M6G and M3G are "chemical chameleons", which can adopt their conformations according to the polarity of the medium in which they find themselves in (e.g., 'folded' or 'extended' conformations). Even though these molecules are polar, they can still cross the blood-brain barrier. Transporters may be involved. But the passive route also can be important. I can't seem to locate reliably measured solubility of these molecules. The closest I could find is that of morphine-6-sulfate, which has the intrinsic aqueous solubility of 9.3 micromolar. Any leads would be most appreciated.

-Alex