Wavelength-Dependent, Orthogonal Photoregulation of DNA Liberation for Logic Operations.

In this study, we synthesized two phosphoramidites based on 2,7-bis-{4-nitro-8-[3-(2-propyl)-styryl]}-9,9-bis-[1-(3,6-dioxaheptyl)]-fluorene (BNSF) and 4,4'-bis-{8-[4-nitro-3-(2-propyl)-styryl]}-3,3'-di-methoxybiphenyl (BNSMB) structures as visible light-cleavable linkers for oligonucleotide conjugation. In addition to the commercial ultraviolet (UV) photocleavable (PC) linker, the BNSMB linker was further applied as a building component to construct photoregulated DNA devices as duplex structures, which are functionalized with fluorophores and quenchers. Selective cleavage of PC and BNSMB is achieved in response to ultraviolet (UV) and visible light irradiations as two inputs, respectively. This leads to controllable dissociation of pieces of DNA fragments, which is followed by changes of fluorescence emission as signal outputs of the system. By tuning the number and position of the photocleavable molecules, fluorophores, and quenchers, various DNA devices were developed, which mimic the functions of Boolean logic gates and achieve logic operations in AND, OR, NOR, and NAND gates in response to two different wavelengths of light inputs. By sequence design, the photolysis products can be precisely programmed in DNA devices and triggered to release in a selective and/or sequential manner. Thus, this photoregulated DNA device shows potential as a wavelength-dependent drug delivery system for selective control over the release of multiple individual therapeutic oligonucleotide-based drugs. We believe that our work not only enriches the library of photocleavable phosphoramidites available for bioconjugation but also paves the way for developing spatiotemporal-controlled, orthogonal-regulated DNA-based logic devices for a range of applications in materials science, polymers, chemistry, and biology.

Two-Photon Sensitive Coumarinyl Photoremovable Protecting Groups with Rigid Electron-Rich Cycles Obtained by Domino Reactions Initiated by a 5-exo-Dig Cyclocarbopalladation.

We herein report the design, synthesis, and photophysical characterization of extended and rigid coumarinyl derivatives showing large two-photon sensitivities (δaΦu ≤ 125 GM) at 740 and 800 nm. To efficiently synthesize these complex photoremovable protecting groups (PPGs), we used step-economic domino reactions. Moreover, those new coumarinyl PPGs display unique bathochromic shifts (≤100 nm) of the uncaging subproducts as a result of the formation of a more conjugated fulvene moiety.