Intramolecular nonbonded S⋯O interaction in acetazolamide and thiadiazolinethione molecules in their dimeric crystalline structures and complex crystalline structures with enzymes

The dimeric crystalline structure of acetazolamide 1 and thiadiazolinethione 2 bearing intramolecular nonbonded S⋯O interactions, in each different hydrogen-bonding manner was clarified by their X-ray crystallographic analysis. Existence of the dimeric structure of 1 and 2 in a MeOH solution could be suggested on the basis of their cold-spray ionization mass spectrometry. The intramolecular nonbonded S⋯O interaction was precisely recognized in the complex crystalline structures of carbonic anhydrase I inhibitor 1 and stromelysin inhibitors 2–4 with each specific enzyme. The computational evaluation of the possible monomeric seven conformers of 1 and two model compounds 5 and 6 of 2–4 based on DFT calculations defined that the conformer bearing the intramolecular nonbonded S⋯O interaction is most stable.