occurs when the amount of titrant (acid or base) added exactly matches the moles of analyte initially present.
For example, when titrating an acid (HA) with a base
HA + OH - ----> A- + H20
We say at the equivalence point you’ve added exactly enough titrant (OH⁻) to convert all HA into A⁻. In this simplified viewpoint, the reaction is considered to proceed completely and irreversibly. Not accounting for equilibrium. This is purely a stoichiometric criterion, defined by mole-to-mole matching.
pI definitionally requires a consideration of all the protonation states - it takes into account equilibrium.
An equivalence point is a specific discreet event which occurs when you’ve added exactly enough titrant to completely neutralize a specific acidic or basic functional group, theoretically converting it 100% from one state to another as it does not account for equilibrium.
The reason there isn’t a single equivalence point for an entire polyprotic molecule, such as an amino acid, is because equivalence points are defined strictly as stoichiometric events tied to individual ionizable groups. Each ionizable functional group has its own distinct equivalence point, marking the theoretical complete neutralization of that specific group. Consequently, polyprotic molecules exhibit multiple distinct equivalence points, each corresponding to the titration of a particular functional group. In contrast, the isoelectric point (pI) reflects an equilibrium condition across all ionizable groups simultaneously, balancing partial protonation states to yield an average net charge of zero. Thus, the concept of a single, whole-molecule equivalence point does not exist, as equivalence points by definition apply to individual groups, not entire molecules.
By this argument, then, you can’t have an equivalence point for a polyprotic species, and I’m not entirely convinced that we don’t see that exact thing referenced.
I understand that, in pure semantics, there is an equivalence point for a given event and a polyprotic species would have multiple equivalence points. I’m also not convinced that is how solutions are always, necessarily, referenced even on the MCAT (or its relevant primary sources)
In any event, can only go back and forth so much I suppose. The other suggestion is open for everyone to take a gander at