Partition coefficient local anaesthetics

Note that the relative spatial arrangement of the phenyl, amine, and hydroxyl functionahties are identical for (R)-alprenolol and (5)-sotalol. In addition to P-blocking activities, some of these compounds also possess potent local anaesthetic activity (see Anesthetics). The membrane stabilizing activity, however, is not stereoselective and correlates directly with the partition coefficient (hydrophobicity) of the compound. 

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

Figure 1.2. Correlation between the biological potency of local anaesthetics, given as the minimum blocking concentration MBC), and activated carbon adsorption (a, filled squares) or octanol-water partition coefficient P (open squares) (data from ref. (3a))...

Ropivacaine has a pKa value of 8.2 and a calculated partition coefficient of 2754. Calculate the partition coefficient for ropivacaine at pH 7.4. Which is the more potent local anaesthetic ... 

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