The entropy of melting is nearly constant according to the empirical Richard’s rule. It is nearly constant also according to the interstitialcy theory of condensed matter: Granato A V 1992 Phys. Rev. Lett. 68 974; Granato A V 2006 J. Non-Cryst. Solids 352 4821.

Concerning fcc metals: M. Polak and L. Rubinovich 2019 J. Phys.: Condens. Matter in press https://doi.org/10.1088/1361-648X/ab0865

Dear Dr. Avdeef,

The GSE is a very simple equation, there are alternatives for it. Machine Learning (ML) is a way for prediction, unfortunately in this way there is no physical sense, but you can get an answer.

Doaa, and Samuel Yalkowsky. "Comments on prediction of the aqueous solubility using the general solubility equation (GSE) versus a genetic algorithm and a support vector machine model." Pharmaceutical development and technology 23.7 (2018): 739-740.

https://doi.org/10.1080/10837450.2017.1321663

Best regards,

Ender Araujo

Dear Ender,

Thank you very much for your suggestion, and the cited reference by Yalkowsky. Walden's rule (Eq. 4) suggests constant entropy of fusion. But does that constancy hold for druglike molecules - especially zwitterions?

Best,

Alex

Dear Dr. Avdeef,

Really is not constant, in GSE is an approximation, in the article refers:

"Walden’s rule states that the entropy of melting for aromatic molecules is relatively constant at 57 kJ/mol."

Now, in the case of zwitterions, an adaptation can be evaluated and also in GSE, but that is not done!. What is certain is that it is one of the limitations of the equation.

Greetings,

Ender Araujo

Many thanks.