meso-Methyl BODIPY Photocages: Mechanisms, Photochemical Properties, and Applications

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(32), P. 17497 - 17514

Published: Aug. 3, 2023

meso-methyl BODIPY photocages have recently emerged as an exciting new class of photoremovable protecting groups (PPGs) that release leaving upon absorption visible to near-infrared light. In this Perspective, we summarize the development these PPGs and highlight their critical photochemical properties applications. We discuss PPGs, structure–photoreactivity studies, insights into photoreaction mechanism, scope functional can be caged, chemical synthesis structures, how substituents alter water solubility PPG direct specific subcellular compartments. Applications exploit unique optical are also discussed, from wavelength-selective photoactivation biological studies photoresponsive organic materials photomedicine.

Language: Английский

---

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

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(27), P. 12421 - 12430

Published: July 1, 2022

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

Language: Английский

---

Photouncaging of Carboxylic Acids from Cyanine Dyes with Near‐Infrared Light**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(33)

Published: May 17, 2022

Near-infrared light (NIR; 650-900 nm) offers unparalleled advantages as a biocompatible stimulus. The development of photocages that operate in this region represents fundamental challenge due to the low energy excitation light. Herein, we repurpose cyanine dyes into are available on multigram scale three steps and efficiently release carboxylic acids aqueous media upon irradiation with NIR up 820 nm. photouncaging process is examined using several techniques, providing evidence it proceeds via photooxidative pathway. We demonstrate practical utility live HeLa cells by delivery acid cargo, was otherwise not uptaken its free form. In combination modularity scaffold, realization these accessible will fully unleash potential emerging field NIR-photoactivation facilitate widespread adoption outside photochemistry community.

Language: Английский

---

Computational Design, Synthesis, and Photochemistry of Cy7‐PPG, an Efficient NIR‐Activated Photolabile Protecting Group for Therapeutic Applications**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(27)

Published: Feb. 19, 2022

Photolabile Protecting Groups (PPGs) are molecular tools used, for example, in photopharmacology the activation of drugs with light, enabling spatiotemporal control over their potency. Yet, red-shifting PPG wavelengths into NIR range, which penetrates deepest tissue, has often yielded inefficient or insoluble molecules, hindering use PPGs clinic. To solve this problem, we report herein a novel concept design, by transforming clinically-applied NIR-dyes suitable orbital configurations new NIR-PPGs using computational approaches. Using method, demonstrate how Cy7, class dyes possessing ideal properties (NIR-absorption, high absorptivity, excellent aqueous solubility) can be successfully converted Cy7-PPG. We facile synthesis towards Cy7-PPG from accessible precursors and confirm its as most redshifted oxygen-independent NIR-PPG to date (λ

Language: Английский

---

Photo-controllable biochemistry: Exploiting the photocages in phototherapeutic window

Chem, Journal Year: 2022, Volume and Issue: 9(1), P. 29 - 64

Published: Dec. 1, 2022

Language: Английский

---

Ligand-Directed Photocatalysts and Far-Red Light Enable Catalytic Bioorthogonal Uncaging inside Live Cells

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6067 - 6078

Published: March 7, 2023

Described are ligand-directed catalysts for live-cell, photocatalytic activation of bioorthogonal chemistry. Catalytic groups localized via a tethered ligand either to DNA or tubulin, and red light (660 nm) photocatalysis is used initiate cascade DHTz oxidation, intramolecular Diels–Alder reaction, elimination release phenolic compounds. Silarhodamine (SiR) dyes, more conventionally as biological fluorophores, serve photocatalysts that have high cytocompatibility produce minimal singlet oxygen. Commercially available conjugates Hoechst dye (SiR-H) docetaxel (SiR-T) localize SiR the nucleus microtubules, respectively. Computation was assist design new class redox-activated photocage phenol n-CA4, microtubule-destabilizing agent. In model studies, uncaging complete within 5 min using only 2 μM 40 photocage. situ spectroscopic studies support mechanism involving rapid reaction rate-determining step. cellular this process successful at low concentrations both (25 nM) SiR-H (500 nM). Uncaging n-CA4 causes microtubule depolymerization an accompanying reduction in cell area. Control demonstrate catalyzes inside cell, not extracellular environment. With SiR-T, same serves photocatalyst fluorescent reporter depolymerization, with confocal microscopy, it possible visualize real time result live cells.

Language: Английский

---

The fate of the contact ion pair determines the photochemistry of coumarin-based photocleavable protecting groups

Chemical Science, Journal Year: 2024, Volume and Issue: 15(6), P. 2062 - 2073

Published: Jan. 1, 2024

Improving the efficiency of photocleavable protecting groups is crucial for their application. Here we reveal how fate contact ion pair intermediate plays a key role in defining this efficiency.

Language: Английский

---

Photochemistry in Medicinal Chemistry and Chemical Biology

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(6), P. 4322 - 4345

Published: March 8, 2024

Photochemistry has emerged as a transformative force in organic chemistry, significantly expanding the chemical space accessible for medicinal chemistry. Light-induced reactions enable efficient synthesis of intricate structures and have found applications throughout different stages drug discovery development processes. Moreover, photochemical techniques provide innovative solutions biology, allowing precise spatiotemporal activation targeted delivery. In this Perspective, we highlight already numerous remarkable even more promising future photochemistry chemistry biology.

Language: Английский

---

Light in a Heartbeat: Bond Scission by a Single Photon above 800 nm

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(12), P. 8417 - 8424

Published: March 18, 2024

Photocages enable scientists to take full control over the activity of molecules using light as a biocompatible stimulus. Their emerging applications in photoactivated therapies call for efficient uncaging near-infrared (NIR) window, which represents fundamental challenge. Here, we report synthetically accessible cyanine photocages that liberate alcohol, phenol, amine, and thiol payloads upon irradiation with NIR up 820 nm aqueous media. The display unique chameleon-like behavior operate via two distinct mechanisms: photooxidation heterolytic bond cleavage. latter process constitutes first example direct scission by single photon ever observed dyes or at wavelengths exceeding 800 nm. Modulation beating rates human cardiomyocytes achieved light-actuated release adrenergic agonist etilefrine submicromolar concentrations low doses (∼12 J cm

Language: Английский

---

Engineering a Green Fluorescent Protein-Core-Inspired NIR-Photocage: Exploring meso-GFP-PRPG toward Alzheimer’s Disease Therapeutics

ACS Central Science, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Language: Английский

---