acid-base properties of drugs

why are acid base properties important in pharmacy

determines drug ionization, which affects absorption, distribution, and excretion

normal blood pH

approximately 7.4

lewis acid

electron-pair acceptor (ex: borane and metal ions)

lewis base

electron-pair donor (ex: atoms with available lone pairs, such as N and O)

bronsted-lowry acid

proton donor

bronsted-lowry base

proton acceptor

conjugate acid

base after accepting a proton

conjugate base

acid after donating a proton

how do conjugate acid-base pairs differ

by one proton

what does an acid-base equilibrium generally favor

weaker acid and weaker base

pKa

single scale for reporting and comparing ionization capacity of acids and bases

Ka

acid dissociation constant, measuring acid ionization in water

Ka equation

Ka=[A-][H3O+]/[HA]

pKa equation

pKa=-logKa

how to calculate Ka from pKa

Ka=10^-pKa

low pka indicates

stronger acid

high pKa indicates

weaker acid

how does acid strength relate to conjugate-base strength

stronger acid=weaker conjugate base

what does difference of one pKa unit represent

tenold difference in Ka

pH equation

pH=-log[H3O+]

how to calculate hydronium concentration from pH

[H3O+][OH-]=10^-14

pH of neutral water at 25 degrees C

7

pKa of water as an acid

15.7

strongest acid that can exist in water

H3O+ due to leveling effect

what happens to acids stronger than H 3O+ in dilute water

dissociates essentially completely

weak-acid approximation for hydronium concentration

[H3O+]=sqrt(KaC), where C is initial acid concentration

how to calculate approximate pH of weak acid

pH=-log(sqrt(KaC))

when can weak-acid approximation be used

when dissociation is small relative to inital acid concentration

approximate pH of 0.1 M procaine hydrochloride with pKa=9

pH=5

approximate pH of 0.1 M procaine hydroschloride with pKA=9

pH=5

why can hydrochloride salts of weak amines produce acidic solutions

protonated amine acts as a weak acid and releases H+ to water

if Ka increases, what happens to pKa

pKa decreases

pKa of p-nitro-aromatic carboxylic acid

3.4

pKa of p-chloro-aromatic carboxylic acid

4.0

pKa of benzoic acid (aromatic acid)

4.2

pKa of aniline (aryl ammonium conjugate acid)

4.6

pKa of acetic acid

4.76

approximate pKa of the aliphatic carboxylic acid example

4.84

pKa of procaine's protonated tertiary amine

8.9

pKa of ammonium (NH₄⁺)

9.2

pKa of phenol

9.6

approximate pKa of amphetamine's protonated amine

10

approximate pKa of guanidinium

14

approximate pKa of an aliphatic alcohol

16

approximate pKa of an amide N–H

18

what determines acidity of compound

stability of conjugate base

how does conjugate-base stability affect acidity

greatger stability means stronger acidity and lower pKa

resonsance stabilization

delocalization of electrons or charge across multip;le atoms

how does resonance stabilization of a conjugate base affect acidity

increases acidity by stabilizing conjugate base

why are carboxylic acids more acidic than alcohols

their conjugate bases are resonance stabilized over two oxygens

why are phenols more acidic than aliphatic alcohols

phenoxide can delocalize its negative charge through the aromatic ring

what is an electron-withdrawing group (ewg)

substituent that pulls electron density away from part of a molecule

how do ewgs generally affect carboxylic acid acidity

increases acidity and decreases pKa

what is an electron donating group (edg)

substituent that increase electron density

how do edgs generally affect carboxylic acid acidity

decreases acidity and increases pKa

inductive effect

transmission of electron-withdrawing or donating effects through sigma bonds

how does distance affect inductive effect

effect decreases as substituent gets farther away

why do halogens near a carboxylic acid increase acidity

there electron-withdrawing inductive effect stabilizes the carboxylate conjugate base

effect of nitro group on aromatic carboxylix acid acidity

generally increases acidity through electron withdraway

why can resonance-donating groups decrease aromatic carboxylic acid acidity

can increase electron density and destabilize negatively charged conjugate base

how does an electron-withdrawing substituent generally affect amine basicity

increases basicity by increasing electrong density on nitrogen