Organic Donor-Acceptor Thermally Activated Delayed Fluorescence Photocatalysts in the Photoinduced Dehalogenation of Aryl Halides.

We report a family of donor-acceptor thermally activated delayed fluorescent (TADF) compounds based on derivatives of DMAC-TRZ, that are strongly photoreducing. Both Eox and thus E*ox could be tuned via substitution of the DMAC donor with a Hammett series of p-substituted phenyl moieties while Ered remained effectively constant. These compounds were assessed in the photoinduced dehalogenation of aryl halides, and analogues bearing electron withdrawing groups were found to produce the highest yields. Substrates of up to Ered=-2.72 V could be dehalogenated at low PC loading (1 mol %) and under air, conditions much milder than previously reported for this reaction. Spectroscopic and chemical studies demonstrate that all PCs, including literature reference PCs, photodegrade, and that it is these photodegradation products that are responsible for the reactivity.

Cyclic GMP-AMP synthase contributes to epithelial homeostasis in intestinal inflammation via Beclin-1-mediated autophagy.

Inflammatory bowel disease (IBD) represents a set of idiopathic and chronic inflammatory diseases of the gastrointestinal tract. Central to the pathogenesis of IBD is a dysregulation of normal intestinal epithelial homeostasis. cGAS is a DNA-sensing receptor demonstrated to promote autophagy, a mechanism that removes dysfunctional cellular components. Beclin-1 is a crucial protein involved in the initiation of autophagy. We hypothesized that cGAS plays a key role in intestinal homeostasis by upregulating Beclin-1-mediated autophagy. We evaluated intestinal cGAS levels in humans with IBD and in murine colonic tissue after performing a 2% dextran sulfate sodium (DSS) colitis model. Autophagy and cell death mechanisms were studied in cGAS KO and WT mice via qPCR, WB analysis, H&E, IF, and TUNEL staining. Autophagy was measured in stimulated intestinal epithelial cells (IECs) via WB analysis. Our data demonstrates cGAS to be upregulated during human and murine colitis. Furthermore, cGAS deficiency leads to worsened colitis and decreased levels of autophagy proteins including Beclin-1 and LC3-II. Co-IP demonstrates a direct binding between cGAS and Beclin-1 in IECs. Transfection of cGAS in stimulated HCT-116 cells leads to increased autophagy. IECs isolated from cGAS KO have diminished autophagic flux. cGAS KO mice subjected to DSS have increased cell death and cleaved caspase-3. Lastly, treatment of cGAS KO mice with rapamycin decreased the severity of colitis. Our data suggest that cGAS maintains intestinal epithelial homeostasis during human IBD and murine colitis by upregulating Beclin-1-mediated autophagy and preventing IEC death. Rescue of autophagy can attenuate the severity of colitis associated with cGAS deficiency.

Aryl-Substituted Acridine Donor Derivatives Modulate the Transition Dipole Moment Orientation and Exciton Harvesting Properties of Donor-Acceptor TADF Emitters.

Thermally activated delayed fluorescence (TADF) compounds are highly attractive as sensitizing and emitting materials for organic light-emitting diodes (OLEDs). The efficiency of the OLED depends on multiple parameters, most of which rely on the properties of the emitter including those that govern the internal quantum and outcoupling efficiencies. Herein, we investigate a series of aryl substituted acridine donor derivatives of the donor-acceptor TADF emitter DMAC-TRZ, with the objective of correlating their properties, such as triplet harvesting efficiency and transition dipole moment orientation, with their corresponding device efficiency. The decoration of the DMAC donor with substituted aryl groups not only modifies the molecular weight and length of the emitter but also affects the emission color and the capacity for the emitters to efficiently harvest triplet excitons. The presence of electron-withdrawing 4-cyanophenyl and 4-trifluoromethylphenyl groups in, respectively, CNPh-DMAC-TRZ and CF3Ph-DMAC-TRZ, blue-shifts the emission spectrum but slows down the reverse intersystem crossing rate constant (k RISC), while the opposite occurs in the presence of electron-donating groups in t BuPh-DMAC-TRZ and OMePh-DMAC-TRZ (red-shifted emission spectrum and faster k RISC). In contrast to our expectations, the OLED performance of the five DMAC-TRZ derivatives does not scale with their degree of horizontal emitter orientation but follows the k RISC rates. This, in turn, demonstrates that triplet harvesting (and not horizontal emitter orientation) is the dominant effect for device efficiency using this family of emitters. Nonetheless, highly efficient OLEDs were fabricated with t BuPh-DMAC-TRZ and OMePh-DMAC-TRZ as emitters, with improved EQEmax (∼28%) compared to the reference DMAC-TRZ devices.

Nix-Mediated Mitophagy Modulates Mitochondrial Damage During Intestinal Inflammation.

Aims: Mitochondrial stress and dysfunction within the intestinal epithelium are known to contribute to the pathogenesis of inflammatory bowel disease (IBD). However, the importance of mitophagy during intestinal inflammation remains poorly understood. The primary aim of this study was to investigate how the mitophagy protein BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like (BNIP3L/NIX) mitigates mitochondrial damage during intestinal inflammation in the hopes that these data will allow us to target mitochondrial health in the intestinal epithelium as an adjunct to immune-based treatment strategies. Results: In the intestinal epithelium of patients with ulcerative colitis, we found that NIX was upregulated and targeted to the mitochondria. We obtained similar findings in wild-type mice undergoing experimental colitis. An increase in NIX expression was found to depend on stabilization of hypoxia-inducible factor-1 alpha (HIF1α), which binds to the Nix promoter region. Using the reactive oxygen species (ROS) scavenger MitoTEMPO, we were able to attenuate disease and inhibit both HIF1α stabilization and subsequent NIX expression, suggesting that mitochondrially derived ROS are crucial to initiating the mitophagic response during intestinal inflammation. We subjected a global Nix-/- mouse to dextran sodium sulfate colitis and found that these mice developed worse disease. In addition, Nix-/- mice were found to exhibit increased mitochondrial mass, likely due to the inability to clear damaged or dysfunctional mitochondria. Innovation: These results demonstrate the importance of mitophagy within the intestinal epithelium during IBD pathogenesis. Conclusion: NIX-mediated mitophagy is required to maintain intestinal homeostasis during inflammation, highlighting the impact of mitochondrial damage on IBD progression.