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Dissociation costants and molecular protonation states prediction by Quantum 3.1.
The figure below demonstrates the correlation between experimental values of the dissociation constants for more than 100 organic acids and bases and those calculated by Quantum 3.1 (see the Table at the bottom of the page).
If all possible protonation states of a molecule are identified and all the corresponding dissociation constants are accurately calculated, then the proper protonation state of a the molecule can be singled out for any given value of pH. The concentrations of different protonated states of a chemical compound are characterized by titration curves.
| Example: Titration curves for 2-amino-3-hydroxypropanoic acid. | |
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For a physiological value of pH=7-8, the molecule is in its fully protonized neutral state "c". QUANTUM uses Quantum Mechanics to calculate electronic densities and dissociation energies. The water environment is simulated with the help of our continous solvation model (theory vs. exp.).
Another sample pKa calculation can be viewed here
The table below contains (in the horizontal order):
- the compound's common name (dissocation stage)
- experimental values of pKa (dimensionless)
- calculated values of pKa
The Root Mean Square (RMS) difference between the calculated and the experimental values of the dissociation constants, pKa, is 1,4 (dimensionless pH units). Identification of the protonation states is crucial for accurate IC50 calculations.
Compound |
pKa exp. |
pKa calc. |
|---|---|---|
2-phenylbenzimidazole(stage1) |
5.2 |
5.2 |
2-phenylbenzoic(stage1) |
3.5 |
3.5 |
diethanamine(stage1) |
10.5 |
10.4 |
2-ethylpyridine(stage1) |
5.9 |
6.0 |
cis-cinnamic(stage1) |
3.9 |
4.0 |
anisicacid(stage1) |
4.5 |
4.6 |
phenylethanoic(stage1) |
4.3 |
4.5 |
3,4-dihydroxybenzoic(stage1) |
4.5 |
4.3 |
diphenylacetic(stage1) |
3.9 |
4.2 |
2-amino-3-hydroxypropanoic(stage2) |
9.2 |
9.0 |
2-methylbenzilamidazole(stage1) |
6.2 |
6.0 |
4-methylquinoline(stage1) |
5.7 |
5.9 |
4-nitrophenylethanoic(stage1) |
3.9 |
4.1 |
3-butenoic(stage1) |
4.3 |
4.7 |
methyl-p-aminobenzoic(stage1) |
5.0 |
5.4 |
iso-quinoline(stage1) |
5.4 |
5.8 |
barbituric(stage1) |
4.0 |
4.4 |
benzoic(stage1) |
4.2 |
4.6 |
3,5-dihydroxybenzoic(stage1) |
4.0 |
4.4 |
2-ethylbenzilamidazole(stage1) |
6.2 |
5.8 |
trans-crotonic(stage1) |
4.7 |
5.1 |
acridine(stage1) |
5.6 |
6.0 |
4-hydroxybenzoic(stage2) |
9.3 |
8.9 |
n-capronic(stage1) |
4.8 |
5.3 |
3,5-dimethylpyridine(stage1) |
6.2 |
5.7 |
2-aminobenzoic(stage1) |
7.0 |
6.5 |
benzimidazole(stage1) |
5.5 |
6.0 |
2-benzylpyridine(stage1) |
5.1 |
5.6 |
dihydroxymalic(stage1) |
1.9 |
1.4 |
5-methylquinoline(stage1) |
5.2 |
5.8 |
2,3-dimethylpyridine(stage1) |
6.6 |
6.0 |
pyridine(stage1) |
5.3 |
5.9 |
nn-diethylaniline(stage1) |
