Tautomerism of N-substituted acridin-9-amines in the context of dynamic NMR and matrix isolation-FT-IR spectroscopy supported by DFT calculations and structural analysis

The physiochemistry of acridin-9-amines (A9As) is an issue that has been investigated by many research groups, due to their intriguing structural and spectroscopic properties as well as their applications in medicine as anticancer, antibacterial and other drugs. In this work we undertake the problem of prototropic tautomerism among simple A9As, substituted at the amine (exocyclic) nitrogen atom with alkyl, acetyl, and phenyl groups, analysed with respect to derivatives of retained amine or imine structure as well as acridin-9-amine itself − the parent compound in this group. Advanced approaches were applied to assess crucial physicochemical features of such compounds, that can be treated as model molecular systems for more advanced drugs − in the context of their potency to tautomerise at various environments. The purity and chemical identity of acridin-9-amines synthesised for this study was confirmed by classical methods (TLC, LC, melting point determination, elemental analysis, typical 1H NMR), and the structure of some A9As in a crystalline solid phase previously assessed was analysed comparatively. The spectroscopic features of investigated acridin-9-amines, assessed by dynamic nuclear resonance spectroscopy (1H and 13C NMR; temperature-dependent spectra) as well as infrared spectroscopy (FT-IR) combined with matrix isolation (MI), are mainly addressed in this work. The above techniques enabled us to obtain their unique spectral characteristics and to confirm experimentally the existence of tautomerism among simple derivatives of acridin-9-amine − not previously investigated applying such approaches. Density functional theory (DFT) was employed to get deeper insight into tautomerisation ability and determine the thermodynamic characteristics such as relative energies, molecular geometry, and atomic charges, characterising studied group of acridin-9-amines. Theoretical data generally remains in agreement with the experimental results and allowed an assessment of how far the N-substitution of A9As has an impact on the tautomerisation process, including the population of specific forms in the equilibrium in various environments. [Display omitted] •A series of N-alkyl, N-phenyl and N-acetyl-substituted acridin-9-amines were synthesised and identified.•Temperature-dependent 1H and 13C NMR experiments enabled to assess the population of imine forms in different conditions.•Matrix isolation-FT-IR and DFT calculations enabled to observe oscillations from both