Design, Synthesis, and Acaricidal/Insecticidal Activities of New Phenylpyrazole Derivatives Comprising an Imide Moiety.

Using nicofluprole as the lead compound, we designed and synthesized a series of new phenylpyrazole analogues through substituting the methyl group on the nitrogen atom of the amide with an acyl group. Bioassay results showed that compounds A12-A17 with a 1-cyanocyclopropimide group exhibited outstanding insecticidal activity. The LC50 values for compounds A12-A17 against Tetranychus cinnabarinus ranged from 0.58 to 0.91 mg/L. Compound A15 showed an LC50 value of 0.29 and 3.10 mg/L against Plutella xylostella and Myzus persicae, respectively. Molecular docking indicated the potential binding interactions of compound A15 with a gamma-aminobutyric acid receptor. Additionally, density functional theory calculations implied that the 1-cyanocyclopropimide structure might be essential for its biological activity. Phenylpyrazole derivatives, containing a 1-cyanocyclopropimide fragment, have the potential for further development as potential insecticides.

Hydrogen-Bonding-Regulated Morphology Control and the Impact on the Antibacterial Activity of Cationic π-Amphiphiles.

This manuscript describes the synthesis, self-assembly, and antibacterial properties of naphthalene-diimide (NDI)-derived cationic π-amphiphiles. Three such asymmetric NDI derivatives with a nonionic hydrophilic wedge and a guanidine group in the two opposite sides of the NDI chromophore were considered. They differ by a single functional group (hydrazide, amide, and ester for NDI-1, NDI-2, and NDI-3, respectively), located in the linker between the NDI and the hydrophilic wedge. For NDI-1, the H-bonding among the hydrazides regulated unilateral stacking and a preferential direction of curvature of the resulting supramolecular polymer, producing an unsymmetric polymersome with the guanidinium groups displayed at the outer surface. NDI-3, lacking any H-bonding group, exhibits π-stacking without any preferential orientation and generates spherical particles with a relatively poor display of the guanidium groups. In sharp contrast to NDI-1, NDI-2 exhibits an entangled one-dimensional (1D) fibrillar morphology, indicating the prominent role of the H-bonding motif of the amide group and flexibility of the linker. The antibacterial activity of these assemblies was probed against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). NDI-1 showed the most promising antibacterial activity with a minimum inhibitory concentration (MIC) of ∼7.8 µg/mL against S. aureus and moderate activity (MIC ∼ 125 µg/mL) against E. coli. In sharp contrast, NDI-3 did not show any significant activity against the bacteria, suggesting a strong impact of the H-bonding-regulated directional assembly. NDI-2, forming a fibrillar network, showed moderate activity against S. aureus and negligible activity against E. coli, highlighting a significant impact of the morphology. All of these three molecules were found to be compatible with mammalian cells from the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and hemolysis assay. The mechanistic investigation by membrane polarization assay, live/dead fluorescence assay, and microscopy studies confirmed the membrane disruption mechanism of cell killing for the lead candidate NDI-1.

Structure-Activity Study on Substituted, Core-Extended, and Dyad Naphthalene Diimide G-Quadruplex Ligands Leading to Potent Antitrypanosomal Agents.

Several G-quadruplex nucleic acid (G4s) ligands have been developed seeking target selectivity in the past decade. Naphthalene diimide (NDI)-based compounds are particularly promising due to their biological activity and red-fluorescence emission. Previously, we demonstrated the existence of G4s in the promoter region of parasite genomes, assessing the effectiveness of NDI-derivatives against them. Here, we explored the biological activity of a small library of G4-DNA ligands, exploiting the NDI pharmacophore, against both Trypanosoma brucei and Leishmania major parasites. Biophysical and biological assays were conducted. Among the various families analyzed, core-extended NDIs exhibited the most promising results concerning the selectivity and antiparasitic effects. NDI 16 emerged as the most potent, with an IC50 of 0.011 nM against T. brucei and remarkable selectivity vs MRC-5 cells (3454-fold). Fascinating, 16 is 480-fold more potent than the standard drug pentamidine (IC50 = 5.3 nM). Cellular uptake and parasite localization were verified by exploiting core-extended NDI red-fluorescent emission.

