Single- and two-photon absorption induced photocleavage of dimeric coumarin linkers: Therapeutic versus passive photocleavage in ophthalmologic applications

Phototriggered chemical reactions are elegant and spatially selective. However, in application a general problem is that aside of the desired changes, e.g. induced by laser, undesired changes may occur, e.g. induced by daylight or sunlight. One such example which we are studying here is the phototriggered release of drugs from materials suitable for polymeric intraocular lenses (IOL). Through such an IOL sunlight needs to pass for several years without affecting the drug loading, but at the therapeutically required moment the drug release shall be triggered also by light. We studied this using a novel coumarin dimer (7,7′-[3-(tert-butyldimethylsilyloxy)propoxy]-dicoumarin) synthesized from the monomer in a photochemical [2π + 2π] cycloaddition reaction. The cleavage of the obtained photodimer by single-photon (SPA) and two-photon absorption (TPA) excitation was investigated in acetonitrile solution and in polymethylmethacrylate in order to exclude major matrix entrapment effects. The cleavage quantum yields and TPA cross-section were determined to be Φ ≈ 0.13 and δTPA ≈ 2.7 GM, respectively. It was found that 10% undesired drug release would require more than 16 years of continuous exposure to sunlight. Release of 90% of drug under therapeutic conditions would be completed within seconds. This shows that photochemically triggered drug release is capable to become a powerful tool for drug delivery in ophthalmology.