Excited state interactions between flurbiprofen and tryptophan in drug–protein complexes and in model dyads. Fluorescence studies from the femtosecond to the nanosecond time domains

Abstract

We report here on the interaction dynamics between flurbiprofen (FBP) and tryptophan (Trp) covalently linked in model dyads and in a complex of FBP with human serum albumin (HSA) probed by time-resolved fluorescence spectroscopy from the femto- to the nano-second timescales. In the dyads, a rapid (k > 10¹⁰ s⁻¹) dynamic quenching of the ¹FBP* fluorescence is followed by a slower (k > 10⁹ s⁻¹) quenching of the remaining ¹Trp* fluorescence. Both processes display a clear stereoselectivity; the rates are 2–3 times higher for the (R,S)-dyad. In addition, a red-shifted exciplex emission is observed, rising in the range of 100–200 ps. A similar two-step dynamic fluorescence quenching is also observed in the FBP–HSA complex, although the kinetics of the involved processes are slower. The characteristic reorientational times determined for the two enantiomeric forms of FBP in the protein show that the interaction is stronger for the (R)-form. This is, to our knowledge, the first observation of stereo-selective flurbiprofen–tryptophan interaction dynamics with femtosecond time resolution.