The control of a bioactive compound´s activity is of crucial importance in the fields of medicine and biology. Photopharmacology offers the possibility of obtaining this control by using light, an external, non-toxic and orthogonal stimulus which can be quantitatively and qualitatively regulated, as well as spatially and temporally controlled. More concretely, in photopharmacology the bioactive compound is covalently bound to a photoswitch, a chemical entity that suffers a reversible chemical transformation after the absorption of one photon. Consequently, the physical properties of the bioactive compound will be different before and after irradiation resulting in a different ability to interact with its target. 1,2
Several photoswitches such as azobenzenes, hemithioindigos, stilbenes, diarylethenes, spiropyrans, thiophenefulgides and, more recently, donor-acceptor Stenhouse adducts are available.3,4 Among all of these, azobenzenes, which reversibly isomerize between the trans and the cis conformation, are probably the most well-studied. Due to their high quantum yields, fast photoisomerization rates and resistance to optical fatigue, they have been used in the study of ion-channels, GABAA and Glutamate receptors, for example.5-7
In this work, we aim to offer a simple, fast and selective way of functionalizing a biomolecule with an azobenzene, by taking advantage of click chemistry. Several photoswitches containing 2 different click chemistry moieties were synthesized, allowing a selective covalent bond to 1 or 2 different molecules. In addition, the photophysical properties of this molecules were studied. This library allows to choose, from a variety of molecules, at least one which is suitable for the desired application according to the photophysical properties and click moieties.
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5. Banghart, M., Borges, K., Isacoff, E., Trauner, D. & Kramer, R. H. Light-activated ion channels for remote control of neuronal firing. Nat. Neurosci. 7, 1381-1386 (2004).
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