Ammonium dihydrogen citrate

Dissociation constant

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

dissociation constant

Type of information:

other: various peer-reviewed data sources

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Both ions of the substance are well-described in the public literature, therefore testing is not deemed necessary.

Principles of method if other than guideline:

Data sources do not state the method/GL used, therefore this information cannot be provided.
Some of the data is expected to be derived based on calculation (e.g. ACD lab), whereas other information may have been obtained from experiments.

Specific details on test material used for the study:

The substance itself was not tested. Instead, reported data for citric acid and ammonia have been used to derive a conlcusion on this endpoint.
For ammonium pKa determination, test solutions at ca. 0.1 M "were prepared by absorption of ammonia gas in conductivity water from which dissolved oxygen had previously been removed by passage of a stream of nitrogen".
For citric acid pKa determinations, in the experimental study (ref.: Hastings and van Sylke) 0.1 M citric acid solution (origin and purity of citric acid and preparation of test solution not further specified) was used.

Dissociating properties:

yes

No.:

#1

pKa:

ca. 3

Remarks on result:

other: reported for H2A-

No.:

#2

pKa:

ca. 4.5 - ca. 4.8

Remarks on result:

other: reported for HA2-

No.:

#3

pKa:

ca. 5.5 - ca. 6.4

Remarks on result:

other: reported for A3-

No.:

#4

pKa:

ca. 9.2

Remarks on result:

other: reported for NH4+

Conclusions:

The pKa values reported for the ionic species in the substance were ca. 3, ca. 4.5-4.8 and ca. 5.5-6.4 for the citrates, and ca. 9.2 for ammonium.

Executive summary:

The substance is a salt in water, thus ionized at all times (non-ionized form not achievable, irrespective of pH).

Literature data found for the cation and anion (both well known ions) are as follows:

For ammonium the pKa = ca. 9.2.

For the citrate part, 3 main ions, and thus 3 pKa are possible:

# 1: H2A- pKa = ca. 3

# 2: HA2- pKa = ca. 4.5 -4.8

# 3: A3 -: pKa = ca. 5.5 -6.4.

Reference 2

Endpoint:

dissociation constant

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

April 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE

2. MODEL (incl. version number)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint:
- Unambiguous algorithm:
- Defined domain of applicability:
- Appropriate measures of goodness-of-fit and robustness and predictivity:
- Mechanistic interpretation:

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain:
- Structural and mechanistic domains:
- Similarity with analogues in the training set:
- Other considerations (as appropriate):

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]1. SOFTWARE

Qualifier:

no guideline followed

Principles of method if other than guideline:

QSAR calculations for pKa in the pH range 1-14 were performed on the starting materials citric acid and ammonia.
Water has not been considered in the calculations.

GLP compliance:

no

Dissociating properties:

yes

No.:

#1

pKa:

3.05

Remarks on result:

other: calculated for H2A-

No.:

#2

pKa:

4.67

Remarks on result:

other: calculated for HA2-

No.:

#3

pKa:

5.39

Remarks on result:

other: calculated for A3-

No.:

#4

pKa:

8.86

Remarks on result:

other: calculated for NH4+ (NH3)

The calculated values for citric acid are in line with reported pKa values for the main citrate species.

The calculated value for ammonia is somewhat lower than the reported pKa for the ammonium ion.

Conclusions:

The pKa values for the ionic species in the substance were calculated to be: 3.05, 4.67 and 5.39 for citrates, and 8.86 for ammonium.

Executive summary:

The pKa values for the ionic species in the substance were calculated to be: 3.05, 4.67 and 5.39 for citrates, and 8.86 for ammonium.

Description of key information

The substance is a salt in water, thus ionized at all times (non-ionized form not achievable, irrespective of pH).

In view of the nature of the cation and anion (both well known ions) QSAR and literature data (for the ions) is reported.

For ammonium the pKa = 9.2 (calc. 8.86).

For the citrate part, 3 main ions, and thus 3 pKa are possible:

# 1: H2A- pKa = ca. 3

# 2: HA2- pKa = ca. 4.5 -4.8

# 3: A3 -: pKa = ca. 5.4 -6.4.