High yield detritylation of surface-attached nucleosides with photoacid generated in an overlying solid film: roles of translational diffusion and scavenging
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Conventional solid-phase oligonucleotide synthesis overcomes the reversibility of acid-dependent detritylation by washing away the released dimethoxytrityl cations (DMT(+)) with acid. This option is unavailable if the acid is photogenerated in an overlying solid film, as in the photolithographic fabrication of oligonucleotide arrays on planar surfaces. To overcome the resulting reversibility problem we developed methods of achieving >= 98% detritylation of glass-attached 5’-O-DMT-thymidine, a model for 5’-O-DMT-protected oligonucleotides, by the photogeneration of trichloroacetic acid in a solid film. Enhanced intrafilm diffusion, insufficient to degrade the photolithographic resolution but enabling DMT(+) to move from its plane of release into the overlying photoacid-generating film, increased detritylation from <= 30% to >= 98%. Inclusion of an intrafilm carbocation scavenger such as a triarylsilane hydride converted the detritylation into a time-dependent irreversible process proceeding to >= 99% detritylation within 60 s following brief photoacid generation. Light sensitivity is high, exceeding direct photodeprotection methods by 15-100 fold.
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ORGANIC & BIOMOLECULAR CHEMISTRY, 2009, 7 pp. 451 - 459
ROYAL SOC CHEMISTRY