2-[7-(diethylamino)-2-oxo-2H-1-benzopyran-3-yl]benzoxazole-5-sulphonamide

Melting point / freezing point

Link to relevant study record(s)

Reference

Endpoint:

melting point/freezing point

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

20 March 2017

Reliability:

2 (reliable with restrictions)

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
EPI Suite Version 4.11

2. MODEL (incl. version number)
MPBPVP (v1.43)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
O=C1C(c3nc4cc(S(=O)(=O)N)ccc4o3)=Cc2ccc(N(CC)CC)cc2O1

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
MPBPWIN estimates melting point by two different methods. The first is an adaptation of the Joback group contribution method for melting point (Joback, 1982; Reid et al; 1987) and the second is a simple Gold and Ogle method suggested by Lyman (1985).
The original Joback methodology used a data set of 388 compounds to derive 41 chemical structure group descriptors via multiple linear regression (Joback, 1982). The Joback adaptation in MPBPWIN is an extension of the original method to include the same groups as in the adapted Stein and Brown boiling point method. In addition, MPBPWIN also uses melting point correction factors for specific structures.
The second estimation method (Gold and Ogle, 1969), simply relates melting point (Tm) to boiling point (Tb) as follows (both values in K): Tm = 0.5839 Tb
MPBPWIN averages the adapted Joback and the Gold and Ogle estimates and reports the average estimate as well as both individual estimates.
MPBPWIN then goes one step further. It reports a "suggested" melting point (MP) that is based upon the two individual estimates and several criteria. First, MPBPWIN looks at the difference between the two estimates. If the difference is small (< 30 K), the suggested MP is simply the average. When this criteria fails, MPBPWIN examines the structure type and the magnitude of the difference. It then decides which estimate is more likely to be accurate and "weights" the suggested MP accordingly. Weighting factors in MPBPWIN were approximated through observation of estimated versus experimental MP.
The adapted Joback method can significantly over-estimate MP for some structures. A similar error occurs in the Stein and Brown (1994) boiling point method (when BP > 500 K) before a quadratic or linear equation corrects the error. This type of correction was not developed for MPBPWIN. Instead, MPBPWIN applies a "cut-off" MP at approximately 350 °C; that is, any MP estimate above 350 °C is reduced to 350 °C. When MPBPWIN detects a large difference between a very high adapted Joback estimate and a much lower Gold and Ogle estimate, it usually weights the suggested MP strongly to the Gold and Ogle estimate (again, it depends on structure). When used alone, the adapted Joback MP method can be very inaccurate for some structures (usually by estimating too high). The simplistic Gold and Ogle method is also inaccurate for various structures. However, when combined in the MPBPWIN format, estimation accuracy improves significantly for very large, diverse datasets.

Estimation Accuracy
Although the suggested MPBPWIN estimates may be adequate for screening purposes, the overall accuracy is not outstanding. In fact, most current methods for estimating MP (for large diverse datasets) have generally poor accuracy and can yield many unreliable estimates (Lyman, 1985; Reid et al, 1987). The failure derives, in part, from ignoring the effects of symmetry in the molecule (Lyman, 1985).
The original Joback method is based on a relatively small training set of 388 compounds with the following accuracy statistics (Joback, 1982; Reid et al, 1987):
- number = 388
- standard deviation = 25 K
- average deviation = 23 K
- absolute error = 11 %
The adapted method in MPBPWIN does not affect these statistics since the original method had already defined the necessary group fragments. The method error is comparable to other MP estimation methods for these types of simple structures (haloalkanes, plain hydrocarbons, acids, esters, alcohols, ethers, ketones, simple aromatics, etc). However, application of the original Joback method (or other estimation methods) to a large dataset of more diverse compounds (such as pesticides, drugs, multi-functional aromatics, etc.) produces much higher error.
For the current EPI Suite, the accuracy of the "suggested" MPBPWIN melting point estimate was tested on a large dataset of 10 051 compounds containing a diverse mix of simple, moderate and very complex structural compounds (includes many pesticides and pharmaceutical compounds). The dataset was taken from the PHYSPROP Database used by the EPI Suite. Compounds having "decompose" designations with MP values were excluded. The complete dataset with experimental values and estimates is available at: http://esc.syrres.com/interkow/EpiSuiteData.htm
Substructure searchable data set of melting point test is available at: http://esc.syrres.com/interkow/EpiSuiteData_ISIS_SDF.htm

5. APPLICABILITY DOMAIN
Currently there is no universally accepted definition of model domain. However, users may wish to consider the possibility that property estimates are less accurate for compounds outside the Molecular Weight range of the training set compounds, and/or that have more instances of a given fragment than the maximum for all training set compounds. It is also possible that a compound may have a functional group(s) or other structural features not represented in the training set, and for which no fragment coefficient was developed. These points should be taken into consideration when interpreting model results.
The complete training sets for MPBPWIN's estimation methodology are not available. Therefore, describing a precise estimation domain for this methodology is not possible.
The original Joback methodology was developed with only 388 compounds. The number of compounds used to derive each of the original Joback descriptors is shown in an Appendix of the EPI Suite help guide, but the maximum number of each descriptor that occurs in each compound is not available. Similar data for the Gold and Ogle method is not available.
The current applicability of the MPBPWIN methodology is best described by its accuracy in predicting melting point. The complete dataset with experimental values and estimates is available via Internet download: http://esc.syrres.com/interkow/EpiSuiteData.htm
This test set probably contains more than 15 times the number of compounds used to train the methodology. As can be seen in the Accuracy section above, significant errors are possible.

6. ADEQUACY OF THE RESULT
A mean or weighted MP value was estimated for this substance; the value is therefore considered to be acceptable for a screening assessment.

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Version / remarks:

May/July 2008

Deviations:

no

GLP compliance:

no

Type of method:

other: calculation

Specific details on test material used for the study:

- Molecular weight: 413.45

Key result

Melting / freezing pt.:

263.11 °C

Melting Point: 349.84 °C (Adapted Joback Method)

Melting Point: 241.43 °C (Gold and Ogle Method)

Mean Melt Pt : 295.63 °C (Joback; Gold,Ogle Methods)

Selected MP: 263.11 °C (Weighted Value)

Conclusions:

The melting point of the test material was calculated to be 263.11 °C.

Executive summary:

The melting point of the test material was calculated using MPBPVP v1.43 (Sept 2010) 2000 U.S. Environmental Protection Agency. Given that the substance is an organic molecule within the Molecular Weight range of the training set compounds, the prediction is considered to be acceptable.

The weighted value for the melting point was calculated to be 263.11 °C.

Description of key information

The weighted value for the melting point was calculated to be 263.11 °C.

Key value for chemical safety assessment

Melting / freezing point at 101 325 Pa:

263.11 °C

Additional information

The melting point of the test material was calculated using MPBPVP v1.43 (Sept 2010) 2000 U.S. Environmental Protection Agency. Given that the substance is an organic molecule within the Molecular Weight range of the training set compounds, the prediction is considered to be acceptable. The study was awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997).

The weighted value for the melting point was calculated to be 263.11 °C.