Dynamics of Oxygen-Independent Photocleavage of Blebbistatin as a One-Photon Blue or Two-Photon Near-Infrared Light-Gated Hydroxyl Radical Photocage

Development of versatile, chemically tunable photocages for photoactivated chemotherapy (PACT) represents an excellent opportunity to address the technical drawbacks of conventional photodynamic therapy (PDT) whose oxygen-dependent nature renders it inadequate in certain therapy contexts such as hypoxic tumors. As an alternative to PDT, oxygen free mechanisms to generate cytotoxic reactive oxygen species (ROS) by visible light cleavable photocages are in demand. Here, we report the detailed mechanisms by which the small molecule blebbistatin acts as a one-photon blue light-gated or two-photon near-infrared light-gated photocage to directly release a hydroxyl radical (•OH) in the absence of oxygen. By using femtosecond transient absorption spectroscopy and chemoselective ROS fluorescent probes, we analyze the dynamics and fate of blebbistatin during photolysis under blue light. Water-dependent photochemistry reveals a critical process of water-assisted protonation and excited state intramolecular proton transfer (ESIPT) that drives the formation of short-lived intermediates, which surprisingly culminates in the release of •OH but not superoxide or singlet oxygen from blebbistatin. CASPT2//CASSCF calculations confirm that hydrogen bonding between water and blebbistatin underpins this process. We further determine that blue light enables blebbistatin to induce mitochondria-dependent apoptosis, an attribute conducive to PACT development. Our work demonstrates blebbistatin as a controllable photocage for •OH generation and provides insight into the potential development of novel PACT agents

An Organic Spin Crossover Material in Water from a Covalently Linked Radical Dyad

A covalently linked viologen radical cation dyad acts as a reversible thermomagnetic switch in water. Cycling between diamagnetic and paramagnetic forms by heating and cooling is accompanied by changes in optical and magnetic properties with high radical fidelity. Thermomagnetic switches in water may eventually find use as novel biological thermometers and in temperature-responsive organic materials where the changes in properties originate from a change in electronic spin configuration rather than a change in structure

An Organic Spin Crossover Material in Water from a Covalently Linked Radical Dyad

A covalently linked viologen radical cation dyad acts as a reversible thermomagnetic switch in water. Cycling between diamagnetic and paramagnetic forms by heating and cooling is accompanied by changes in optical and magnetic properties with high radical fidelity. Thermomagnetic switches in water may eventually find use as novel biological thermometers and in temperature-responsive organic materials where the changes in properties originate from a change in electronic spin configuration rather than a change in structure

Access to Aryl Mellitic Acid Esters through a Surprising Oxidative Esterification Reaction

A serendipitously discovered oxidative esterification reaction of cyclohexane hexacarboxylic acid with phosphorus pentachloride and phenols provides one-pot access to previously unknown aryl mellitic acid esters. The reaction features a solvent-free digestion and chromato­graphy-free purifications and demonstrates the possibility of cyclohexane-to-benzene conversions under relatively mild, metal-free conditions

Effect of Substituents on the Bond Strength of Air-Stable Dicyanomethyl Radical Thermochromes

A series of substituted aryl dicyanomethyl radicals were synthesized, and the bonding thermodynamic parameters for self-dimerization were determined from van’t Hoff plots obtained from variable-temperature electron paramagnetic resonance and ultraviolet–visible spectroscopy. At low temperatures, the radicals dimerize, but the colored, air-stable free radicals return upon heating. Heating and cooling cycles (5–95 °C) can be repeated without radical degradation and with striking thermochromic behavior. We find a linear free energy relationship between the Hammett <i>para</i> substituent parameter and the dimerization equilibrium constant, with <i>para</i> electron-donating substituents leading to a weaker bond and electron-withdrawing substituents leading to stronger bonds, following a captodative effect. Density functional theory investigations [B98D/6-31+G­(d,p)] reveal that the dimers prefer a slip-stacked geometry and feature elongated bonds

Effect of Substituents on the Bond Strength of Air-Stable Dicyanomethyl Radical Thermochromes

A series of substituted aryl dicyanomethyl radicals were synthesized, and the bonding thermodynamic parameters for self-dimerization were determined from van’t Hoff plots obtained from variable-temperature electron paramagnetic resonance and ultraviolet–visible spectroscopy. At low temperatures, the radicals dimerize, but the colored, air-stable free radicals return upon heating. Heating and cooling cycles (5–95 °C) can be repeated without radical degradation and with striking thermochromic behavior. We find a linear free energy relationship between the Hammett <i>para</i> substituent parameter and the dimerization equilibrium constant, with <i>para</i> electron-donating substituents leading to a weaker bond and electron-withdrawing substituents leading to stronger bonds, following a captodative effect. Density functional theory investigations [B98D/6-31+G­(d,p)] reveal that the dimers prefer a slip-stacked geometry and feature elongated bonds