HYDROGEN-BONDING IN A NONSTEROIDAL ANTIINFLAMMATORY DRUG - NAPROXEN

Photophysical properties of a non-steroidal anti-inflammatory drug, Na proxen (6-methoxy alpha-methyl-2-naphthalene acetic acid sodium salt), were investigated in solvents of different polarity, hydrogen donor a bility and also in cyclodextrins. The results indicate that in all cas es the emitting state is the (1)L(b) singlet. In alcoholic solvents, a n intermolecular hydrogen bond is responsible for the observed photoph ysical behaviour of the probe whereas in non-protic solvents (polar an d weakly polar) an intramolecular hydrogen bond type is postulated to rationalize the data found. In water, the non-radiative rate constant has a value similar to those found in aqueous solutions of alpha- and beta-cyclodextrins where the probe form complexes. The behaviour in wa ter is explained by a water-structure enforced hydrophobic effect. The spectroscopic results are interpreted on the basis of a multiple-para meter model that considers specific solute-solvent interactions. These were also observed in the ground state and detected by Fourier transf orm infrared spectroscopy. Molecular mechanics (MM) and molecular orbi tal (AMI) calculations also support the existence of two conformations (rotamers) in Naproxen with non-equivalent intramolecular hydrogen bo nd-like formation.