Leveraging phenazine and dihydrophenazine redox dynamics in conjugated microporous polymers for high-efficiency overall photosynthesis of hydrogen peroxide.

Harnessing solar energy for hydrogen peroxide (H2O2) production from water and oxygen is crucial for sustainable solar fuel generation. Conjugated microporous polymers (CMPs), with their vast structural versatility and extended π-conjugation, are promising photocatalysts for solar-driven H2O2 generation, though enhancing their efficiency is challenging. Inspired by the crucial role of phenazine derives in biological redox cycling and electron transfer processes, the redox-active phenazine moiety is rationally integrated into a CMP framework (TPE-PNZ). By leveraging the reversible redox dynamics between phenazine and dihydrophenazine, TPE-PNZ sets a new benchmark for H2O2 production among CMP-based photocatalysts, reaching a production rate of 5142 µmol g-1 h-1 and a solar-to-chemical conversion efficiency of 0.58% without requiring sacrificial agents. This interconversion allows for the storage of photogenerated electrons by phenazine and subsequent conversion into dihydrophenazine, which then reduces O2 to H2O2 while reverting to phenazine, markedly facilitating charge transfer and mitigating charge recombination. Experimental and computational investigations further reveal that this reversible process enhances O2 adsorption and reduction, significantly lowering the energy barrier towards H2O2 formation. This study offers critical insights into designing advanced materials for sustainable energy research.

A Diketopyrrolopyrrole-Based All-in-One Nanoplatform for Self-Reinforcing Mild Photothermal Therapy Cascade Immunotherapy for Tumors.

Mild photothermal therapy (PTT) has attracted attention for effectively avoiding the severe side effects associated with high-temperature tumor ablation. However, its progress is hindered by the limited availability of high-performance photothermal agents (PTAs) and the thermoresistance of cancer cells induced by heat shock reactions. Herein, this work proposes a new strategy to expand the library of high-performance organic small-molecule PTAs and utilize it to construct a multifunctional nano-theranostic platform. By incorporating additional acceptors and appropriate π-bridges, a diketopyrrolopyrrole-based dye BDB is developed, which exhibits strong absorption and bright fluorescence emission in the near-infrared (NIR) region. Subsequently, BDB is co-coated with the heat shock protein (HSP) inhibitor tanespimycin (17-AAG) using the functional amphiphilic polymers DSPE-Hyd-PEG2000-cRGD to form an all-in-one nanoplatform BAG NPs. As a result, BAG NPs can precisely target tumor tissue, guide the treatment process in real-time through NIR-II fluorescence/photoacoustic/photothermal imaging, and release 17-AAG on demand to enhance mild PTT. Additionally, the mild PTT has been demonstrated to induce immunogenic cell death (ICD) and activate a systemic anti-tumor immune response, thereby suppressing both primary and distant tumors. Overall, this study presents a multifunctional nanoplatform designed for precise mild PTT combined with immunotherapy for effective tumor treatment.

Regulating donor configuration to develop AIE-active type I photosensitizers for lipid droplet imaging and high-performance photodynamic therapy under hypoxia.

Type I photodynamic therapy is considered to be a more promising cancer treatment than type II photodynamic therapy due to its non-oxygen-dependent characteristics. In this work, three D-A structure N,N'-dihydrophenazine (DHP)-based photosensitizers DP-CNPY, SMP-CNPY and DMP-CNPY were designed and synthesized by introducing different numbers of methyl groups in the backbone neighbor of DHP as the donor and combined with the typical strong electron acceptor 2-(pyridin-4-yl)acetonitrile. Among the three photosensitizers, SMP-CNPY with one methyl modification showed the best type I ROS (O2-˙, ˙OH) generation capacity and AIE performance. By encapsulation, SMP-CNPY was fabricated into nanoparticles, and SMP-CNPY NPs exhibited lipid droplet targeting ability with near-infrared (NIR) emission. Cell experiments have proved that SMP-CNPY NPs can effectively kill different kinds of cancer cells under normal oxygen conditions. Even under hypoxic and extreme hypoxic conditions, SMP-CNPY NPs can still produce ROS and kill cancer cells. This work holds significant potential in the field of type I AIE-active photosensitizers and provides a new strategy for overcoming the hypoxic dilemma in the malignant tumor microenvironment.

Promoting the Near-Infrared-II Fluorescence of Diketopyrrolopyrrole-Based Dye for In Vivo Imaging via Donor Engineering.

