Biochem Question

[jkn1121]

1. Benzylamine is a chemical used as a precursor in the synthesis of some drugs. The amino group in benzylamine has a pKa of 9.3. The other groups in this molecule can be considered not ionizable.

 

 

Structure 1

 

 

 

 

 

The picture above shows the unprotonated form of the benzylamine. Draw the protonated state of this compound.

 

 

Structure 2

 

 

 

 

* Suppose to be a NH3

 

 

 

Which structure (or structures) will predominated at the following pHs? (Structure 1 is the original picture (unprotonated) and structure 2 is the one you drew (protonated).

 

 

pH 3: ______Structure 2____________________________

 

 

pH 7 – 8: _____Structure 1__________________________

 

 

pH 11: _______________Structure 1__________________

 

I dont undrstand how this can link into a T/F answerable

 

Based on the structures above (your structure and the original unprotonated structure), which is true about benzylamine? (mark true or false)

 

 

a. This molecule will be more soluble in water at low pH (for example at pH 3) _____________

 

b. This molecule will be more soluble in water at high pH (for example at pH 11) _____________

 

c. If ingested, this molecule is more likely to be absorbed (go through the cellular membrane) in the stomach, at a pH of ~ 1 _____________

 

d. If ingested, this molecule is more likely to be absorbed in the intestines, at pH ~ 7 or 8 _____________

[Mr Skeptic]

For solubility in water, which form is more hydrophobic?

 

As for the membrane, do polar or non-polar things pass through the membrane more easily?

[jkn1121]

Structure 1 is hydrophobic since its neutral and nonpolar can pass through the membrane easily

For solubility in water, which form is more hydrophobic?

 

As for the membrane, do polar or non-polar things pass through the membrane more easily?

 

I think the answer is

A. F since the pka is very high it wont be soluble in a low ph

B. T since the pka will be solube in a hgh ph

C. F, ph too low

D. T, ph similar close to ph 7,8

[cypress]

 

 

pH 7 – 8: _____Structure 1__________________________

 

Review the definition of pKa and the relationship to pH and let me know if still think this is correct and why you think so.

[jkn1121]

its a neutral structure and its in a chargeless stage but if the unpronated structure is with a pka of 9.2, i think it should be structure 2 instead, right?

Edited October 11, 2010 by jkn1121

[Mr Skeptic]

Hm, I should also have mentioned you neglected the charge on structure 2, though I thought it was just a careless omission.

 

And also, why do you say that structure 1 would dominate at a pH lower than the pKa? (edit: looks like cypress beat me to this)

 

(Incidentally, I'm pretty sure the pKa is for the protonated form.)

[jkn1121]

Because it has the charge and it goes with the lower ph since it more acidic

[cypress]

Structure 1 is hydrophobic since its neutral and nonpolar can pass through the membrane easily

 

 

I think the answer is

A. F since the pka is very high it wont be soluble in a low ph

 

You said above that structure 1 is hydrophobic and at pH 3 it is mostly in the protonated form so.... You might want to think this over a bit.

 

B. T since the pka will be solube in a hgh ph

 

hmm..... are you sure? You said the neutral form would dominate at high pH and it is hydrophobic....

 

C. F, ph too low

 

Yes the pH is low but the issue preventing transport is the polarity of benzylamine at this pH right? At pH of 1 the ratio of protonated to nonprotonated is about 2*10^8 so there is very little nonpolar form to be transported right?

 

Because it has the charge and it goes with the lower ph since it more acidic

 

While this is a true observation, it is not relevant. What is relevant is the equilibrium concentrations of the various constituents. Try to find an equation that represents the relationship between pH and pKa and then let's work through it to see what dominates at pH7 - 8.

[jkn1121]

ph3: Structure 2

ph7-8: Structure 2

ph11: Structure 1

 

A. T since the structure is hydrophic then structure 2 would be capactible

B. F since it at ph 11, therefore sturcture is more basic to be capatible

C. F, since the structure 2 has the charge to make it acidic

[Mr Skeptic]

Well now your answers are correct, but your reasoning is still not. It is not a question of acidity or basicity (that's not the right word but you know what I mean), that part was for determining which structure at which pH.

 

But for the second part, it is a question of polar vs non-polar. The first structure has a benzene ring, which is very non-polar, a carbon with hydrogens which is also non-polar, and a nitrogen with hydrogens that is significantly polar but not enough to make the overall molecule non-polar. The second structure has a charge on it instead of the -NH2, and the charge is very polar. Since water is a polar solvent, it can dissolve polar things. The membrane is mostly non-polar and keeps polar things from passing through it, but non-polar things can pass through.

[jkn1121]

I just want to make sure, D is True right?

 

 

[Mr Skeptic]

Yes, though it would probably do better at a slightly higher pH... but the digestive track doesn't have the full range of pH, so its as close as you can get. But then the digestive track is optimized for absorbing, and it has a huge surface area to do it with so it doesn't have to be optimal. But in the stomach the non-polar form would be outnumbered by almost a billion to one which would be problematic.

[cypress]

Yes, though it would probably do better at a slightly higher pH... but the digestive track doesn't have the full range of pH, so its as close as you can get. But then the digestive track is optimized for absorbing, and it has a huge surface area to do it with so it doesn't have to be optimal. But in the stomach the non-polar form would be outnumbered by almost a billion to one which would be problematic.

 

But, because the intestine is a highly speciallized flow through absorber and equillibrioum is involved, therefore as C6H6-CH2-NH2 is absorbed, the concentratiion gradient will drive C6H6-CH2-NH3 back to C6H6-CH2-NH2 to maintain the concentration ratio. At a pH of 8, the concentration ratio [C6H6-CH2-NH2]/[C6H6-CH2-NH3+] is 0.05 or about 1 in 20 molecules is easily absorbed and at pH of 7 the ratio is still 1 in 200. In this range, even at the low end of 1 in 200, a flow through absorber with good retention time is more than enough to absorb nearly all the chemical even when radial diffusion is fairly low.

 

When one considers that there is a wide range of chemicals to be absorbed with a range of pKa's, pH of 7-8 is optimal for the job being performed.

 

The key to answering these problems is to understand how to compute these ratios for various pH's and to have an idea of the process involved. The stomach is a well-mixed batch absorber while the intestine is a continuous flow through absorber. Even a batch absorber can work pretty efficiently if the retention time is reasonable (30 minutes or longer) but the stomach is primarily a batch chemical reactor/digestor. As this problem illustrates, the stomach is set up to absorb chemicals that are insensitive to pH (very very low pKA's)