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.

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.

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.

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.

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.

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.

Vortex-assisted microextraction of melamine from milk samples using green short chain ionic liquid solvents coupled with high performance liquid chromatography determination.

Melamine is added illegally to milk and dairy products to increase the amount of apparent protein. This organic nitrogen rich chemical compound has been of great challenge in food safety based on its adverse effect on health. Therefore, the extraction and determination of melamine from milk is necessary. Recently, ionic liquid (ILs) as solvent usage has been noticeable for low melting point, low toxicity, high thermal stability, and high extraction capabilities in a wide range of separation processes. ILs are introduced as organic-inorganic salts and green solvents in microextraction preparation. Therefore, in this study, three ionic liquids ([C6mim][NTF2], [C4mim][NTF2] and [C2mim][NTF2] ILs) were prepared and employed as an extraction solvent in dispersive liquid-liquid microextraction (DLLME) of melamine from milk samples followed by HPLC-UV. The selected ILs were designed using three types of alkyl-imidazolium (as the short organic cations) and bis (tri fluoro methyl sulfonyl) imide as anion and characterized by ATR-FTIR spectra, carbon, and hydrogen Nuclear Magnetic Resonance spectroscopy (H&C-NMR) and energy-dispersive X-ray spectroscopy (EDX). These techniques confirmed the formation of functional groups, the structure of hydrogen and carbon atoms, and various elements of ionic bond between imidazolium and bis (tri fluoro methyl sulfonyl) imide. In the next step, the effect of significant parameters, including type and volume of ILs, adsorption time, pH of the sample solution, and sample volume, were optimized. Under the optimal conditions, the limits of detection (LOD), limits of quantification (LOQ), and linearity range were obtained 63.64 µg kg-1, 210.03 µg kg-1, and 210.03-1000 µg kg-1, respectively, for as prepared [C6mim][NTF2] as the best ILs. Notably, the achieved LOQ was lower than the maximum residue level (MRL) for the melamine residue in dairy products. Eventually, the proposed method was applied to detect melamine in milk samples, and the relative recoveries were examined as 79.6-105.0 %.

Fluorescent detection of tartrazine based on the supramolecular self-assembly of cationic perylene diimide.

A cationic perylene probe was designed and synthesized for sensitive determination of tartrazine. In the presence of tartrazine, the fluorescence of the perylene probe was quenched by efficient supramolecular self-assembly of the perylene derivate. The quenching is caused by the synergistic effect of noncovalent interactions including static electricity, π-π stacking, and hydrophobic interaction. Benefiting from these advantages, the probe exhibited excellent sensing performance to tartrazine within 2 min. The detection and quantification limit of tartrazine are as low as 2.42 and 8.07 nmol L-1, respectively, with a wide linear operation range from 15 to 500 nmol L-1. Most importantly, due to the high binding affinity (3.22 × 107 mol L-1) between the perylene probe and tartrazine, the sensing system shows great anti-interference capacity. Subsequently, the visualization application of the approach was evaluated by portable device, and the limits of detection for visual detection for test strip, membrane, and hydrogel were 0.5, 0.5, and 5 µmol L-1, respectively. The approach has been applied to monitor tartrazine in various food condiments with recoveries in the range 91.29-108.83%. As far as we know, this is the first report of using perylene-based probe for tartrazine determination, offering a promising strategy for the construction of perylene-based detection system in the field of food safety.

Lewis Acid-Mediated Electrophilic Thiolative Difunctionalization of Enimides: Rapid Access to ß-Amino Sulfides.

An efficient and practical route for the synthesis of ß-amino sulfides by Lewis acid-mediated electrophilic thiolative difunctionalization of enimides is disclosed. A series of free phenols, electron-rich arene, alcohol, azide, and hydride, are successfully incorporated into the substrates in high regio- and stereoselectivities under mild conditions. The obtained products possess multiple functional groups and can be easily transformed to other valuable molecules.

Development of On-DNA Cyclic Imide Synthesis for DNA Encoded Library Construction.

Here, we describe a novel method for the on-DNA synthesis of cyclic imides, an important class of molecules that includes several well-known medications. Significantly, the new method enabled on-DNA synthesis under mild conditions with high conversions and a broad functional group tolerance, utilizing ubiquitous bifunctional amines and bis-carboxylic acid, or alkyl halides, and therefore served as the linchpin for DNA encoded library (DEL) synthesis. The mechanism study of off-DNA and on-DNA chemical transformations revealed unique insights in contrast to conventional chemical transformation.

