Tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate

Dissociation constant

Link to relevant study record(s)

Reference

Endpoint:

dissociation constant

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

2012

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accepted calculation method

Justification for type of information:

QSAR prediction

Guideline:

other: REACH guidance on QSARs R.6, May 2008

Principles of method if other than guideline:

ACD 7.0 software program for estimating the dissociation constant (pKa) in water.The recommended method, “apparent constants, approximated”, was used for the estimation. The program was developed by Advanced Chemistry Development Inc.
90 Adelaide Street West, Toronto, Ontario, M5H 3V9, Canada (http://www.acdlabs.com); Copyright © 1994-2003; Build: 18 April 2003

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

pKa:

8.59

Temp.:

25 °C

Remarks on result:

other: HL/H+L

No.:

#2

pKa:

4.99

Temp.:

25 °C

Remarks on result:

other: H2L/H+HL

No.:

#3

pKa:

4.44

Temp.:

25 °C

Remarks on result:

other: H3L/H+H2L

No.:

#4

pKa:

3.99

Temp.:

25 °C

Remarks on result:

other: H4L/H+H3L

No.:

#5

pKa:

1.08

Temp.:

25 °C

Remarks on result:

other: H5L/H+H4L

1. Defined endpoint: Dissociation constant (pKa) in water

2. Unambiguous algorithm: For 2-phosphonobutane-1,2,4-tricarboxylic acid the following fragments descriptors (parent compound) and one structure (parent compound) descripter were identified as reaction centres: R-P(=O)(OH)(O^-), C(=O)(O)-R-CH2 -CH2 -CH3, R-P(=O)(OH)(OH), R-C(=O)-CH2 -CH2 -C(=O)(OH) and C(=O)(OH)-CH2 -P(=O)(OH)(O^-).

3. Applicable domain: The identified reaction centers have been found as fragments in the Internal Reaction Centers Database with experimental equations. The substance only contains 28 atoms, which is much less than the limit of ACD/pKa DB of 255. The substance only contains five ionization centres with one fragment for each. The substance does not contain the atoms, what are not accepted by ACD/pKa DB. The fragment that occurs in the structure of 2-phosphonobutane-1,2,4-tricarboxylic acid applied by the program is verified by the user. The rules applied for the substance appears appropriate. An individual uncertainty for the investigated substance is not available.

4. Statistical characteristics: Each calculation from ACD/pKa DB is provided with its 95 % confidence interval and, when available, literature references with experimental results. The accuracy of calculations for simple structures is usually better than ±0.2 pKa units (for complex structures it is better than ±0.5 pKa units).

5. Mechanistic interpretation: The mechanistic basis of the model is the linear free energy relationship (LFER), which is an empirical correlation between the standard free energies of reaction or activation for two series of reactions, both subjected to the same variations in reactant structures or reaction conditions. As applied to the estimation of acid dissociation constants, the LFER is basically a substituent-effect approach.

6. Adequacy of prediction: The result for 2-phosphonobutane-1,2,4-tricarboxylic acid falls within the applicability domain described above and the estimation rulesapplied for the substance appears appropriate. Therefore the predicted value can be considered reliable yielding a useful result for further assessment.

Conclusions:

As generally dissociating properties of salts cannot be estimated by the program, estimation results of the parent acid 2-phosphonobutane-1,2,4-tricarboxylic acid are taken into account for this endpoint. The dissociation constants for 2-phosphonobutane-1,2,4-tricarboxylic acid are estimated to be pKa1 of 8.59, pKa2 of 4.99, pKa3 of 4.44, pKa4 of 3.99 and pKa5 of 1.08.

Executive summary:

As generally dissociating properties of salts cannot be estimated by the program, the dissociation constants of the parent acid 2-phosphonobutane-1,2,4-tricarboxylic acid were estimated by ACD/pKa DB included in ACD/labs 7.00 Release. According to the estimated results, this substance presents mainly as ionic form under environmentally relevant pH 5 - 9.

Description of key information

As generally dissociating properties of salts cannot be estimated by the program, estimation results of the parent acid 2-phosphonobutane-1,2,4-tricarboxylic acid are taken into account for this endpoint. The dissociation constants for 2-phosphonobutane-1,2,4-tricarboxylic acid are estimated to be pKa1 of 8.59, pKa2 of 4.99, pKa3 of 4.44, pKa4 of  3.99 and pKa5 of 1.08 indicating that this substance presents mainly as ionic form under environmentally relevant pH 5 - 9.

Key value for chemical safety assessment

pKa at 20°C:

8.59

Additional information

The calculation of the dissociation constants of 2-phosphonobutane-1,2,4-tricarboxylic acid in water was performed by software ACD ChemSketch ACD/Labs 7.00 Release, Product Version 7.05. Usually the resulting dissociation constants are calculated for 20°C.

2-phosphonobutane-1,2,4-tricarboxylic acid in water can release 5 protons step by step.

Each release is described by one equilibrium reaction or equilibrium constant (pKa):

1. pKa (HL = H+L) = 8.59 ± 0.50

2. pKa (H2L = H+HL) = 4.99 ± 0.14

3. pKa (H3L = H+H2L) = 4.44 ± 0.10

4. pKa (H4L = H+H3L) = 3.99 ± 0.21

5. pKa (H5L = H+H4L) = 1.08 ± 0.42

Depending on the pKa value, the acid dissociation constants indicate strong (pKs < 3.8), medium strong (pKs < 7.2) and weak (pKs < 16) acids.

The pKa values indicate neither very strong nor very weak acids.