Small-molecule dyes for fluorescence imaging in the second near-infrared region (NIR-II, 900-1880 nm) hold great promise in clinical applications. Constructing donor-acceptor-donor (D-A-D) architectures has been recognized to be a feasible strategy to achieve NIR-II fluorescence. However, the development of NIR-II dyes via such a scheme is hampered by the lack of high-performance electron acceptors and donors. Diketopyrrolopyrrole (DPP), as a classic organic optoelectronic material, enjoys strong light absorption, high fluorescence quantum yield (QY), and facile derivatization. Nevertheless, its application in the NIR-II imaging field has been hindered by its limited electron-withdrawing ability and the aggregation-caused quenching (ACQ) effect resulting from the planar structure of DPP. Herein, with DPP as an electron acceptor and through donor engineering, we have successfully designed and synthesized a DPP-based dye named T-27, in which the strong D-A interaction confers excellent NIR absorption and high-brightness NIR-II fluorescence tail emission. By strategically introducing long alkyl chains on the donor unit to increase intermolecular spacing and reduce the influence of solvent molecules, T-27 exhibits an improved anti-ACQ effect in aqueous solutions. After being encapsulated into DSPE-PEG2000, T-27 nanoparticles (NPs) show a relative NIR-II fluorescence QY of 3.4% in water, representing the highest value among the DPP-based NIR-II dyes reported to date. The outstanding photophysical properties of T-27 NPs enable multimode NIR-IIa bioimaging under 808 nm excitation. As such, the T-27 NPs can distinguish mouse femoral vein and artery and achieve cerebral vascular microscopic imaging with a penetrating depth of 800 µm, demonstrating the capability for high-resolution deep-tissue imaging. This work holds significant potential in the field of bioimaging and provides a new strategy for developing bright NIR-II dyes.

A High Crystalline Perylene-Based Hydrogen-Bonded Organic Framework for Enhanced Photocatalytic H2O2 Evolution.

Hydrogen-bonded organic frameworks (HOFs) are a kind of crystalline porous material that have shown great potential for photocatalysis on account of their mild synthesis conditions and high crystallinity. Perylene-based photocatalysts have great potential for photocatalytic H2O2 production due to their excellent photochemical stability and broad spectral absorption. In this work, we designed and synthesized a high crystalline perylene-based HOF (PTBA) and an amorphous analog sample PTPA for photocatalytic H2O2 evolution. Under visible light irradiation, PTBA shows a higher photocatalytic H2O2 production rate of 2699 µmol g-1 h-1 than PTPA (2176 µmol g-1 h-1) and an apparent quantum yield (AQY) of 2.96% at 500 nm. The enhanced photocatalytic performance of PTBA is attributed to the promotion of the separation and transfer of photocarriers due to its high crystallinity. This work provides a precedent for the application of HOFs in the field of photocatalytic H2O2 generation.

A Turn-On Lipid Droplet-Targeted Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Intracellular Carboxylesterases and Cell Viability Imaging.

Carboxylesterases (CEs) play important physiological roles in the human body and are involved in numerous cellular processes. Monitoring CEs activity has great potential for the rapid diagnosis of malignant tumors and multiple diseases. Herein, we developed a new phenazine-based "turn-on" fluorescent probe DBPpys by introducing 4-bromomethyl-phenyl acetate to DBPpy, which can selectively detect CEs with a low detection limit (9.38 × 10-5 U/mL) and a large Stokes shift (more than 250 nm) in vitro. In addition, DBPpys can also be converted into DBPpy by carboxylesterase in HeLa cells and localized in lipid droplets (LDs), emitting bright near-infrared fluorescence under the irradiation of white light. Moreover, we achieved the detection of cell health status by measuring the intensity of NIR fluorescence after co-incubation of DBPpys with H2O2-pretreated HeLa cells, indicating that DBPpys has great potential applications for assessing CEs activity and cellular health.

Interplay of Steric Effects and Aromaticity Reversals to Expand the Structural/Electronic Responses of Dihydrophenazines.