Visible-Light-Induced Four-Component Ritter-Type Reaction: Access to ß-Trifluoromethyl Imides.

A visible-light-induced four-component Ritter-type reaction was developed for the synthesis of ß-trifluoromethyl imides from CF3Br, alkenes, carboxylic acids, and nitriles. This protocol features mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Furthermore, this method has been proven to be suitable for the late-stage diversification of drug molecules. A mechanism involving a Ritter-type reaction and Mumm rearrangement was proposed on the basis of the control experiments.

Recent Advances in Applications of Fluorescent Perylenediimide and Perylenemonoimide Dyes in Bioimaging, Photothermal and Photodynamic Therapy.

The emblematic perylenediimide (PDI) motif which was initially used as a simple dye has undergone incredible development in recent decades. The increasing power of synthetic organic chemistry has allowed it to decorate PDIs to achieve highly functional dyes. As these PDI derivatives combine thermal, chemical and photostability, with an additional high absorption coefficient and near-unity fluorescence quantum yield, they have been widely studied for applications in materials science, particularly in photovoltaics. Although PDIs have always been in the spotlight, their asymmetric counterparts, perylenemonoimide (PMI) analogues, are now experiencing a resurgence of interest with new efforts to create architectures with equally exciting properties. Namely, their exceptional fluorescence properties have recently been used to develop novel systems for applications in bioimaging, biosensing and photodynamic therapy. This review covers the state of the art in the synthesis, photophysical characterizations and recently reported applications demonstrating the versatility of these two sister PDI and PMI compounds. The objective is to show that after well-known applications in materials science, the emerging trends in the use of PDI- and PMI-based derivatives concern very specific biomedicinal applications including drug delivery, diagnostics and theranostics.

Synthesis of 1,6/7-(NO2 )2 -Perylenediimide and 1,6/7-(NH2 )2 -Perylenediimide as Regioisomerically Pure Materials.

The use of perylenediimide (PDI) building blocks in materials for organic electronic is of considerable interest. This popular n-type organic semiconductor is tuned by introducing peripheral groups in their ortho and bay positions. Such modifications radically alter their optoelectronic properties. In this article, we describe an efficient method to afford regioisomerically pure 1,6/7-(NO2 )2 - and (NH2 )2 -PDIs employing two key steps: the selective crystallization of 1,6-(NO2 )2 -perylene-3,4,9,10-tetracarboxy tetrabutylester and the nitration of regiopure 1,7-Br2 -PDI with silver nitrite. The optoelectronic properties of the resulting regioisomerically pure dinitro, diamino-PDIs and bisazacoronenediimides (BACDs) are reported and demonstrate the need to separate both regioisomers of such n-type organic semiconductors for their inclusion in advanced optoelectronic devices. For the first time, the two regioisomers of the same PDI starting material are available on the multigram scale, which will stimulate the exploration of regioisomerism/properties relationship for this family of dyes.

The effect of silicon groups on the physicochemical property and bioactivity of L-phenylalanine derived poly(amide-imide).

Poly(amide-imide) (PAI), serving as a synthetic polymer, has been widely used in industry for excellent mechanical properties, chemical resistance and high thermal stability. However, lack of suitable cell niche and biological activity limited the further application of PAI in biomedical engineering. Herein, silicon modified L-phenylalanine derived poly(amide-imide) (PAIS) was synthesized by introducing silica to L-phenylalanine derived PAI to improve physicochemical and biological performances. The influence of silicon amount on physicochemical, immune, and angiogenic performances of PAIS were systemically studied. The results show that PAIS exerts excellent hydrophilic, mechanical, biological activity. PAIS shows no effects on the number of macrophages, but can regulate macrophage polarization and angiogenesis in a dose-dependent manner. This study advanced our understanding of silicon modification in PAI can modulate cell responses via initiating silicon concentration regulation. The acquired knowledge will provide a new strategy to design and optimize biomedical PAI in the future.

Salt-Melt Synthesis of Poly Heptazine Imides with Enhanced Optical Absorption for Photocatalytic Hydrogen Production.

