I have a series of heterocyclic ligands needed for a medicinal chemistry study. These ligands in their neutral forms are unstable and decompose. Since they have trialkylamino sustituents I am looking at making salts which could be more stable. Initial attempts to make the HCl salts gave good yields of salt products but they were hygroscopic making prolonged storage of the samples tricky. I need to make water soluble salts that are not going to be hygroscopic. Any suggestions would be welcome.
water soluble compounds are ideal for pharmacological studies.If solubility is the problem you can make suspension/emulsion of the molecule with Pharmacologically inert substances like C.MC,Gum agar,DMSO,Polyethylene glycols of lower molecular weight
usually salts of mineral acids are more polar (hygroscopic) than organic acid salts. Pay attention for the Pka and try with organic acids.
As above, HBr is a must try just as methanesulfonic acid. Try - as Muhammad sad - citric acid and tartaric acid too.
I think, HCl-salt form is the best regarding biological activity testing. Hygroscopicity in the most cases is a result of the superstechiometric HCl adsorbtion on the surface of your salt. To avoid this don't use nonpolar solvents (hexane, benzene, toluene) for the HCl-salt forming. We use dioxane, THF, acetone for the HCl-salt form synthesis from the bases, following with recrystallisation using MeOH(EtOH)/iPrOH(acetone) system or simething like it. Vacuum drying under 40 - 60 oC and hermetically sealed container provide good long-range stability.
We used to prepare HCl salt, and store it in the dry and cool condition for prolong time,
the main reason for preparing HCl salt:
It was reported that out of 300 new chemical entities approved by the FDA during 1995 to 2006, 120 were in salt forms. In addition, out of the 101 approved salts of basic drugs, 54 salts were prepared with hydrochloric acid. over 50% was HCl salt,
good luck
We used to face this type of problem with inorganic acid, especially with HCl. You can try with H2SO4, HNO3. Some salts are soluble with lower pH
- Badges
- Science method
- Similar topics
- Chemistry
- General Biochemistry
- Biochemical Techniques
- Analytical Chemistry