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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
Arginine
positively charged, polar AA

Histidine
positively charged, polar AA

Lysine
positively charged, polar AA

Aspartic Acid
negatively charged, polar AA

Glutamic Acid
negatively charged, polar AA

Serine
no charge, polar AA

Threonine
no charge, polar AA

Asparagine
no charge, polar AA

Glutamine
no charge, polar AA

Cysteine
special case
forms disulfide bonds

Selenocysteine
special case
forms diselenium bonds (not as strong as disulfide bonds)

Glyceine
special case, no side chain

Proline
special case

Alanine
non-polar/hydrophobic

Valine
non-polar/hydrophobic

Isoleucine
non-polar/hydrophobic

Leucine
non-polar/hydrophobic

Methionine
non-polar/hydrophobic

Phenylalanine
non-polar/hydrophobic

Tyrosine
non-polar/hydrophobic

Tryptophan
non-polar/hydrophobic