Carbohydrate-Functionalized Anthracene Carboximides as Multivalent Ligands and Bio-Imaging Agents.

Anthracene carboximides (ACIs) conjugated with gluco-, galacto- and mannopyranosides are synthesized, by glycosylation of N-hydroxyethylanthracene carboximide acceptor with glycosyl donors. Glycoconjugation of anthracene carboximide increases the aq. solubility by more than 3-fold. The glycoconjugates display red-shifted absorption and emission, as compared to anthracene. Large Stokes shift (λabs/λem=445/525 nm) and high fluorescence quantum yields (Φ) of 0.86 and 0.5 occur in THF and water, respectively. The ACI-glycosides undergo facile photodimerization in aqueous solutions, leading to the formation of the head-to-tail dimer, as a mixture of syn and anti-isomers. Solution phase and solid-state characterizations by dynamic light scattering (DLS), microscopic imaging by atomic force (AFM) and transmission electron (TEM) microscopies reveal self-assembled vesicle structures of ACI glycosides. These self-assembled structures act as multivalent glycoclusters for ligand-specific lectin binding, as evidenced by the binding of Man-ACI to Con A, by fluorescence and turbidity assays. The conjugates do not show cellular cytotoxicity (IC50) till concentrations of 50 µM with HeLa and HepG2 cell lines and are cell-permeable, showing strong fluorescence inside the cells. These properties enable the glycoconjugates to be used in cell imaging. The non-selective cellular uptake of the glycoconjugates suggests a passive diffusion through the membrane.

Soluble Fluorinated Cardo Copolyimide as an Effective Additive to Photopolymerizable Compositions Based on Di(meth)acrylates: Application for Highly Thermostable Primary Protective Coating of Silica Optical Fiber.

The development of photocurable compositions is in high demand for the manufacture of functional materials for electronics, optics, medicine, energy, etc. The properties of the final photo-cured material are primarily determined by the initial mixture, which needs to be tuned for each application. In this study we propose to use simple systems based on di(meth)acrylate, polyimide and photoinitiator for the preparation of new photo-curable compositions. It was established that a fluorinated cardo copolyimide (FCPI) based on 2,2-bis-(3,4-dicarboxydiphenyl)hexafluoropropane dianhydride, 9,9-bis-(4-aminophenyl)fluorene and 2,2-bis-(4-aminophenyl)hexafluoropropane (1.00:0.75:0.25 mol) has excellent solubility in di(met)acrylates. This made it possible to prepare solutions of FCPI in such monomers, to study the effect of FCPI on the kinetics of their photopolymerization in situ and the properties of the resulting polymers. According to the obtained data, the solutions of FCPI (23 wt.%) in 1,4-butanediol diacrylate (BDDA) and FCPI (15 wt.%) in tetraethylene glycol diacrylate were tested for the formation of the primary protective coatings of the silica optical fibers. It was found that the new coating of poly(BDDA-FCPI23%) can withstand prolonged annealing at 200 °C (72 h), which is comparable or superior to the known most thermally stable photo-curable coatings. The proposed approach can be applied to obtain other functional materials.

Enzymatic Reaction-Coupled, Cooperative Supramolecular Polymerization.

Nature employs sophisticated mechanisms to precisely regulate self-assembly and functions within biological systems, exemplified by the formation of cytoskeletal filaments. Various enzymatic reactions and auxiliary proteins couple with the self-assembly process, meticulously regulating the length and functions of resulting macromolecular structures. In this context, we present a bioinspired, reaction-coupled approach for the controlled supramolecular polymerization in synthetic systems. To achieve this, we employ an enzymatic reaction that interfaces with the adenosine triphosphate (ATP)-templated supramolecular polymerization of naphthalene diimide monomers (NSG). Notably, the enzymatic production of ATP (template) plays a pivotal role in facilitating reaction-controlled, cooperative growth of the NSG monomers. This growth process, in turn, provides positive feedback to the enzymatic production of ATP, creating an ideal reaction-coupled assembly process. The success of this approach is further evident in the living-growth characteristic observed during seeding experiments, marking this method as the pioneering instance where reaction-coupled self-assembly precisely controls the growth kinetics and structural aspects of supramolecular polymers in a predictive manner, akin to biological systems.

