Unveiling the photophysical properties of 3-acyl-6-amino-4-quinolones and their use as proton probes

4-quinolone derivatives are widely explored in Medicinal Chemistry for the development of drug candidates for the treatment of different pathologies. However, their optical properties remain underexploited. In this work, the photophysical properties of a family of 3-acyl-6-amino-4-quinolone derivatives were investigated, highlighting their optical behaviour towards acids. Although the substances did not show significant solvatochromism, in the presence of trifluoroacetic acid alterations were observed in their photophysical profile, especially regarding their emissive response. The ester derivatives 1-alkyl-6-amino-4-oxo-1,4-dihydroquinoline-3-carboxylate exhibit a more significant increase in intensity (>2 times-fold) and a considerable redshift (similar to 90 nm), leading to emission colour change from blue to green in acidic condition. The changes were highly sensitive, detecting proton concentrations as low as 10 mu M in MeCN. This molecular system was studied by NMR and DFT calculations that show the 1,3-diketone as the preferred protonation site. The establishment of an intramolecular hydrogen bond between the ketone and carbethoxy groups leads to LUMO stabilization and a practically coplanar protonated structure, favouring fluorescence. Notably, the presence of intra- or intermolecular hydrogen bonding has a major impact on their sensing behaviour, making the changes for the acid and amide derivates require a 1000-fold higher concentration of TFA than the ester analogue. The calculated thermodynamic values for the acid equilibrium show that the established hydrogen bond in the neutral species reduces the basicity of these quinolones, agreeing with the experimentally calculated pK values of 4.53, 2.56 and 1.75 for the ester, amide and acid derivatives respectively. Finally, the presence of the amino substituent, linked to the C-6 of the 4-quinolone structure, was shown to be important for the optical profiles and sensitivity observed.

Automated summary

This study investigated the photophysical properties of a family of 3-acyl-6-amino-4-quinolone derivatives and revealed changes in their optical behavior in acidic conditions, showing increased emissive response and redshift. These changes were highly sensitive to proton concentrations and the presence of intra- or intermolecular hydrogen bonding had a major impact on their sensing behavior.