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

Chaud, Juliane; Morville, Clément; Bolze, Frédéric; Garnier, Delphine; Chassaing, Stefan; Blond, Gaëlle; Specht, Alexandre

doi:10.1021/acs.orglett.1c02778

Cited by 22 publications

(27 citation statements)

References 38 publications

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“…26 Few exceptions to this trend often rely on the introduction of extended π-systems with strongly electrondonating moieties into the PPG structure, yet these strategies come at a great synthetic step cost, and the flat, extended πsystems suffer from low aqueous solubility, restricting their use in photopharmacology. 27,28 Here, we present a rational strategy for increasing PPG efficiency, hinging on a detailed investigation into the important factors that determine PPG QYs. Taking fundamental organic chemistry principles as the starting point and supporting them with a DFT computational approach, we focused on 7-diethylaminocoumarins as a model class of PPGs.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Subsequent on-site release of the bioactive molecule is achieved through light irradiation, preventing systemic side effects in nonirradiated areas. ,,− The importance of molar absorptivity (ε) has been widely recognized in photopharmacology and has led to impressive progress for red- or green-light responsive PPGs featuring high ε, such as those derived from the BODIPY and coumarin scaffolds. ,− , However, in most cases, high ε at long irradiation wavelengths was achieved at the expense of photochemical QY, negatively affecting the overall efficiency of these PPGs . Few exceptions to this trend often rely on the introduction of extended π-systems with strongly electron-donating moieties into the PPG structure, yet these strategies come at a great synthetic step cost, and the flat, extended π-systems suffer from low aqueous solubility, restricting their use in photopharmacology. , …”

Section: Introductionmentioning

confidence: 99%

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Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups through Cation Stabilization

et al. 2022

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Photolabile protecting groups (PPGs) enable the precise activation of molecular function with light in many research areas, such as photopharmacology, where remote spatiotemporal control over the release of a molecule is needed. The design and application of PPGs in recent years have particularly focused on the development of molecules with high molar absorptivity at long irradiation wavelengths. However, a crucial parameter, which is pivotal to the efficiency of uncaging and which has until now proven highly challenging to improve, is the photolysis quantum yield (QY). Here, we describe a novel and general approach to greatly increase the photolysis QY of heterolytic PPGs through stabilization of an intermediate chromophore cation. When applied to coumarin PPGs, our strategy resulted in systems possessing an up to a 35-fold increase in QY and a convenient fluorescent readout during their uncaging, all while requiring the same number of synthetic steps for their preparation as the usual coumarin systems. We demonstrate that the same QY engineering strategy applies to different photolysis payloads and even different classes of PPGs. Furthermore, analysis of the DFT-calculated energy barriers in the first singlet excited state reveals valuable insights into the important factors that determine photolysis efficiency. The strategy reported herein will enable the development of efficient PPGs tailored for many applications.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups through Cation Stabilization

et al. 2022

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“…Previously, effective one-photon uncaging performances of BNSF and BNSMB in glutamate and the polymer were reported. , However, the photolytic efficiency of two molecules was never reported in DNA oligonucleotides, so their photolysis was investigated qualitatively. In the literature, one-photon uncaging processes could be examined by monitoring the decreasing absorption of PPGs and increasing absorption of photolyzed products by UV–Vis spectroscopy. ,,, In our studies, one-photon induced photolysis was examined by irradiation of d15-BNSF-d19 and d15-BNSMB-d19 oligonucleotides (15 μM) at 430 nm (using a LUMOS 43 LED source from Atlas Photonics Inc.) in 1× PBS (pH 7.2). During these photolysis experiments, both caged DNA oligonucleotides showed new broad absorbance features from 300 to 600 nm, while the initial absorbance features at 405 or 415 nm gradually diminished, as shown in Figure a,b.…”

Section: Resultsmentioning

confidence: 99%

“…One-photon photolytic uncaging was done on 415 or 430 nm light sources, which was achieved using a UV TaoYuan (415 nm, 200 mW/cm 2 ) or LUMOS 43 LED (430 nm, 200 mW/cm 2 ) LED lamps. Two-photon photolysis experiments were performed on our homemade setup at the “Plateforme d’Imagerie Quatitative” PIQ at the faculty of pharmacy (University of Strasbourg) as described recently . The excitation source was a Ti:sapphire femtosecond laser Insight DS (680–1300 nm) with a pulse width of <120 fs and a repetition rate of 80 MHz (Spectra-Physics).…”

Section: Methodsmentioning

confidence: 99%

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

Liu

Leung

Morville

et al. 2022

ACS Appl. Mater. Interfaces

Self Cite

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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.

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“…[20] Few exceptions to this trend often rely on the introduction of extended π-systems with strongly electron-donating moieties into the PPG structure, yet these strategies come at a great synthetic step cost and the flat, extended π-systems suffer from low aqueous solubility, restricting their use in photopharmacology. [28,29] Here, we present a rational strategy for increasing PPG efficiency, hinging on detailed investigation into the important factors that determine PPG QYs. Taking fundamental organic chemistry principles as the starting point, and supporting them with a DFT computational approach, we focused on 7diethylaminocoumarins as a model class of PPGs.…”

Section: Introductionmentioning

confidence: 99%

A Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups Through Cation Stabilization

Schulte

Alachouzos

Szymański

et al. 2022

Preprint

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Photolabile protecting groups (PPGs) enable the precise activation of molecular function with light in many research areas, such as photopharmacology, where remote spatiotemporal control over the release of a molecule is needed. The design and application of PPGs in recent years has particularly focused on the development of molecules with high molar absorptivity at long irradiation wavelengths. However, a crucial and until now mostly neglected parameter, pivotal to the efficiency of uncaging, is the photolysis quantum yield (QY). Here, we describe a novel and general approach to greatly increase the photolysis QY of heterolytic PPGs through stabilization of an intermediate chromophore cation. When applied to coumarin PPGs, our strategy resulted in systems possessing an up to 35-fold increase in QY and a convenient fluorescent readout during their uncaging, all while requiring the same number of synthetic steps for their preparation as the usual coumarin systems. We demonstrate that the same QY-engineering strategy applies to different photolysis payloads and even different classes of PPGs. Furthermore, analysis of the DFT-calculated energy barriers in the first singlet excited state have revealed valuable insights into the important factors that determine photolysis efficiency. The strategy reported herein will enable the development of efficient PPGs tailored for many applications.

show abstract

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

Cited by 22 publications

References 38 publications

Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups through Cation Stabilization

Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups through Cation Stabilization

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

A Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups Through Cation Stabilization

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