Solid-State Investigation of Polymorphism and Tautomerism of Phenylthiazole-thione: A Combined Crystallographic, Calorimetric, and Theoretical Survey

In the context of solid-state polymorphism, a detailed crystallographic and theoretical investigation has been carried out on a dimorphic phenylthiazole-derived compound (4-phenylthiazole-2-thiol, labeled here as compound 1), considered here as a potential lead compound, for which we discovered original polymorphic behavior. A detailed crystallographic study and calorimetric investigation permit us to assess the monotropic relationship between polymorphic forms, and ab initio quantum methods, combined with Monte Carlo polymorphic prediction, allow rationalization of the thiol-thione tautomeric preferential character of the compound. The experimental and theoretical conclusions prove once more that in an early process of lead compound optimization, a combination of solid-state analysis and phase prediction with modeling methods can be a fast and efficient tool to select/disable a particular compound, in addition to well-known potential alert flags such as adsorption–distribution–metabolism–excretion/toxicology pharmacokinetic markers.