A perylene diimide probe for NIR-II fluorescence imaging guided photothermal and type I/type II photodynamic synergistic therapy.

Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O2•- and 1O2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications.

Determination of genotoxic impurities of aromatic aldehydes in pharmaceutical preparations by high performance liquid chromatography after derivatization with N-Cyclohexyl-4-hydrazino-1,8-naphthalenediimide.

The detection of aromatic aldehydes, considered potential genotoxic impurities, holds significant importance during drug development and production. Current analytical methods necessitate complex pre-treatment processes and exhibit insufficient specificity and sensitivity. This study presents the utilization of naphthalenediimide as a pre-column derivatisation reagent to detect aromatic aldehyde impurities in pharmaceuticals via high-performance liquid chromatography (HPLC). We screened a series of derivatisation reagents through density functional theory (DFT) and investigated the phenomenon of photoinduced electron transfer (PET) for both the derivatisation reagents and the resulting products. Optimal experimental conditions for derivatisation were achieved at 40 °C for 60 min. This approach has been successfully applied to detect residual aromatic aldehyde genotoxic impurities in various pharmaceutical preparations, including 4-Nitrobenzaldehyde, 2-Nitrobenzaldehyde, 1,4-Benzodioxane-6-aldehyde, and 5-Hydroxymethylfurfural. The pre-column derivatisation method significantly enhanced detection sensitivity and reduced the limit of detection (LOD), which ranged from 0.002 to 0.008 µg/ml for the analytes, with relative standard deviations < 3 %. The correlation coefficient (R2) >0.998 demonstrated high quality. In chloramphenicol eye drops, the concentration of 4-Nitrobenzaldehyde was measured to be 8.6 µg/mL below the specified concentration, with recoveries ranging from 90.0 % to 119.2 %. In comparison to existing methods, our work simplifies the pretreatment process, enhances the sensitivity and specificity of the analysis, and offers comprehensive insights into impurity detection in pharmaceutical preparations.

Activable Nano-Immunomodulator Assembled from π-Extended Naphthalenediimide for Precision Photothermal Immunotherapy.

A nano-immunomodulator (R-NPT NP) comprising a tumor microenvironment (TME) activable resiquimod (R848) and a π-extended NIR-absorbing naphthophenanthrolinetetraone (NPT) has been engineered for spatiotemporal controlled photothermal immunotherapy. R-NPT NP demonstrated excellent photostability, while R848 promoted synergistic immunity as a toll-like receptor 7/8 (TLR7/8) agonist. Upon accumulation at the tumor site, R-NPT NP released R848 in response to redox metabolite glutathione (GSH), triggering dendritic cell (DC) activation. The photothermal effect endowed by R-NPT NP can ablate tumors directly and trigger immunogenic cell death to augment immunity after photoirradiation. The synergistic effect of GSH-liable TLR7/8 agonist and released immunogenic factors leads to a robust evocation of systematic immunity through promoted DC maturation and T cell infiltration. Thus, R-NPT NP with photoirradiation achieved 99.3 % and 98.2 % growth inhibition against primary and distal tumors, respectively.

Comparative hepatotoxicity of novel lithium bis(trifluoromethanesulfonyl)imide (LiTFSI, ie. HQ-115) and legacy Perfluorooctanoic acid (PFOA) in male mice: Insights into epigenetic mechanisms and pathway-specific responses.

