Fluorescence and mass spectrometry studies of the interaction between naproxen and synthetic pseudopeptidic models in organic media

Time-resolved/steady-state fluorescence and mass spectrometry measurements have shown the preferential binding of a non-steroidal anti-inflammatory drug (NSAID) like naproxen 4 to a synthetic pseudopeptidic receptor built using Phe (9), i.e., bearing an aromatic ring, compared to another model synthesized using Lys (8), i.e., lacking such aromatic ring but with a basic binding site. The quenching of the emission of naproxen by models 8 and 9 has been measured in solvents of different nature and analyzed by means of the Stern-Volmer methodology. In non-polar solvent (dichloromethane) the fluorescence of 4 is quenched to a higher extent by 8 than by 9 but in polar medium (methanol) the opposite occurs. The result in methanol is compatible with the existence of π-π stacking interactions between the aromatic rings of naproxen and the aromatic ring of 9. In order to proof this model, mass spectrometry measurements have confirmed the higher stability of the complex formed by 4 and 9 over the related one formed with 8. The observed phenomenon could help to understand the importance of aromaticity in the interactions between NSAIDs and more complex biological macromolecules like misfolded proteins, involved in the development of Alzheimer's disease and other neuropathologies.