Combinatorial discovery of two-photon photoremovable protecting groups

Abstract

A design principle for a two-photon photochemically removable protecting group based on sequential one-photon processes has been established. The expected performance of such groups in spatially directed photoactivation͞photodeprotection has been shown by a kinetic analysis. One particular molecular class fitting into this design, the nitrobenzyl ethers of o-hydroxycinnamates, has been presented. An initial demonstration of two-photon deprotection of one such group prompted further optimization with respect to photochemical deprotection rate. This was accomplished by the preparation and screening of a 135-member indexed combinatorial library. Optimum performance for >350 nm deprotection in organic solvent was found with 4,5-dialkoxy and ␣-cyano substitution in the nitrobenzyl group and 4-methoxy substitution in the cinnamate.

o‐Nitrobenzyl Photolabile Protecting Groups with Red‐Shifted Absorption: Syntheses and Uncaging Cross‐Sections for One‐ and Two‐Photon Excitation

“…In particular, we did not obtain the favorable results reported with the trifluoromethyl as well as with the cyano substituents. [10,30] The corresponding discrepancy questions the use of the benzylic substituent to improve quantum yields of uncaging after onephoton excitation; efficiencies could be strongly dependent on the nature of the caged substrate.…”

“…In fact, different reports suggested using this strategy to provide significant improvements over the parent compounds. [5,10,30] In view of the nature of the substituents used in the latter studies, we chose to introduce electron-attracting substituents at the benzylic position of the popular 4,5-dimethoxy-2-nitrobenzyl group. Scheme 2 shows the second series of molecules that were synthesized.…”

“…[29] We evaluated independently the significance of a benzylic substituent in the second series. [5,10,30] We then synthesized two series of caged model compounds that result from the protection of a phenol or a carboxylic acid group, respectively, and report the linear absorption and emission properties of these synthesized species. The action uncaging cross-sections for one-and twophoton excitation were measured.…”

Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy

“…190 Interestingly, the cyano compound had been independently identified by a clever combinatorial technique by Pirrung and co-workers as being quite efficient. 191 Such apparent contradictions have been reported in the field of PPGs for decades and could potentially slow down future development of new or modified PPGs, as no clear trend emerges from the huge amount of sometimes unreliable data accumulated. The determination of quantum yields remains a delicate operation subject to significant experimental error; furthermore, all these different groups are frequently tested for the release of different leaving groups (phenols, carboxylic acids, amine, aliphatic alcohols, and carbamates) under different irradiation wavelengths, in different solvents and buffers, and each with a different photochemical apparatus.…”

Reversible metallisation of soft UV patterned substrates

“…35,36 Compared to deep UV photolithography, soft UV lithography also has the advantage that it can be used for patterning that overcomes the diffraction limit by exploiting two-photon photochemistry. [37][38][39][40][41][42][43] In this paper we use thiol-on-gold SAMs, acid-catalyzed soft UV photolithography and also two-photon soft UV lithography to create patterned SAMs coupled with ECD to deposit copper on the photo-deprotected regions of the surface in a reversible, repeatable manner…”