Lithium Bis(trifluoromethanesulfonyl)imide (LiTFSI ie. HQ-115), a polymer electrolyte used in energy applications, has been detected in the environment, yet its health risks and environmental epigenetic effects remain unknown. This study aims to unravel the potential health risks associated with LiTFSI, investigate the role of DNA methylation-induced toxic mechanisms in its effects, and compare its hepatotoxic impact with the well-studied Perfluorooctanoic Acid (PFOA). Using a murine model, six-week-old male CD1 mice were exposed to 10 and 20 mg/kg/day of each chemical for 14 days as 14-day exposure and 1 and 5 mg/kg/day for 30 days as 30-day exposure. Results indicate that PFOA exposure induced significant hepatotoxicity, characterized by liver enlargement, and elevated serum biomarkers. In contrast, LiTFSI exposure showed lower hepatotoxicity, accompanied by mild liver injuries. Despite higher bioaccumulation of PFOA in serum, LiTFSI exhibited a similar range of liver concentrations compared to PFOA. Reduced Representative Bisulfite Sequencing (RRBS) analysis revealed distinct DNA methylation patterns between 14-day and 30-day exposure for the two compounds. Both LiTFSI and PFOA implicated liver inflammatory pathways and lipid metabolism. Transcriptional results showed that differentially methylated regions in both exposures are enriched with cancer/disease-related motifs. Furthermore, Peroxisome proliferator-activated receptor alpha (PPARα), a regulator of lipid metabolism, was upregulated in both exposures, with downstream genes indicating potential oxidative damages. Overall, LiTFSI exhibits distinct hepatotoxicity profiles, emphasizing the need for comprehensive assessment of emerging PFAS compounds.

Two Birds with one Stone: Dual-mode immunoassay constructed using a novel emitter ethylene glycol-induced perylene diimide and a multifunctional ANS probe.

Perylene diimide (PDI) is a readily reducible electron-deficient dye that exhibits strong photoluminescent properties, providing new opportunities for synthesizing novel electrochemiluminescence (ECL) emitters. In this study, ethylene glycol (EG) was used to induce the self-assembly of PDI supramolecules for the preparation of ultrathin EG-PDI nanosheets characterized by low crystallinity and weak stacking interaction. Notably, EG-PDI integrates luminescent and catalytic functions into one device, accelerating the interfacial electron transfer and the faster charge transfer kinetics of EG-PDI with K2S2O8. Furthermore, the narrow band gap of EG-PDI facilitates its excitation at an ultra-low potential (-0.3 V). To improve the efficiency of tumor marker analysis, multifunctional Au nanostars (ANS) was introduced both as an energy acceptor of the ECL system and a probe for the photothermal system. Dual-mode immunoassay have demonstrated superior analytical performance in detecting alpha-fetoprotein (AFP), meeting the requirements of modern clinical diagnostics in resource-limited environments.

Ionic Thermoelectric Generators in Vertical and Planar Topologies Based on Fluorinated Polymer Hybrid Materials with Ionic Liquids.

Ionic thermoelectrics (TEs), in which voltage generation is based on ion migration, are suitable for applications based on their low cost, high flexibility, high ionic conductivity, and wide range of Seebeck coefficients. This work reports on the development of ionic TE materials based on the poly(vinylidene fluoride-trifluoroethylene), Poly(VDF-co-TrFE), as host polymer blended with different contents of the ionic liquid, IL, 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, [EMIM][TFSI]. The morphology, physico-chemical, thermal, mechanical, and electrical properties of the samples are evaluated together with the TE response. It is demonstrated that the IL acts as a nucleating agent for polymer crystallization. The mechanical properties and ionic conductivity values are dependent on the IL content. A high room temperature ionic conductivity of 0.008 S cm-1 is obtained for the sample with 60 wt% of [EMIM][TFSI] IL. The TE properties depend on both IL content and device topology-vertical or planar-the largest generated voltage range being obtained for the planar topology and the sample with 10 wt% of IL content, characterized by a Seebeck coefficient of 1.2 mV K-1. Based on the obtained maximum power density of 4.9 µW m-2, these materials are suitable for a new generation of TE devices.

S-scheme heterojunction of crystalline carbon nitride nanosheets and ultrafine WO3 nanoparticles for photocatalytic CO2 reduction.

