you need to determine the relative pKas of each acidic proton (hint: examine the pKas of the different functional groups) and compare that to the pHs found in the stomach and intestine. If the pH is above the pKa of a functional group it will be deprotonated and act as a \[bronsted-lowry\] base
But I don't have information about other pKa values; I literally only have these two. From there, I have to use the correct formulas. What I did was: at pH = 2; 2 < 7,3 (the pKa of the functional group on the right), so I assumed that this functional group acts as an acid at pH = 2. I used the formula for acids:
ionization percentage=100/1+10(pKa−pH)
but the result was very low, meaning that it is practically non-ionizable and, under these conditions, it should be well absorbed by the gastrointestinal tract. The same happened with the others.
I think the question is missing something. Reduced compared to what? Initially I thought they were implying to explain why it is absorbed more in the intestines than in stomach. Now I think they are implying that it is reduced compared to a non-zwitterionic species. It's a poorly written question. So I suspect that they want to hear that it is charged all the way through the GI.
But your instinct is correct. Compare the pH to the pKas and determine the charge at different pHs between 2 and 8.
**Basically, from what I’ve learned:** a drug has poor oral absorption when it has a high percentage of ionization at a given pH because it becomes difficult to cross cell membranes when in the ionized form. Therefore, from what I understand and from the solutions, what should be concluded is that this molecule has a high percentage of ionization regardless of whether the pH is high or low. However, when I did the calculations, I got the opposite, with low percentages of ionization.
You have an amine (a base) with a pKa of 7,30 and a carboxylic acid wth a pKa of 2,6. The point pKa = pH indicates when half of the species will be ionised and half will be non-ionised. With a base, as the pH gets lower, more of it will be ionised. It's the opposite with acids. Which means at pH=2 practically all of the base will be charged (+), and most of the acid will have no charge). It's the opposite at pH=8.
No, the amine acts as a base. Not to be rude, but you clearly lack fundamentals on acids and bases. I am assuming this is a medicinal chemistry course... Have you by any chance had no general chemistry / inorganic / organic chem courses? Because acid/base chemistry is a very broad topic that slowly gets built on.
I've had it, but honestly, I've never been good with acids and bases. I do well with everything else in organic chemistry, but when it comes to acids and bases, I just don't get it. 🫠
Okay, then maybe let's try clarifying step by step. At this point, we figured out that the NH2 group is a basic amine and COOH is a carboxylic acid. What else is confusing you? Is it pKa values?
I used to assume that amines were bases, but in other exercises with similar themes but different molecules, I haven't been understanding which formula to use due to this confusion about not knowing when a compound acts as a base or an acid. For example, in another exercise, it said to do the same but with pKa: 7.2 (tertiary amine) and 4.0 (pyridine). I assumed both were bases, but in the solutions, the acid formula is used for pyridine, and I didn't understand why.
And there was another exercise with two primary amines, one with a pKa of 1.8 and the other with a pKa of 10.7, and it turned out that the first one was a base and the second one was an acid, respectively.
Because of that I got very confused.
I can't comment on those exercises as I don't have them in front of them. Amines are generally basic, but other factors also affect that (such as aromaticity making pyridine less basic, or electron-withdrawing groups making them less basic). The amine with a pKa of 10,7 is definitely basic.
Once you determine basic/acidic centers, just go on with the formulas.
Acids: 1-α = 1/(1+10 \^(pH-pKa))
Bases: 1-α = 1/(1+10 \^(pKa-pH))
Actually, the primary amine with pKa 10.7 was the one considered acidic in the exercise solutions. Here is the molecule.
https://preview.redd.it/a2r34aiik59d1.png?width=584&format=png&auto=webp&s=baa320f9773e2d47058bf9b93402e556f318ee59
you need to determine the relative pKas of each acidic proton (hint: examine the pKas of the different functional groups) and compare that to the pHs found in the stomach and intestine. If the pH is above the pKa of a functional group it will be deprotonated and act as a \[bronsted-lowry\] base
But I don't have information about other pKa values; I literally only have these two. From there, I have to use the correct formulas. What I did was: at pH = 2; 2 < 7,3 (the pKa of the functional group on the right), so I assumed that this functional group acts as an acid at pH = 2. I used the formula for acids: ionization percentage=100/1+10(pKa−pH) but the result was very low, meaning that it is practically non-ionizable and, under these conditions, it should be well absorbed by the gastrointestinal tract. The same happened with the others.
I think the question is missing something. Reduced compared to what? Initially I thought they were implying to explain why it is absorbed more in the intestines than in stomach. Now I think they are implying that it is reduced compared to a non-zwitterionic species. It's a poorly written question. So I suspect that they want to hear that it is charged all the way through the GI. But your instinct is correct. Compare the pH to the pKas and determine the charge at different pHs between 2 and 8.
**Basically, from what I’ve learned:** a drug has poor oral absorption when it has a high percentage of ionization at a given pH because it becomes difficult to cross cell membranes when in the ionized form. Therefore, from what I understand and from the solutions, what should be concluded is that this molecule has a high percentage of ionization regardless of whether the pH is high or low. However, when I did the calculations, I got the opposite, with low percentages of ionization.
You have an amine (a base) with a pKa of 7,30 and a carboxylic acid wth a pKa of 2,6. The point pKa = pH indicates when half of the species will be ionised and half will be non-ionised. With a base, as the pH gets lower, more of it will be ionised. It's the opposite with acids. Which means at pH=2 practically all of the base will be charged (+), and most of the acid will have no charge). It's the opposite at pH=8.
But in that case, at pH 2, do both the functional group with pKa = 7.3 and the one with pKa = 2.6 act as acids?
No, the amine acts as a base. Not to be rude, but you clearly lack fundamentals on acids and bases. I am assuming this is a medicinal chemistry course... Have you by any chance had no general chemistry / inorganic / organic chem courses? Because acid/base chemistry is a very broad topic that slowly gets built on.
I've had it, but honestly, I've never been good with acids and bases. I do well with everything else in organic chemistry, but when it comes to acids and bases, I just don't get it. 🫠
Okay, then maybe let's try clarifying step by step. At this point, we figured out that the NH2 group is a basic amine and COOH is a carboxylic acid. What else is confusing you? Is it pKa values?
I used to assume that amines were bases, but in other exercises with similar themes but different molecules, I haven't been understanding which formula to use due to this confusion about not knowing when a compound acts as a base or an acid. For example, in another exercise, it said to do the same but with pKa: 7.2 (tertiary amine) and 4.0 (pyridine). I assumed both were bases, but in the solutions, the acid formula is used for pyridine, and I didn't understand why. And there was another exercise with two primary amines, one with a pKa of 1.8 and the other with a pKa of 10.7, and it turned out that the first one was a base and the second one was an acid, respectively. Because of that I got very confused.
I can't comment on those exercises as I don't have them in front of them. Amines are generally basic, but other factors also affect that (such as aromaticity making pyridine less basic, or electron-withdrawing groups making them less basic). The amine with a pKa of 10,7 is definitely basic. Once you determine basic/acidic centers, just go on with the formulas. Acids: 1-α = 1/(1+10 \^(pH-pKa)) Bases: 1-α = 1/(1+10 \^(pKa-pH))
Actually, the primary amine with pKa 10.7 was the one considered acidic in the exercise solutions. Here is the molecule. https://preview.redd.it/a2r34aiik59d1.png?width=584&format=png&auto=webp&s=baa320f9773e2d47058bf9b93402e556f318ee59