To gain insights into the coupling of conformational and electronic variables, we exploited steric hindrance to modulate a polycyclic skeleton with a bent conformation in the S0 state and a twisted conformation in the S1 state under the guidance of photoexcited aromaticity reversals. Polycyclic 5,10-dihydrophenazine (DHP) adopted a bent structure in S0 but involved a bent-to-planar transformation in S1 due to the excited-state aromaticity of the 8π-electron central ring. The N,N'-locations and 1,4,6,9-sites of the DHP skeleton provided a versatile chemical handle for fine-tuning intramolecular steric hindrance. Specifically, N,N'-diphenyl-5,10-dihydrophenazine (DPP-00) and its derivatives DPP-10-DPP-22 were synthesized with different numbers of methyl groups on the 1,4,6,9-sites. X-ray crystal analyses suggested that the DHP skeletons of DPP-00-DPP-22 had more bending configurations along the N···N axis with an increase in the number of methyl groups. Following the bending-promoted interruption of π-conjugation, the absorption spectra of DPP-00-DPP-22 significantly blue-shifted from 416 to 324 nm. By contrast, the emission bands exhibited a reverse shift to longer wavelengths from 459 to 584 nm as the number of methyl substituents increased. Theoretical calculations revealed that introducing methyl groups caused the planar DHP skeleton in S1 to further twist along the N···N axis, resulting in a twisted high-strain conformation. The greater Stokes shift of the more steric-hindered structure can be attributed to the release of larger strain and aromatic stabilization energy. This research highlighted the potential promise associated with the interplay of steric effects and aromaticity reversals in a single fluorophore.

NIR Fluorescent Probe for In Situ Bioimaging of Endogenous H2S in Rice Roots under Al3+ and Flooding Stresses.

Hydrogen sulfide (H2S) is one of the typical reactive sulfur species, which exhibits an important role in regulating both physiological and pathological processes. Recent studies indicate that H2S also serves as a key signaling molecule in a broad range of regulatory processes in plants. However, in situ imaging and detection of the levels of H2S in plant tissues remains a challenge. In this work, a NIR fluorescent probe (HBTP-H2S) was synthesized to achieve H2S imaging in living plant tissues. HBTP-H2S exhibited high sensitivity toward H2S with a large Stokes shift (250 nm). HBTP-H2S could be applied to HeLa cells to detect the fluctuation of endogenous H2S levels in response to physiological stimulations. Importantly, HBTP-H2S was utilized for direct H2S imaging of rice roots and revealed the upregulation of H2S signaling in response to aluminum ions and flooding stresses. Our work thus provides a new tool to investigate H2S-involved signal interaction and protective resistance of crops under environmental stresses.

A diketopyrrolopyrrole-based ratiometric fluorescent probe for endogenous leucine aminopeptidase detecting and imaging with specific phototoxicity in tumor cells.

Leucine aminopeptidase (LAP) is a vital proteolytic enzyme, and its overexpression is often associated with many physiological diseases, such as liver dysfunction and breast cancer. Therefore, the accurate measurement of LAP concentrations in cells is critical for the diagnosis and prevention of related diseases. Herein, a new ratiometric fluorescent probe, DPP-Leu, based on diketopyrrolopyrrole (DPP) was designed and synthesized for LAP detection based on the specific enzymatic cleavage of the N-terminal leucine residue. The fluorescence intensity ratio of DPP-Leu (I548/I651) showed a remarkable change in the presence of LAP, with a limit of detection of 0.011 U L-1, and DPP-Leu was successfully applied to detect LAP in fetal bovine serum (FBS) and artificial urine. Cell imaging experiments revealed that DPP-Leu could target mitochondria and distinguish tumor cells with high LAP content from normal cells. Importantly, benefiting from the structural transformation of DPP-Leu to the photosensitizer 4 under LAP catalysis, the probe could kill tumor cells under light irradiation without damaging normal cells.

A Small-Molecule Diketopyrrolopyrrole-Based Dye for in†vivo NIR-IIa Fluorescence Bioimaging.

Organic small-molecule fluorophores with near-infrared IIa (NIR-IIa) emission have great potential in pre-clinical detection and inoperative imaging due to the high-spatial resolution and deep penetration. However, developments of the NIR-IIa fluorophores are still facing considerable challenges. In this work, a series of diketopyrrolopyrrole (DPP)-based fluorophores were designed and synthesized. Subsequently, nanomaterial T25@F127 with significant NIR-IIa emission properties was rationally prepared by encapsulating DPP-based fluorophore T25, and was selected for fluorescence angiography and cerebral vascular microscopic imaging with nearly 800 µm penetrating depth and excellent signal-background ratio of 4.07 and 2.26 (at 250 and 400 µm), respectively. Furthermore, the nanomaterial T25@cRGD with tumor targeting ability can image tiny metastatic tumor on intestine with a small size of 0.3 mm×1.0 mm and high-spatial resolution (SBR=3.84). This study demonstrates that the nanomaterials which encapsulated T25 behave as excellent NIR-IIa fluorescence imaging agents and have a great potential for in vivo biological application.

Diketopyrrolopyrrole-based fluorescent probe for endogenous bisulfite detection and bisulfite triggered phototoxicity specific in liver cancer cells.

