Wang Med Chem

Sulfonic acid

pKa = -2 to 1

fully deprotonated anion at pH = 7.4

Phosphonic acid

pKa (1) = 1-3

pKa (2) = 5-8

usually more mono or dianionic

Carboxylic acid

pKa = 3-5

mostly deprotonated, common in NSAIDs and acidic metabolites

Tetrazole

pKa = 4.5-5.5

carboxylate bioisostere

mostly anionic at pH = 7.4

Sulfonamide

pKa = 7-10

ionization is highly substituent dependent

Imide

pKa = 6-9

often partially ionized

acidic N-H between two carbonyls

Phenol

pKa = 9-11

mostly neutral at pH = 7.4

phenolate increases polarity

Thiol

pKa = 8-10.5

mostly neutral to partially thiolate, depending on substituents

Alcohol

pKa = 15-18

neutral under physiological conditions

Guanidine

pKa = 12-13.5

almost fully protonated, strong cation

Amidine

pKa = 11-13

mostly protonated, strong cationic center

Aliphatic amines

RNH2, R2NH, R3N

pKa = 8-11

usually protonated, key driver of salt formation

Piperidine

pKa = 10-11.5

mostly protonated, common saturated basic heterocycle

Morpholine

pKa = 7-8.5

partially protonated, oxygen lowers basicity

Imidazole

pKa = 6-7.5

both neutral and protonated forms may matter

Pyridine

pKa = 5-6.5

mostly neutral at physiological pH

Aniline

pKa = 4-6

mostly neutral, resonance lowers N basicity

Amide (NHR)

~1 - 1

essentially non-basic

N lone pair delocalized into carbonyl

Quaternary ammonium

R4N+

no pKa

permanently charged