Biochemistry Questions Biochemistry Questions / How does fluorine substitution next to an oxygen atom impact a drug's polarity and solubility in water? Discuss the implications of fluorine's effect on the distribution and bioavailability of the drug.

Where a fluorine is substituted next to an oxygen on a drug molecule, the lipophilicity (partition coefficient) decreases. This is because of the polarity in the molecule making it more difficult to partition through phospholipid bilayers.

Both oxygen and fluorine are highly electronegative, and will draw electrons (negative charge) towards them, away from the carbons they are bound to.

Ensuring the fluorination of a drug molecule does not have a negative impact on its absorption and distribution is important, as these modifications could alter the bioavailability.