Photoinduced processes in flurbiprofen–carprofen dyads

A common tool for investigating the specific distribution of a ligand between different protein microenvironments is the use of displacement probes, which force the ligand to move from one to another site or from the protein to the bulk aqueous solution. Open problems associated with this methodology are the possibility of two different molecules sharing the same site and the potential appearance of allosteric effects. A possible approach to address these issues could be based on the use of two different singlet excited states, together with the corresponding triplets, acting as reporters. irst step towards the development of this concept, we have synthesized two model diastereomeric dyads containing covalently linked flurbiprofen (FBP) and carprofen (CPF) moieties and studied their photophysical and photochemical behaviour, looking for spectroscopically detectable excited state interactions between the two chromophores. in deactivation processes that take place upon excitation of dyads (R,R)-FBP–CPF and (S,R)-FBP–CPF are the following: initial excitation at 266 nm leads to the first singlet excited states of both subunits. Singlet–singlet energy transfer (SSET) from 1FBP* to CPF is thermodynamically allowed and indeed it appears to take place very efficiently. Radiative deactivation of 1CPF* is followed by intersystem crossing (ISC) and triplet–triplet energy transfer (TTET) from 3CPF* to FBP, which is also downhill in energy. The final step corresponds to deactivation of 3FBP* to the ground state. nection with the possibility of making use of the photophysical properties of FBP and CPF to investigate drug–drug interactions in protein binding studies, the most clear-cut conclusions are the following: (a) if the two drugs are within the same protein molecule (irrespective of the site) the only detectable emission will likely correspond to CPF, as its excited singlet is lower in energy, and SSET via the Förster mechanism is feasible, and (b) the transient triplet–triplet absorptions corresponding to the two chromophores are in principle detectable by laser flash photolysis; however, if the two drugs share the same binding site of a protein only the FBP triplet will be observed, as TTET occurs via the Dexter mechanism, which can only operate at very short distances.