# Why can curcumin cross the blood-brain barrier, but not congo red?

I've read that both congo red and curcumin are able to inhibit the clumping together of amyloid $\mathrm{β_{42}}$ in the brain, which would otherwise result in Alzheimer's disease.

Apparently, congo red cannot cross the blood-brain barrier (BBB) while curcumin can.

From what I learned at my biology classes, the BBB is lined by squamous, endothelial cells. Those cells are, as far as I know, the most permeable kind of cells you could come across in the human body, and if congo red doesn't pass through that, then it must be one stubborn molecule.

Now the cell membrane, itself being composed of a phospholipid bilayer, normally shouldn't have a problem transporting lipophilic molecules across the membrane. From an earlier conversation with Jan, I believe congo red is a lipohilic molecule. Yet inspite of it being lipophilic, it still isn't able to cross the BBB.

Comparing the structures wasn't particularly enlightening.

But the possibility congo red could act as a bidentate ligand, does seem to make it stand out from curcumin. Am I onto something here? Apart from that, and a somewhat larger size, I don't see why congo red shouldn't be able to cross the BBB.

Now, I'd like to know two things,

1) What enables curcumin to cross the BBB?

2) Why isn't congo red able to cross the BBB, even though it has a structure similar to that of curcumin?

• Congo red is charged. That's ten times worse than merely being hydrophilic. Nov 12 '16 at 15:39

The key difference between the two molecules is comparing the extent of their lipophilicity and their hydrophilicity. Curcumin has a rather low water solubility of $3.2~\mathrm{mg/l}$, in line with the fact that it has rather little features that can enhance solubility. Basically, it boils down to the two keto-groups and the phenol moiety.
Congo red has two sulphonic acid groups and two aromatic amino groups. This means that there is a much greater relative charge present, and indeed its solubility in water is reported to be $1.16 \times 10^{2}~\mathrm{g/l}$ — notice the different unit. So congo red is already much more hydrophilic than curcuminis.