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

Abstract

A very facile reaction between photochemically generated o-naphthoquinone methides (oNQMs) 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 oNQM species in the exposed areas. The latter react with thiol groups on the surface, producing thioether links between the substrate and the surface. Unreacted oNQM groups are rapidly hydrated to regenerate NQMP. The short lifetime of oNQM 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 oNQM-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 oNQM 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.

Reversible and Rewritable Surface Functionalization and Patterning via Photodynamic Disulfide Exchange

“…Popik et al [18] showed that reactive o-naphthoquinone methides (oNQMs) produced under UV light from 3-(hydroxymethyl)-2-naphtholcould react with surface thiol groups to yield thioether conjugates, which could be subsequently cleaved by a secondary UV irradiation to regenerate surface thiol groups. [18] In a recent publication, Anseth et al described the use of allyl sulfides incorporated into a hydrogel to achieve reversible modification with thiol-containing biomolecules. [19] Here, we present a new reversible photo-patterning strategy based on a photo-induced disulfide exchange reaction that allows for reversible photo-functionalization, patterning, as well as exchange or removal of surface functional groups (Figure 1).…”

A walk along DNA using bipedal migration of a dynamic and covalent crosslinker

“…QMs represent a readily available class of electrophiles capable of both capture and release of various nucleophiles 34 . These species are typically formed only transiently, and yet have found utility in the synthesis of natural products 35,36 , polymers 37 and cytotoxic agents 38 , as well as in functionalization of molecular surfaces 39 . QM formation and regeneration are exquisitely sensitive to electronic effects as evident from the five orders of magnitude separating rate constants for QMs differing by a single substituent 31,40 .…”

Protected thiol strategies in macromolecular design

“…Functional surfaces were obtained by reacting the liberated thiol with maleimides or isocyanates. An interesting contribution from Popik and co-workers [144] describes a different approach for surface photoderivatization, based on the use of onaphthoquinone methides (oNQM). The thioether linkage created by reaction of thiol and oNQM is stable under ambient conditions but can be cleaved by UV-irradiation, regenerating the free thiol.…”