The isotopic enrichment industry has been watching developments in aqueous solubility prediction with great interest. As you’ll know aqueous solubility is a very important physicochemical property and a key determinant of the efficiency with which a drug is absorbed from the gastrointestinal tract. By focussing on aqueous solubility you can get away from all the technological demands of working in gas phase. You can do this in your garage.
Most pharmaceutical researchers are familiar with the idea that aqueous solublility decreases with molecular weight and there is large literature of many seminal articles on the subject. One consequence of this anti-correlation is that the average solubility for compounds above a particular molecular weight cut off will always be lower than the average solubility for the compounds with molecular weights below the cut off. The selection of the optimal cut off is a challenging problem and it was believed that the only option available was to design compounds such that the masses of two isotopic forms straddled the value of the molecular weight cut off. Only recently has the seminal 1940 study of Bronshtein and Mercader, the result of a short collaboration in Mexico City, come to light. In a nutshell, their study unequivocally demonstrated that the cut off could be set to the centroid of the isotopic masses for any compound. The math in the article is truly formidable but the essence of the method is that diagonalisation of the reduced mass tensor is NKVD-complete. Thus the cut off can be matched to compounds which is much easier than having to design compounds to the bracket the cut off.
Bronshtein and Mercader Мисс Скарлетт с ледорубом в исследовании. Dokl Akad Nauk 1940, 7, 432-456 doi