acid-base properties of drugs part 3

amidine

functional group containing carboin bonded to two nitrogen atoms, including C=N bond

guanidine

functional group containing cabron bonded to three nitrogen atoms

aproximate pKa range of protonated amidines

9-12

approximate pKa of protonated guanidines

14

why are amidines and guanidines strongly basic

their protonated conjugate acids are stabilized by resonance

how does resonance affect amidine and guanidine basicity

delocalization of prositve charges stabilizes the conjugate acid, favoring protonation

which is generally more basic: amidines or guanidines

guanidines

what is the predominant form of amidines and guanidies at physiological pH

protonated, positively charged

phenol

hydroxyl group (-OH) directly attached to aromatic ring

enol

hydroxyl group attached to carbon of C=C double bond

approximate pKa of phenol

10

approximate pKa of cyclohexanol

15-16

why are phenols more acidic than aliphatic alcohols

conjugate bases are stabilized by resonance

conjugate base of phenol

phenolate (phenoxide) anion

how is negative charge stabilized in phenoxide

through resonance delocalization across aromatic ring

why can enols be acidic

conjugate bases can be stabilized by resonance

what happens when phenol loses a proton

forms a negatively charge phenolate ion

what is the predominant form of typical phenol at physiological pH

neutral, protonated phenol (-OH)

sulfonamide

functional group containing –SO₂–N–

approximate pKa range of acidic sulfonamides

5-11, depending on substituents

why can sulfonamides be acidic

sulfonyl group helps stabilize conjugate abse after N-H deprotonation

how do substituents affect sulfonamide acidity

they alter electron distirbution and conjuigate-base stability, changing pKa

imide

functional group with nitrogen bonded to two carbonyl groups

approximate pKa of succinimide

9.6

why are imides more acidic than typical amides

their conjugate bases are stabilized by resonance with two carbonyl groups

what happens when an imide loses its N-H proton

forms a resonance-stabilized negatively charged conjugate base

what determines whether aromatic nitrogen is basic

whether its lone pair is available to accept proton

why is pyridine basic

its nitrogen lone pair doesn’t participate in aromatic pi system

why is pyrrole considered nonbasic

its nitrogen lone pair participates in aromaticity

what happens when nitrogen lone pair participates in aromaticity

becomes much less available for protonation

are most aromatic nitrogen heterocycles strongly basic

no, many are weakly basic

conjugate-acid pKa values of pyridine and imidazole

5.2, 6.9

conjugate-acid pKa values of pyrazine, pyrimidine, and pyridazine

0.6, 1.3, and 2.3

conjugate-acid pKa of 1,2,4-triazole

2.2

what is a tetrazole group used to mimic

carboxylic acid group

waht happens when acidic tetrazole N-H loses a proton

forms a negatively charged conjugate base

zwitterion

molecuile containing both positive and negative charges with overall net charge of zero

why do amino acids exist as zwitterions at physiological pH

their carboxyl groups are deprotonated while their amino groups are protonated

two pKa values of glycine

2.35 (carboxyl) and 9.78 (ammonium)

which amino acids contain acidic carboxylic acid side chains

aspartic acid and glutamic acid

predominant form of acidic amino acid chains at pH 7

deprotonated, negatively charged carboxylate (COO-)

side chain pKa fvalues of tyrosine and cysteine

10, 8

which amino acids basic side chains, and what are their pKa values

lysine = 10.5; arginine = 12.5; histidine = 7

why can amino acids have multiple pKa values

they contain multiple ionizable functional groups

what does each buffering region of an amino acid titration curve represent

ionizable group undergoign protonation/deprotonation near its pKa