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Dissociation constant

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Endpoint:
dissociation constant
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE

Pallas 3.0, CompuDrug International, San Francisco, CA, USA

2. MODEL (incl. version number)

pKalc 5.0 module

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

CCC(Cc1ccc(C)cc1)(C(=O)c3ccc(N2CCOCC2)cc3)N(C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See QMRF

5. APPLICABILITY DOMAIN
See QMRF

6. ADEQUACY OF THE RESULT
See QMRF
Principles of method if other than guideline:
QSAR
GLP compliance:
yes
Specific details on test material used for the study:
Identification: Omnirad 379
Appearance: Slightly yellow powder
Purity/Composition: See Certificate of Analysis
Test item storage: At room temperature protected from light
Dissociating properties:
yes
No.:
#1
pKa:
5.94
Remarks on result:
other: RNH+(CH3)2
Remarks:
Basic
No.:
#2
pKa:
3.49
Remarks on result:
other: RAR(R1R2)
Remarks:
Basic

Acidic

Basic

none

 

 

RNH+(CH3)2

pKa 5.94

RARN(R1R2)

pKa 3.49

 

 

Conclusions:
The calculation method was chosen for the estimation of the pKa values of Omnirad 379.
 The pKavalues of the test item are:
RNH+(CH3)2 pKa 5.94
RARN(R1R2) pKa 3.49
Executive summary:

The objective of this study was to determine the Dissociation Constants of Omnirad 379.

The Dissociation Constants is calculated at 5.94 and 3.49.

Endpoint:
dissociation constant
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
OECD Guideline 112 (Dissociation Constants in Water)
Version / remarks:
May 12, 1981
Deviations:
no
GLP compliance:
yes
Specific details on test material used for the study:
Data of test item as supplied by the sponsor.

Identity: TK 11005

Product Name: CGI 113

Purity: 99.1 %

Molecular Weight: 380.53 g/mol

Appearance: Solid

Storage: At room temperature at about 20 "C
Dissociating properties:
yes
No.:
#1
pKa:
6.25
Temp.:
20 °C
No.:
#2
pKa:
6.26
Temp.:
20 °C
No.:
#3
pKa:
6.23
Temp.:
20 °C
No.:
#4
pKa:
6.14
Temp.:
20 °C

The determination of the dissociation constant (pKa) of TK 11005 (CGI 113) was performed according to the OECD Guideline For Testing of Chemicals, No. 112, "Dissociation Constants in Water", adopted May 12, 1981. During this study the titration method was performed.

During the titration of the test item with 0.01 mol/l sodium hydroxide solution, the conversion could not be reached. The progression of the titration curve for the test item during alkalic titration is the same as for the blank solution. Therefore, no pKa value could be calculated for alkalic titration and the determination of the dissociation constant was repeated by titration with 0.01 mol/l hydrochloric acid.

The results of four determinations of the dissociation constant (pKa) of TK 11005 (CGI 113) are presented in Tables 1 to 4.

For the titration with 0.01 mol/l hydrochloric acid, the following pKa values of the protonated test item were calculated according to Albert and Sergeant [1]

Mean ± Std. dev. = 6.22 ± 0.05

The pKa value determined might vary to a low extent to that equivalent in pure water. The addition of acetone was necessary due to the relatively low water solubility of TK 11005 (CGI 113). The acetone content should not influence the dissociation behaviour of TK 11005 (CGI 113).

Conclusions:
TK 11005 (CGI 113) was found to have a dissociation constant (pKa) of 6.22 ± 0.05.
Executive summary:

In the present study, the dissociation constant (pKa) of the protonated form of TK 11005 (CGI 113) in water was determined by titration with 0.01 mol/l hydrochloric acid. The dissociation constant was found to be:

Item pKa
TK 11005 (CGI 113) 6.22 ± 0.05

Description of key information

pKa= 6.22 at 20°C

Key value for chemical safety assessment

pKa at 20°C:
6.22

Additional information

The dissociation constant of test item was determined by titration with 0.01 mol/l hydrochloric acid.