6.6 |
7.3 |
dimethylpropanoic(stage1) |
5.0 |
4.4 |
6-methoxyquinoline(stage1) |
5.0 |
5.7 |
hippuric(stage1) |
3.8 |
3.1 |
2-methylquinoline(stage1) |
5.8 |
6.6 |
3-nitrobenzoic(stage1) |
3.5 |
4.2 |
iso-butanoic(stage1) |
4.8 |
4.1 |
trans-cinnamic(stage1) |
4.4 |
3.6 |
n-butanoic(stage1) |
4.8 |
5.7 |
3-hydroxybenzoic(stage2) |
9.9 |
9.0 |
cyclopropane-11-dicarboxylic(stage1) |
1.8 |
2.7 |
cyclohexane-1,1-dicarboxylic(stage1) |
3.5 |
2.5 |
quinoline(stage1) |
4.9 |
5.8 |
3-hydroxybenzoic(stage1) |
4.1 |
3.1 |
hexahydrobenzoic(stage1) |
4.9 |
3.9 |
aziridine(stage1) |
8.0 |
9.0 |
4-hydroxybenzoic(stage1) |
4.5 |
5.5 |
2,4-dimethylpyridine(stage1) |
7.0 |
6.0 |
c6h5co2h(stage1) |
4.2 |
5.2 |
methyl-o-aminobenzoic(stage1) |
5.3 |
4.3 |
ethylbenzoic(stage1) |
4.4 |
5.4 |
4-aminobenzoic(stage1) |
4.9 |
6.0 |
3-methylaceticacid(stage1) |
5.0 |
6.1 |
2-hydroxybenzoic(stage1) |
3.0 |
4.1 |
2,5-dihydroxybenzoic(stage1) |
3.0 |
4.1 |
methyl-m-aminobenzoic(stage1) |
5.1 |
6.2 |
n-ethylaniline(stage1) |
5.1 |
6.3 |
ch3co2h(stage1) |
4.8 |
5.9 |
3-aminobenzoic(stage1) |
4.8 |
6.0 |
imidazol(stage1) |
7.0 |
5.7 |
2-nitrophenylethanoic(stage1) |
4.0 |
5.3 |
methylamine(stage1) |
10.7 |
9.3 |
2,4,5-trihidroxybenzoic(stage1) |
1.7 |
3.1 |
ethylamine(stage1) |
10.8 |
9.4 |
4-nitrobenzoic(stage1) |
3.4 |
4.9 |
methanamine(stage1) |
10.7 |
9.2 |
2,4,6-trimethylpyridine(stage1) |
7.4 |
5.9 |
1-methylimidazol(stage1) |
7.0 |
5.3 |
n-methylaniline(stage1) |
4.8 |
6.5 |
3-methylbutanoic(stage1) |
4.8 |
3.1 |
cyanoacetic(stage1) |
2.5 |
4.2 |
ethanoic(stage1) |
4.8 |
6.5 |
4-hydroxybutanoic(stage1) |
4.7 |
6.6 |
pcresol(stage1) |
10.2 |
8.2 |
2-amino-3-hydroxypropanoic(stage1) |
2.2 |
4.1 |
cyclohexane-1,1-dicarboxylic(stage2) |
6.1 |
8.1 |
trans-fumaric(stage1) |
3.0 |
5.0 |
3-nitrophenylethanoic(stage1) |
4.0 |
6.0 |
c6h5oh(stage1) |
9.9 |
7.8 |
cyclopropane-11-dicarboxylic(stage2) |
7.4 |
5.3 |
3-hydroxybutanoic(stage1) |
4.7 |
2.5 |
ocresol(stage1) |
10.2 |
7.8 |
n-methylmethanamine(stage1) |
10.7 |
8.4 |
4-phenylbutanoic(stage1) |
4.8 |
2.4 |
nn-dimethylaniline(stage1) |
5.2 |
7.5 |
2-nitrobenzoic(stage1) |
2.2 |
4.7 |
benzidine(stage1) |
4.7 |
7.3 |
formic(stage1) |
3.8 |
6.4 |
2-hydroxybenzoic(stage2) |
13.4 |
10.7 |
2-aldoximepyridine(stage1) |
3.6 |
6.3 |
hydroquinone(stage1) |
10.4 |
7.6 |
citric(stage2) |
5.0 |
2.1 |
2,4-dimethylimidazol(stage1) |
8.4 |
5.5 |
pyrrolidine(stage1) |
11.3 |
8.4 |
anilin(stage1) |
4.6 |
7.5 |
mcresol(stage1) |
10.0 |
7.1 |
1,2-dimetilpyrrolidine(stage1) |
10.2 |
7.3 |
n-methylpyrrolidine(stage1) |
10.3 |
7.3 |
acrylicacid(stage1) |
4.3 |
7.4 |
pyridazine(stage1) |
2.2 |
5.4 |
4-cyanobutanoic(stage1) |
2.4 |
5.6 |
n,n-diethylethanamine(stage1) |
11.0 |
7.8 |
dimethylmalonic(stage1) |
3.2 |
6.5 |
2-methylpyrazine(stage1) |
1.5 |
4.8 |
3,6-dinitrophenol(stage1) |
5.2 |
8.6 |
2-aminoethylbenzene(stage1) |
9.8 |
6.3 |