Attach, Remove, or Replace: Reversible Surface Functionalization Using Thiol–Quinone Methide Photoclick Chemistry

A very facile reaction between photochemically generated <i>o</i>-naphthoquinone methides (<i>o</i>NQMs) and thiols is employed for reversible light-directed surface derivatization and patterning. A thiol-functionalized glass slide is covered with an aqueous solution of a substrate conjugated to 3-(hydroxymethyl)-2-naphthol (NQMP). Subsequent irradiation via shadow mask results in the efficient conversion of NQMP into reactive <i>o</i>NQM species in the exposed areas. The latter react with thiol groups on the surface, producing thioether links between the substrate and the surface. Unreacted <i>o</i>NQM groups are rapidly hydrated to regenerate NQMP. The short lifetime of <i>o</i>NQM in aqueous solution prevents its migration from the site of irradiation, thus allowing for the spatial control of the surface derivatization. A two-step procedure was employed for protein patterning: photobiotinylation of the surface with an NQMP–biotin conjugate followed by staining with FITC–avidin. The orthogonality of <i>o</i>NQM–thiol and azide click chemistry allowed for the development of a sequential click strategy, which might be useful for the immobilization of light-sensitive compounds. The thioether linkage produced by the reaction of <i>o</i>NQM and a thiol is stable under ambient conditions but can be cleaved by UV irradiation, regenerating the free thiol. This feature allows for the removal or replacement of immobilized substrates