Need help understanding organic chem concept

[greenbee2495]

Hey guys, Im having a hard time understanding how pH changes affect charged molecules or amino acids. Ive noticed while studying for the MCAT that this concept is crucial to solving some problems but Im having a hard time wrapping my head around it and predicting what happens. I did well in organic chemistry but just forgot how this made sense before to me.

Like how does the charges change of an amino acid when the pH is changed

OR

phosphoric acid is negatively charged at pH 7 which allows it to be unreactive to nuc attacks because the negative charge stabilizes the partial positive charge on the P.

If someone can explain it in an easy way on whats happening at the molecular level, I'd really appreciate it. I want to be able to predict what happens to a molecule when it is placed in different pH environments.

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[PNWMedStudent]

This is a super important concept and very high yield for most MCAT tests - seems to be on >80% of the FLs and I've had this question on both of my real MCAT exams.

Essentially, you want to take note of how many basic and acidic AA's are in the chain. Basic AA's are R, H, and K and will have a positive charge at physiological pH of 7 (really 7.4). Acidic AA's are D and E and will have a negative charge at physiological pH of 7. The thing that matters here is the pKa value of each of the relevant side chains within these AA's.

Histidine (H) has a pKa of 6
Arginine (R) has a pKa of 12
Lysine (K) has a pKa of 11

Glutamic Acid (E) has a pKa of 4
Aspartic Acid (D) has a pKa of 3.7

Also, note that COOH has a pKa of about 2 and NH3 has a pKa of about 9

So.... what does all of this mean? Well, if the pH of the solution is higher than the pKa of the AA side chain group, that group will be deprotonated (lose H+). For a group like COOH, at a pH of 7, the pKa value is lower (2) so this group loses it's H+ and receives a negative charge. Also, NH3 at pH 7 (has a pKa of 9), will be protonated resulting in a positive charge. These charges (+ and -) balance each other out - resulting in a neutral charge of the AA. This is where the side chain matters. Take Glutamic acid for example: the NH3 and COOH with their + and - respectively cancel, so the resulting side chain of E, having pKa of 4, is negatively charged. This leads to the E having an overall negative charge (-1)+(-1)+(+1)=(-1).

Now let's look at an entire AA chain, as the MCAT tests on regularly.

Question: what is the overall charge of the following AA chain at pH 7 AVEMDRDMFYWKEDA (this represents a sequence of AA's via single letter abbreviations)

AVEMDRDMFYWKEDA - I have made the acidic AA's bold, we see there is a total of 5 of them

AVEMDRDMFYWKEDA - I have underlined the basic AA's, we see there are 2 of these

Overall, we can assume the non acidic/basic (D,E,R,K,H) AA's have a neutral charge at pH 7. The rest is simple addition. We have 5 negatively charged AA's (-5) and 2 positively charged AA's (+2) so we would expect an overall charge of -3 for this chain.

Use the rule mentioned previously to determine charge if the pH is above or below 7.

Histidine is an outlier in this. For the purposes of the MCAT, it seems that H at pH 7 is still + charged. In reality, it's only about 25% positively charged but this seems to lie outside of the scope fo the exam.

 

[PNWMedStudent]

Regarding your question about the effect of pH on charge at the molecular level, think of it in these simple terms. The pKa is the pH at which an acid is exactly 50% deprotonated - thus neutral in charge. If you increase pH (higher pH means more basic, less H+ floating around) the solution will want more H+ and will strip it from the molecules. Ex: COOH with pKa of 2 will be stripped of it's H+ resulting in COO- at pH 7.

When the pH drops below the pKa (low pH generally means excess of H+ in solution), it has a lot of H+ to give to the groups. Ex: NH3 (pKa of 9) will receive a H+ from the solution when pH is 7.

The relationship is easily understood by thinking of greediness. pKa is how greedy the side chain group is and pH is how giving the solution is.

 

[greenbee2495]

Regarding your question about the effect of pH on charge at the molecular level, think of it in these simple terms. The pKa is the pH at which an acid is exactly 50% deprotonated - thus neutral in charge. If you increase pH (higher pH means more basic, less H+ floating around) the solution will want more H+ and will strip it from the molecules. Ex: COOH with pKa of 2 will be stripped of it's H+ resulting in COO- at pH 7.

When the pH drops below the pKa (low pH generally means excess of H+ in solution), it has a lot of H+ to give to the groups. Ex: NH3 (pKa of 9) will receive a H+ from the solution when pH is 7.

The relationship is easily understood by thinking of greediness. pKa is how greedy the side chain group is and pH is how giving the solution is.

Thank you, this really helps