Hydrogen bonding in a non-steroidal anti-inflammatory drug—Naproxen

Abstract

Photophysical properties of a non-steroidal anti-inflammatory drug, Naproxen (6-methoxy α-methyl-2-naphthalene acetic acid sodium salt), were investigated in solvents of different polarity, hydrogen donor ability and also in cyclodextrins. The results indicate that in all cases the emitting state is the 1L b singlet. In alcoholic solvents, an intermolecular hydrogen bond is responsible for the observed photophysical behaviour of the probe whereas in non-protic solvents (polar and 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 α- and β-cyclodextrins where the probe form complexes. The behaviour in water is explained by a water-structure enforced hydrophobic effect. The spectroscopic results are interpreted on the basis of a multiple-parameter model that considers specific solute-solvent interactions. These were also observed in the ground state and detected by Fourier transform infrared spectroscopy. Molecular mechanics (MM) and molecular orbital (AM1) calculations also support the existence of two conformations (rotamers) in Naproxen with non-equivalent intramolecular hydrogen bond-like formation.