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.