Caging groups are photoremovable protecting groups that render a molecule biologically inactive until light illumination, thereby allowing for temporal and spatial control of activity. While nitrobenzyl‐based caging groups have advantageous synthetic and photochemical properties, red shifting of the absorption spectrum through chemical modification has led to reduced decaging efficiency. 6‐Nitropiperonyloxymethylene (NPOM), a group with broad applicability in the caging of heterocyclic structures, in particular nucleic acids, traditionally requires ultraviolet (UV) irradiation for decaging. Herein, we investigated the decaging properties of NPOM under near visible light (400–450 nm) using N3‐caged 5’‐dimethoxytrityl (DMTr)‐thymidine as a substrate. To our surprise, we discovered highly efficient decaging at wavelengths outside the UV range, in particular when compared to other nitrobenzyl chromophores. These results have implications in the selection of light sources for photoactivation and for sequential photolysis to achieve selective control of biological processes.
Two-photon uncaging of bioactive thiols in live cells at wavelengths above 800 nm
Photoactivatable protecting groups (PPGs) are useful for a broad range of applications ranging from biology to materials science. In chemical biology, induction of biological processes via photoactivation is a powerful strategy for achieving spatiotemporal control. The importance of cysteine, glutathione, and other bioactive thiols in regulating protein structure/activity and cell redox homeostasis makes modulation of thiol activity particularly useful. One major objective for enhancing the utility of photoactivatable protecting groups (PPGs) in living systems is creating PPGs with longer wavelength absorption maxima and efficient two-photon (TP) absorption. Toward these objectives, we developed a carboxyl- and dimethylamine-functionalized nitrodibenzofuran PPG scaffold (cDMA-NDBF) for thiol photoactivation, which has a bathochromic shift in the one-photon absorption maximum from λ max = 315 nm with the unfunctionalized NDBF scaffold to λ max = 445 nm. While cDMA-NDBF-protected thiols are stable in the presence of UV irradiation, they undergo efficient broad-spectrum TP photolysis at wavelengths as long as 900 nm. To demonstrate the wavelength orthogonality of cDMA-NDBF and NDBF photolysis in a biological setting, caged farnesyltransferase enzyme inhibitors (FTI) were prepared and selectively photoactivated in live cells using 850–900 nm TP light for cDMA-NDBF-FTI and 300 nm UV light for NDBF-FTI. These experiments represent the first demonstration of thiol photoactivation at wavelengths above 800 nm. Consequently, cDMA-NDBF-caged thiols should have broad applicability in a wide range of experiments in chemical biology and materials science.
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- Award ID(s):
- 1904865
- NSF-PAR ID:
- 10291099
- Date Published:
- Journal Name:
- Organic & Biomolecular Chemistry
- Volume:
- 19
- Issue:
- 10
- ISSN:
- 1477-0520
- Page Range / eLocation ID:
- 2213 to 2223
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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ABSTRACT Triplet arylnitrenes may provide direct access to aryl azo‐dimers, which have broad commercial applicability. Herein, the photolysis of
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null (Ed.)Reported here is the design and synthesis of among the first pyridine terminated acceptor–donor–acceptor–donor–acceptor (A–D–A–D–A) based π-conjugated oligomers, EH_DPP_2T_Pyr ( 1 ), EH_II_2T_Pyr ( 2 ), and EH_II_1T_Pyr ( 3 ). The molecules incorporate thiophenes as electron donors, isoindigo/diketopyrrolopyrrole as electron acceptors, and are capped with pyridine, a weak electron acceptor, on both ends. All target oligomers show attractive photophysical properties, broad absorption in the visible region ( λ max = 636 nm, 575 nm, and 555 nm, for 1 , 2 , and 3 , respectively) and emission which extends to the IR region (emission λ max = 734 nm and 724 for 1 and 2 , respectively). Given the pyridine nitrogens, the optoelectronic properties of the compounds can be further tuned by protonation/metalation. All compounds show a bathochromic shift in visible absorption and fluorescence quenching upon addition of trifluoroacetic acid (TFA). Similar phenomena are observed upon addition of metals with a particularly strong response to Cu 2+ and Pd 2+ as indicated by Stern–Volmer analysis ( e.g. , for Pd 2+ ; K sv = 7.2 × 10 4 M −1 ( λ = 673 nm), 8.5 × 10 4 M −1 ( λ = 500 nm), and 1.1 × 10 5 ( λ = 425 nm) for 1 , 2 , and 3 , respectively). The selective association of the molecules to Cu 2+ and Pd 2+ is further evidenced by a color change easily observed by eye and under UV light, important for potential use in colorimetric sensing.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D0OB01986K