As the main existing form of SO2 derivatives, bisulfite showed closely relationship to many diseases. In this work, a new fluorescent probe (SDPP-DM) based on thienyl-substituted diketopyrrolopyrrole (SDPP) was designed and synthesized for the detection of endogenous bisulfite. The probe displayed obvious color changes from green to pink towards bisulfite due to the reduced conjugated length caused by the addition to the α,ß-unsaturated double bond of its structure, and the change of the fluorescence intensity of SDPP-DM (I/I0) was about 16 folds. In addition, SDPP-DM was prepared a test strip for bisulfite identified by naked eye through color and fluorescence changes. Besides, SDPP-DM was successfully applied to imaging and discriminating different endogenous bisulfite levels in normal and cancer cells of liver. More importantly, the ROS generation and cell viability tests showed the phototoxicity of SDPP-DM triggered by bisulfite, indicating the specific phototoxicity of SDPP-DM towards liver cancer cells than normal liver cells.

Pure organic quinacridone dyes as dual sensitizers in tandem photoelectrochemical cells for unassisted total water splitting.

Pure organic dye QAP-C8 based on quinacridone (QA) with octyl side chains as the donor and pyridine dicarboxylic acid (PDA) as the acceptor was first used in both the photoanode and the photocathode of photoelectrochemical cells. A tandem device with QAP-C8 as the photosensitizer realized overall water splitting and showed a STH of 0.11% under neutral pH conditions without an external bias.

Aggregation-induced emission fluorophores based on strong electron-acceptor 2,2'-(anthracene-9,10-diylidene) dimalononitrile for biological imaging in the NIR-II window.

In this communication, three novel donor-acceptor-donor type second near-infrared AIE fluorophores based on strong electron-acceptor 2,2'-(anthracene-9,10-diylidene) dimalononitrile have been successfully developed for bioimaging, in which they exhibit good photostability and can be used in mouse ear vessel imaging with high resolution (FWHM = 93.4 µm/SBR = 1.5) after capsuling in nanoparticles with good biocompatibility.

Construction of polymeric carbon nitride and dibenzothiophene dioxide-based intramolecular donor-acceptor conjugated copolymers for photocatalytic H2 evolution.

Polymeric carbon nitride (g-C3N4) has succeeded as a striking visible-light photocatalyst for solar-to-hydrogen energy conversion, owing to its economical attribute and high stability. However, due to the lack of sufficient solar-light absorption and rapid photo-generated carrier recombination, the photocatalytic activity of raw g-C3N4 is still unsatisfactory. Herein, new intramolecular g-C3N4-based donor-acceptor (D-A) conjugated copolymers have been readily synthesized by a nucleophilic substitution/condensation reaction between urea and 3,7-dihydroxydibenzo[b,d]thiophene 5,5-dioxide (SO), which is strategically used to improve the photocatalytic hydrogen evolution performance. The experimental results demonstrate that CNSO-X not only improves light utilization, but also accelerates the spatial separation efficiency of the photogenerated electron-hole pairs and increases the wettability with the introduction of SO. In addition, the adsorption energy barrier of CNSO-X to H* has a significant reduction via theoretical calculation. As expected, the CNSO-20 realizes the best photocatalytic H2 evolution activity of 251 µmol h-1 (50 mg photocatalyst, almost 8.5 times higher than that of pure CN) with an apparent quantum yield of 10.16% at 420 nm, which surpasses most strategies for the organic molecular copolymerization of carbon nitride. Therefore, this strategy opens up a novel avenue to develop highly efficient g-C3N4 based photocatalysts for hydrogen production.

A glycine-functionalized graphene quantum dots synthesized by a facile post-modification strategy for a sensitive and selective fluorescence sensor of mercury ions.

In this work, we have developed a facile method for the synthesis of glycine-functionalized graphene quantum dots (Gly-GQDs) through post-modification of graphene quantum dots with Gly under alkaline conditions. The as-synthesized Gly-GQDs exhibit an excellent blue emission at 444 nm, independent of excitation, as well as a high quantum yield (QY) of 35.7%. The Gly-GQDs have a narrow size distribution with an average size of 5.9 nm. Moreover, the as-prepared Gly-GQDs showed a better selective and sensitive recognition capability towards mercury ion (Hg2+) in aqueous solutions with a low detection limit of 8.3 nM, compared with GQDs and other nitrogen-doped GQDs synthesized through the one-step solvent thermal method. Gly-GQDs are successfully applied for the determination of Hg2+ in real water samples. This work shows a new promising approach for the design and synthesis of desirable GQDs with a given function.

