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Dissociation constant

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Endpoint:
dissociation constant
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
lonisation constants of catechin, robinetinidol, leuco-fisetinidin, fustin, dihydrorobinctin, dihydroquercetin and a series of polyphenols including the 4-ter-pyrocatechol are reported.
GLP compliance:
not specified
Specific details on test material used for the study:
The phenols tested are commercially available and were purified by either vacuum distillation or recrystallisation
Dissociating properties:
yes
No.:
#1
pKa:
9.53
Temp.:
20 °C
Remarks on result:
other: pKa1 (hydroxyl in position 2)
No.:
#2
pKa:
14
Temp.:
20 °C
Remarks on result:
other: pKa2 (hydroxyl in position 1)
Conclusions:
For the 4-ter-butylpyrocatechol, the pKa1 and the pKa2 were determined as 9.53 and 14.0 respectively.
Executive summary:

In this study, the ionisation constants of catechin, robinetinidol, leuco-fisetinidin, fustin, dihydrorobinctin, dihydroquercetin and a series of polyphenols including the 4-ter-butylpyrocatechol were investigated.

The pKa values of these flavonoids are shown to fit the linear relationships between pKa and substituent a constant for a series of related phenols.

For the 4-ter-butylpyrocatechol (substance of interest) the pKa1 and the pKa2 were determined as 9.53 (for hydroxyl in position 2) and 14.0 (for hydroxyl in position 1) respectively.

Endpoint:
dissociation constant
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Model usually accepted for estimation of pKa values.
Justification for type of information:
1. SOFTWARE
SPARC

2. MODEL
version available in 2010

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC(C)(C)c1ccc(O)c(O)c1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: yes, 1.10 Dissociation constant
- Unambiguous algorithm: not available for this commercial QSAR
- Defined domain of applicability: not available for this commercial QSAR
- Appropriate measures of goodness-of-fit and robustness and predictivity: Not available for this commercial QSAR
- Mechanistic interpretation:

5. APPLICABILITY DOMAIN
- Descriptor domain: not available for this commercial QSAR
- Structural and mechanistic domains: not available for this commercial QSAR
- Similarity with analogues in the training set: not available for this commercial QSAR

6. ADEQUACY OF THE RESULT
Principles of method if other than guideline:
SPARC was developed by Karickhoff (Karickhoff et al., 1991). It estimates the following physico-chemical properties by means of linear free energy relationships and molecular orbital properties: boiling point, density, vapour pressure, water solubility, octanol/water partition coefficient, Henry’s law constant, acid dissociation constant.

Major reference:Hilal, Said, S. W. Karickhoff and L. A. Carreira,
"A Rigorous Test for SPARC's Chemical Reactivity Models: Estimation of More Than 4300 Ionization pKa's," Quant. Struc. Act. Rel., 14, 348 1995.
GLP compliance:
no
Dissociating properties:
yes
No.:
#1
pKa:
9.54
Temp.:
25 °C
Remarks on result:
other: The reaction linked to this pKa is illustred in the attached document.
No.:
#2
pKa:
9.73
Temp.:
25 °C
Remarks on result:
other: The reaction linked to this pKa is illustred in the attached document.
Conclusions:
The pKa values for 4-TBC have been calculated by the SPARC model to be 9.53 (for hydroxyl in position 2) and 9.73 (for hydroxyl in position 1), at a temperature of 25°C.

Description of key information

One reliable experimental study is available (Klimisch reliability 2).

In this study, the ionisation constants of several polyphenols including the 4-ter-butyl pyrocatechol were investigated in water. For the 4-ter-butylpyrocatechol, the pKa1 and the pKa2 were determined as 9.53 and 14.0 respectively. Based on these dissociation constants, we can conclude that the test item is in neutral form (non ionised) up to a pH value of 7.53. Between 7.53 and 9 the test iem is present in majority under neutral and partially in its ionised form.

Key value for chemical safety assessment

pKa at 20°C:
9.53

Additional information

As supporting data, the pKa values for 4-TBC have been also calculated by the SPARC model. The pKa values are 9.53 (for hydroxyl in position 2) and 9.73 (for hydroxyl in position 1) at a temperature of 25°C. The lowest value obtained is consitent with the lowest value determined in the experimental key study.

Another experimental study providing a pK value for the 4-ter-butylpyrocatechol is available (Corse et al 1951). However as the pK value was determined in a 40% dioxane solution, it was considered as not relevant and therefore not reported in this dataset.