Chapter 12: Biological Molecules

[skogias6733]

Hi,

For question 27

Correct Answer: B
Discuss this question
Worked Solution
The pKa (the pH at which 50% of the drug is ionized and 50% is present as base) of the anaesthetic is related to pH and the concentrations of the cationic and base forms by the Henderson-Hasselbalch equation: pH = pKa + log ([base]/ [cation]). When an anaesthetic solution is injected into healthy tissue, it eventually takes on the pH of the surrounding tissue which is 7.4. As pKa approaches pH there is more of the uncharged base form present.

wondering why is the 'uncharged' form the base here? I thought that a conjugate base always has a negative charge? I would have thought that the uncharged version would be the conjugate acid (HA). I get that in the question we need the "non ionised base" to to ensure it passes through the membrane, and in the diagram it shows that the base is RN (uncharged) and the acid is H+
but confused as this doesnt follow what i learned previously about the HH equation as the denominator of the equation is 'cation' when i thought it was meant to be neutral conjugate acid?

Also confused with the part that says "As pKa approaches pH there is more of the uncharged base form present." I thought that as the pkA approaches the pH that there is more of an equal ratio of acid to base??? and that if we want it to be more BASIC so it can pass through, then we need
pH > pkA
7.4 > pKA

but there is no pKa option that is less than pH 7.4

I would have that, that if the ph = 7.4 and all the pKas in the table are above this value, that this would mean that there is more of the acidic/protonated form (because pH < pKa = acidic/protonated ) , not more of the uncharged Basic form.

but i guess the rules would be different given the 'uncharged base', very confused, are you able to please tell me where i am going wrong?

Thanks in advance!

[goldstanda3269]

I thought that a conjugate base always has a negative charge?

From General Chemistry Chapter 6, a very famous case of amphoteric water which, even as neutral, can indeed be a conjugate base because it has a lone pair on oxygen that can accept a proton to make its conjugate acid H3O+.

what i learned previously about the HH equation as the denominator of the equation is 'cation' when i thought it was meant to be neutral conjugate acid?

The denominator is the conjugate acid (in the form of the HH equation in the solution) which may or may not be a cation. H3O+ could be the conjugate acid, but neutral H2O could be the conjugate acid if the conjugate base is OH-.

Also confused with the part that says "As pKa approaches pH there is more of the uncharged base form present." I thought that as the pkA approaches the pH that there is more of an equal ratio of acid to base???

Let's deal with your statement first: The maths of the HH equation is such that if pH EQUALS pKa then there "an equal ratio of acid to base". However, just a matter of the maths of the equation, if the pKa is higher than the pH, as in the examples in this question, it means that the relatively low pH makes it such that that molecule is predominantly in the acid form. So if we choose lower and lower pKa's, then we have more and more of the base form (in the scenario of this problem where all pKa's are above the pH).

I would have that, that if the ph = 7.4 and all the pKas in the table are above this value, that this would mean that there is more of the acidic/protonated form (because pH < pKa = acidic/protonated ) , not more of the uncharged Basic form.

True!!!


In restrospect, perhaps we should not discuss the HH equation! Although it does show up on the exam on a regular basis, it is always provided when needed. However, we will divide the worked solution into "On the Surface" and "Going Deeper" as we have done for some other practice questions.

Now for the simple reasoning that ACER expects from students...

On the Surface: For the equilibrium RNH+ ↔ RN + H+ (see Figure 2) and in the circumstance that all of the answer choices in this question have pKa values above the pH of 7.4 (see Table 1), this means that all of the stated anaesthetics will be predominantly in the acid form RNH+ (because the pH is low as compared to the pKa).

We must now seek the anaesthetic with the least difference between the pH and the pKa which will increase the balance between the acid form and the base form RN. In other words, according to the equilibrium equation, the base form will be relatively higher (again, note that we are only choosing between pKa values above the pH). Mepivacaine has the smallest difference, thus a higher percentage of the diffusible form RN.