I want to hydrophobize doxorubicin HCl as indicated by literature before encapsulation into the solvent with the PLGA polymer to prepare nanoparticles.
I am using this protocol: incubate 3 molar excess of triethylamine with DOX in water for 24 hours, then extract with DCM.
Question is: Can pH be a good indicator for the success of the desalting process? and what is the expected the results of it?
Okay this is so simple Thank you very much for the valuable answer Prof.
Actually once I added the TEA, the water solution of DOX turned into bluish color write away... Tomorrow I ll extract the DOX. and see. Thanks again
Dear Hassan,
The pKa of triethylamine is about 11. Therefore all DOX.HCl will be converted to DOX once you add an excess of triethylamine. There is no necessity to measure the pH since for sure it will be basic enough to convert the salt to free base.
I believe that by three times extraction with CH2Cl2 you can recover all DOX free base.
Good luck,
Rafik
Okay this is so simple Thank you very much for the valuable answer Prof.
Actually once I added the TEA, the water solution of DOX turned into bluish color write away... Tomorrow I ll extract the DOX. and see. Thanks again
the recovery of the extraction is very low (after four times)... and a precipitate is formed and is lying in between the water and the DCM...
Dear Hassan,
It seems that you have an emulsion for med between the two layers. Now you should add a brine solution (saturated solution of NaCl) for breaking the emulsion. Once this emulsion is broken, separate the two layers.
Good luck,
Rafik
Hi,
I used the same protocol: TEA overnight followed by DCM extraction (three times). I played around with adding saturated salt solution and various amounts of DCM. In the end I was able to extract some of the doxorubicin base, but the yield is low. If anyone has extra tips for improving the yield, I'd appreciate it!
Picture: extracted dox base on the left; starting material on the right
it was always low with me actually... wondering how people report this in every single paper. I gave up on the idea and went another way to be honest. I was always afraid of the stability of the dox during my work
Based on the provided structure of Doxorubicin HCl, it would seem that addition of base simultaneously leads to deprotonation of the amine (as desired) and deprotonation of at least one of the phenols, possibly both (pKa around 7.3 according to: https://pubchem.ncbi.nlm.nih.gov/compound/doxorubicin#section=Caco2-Permeability) . The latter will lead to formation of a triethylammonium salt, which is likely to limit the solubility in organic solvent. In other words, you may go from the cation to the anion, thereby limiting the solubility, which may be the source of the observed precipitate?
Would careful titration with base lead to an easily extractable zwitterion rather than the anion?
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