Conformations of a non-steroidal anti-inflammatory drug nabumetone in aqueous environments

Abstract

[EN]Spectroscopic and photophysical properties of a non-steroidal anti-inflammatory drug, Nabumetone, were studied in dioxane/water mixtures, cyclodextrins (α-CD, β-CD and HP-β-CD) and besides that, for comparison, in a wide range of solvents with different polarities, viscosities and hydrogen bonding ability. The fluorescence quantum yields (φf) and lifetimes (τf) in aqueous and in non-aqueous media, present some evidence which points to the existence of two preferred conformations in aqueous media: one with global φf=0.1–0.3 and τf2=7 ns, corresponding to the side chain completely extended and the other one, with lower global φf=0.02–0.08 and τf1=0.7–2 ns, likely associated with a folded conformation responsible for the fluorescence quenching of the naphthalene moiety by the butanone chain. The formation of one or other conformation is not much affected by the physical properties of the solvent. By contrast, the presence of water creates a very favourable environment for the formation of the folded conformation, which is essentially the only one in pure water. This behaviour is explained by a water-structure enforced hydrophobic effect and makes this drug a good water sensitive probe. Inclusion of the drug in the β-cyclodextrin emphasises the existence of two conformations, whereas in α-CD only the extended one is present, with a much higher φf=0.4 and τf=15.7 ns. Molecular mechanics (MM) and molecular orbital (MNDO) calculations also support the existence of two possible conformations in Nabumetone.