Multi-model ensemble simulated non-point source pollution based on Bayesian model averaging method and model uncertainty analysis.

Watershed models are cost-effective and powerful tools for evaluating and controlling non-point source pollution (NPSP), while the reliability of watershed models in a management context depends largely on inherent uncertainties in model predictions. The objective of this study is to present the use of multi-model ensemble applied to streamflow, total nitrogen (TN), and total phosphorus (TP) simulation and quantify the uncertainty resulting from model structure. In this study, three watershed models, which have different structures in simulating NPSP, were selected to conduct watershed monthly streamflow, TN load, and TP load ensemble simulation and 90% credible intervals based on Bayesian model averaging (BMA) method. The result using the observed data of the Yixunhe watershed revealed that the coefficient of determination and Nash-Sutcliffe coefficient of the BMA model simulate streamflow, TN load, and TP load were better than that of the single model. The higher the efficiency of a single model is, the greater the weight during the BMA ensemble simulation is. The 90% credible interval of BMA has a high coverage of measured values in this study. This indicates that the BMA method can not only provide simulation with better precision through ensemble simulation but also provide quantitative evaluation of the model structure through interval, which could offer rich information of the NPSP simulation and management.

A NIR fluorescent probe based on phenazine with a large Stokes shift for the detection and imaging of endogenous H2O2 in RAW 264.7 cells.

Hydrogen peroxide (H2O2), one of the reactive oxygen species (ROS), plays vital roles in diverse physiological processes. Thus, herein, to improve the signal-to-noise ratio, a new near-infrared region (NIR) fluorophore (PCN) based on reduced phenazine was developed. PCN was further designed as a "turn on" fluorescent probe (PCN-BP) for the detection of H2O2 by introducing p-boratebenzyl. After H2O2 was added, the p-boratebenzyl group in PCN-BP was oxidized to p-hydroxy benzyl; it then self-departed, forming PCN, which displayed 24-fold NIR emission at 680 nm with a large Stokes shift (more than 200 nm). This probe presented an excellent linear relation with the concentration of H2O2 and good selectivity to various ions, ROS and biothiols; thus, it can be utilized as a colorimetric and fluorescence turn-on probe. More importantly, the probe was also employed for the exogenous and endogenous imaging of H2O2 in RAW 264.7 cells.

A photo-stable and reversible pH-responsive nano-agent based on the NIR phenazine dye for photoacoustic imaging-guided photothermal therapy.

Different from traditional "always on" photothermal therapy (PTT) agents, tumor microenvironment responsive agents showed more tumor specificity and lower photo-toxicity to normal tissues. Herein, a photo-stable and reversible pH responsive phenazine dye (PIOH) was synthesized and assembled with liposomes forming nanoparticles (PIOH-NPs), which exhibited a strong NIR absorption in a weak acid environment and were successfully utilized for photoacoustic (PA) imaging-guided photothermal therapy in mice.

A self-assembled perylene diimide nanobelt for efficient visible-light-driven photocatalytic H2 evolution.

In this communication, a self-assembled supramolecular system consisting of phosphoric acid substituted perylene diimide (P-PMPDI) has been successfully developed for highly efficient photocatalytic hydrogen evolution. Compared with a carboxylic substituent perylene diimide (P-CMPDI), P-PMPDI showed a superior H2 evolution reaction rate of 11.7 mmol g-1 h-1 and a recorded apparent quantum yield (AQY) of 2.96% at 550 nm.

Mitochondria-Targeted Ratiometric Fluorescent Probe Based on Diketopyrrolopyrrole for Detecting and Imaging of Endogenous Superoxide Anion in Vitro and in Vivo.

Intracellular reactive oxygen species is involved in a wide variety of physiological and pathological processes. In this work, we have developed a new mitochondria-targeting probe (DPP-S) for superoxide anion detection with ratiometric fluorescence response. DPP-S exhibited an obvious color change from violet to orange along with a distinct fluorescence change with maximum emission peak from 652 to 545 nm in response to superoxide anion. The limit of detection of DPP-S for superoxide anion was calculated to be 20.5 nM. Imaging studies taken in MCF-7 and RAW264.7 cells showed that DPP-S could be employed as a ratiometric fluorescent probe for endogenous superoxide anion detection and imaging in living cells with a large emission shift. Furthermore, the colocalization study indicated that DPP-S can localize in mitochondria specifically. Finally, the fluorescent probe was successfully applied for superoxide anion imaging in mice.