Highly crystalline carbon nitride polymers have shown great opportunities in overall water photosplitting; however, their mission in light-driven CO2 conversion remains to be explored. In this work, crystalline carbon nitride (CCN) nanosheets of poly triazine imide (PTI) embedded with melon domains are fabricated by KCl/LiCl-mediated polycondensation of dicyandiamide, the surface of which is subsequently deposited with ultrafine WO3 nanoparticles to construct the CCN/WO3 heterostructure with a S-scheme interface. Systematic characterizations have been conducted to reveal the compositions and structures of the S-scheme CCN/WO3 hybrid, featuring strengthened optical capture, enhanced CO2 adsorption and activation, attractive textural properties, as well as spatial separation and directed movement of light-triggered charge carriers. Under mild conditions, the CCN/WO3 catalyst with optimized composition displays a high photocatalytic activity for reducing CO2 to CO in a rate of 23.0 µmol/hr (i.e., 2300 µmol/(hr·g)), which is about 7-fold that of pristine CCN, along with a high CO selectivity of 90.6% against H2 formation. Moreover, it also manifests high stability and fine reusability for the CO2 conversion reaction. The CO2 adsorption and conversion processes on the catalyst are monitored by in-situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), identifying the crucial intermediates of CO2*-, COOH* and CO*, which integrated with the results of performance evaluation proposes the possible CO2 reduction mechanism.

Naphthalene Diimide-Tetraazacycloalkane Conjugates Are G-Quadruplex-Based HIV-1 Inhibitors with a Dual Mode of Action.

Human immunodeficiency virus 1 (HIV-1) therapeutic regimens consist of three or more drugs targeting different steps of the viral life cycle to limit the emergence of viral resistance. In line with the multitargeting strategy, here we conjugated a naphthalene diimide (NDI) moiety with a tetraazacycloalkane to obtain novel naphthalene diimide (NDI)-tetraazacycloalkane conjugates. The NDI inhibits the HIV-1 promoter activity by binding to LTR G-quadruplexes, and the tetraazacycloalkane mimics AMD3100, which blocks HIV entry into cells by interfering with the CXCR4 coreceptor. We synthesized, purified, and tested the metal-free NDI-tetraazacycloalkane conjugate and the two derived metal-organic complexes (MOCs) that incorporate Cu2+ and Zn2+. The NDI-MOCs showed enhanced binding to LTR G4s as assessed by FRET and CD assays in vitro. They also showed enhanced activity in cells where they dose-dependently reduced LTR promoter activity and inhibited viral entry only of the HIV-1 strain that exploited the CXCR4 coreceptor. The time of addition assay confirmed the dual targeting at the different HIV-1 steps. Our results indicate that the NDI-MOC conjugates can simultaneously inhibit viral entry, by targeting the CXCR4 coreceptor, and LTR promoter activity, by stabilizing the LTR G-quadruplexes. The approach of combining multiple targets in a single compound may streamline treatment regimens and improve the overall patient outcomes.

Constructing Novel High Dielectric Constant Polyimides Containing Dipolar Pendant Groups with Enhanced Orientational Polarization.

Polymer dielectrics with high dielectric constant are urgently demanded for potential electrical and pulsed power applications. The design of polymers with side chains containing dipolar groups is considered an effective method for preparing materials with a high dielectric constant and low loss. This study synthesizes and comprehensively compare the dielectric properties of novel polyimides with side chains containing urea (BU-PI), carbamate (BC-PI), and sulfonyl (BS-PI) functional groups. The novel polyimides exhibit relatively high dielectric constant and low dielectric loss values due to the enhanced orientational polarization and suppressed dipole-dipole interactions of dipolar groups. In particular, BU-PI containing urea pendant groups presents the highest dielectric constant of 6.14 and reasonably low dielectric loss value of 0.0097. The strong γ transitions with low activation energies derived from dielectric spectroscopy measurements have been further evaluated to demonstrate the enhanced free rotational motion of urea pendant dipoles. In energy storage applications, BU-PI achieves a discharged energy density of 6.92 J cm-3 and a charge-discharge efficiency above 83% at 500 MV m-1. This study demonstrates that urea group, as dipolar pendant group, can provide polymers with better dielectric properties than the most commonly used sulfonyl groups.

amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/ß-Catenin Pathway.

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/ß-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/ß-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/ß-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/ß-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.

A perylene diimide electrochemical probe with persulfate as a signal enhancer for dopamine sensing.

