Interrogating bioinspired ESIPT/PCET-based Ir(iii)-complexes as organelle-targeted phototherapeutics: a redox-catalysis under hypoxia to evoke synergistic ferroptosis/apoptosis.

Installing proton-coupled electron transfer (PCET) in Ir-complexes is indeed a newly explored phenomenon, offering high quantum efficiency and tunable photophysics; however, the prospects for its application in various fields, including interrogating biological systems, are quite open and exciting. Herein, we developed various organelle-targeted Ir(iii)-complexes by leveraging the photoinduced PCET process to see the opportunities in phototherapeutic application and investigate the underlying mechanisms of action (MOAs). We diversified the ligands' nature and also incorporated a H-bonded benzimidazole-phenol (BIP) moiety with π-conjugated ancillary ligands in Ir(iii) to study the excited-state intramolecular proton transfer (ESIPT) process for tuning dual emission bands and to tempt excited-state PCET. These visible or two-photon-NIR light activatable Ir-catalysts generate reactive hydroxyl radicals (˙OH) and simultaneously oxidize electron donating biomolecules (1,4-dihydronicotinamide adenine dinucleotide or glutathione) to disrupt redox homeostasis, downregulate the GPX4 enzyme, and amplify oxidative stress and lipid peroxide (LPO) accumulation. Our homogeneous photocatalytic platform efficiently triggers organelle dysfunction mediated by a Fenton-like pathway with spatiotemporal control upon illumination to evoke ferroptosis poised with the synergistic action of apoptosis in a hypoxic environment leading to cell death. Ir2 is the most efficient photochemotherapy agent among others, which provided profound cytophototoxicity to 4T1 and MCF-7 cancerous cells and inhibited solid hypoxic tumor growth in vitro and in vivo.

A two-photon responsive hydroxyphenylquinazolinone (HPQ)-based fluorescent organic nanoprodrug for H2S release against oxidative stress.

Light-activated H2S donors have attracted considerable interest in understanding the physiological role and clinical potential of H2S, as their release is highly localized and controlled. Herein, we have evolved a new HPQ chromophore-based fluorescent organic nanosystem localized in a target area that tolerates oxidative stress and precisely releases H2S under one- and two-photon irradiation with real-time monitoring capability. The two-photon absorption cross-section of this new phototrigger was calculated to be 283 GM at 720 nm. H2S photorelease was also demonstrated in vitro on the MDA-MB-468 cell line in the presence of excess ROS. Our developed H2S nanoprodrug can be applied to living systems to release the H2S-gasotransmitter under laser irradiation in a phototherapeutic window.

Chemical versatility of azide radical: journey from a transient species to synthetic accessibility in organic transformations.

The generation of azide radical (N3˙) occurs from its precursors primarily via a single electron transfer (SET) process or homolytic cleavage by chemical methods or advanced photoredox/electrochemical methods. This in situ generated transient open-shell species has unique characteristic features that set its reactivity. In the past, the azide radical was widely used for various studies in radiation chemistry as a 1e- oxidant of biologically important molecules, but now it is being exploited for synthetic applications based on its addition and intermolecular hydrogen atom transfer (HAT) abilities. Due to the significant role of nitrogen-containing molecules in synthesis, drug discovery, biological, and material sciences, the direct addition onto unsaturated bonds for the simultaneous construction of C-N bond with other (C-X) bonds are indeed worth highlighting. Moreover, the ability to generate O- or C-centered radicals by N3˙ via electron transfer (ET) and intermolecular HAT processes is also well documented. The purpose of controlling the reactivity of this short-lived intermediate in organic transformations drives us to survey: (i) the history of azide radical and its structural properties (thermodynamic, spectroscopic, etc.), (ii) chemical reactivities and kinetics, (iii) methods to produce N3˙ from various precursors, (iv) several significant azide radical-mediated transformations in the field of functionalization with unsaturated bonds, C-H functionalization via HAT, tandem, and multicomponent reaction with a critical analysis of underlying mechanistic approaches and outcomes, (v) concept of taming the reactivity of azide radicals for potential opportunities, in this review.

Photocatalytic Conversion of Benzyl Alcohols/Methyl Arenes to Aryl Nitriles via H-Abstraction by Azide Radical.

This report presents the visible-light-assisted synthesis of aryl nitriles from easily accessible alcohols or methyl arenes in the presence of O2 . Organic photoredox catalyst, 4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene), induces single electron transfer (SET) from azide N3 - and generates azide radical N3 ⋅.The photogenerated N3 ⋅ abstracts H atom from α-C-H bond of benzylic system, which provides aldehyde and hydrazoic acid (HN3 ) in situ. This reaction subsequently forms azido alcohol intermediate that transforms into nitrile with the assistance of triflic acid (Brønsted acid). A range of alcohols and methyl arenes successfully underwent cyanation at room temperature with good to excellent yields and showed good functional group tolerance.

Organophotoredox assisted cyanation of bromoarenes via silyl-radical-mediated bromine abstraction.

The insertion of a nitrile (-CN) group into arenes through the direct functionalization of the C(sp2)-Br bond is a challenging reaction. Herein, we report an organophotoredox method for the cyanation of aryl bromides using the organic photoredox catalyst 4CzIPN and tosyl cyanide (TsCN) as the nitrile source. A photogenerated silyl radical, via a single electron transfer (SET) mechanism, was employed to abstract bromine from aryl bromide to provide an aryl radical, which was concomitantly intercepted by TsCN to afford the aromatic nitrile. A range of substrates containing electron-donating and -withdrawing groups was demonstrated to undergo cyanation at room temperature in good yields.

Organophotoredox-Mediated Amide Synthesis by Coupling Alcohol and Amine through Aerobic Oxidation of Alcohol.

The combination of an organic photocatalyst [4CzIPN (1,2,3,5-tetrakis(carbazol-9-yl)-4,6 dicyanobenzene) or 5MeOCzBN (2,3,4,5,6-pentakis(3,6-dimethoxy-9 H-carbazol-9-yl)benzonitrile)], quinuclidine, and tetra-n-butylammonium phosphate (hydrogen-bonding catalyst) was employed for amide bond formations. The hydrogen-bonded OH group activated the adjacent C-H bond of alcohols towards hydrogen atom transfer (HAT) by a radical species. The quinuclidinium radical cation, generated through single-electron oxidation of quinuclidine by the photocatalyst, employed to abstract a hydrogen atom from the α-C-H bond of alcohols selectively due to a polarity effect-produced α-hydroxyalkyl radical, which subsequently converted to the corresponding aldehyde under aerobic conditions. Then the coupling of the aldehyde and an amine formed a hemiaminal intermediate that upon photocatalytic oxidation produced the amide.

Direct Oxygenation of C-H Bonds through Photoredox and Palladium Catalysis.

This report presents the oxygenation of C-H bonds via the merger of photocatalysis and Pd catalysis. Herein, we describe the utilization of a photocatalyst to oxidize an organopalladium(II) intermediate to high-valent PdIII or PdIV intermediates, which promotes the formation of C-O bonds. The demonstrated method works efficiently with various directing groups, such as oxime ether and benzothiazole. The applicability of this direct C-O bond formation method is shown by synthesizing several metal complexes of 2-(benzo[d]thiazol-2-yl)phenol that can be used in organic light-emitting diodes and pharmaceuticals.