Unveiling geometrical isomers and tautomers of isatin-hydrazones by NMR spectroscopy

Molecular recognition is a crucial issue in studies on interactions between biomolecules, or potential pharmacological agents and biomolecules. Isatin-hydrazones are interesting compounds since the presence of an imine bond combined with a set of heteroatoms lead to the formation of numerous isomers whose distribution can be modulated by solvent polarity, concentration, and pH range, among other factors. Herein we report NMR spectroscopic studies, complemented by UV/Vis and IR, to characterize geometrical isomers and tautomers of two isatin-derived hydrazones, isahim and isahpy. By using different spectroscopic methods, it was possible to detect and identify among diverse possible configurations of isahim molecule the preferential species and verify its stability in solution at different temperatures. NMR spectra indicated the co-existence of diverse isomer and/or tautomer forms in solution, corroborated by UV/VIS spectra in different solvents, at varied concentrations and pHs. Further, IR spectra allowed to better identify and characterize the proposed structures. DFT simulations supported the experimental results, attesting that the most stable isomers in solution are the keto in corresponding Z forms for both hydrazone compounds. These studies provided suitable spectroscopic tools to understand and elucidate molecular interactions of such hydrazones with amyloid peptides and with essential metal ions implicated in Alzheimer disease, in subsequent studies. (c) 2021 Elsevier B.V. All rights reserved.

Automated summary

Molecular recognition is crucial in the study of biomolecule interactions and potential pharmacological agents. Isatin-hydrazones, with their imine bond and heteroatoms, form numerous isomers whose distribution can be modulated by various factors. Spectroscopic studies were used to characterize geometrical isomers and tautomers, with experimental results supporting the most stable forms identified.