Ibuprofen molecular association from direct back-face transmission steady-state fluorescence

STEINBERG, PAULA YAEL; KRIMER, NICOLÁS IVÁN; SARMIENTO, GABRIELA P.; RODRIGUES, DARIO; HUCK-IRIART, CRISTIÁN; CLEMENS, D.; ZELCER, ANDRÉS; MIRENDA, MARTÍN

Ginebra

Conferencia; XXX INTERNATIONAL CONFERENCE ON PHOTOCHEMISTRY; 2021

Universidad de Ginebra

Ibuprofen is a non-steroidal anti-inflammatory drug widely used all over the world for treating pain, fever, and inflammation. Its sodium salt was recently proposed to be used as a component in nebulizable solutions for treatment of SARS-CoV-2 disease, taking profit of its amphipathic characteristics that favors its insertion into the bilayer membranes, destabilizing the lipidic structure and altering its biological properties.[1] There are several classical methods that incorporate external luminescent probes or quenchers to determine molecular associations and micelle formation of amphipathic compounds in solution.[2-3] In this work we developed an alternative non-destructive and non-invasive methodology based on direct back-face steady-state fluorescence measurements to study the aggregation of ibuprofen molecules. For such purpose, three different systems were studied: Ibuprofen (HIbu) in ethanol, and both sodium ibuprofenate (NaIbu) and 1-butyl-3-methylimidazolium ibuprofenate (BMimIbu) in aqueous alkaline solutions. Steady-state fluorescence spectra were obtained using a transmission geometry and a short optical path-length. The re-absorption of the emitted light was accounted by using a Differential Reabsorption Model.[4] The presence of aggregates was also monitored by means of Small-Angle Neutron Scattering (SANS) and Nuclear Magnetic Resonance (NMR) techniques.HIbu in ethanolic solution shows a fluorescence quantum yield, ΦF , constant along the entire concentration range studied (7mM to 300mM). On the other hand, (NaIbu) shows an increase in ΦF after the Critical Micelle Concentration (CMC) of 180mM is reached. The shape of the absorption and fluorescence spectra at higher concentrations remains the same as those observed in the diluted conditions, discarding the formation of ground-state dimers and excimers. The increase of the fluorescence intensity after CMC can be ascribed to a partial stiffening of the Ibu moiety into the micelle environment, as confirmed in 1 H-NMR experiments. Finally, ΦF of BMimIbu drastically decreases as concentration increases until reaching a constant value. The quenching of ibuprofenate fluorescence in this system was produced by the imidazolium cations, and can be accurately described by combining the Stern-Volmer expression with a Closed Association Model for the micelle formation. Micelle sizes were complementary determined in this case by means of SANS.