Dopamine (DA) is an important biomarker related to parkinsonism, schizophrenia and renal disease. Traditional electrochemical sensors for DA were based on the direct electrochemical oxidation of DA. In this paper, we report a new sensing strategy using N,N'-di(trimethylaminoethyl)perylene diimide (TMPDI) as an electrochemical probe and K2S2O8 as a signal enhancer for DA detection between 0 and -0.7 V with the DPV technique. MoS2 nanoflowers prepared by the hydrothermal method were used as a nanocarrier to load TMPDI. The reduction current of TMPDI was found to show a stepwise and significant increase at -0.24 V with the increase of concentration of K2S2O8 due to the continuous cycle of TMPDI molecules' electrochemical reduction and chemical oxidation. The presence of DA caused a large decrease of the reduction current of TMPDI due to the synergistic interaction of the competitive consumption of DA for K2S2O8 and the blocking effect of polyDA adhering to the electrode surface. The decreased current exhibited a linear response for DA from 10 pM to 100 µM with a detection limit of 4.1 pM and the proposed sensor showed high selectivity and excellent feasibility in human urine/serum sample detection.

A Self-Assembly-Induced Exciton Delocalization Strategy for Converting a Perylene Diimide Derivative from a Type-II to Type-I Photosensitizer.

Type-I photosensitizers have shown advantages in addressing the shortcomings of traditional oxygen-dependent type-II photosensitizers for the photodynamic therapy (PDT) of hypoxic tumors. However, developing type-I photosensitizers is yet a huge challenge because the type-II energy transfer process is much faster than the type-I electron transfer process. Herein, from the fundamental point of view, an effective approach is proposed to improve the electron transfer efficiency of the photosensitizer by lowering the internal reorganization energy and exciton binding energy via self-assembly-induced exciton delocalization. An example proof is presented by the design of a perylene diimide (PDI)-based photosensitizer (PDIMp) that can generate singlet oxygen (1O2) via a type-II energy transfer process in the monomeric state, but induce the generation of superoxide anion (O2˙-) via a type-I electron transfer process in the aggregated state. Significantly, with the addition ofcucurbit[6]uril (CB[6]), the self-assembled PDIMp can convert back to the monomeric state via host-guest complexation and consequently recover the generation of 1O2. The biological evaluations reveal that supramolecular nanoparticles (PDIMp-NPs) derived from PDIMp show superior phototherapeutic performance via synergistic type-I PDT and mild photothermal therapy (PTT) against cancer under either normoxia or hypoxia conditions.

Toward Type I/II ROS Generation Photoimmunotherapy by Molecular Engineering of Semiconducting Perylene Diimide.

As prospective phototheranostic agents for cancer imaging and therapy, semiconducting organic molecule-based nanomedicines are developed. However, near-infrared (NIR) emission, and tunable type I (O2 • -) and type II (1O2) photoinduced reactive oxygen species (ROS) generation to boost cancer photoimmunotherapy remains a big challenge. Herein, a series of D-π-A structures, NIR absorbing perylene diimides (PDIs) with heavy atom bromide modification at the bay position of PDIs are prepared for investigating the optimal photoinduced type I/II ROS generation. The heavy atom effect has demonstrated a reduction of molecular ∆EST and promotion of the intersystem crossing processes of PDIs, enhancing the photodynamic therapy (PDT) efficacy. The modification of three bromides and one pyrrolidine at the bay position of PDI (TBDT) has demonstrated the best type I/II PDT performance by batch experiments and theoretical calculations. TBDT based nanoplatforms (TBDT NPs) enable type I/II PDT in the hypoxic tumor microenvironment as a strong immunogenic cell death (ICD) inducer. Moreover, TBDT NPs showing NIR emission allow in vivo bioimaging guided phototherapy of tumor. This work uses novel PDIs with adjustable type I/II ROS production to promote antitumor immune response and accomplish effective tumor eradication, consequently offering molecular guidelines for building high-efficiency ICD inducers.

A perylenemonoimide-based fluorescent probe: ultrasensitive and selective tracing of endogenous peroxynitrite in living cells.

Peroxynitrite (ONOO-), a highly reactive species, plays a key role in various physiological and pathological processes. Herein, a red-emitting fluorescent reporter perylenemonoimide-boronate ester (PMI-BE) was synthesized and utilized for ultrasensitive detection of ONOO-. The unique feature of PMI-BE is its nanomolar sensitivity with high selectivity towards ONOO-. Moreover, PMI-BE also detects endogenously generated ONOO- in live cells.