Broadening the visible light absorption range and accelerating the separation and migration process of charge carriers are effective ways to improve photocatalytic quantum efficiencies. In this study, we show that poly heptazine imides with enhanced optical absorption and promoted charge carrier separation and migration could be obtained by means of a rational design of the band structures and crystallinity of polymeric carbon nitride. Copolymerization of urea with monomers such as 2-aminothiophene-3-carbonitrile would first generate amorphous melon with enhanced optical absorption, while further ionothermal treatment of melon in eutectic salts would increase the polymerization degree and create condensed poly heptazine imides as final products. Accordingly, the optimized poly heptazine imide presents an apparent quantum yield of 12 % at 420 nm for photocatalytic hydrogen production.

Double Hook Perylene Diimide as a New Receptor for PAHs: An Experimental and Theoretical Study.

In a one-step reaction, we prepared a dibenzylamine perylene diimide derivative (PDI). Its double hook structure allows for self-association with a constant of Kd ∼108  M-1 determined by fluorescence. We confirmed its ability to bind PAHs using UV/Vis, fluorescence, and 1 H NMR titrations in CHCl3 . The complex formation signature in UV/vis is a new band at 567 nm. The calculated binding constants (Ka ∼104  M-1 ) follow the trend pyrene>perylene>phenanthrene>naphthalene>anthracene. Theoretical modeling of these systems using DFT ωB97X-D/6-311G(d,p) proved helpful in rationalizing the complex formation and the observed association trend. The distinctive signal in UV/vis is due to a charge transfer in the complex from orbitals in the guest to the host. SAPT(DFT) confirmed that the driving forces in the complex formation are exchange and dispersion (π-π interactions). Still, the recognition ability depends on the electrostatic component of the interaction, a minor fraction.

Supramolecular Recognition of Phosphodiester-Based Donor and Acceptor Oligomers Forming Gels in Water.

Inspired by automated DNA synthesis, electron-rich dialkoxynaphthalene (DAN) donor and electron-deficient naphthalene-tetracarboxylic diimide (NDI) acceptor phosphodiester-linked homohexamers were synthesized by the phosphoramidite method. Two types of hexamers were prepared, one with only one phosphodiester between the aromatics (i.e., DAN or NDI) and a second with two phosphodiesters around a propanediol between the aromatics, leading to the latter more flexible and more hydrophilic hexamers. The folding properties of these homohexamers alone or mixed together, in water only, were studied by UV-visible absorption spectroscopy and atomic force microscopy (AFM). AFM imaging revealed that a 1:1 mixture of hexaDAN and hexaNDI formed fibers by charge transfer donor-acceptor recognition leading to a hydrogel after drying. The organization of the resulting structures is strongly dependent on the nature of the complementary partner, leading to the formation of mono- or multilayer hydrogel networks with different compactness.

Preferential molecular recognition of heterochiral guests within a cyclophane receptor.

The discrimination of enantiomers by natural receptors is a well-established phenomenon. In contrast the number of synthetic receptors with the capability for enantioselective molecular recognition of chiral substrates is scarce and for chiral cyclophanes indicative for a preferential binding of homochiral guests. Here we introduce a cyclophane composed of two homochiral core-twisted perylene bisimide (PBI) units connected by p-xylylene spacers and demonstrate its preference for the complexation of [5]helicene of opposite helicity compared to the PBI units of the host. The pronounced enantio-differentiation of this molecular receptor for heterochiral guests can be utilized for the enrichment of the P-PBI-M-helicene-P-PBI epimeric bimolecular complex. Our experimental results are supported by DFT calculations, which reveal that the sterically demanding bay substituents attached to the PBI chromophores disturb the helical shape match of the perylene core and homochiral substrates and thereby enforce the formation of syndiotactic host-guest complex structures. Hence, the most efficient substrate binding is observed for those aromatic guests, e. g. perylene, [4]helicene, phenanthrene and biphenyl, that can easily adapt in non-planar axially chiral conformations due to their inherent conformational flexibility. In all cases the induced chirality for the guest is opposed to those of the embedding PBI units, leading to heterochiral host-guest structures.

From Divalent to Pentavalent Iron Imido Complexes and an Fe(V) Nitride via N-C Bond Cleavage.

As key intermediates in metal-catalyzed nitrogen-transfer chemistry, terminal imido complexes of iron have attracted significant attention for a long time. In search of versatile model compounds, the recently developed second-generation N-anchored tris-NHC chelating ligand tris-[2-(3-mesityl-imidazole-2-ylidene)-methyl]amine (TIMMNMes) was utilized to synthesize and compare two series of mid- to high-valent iron alkyl imido complexes, including a reactive Fe(V) adamantyl imido intermediate en route to an isolable Fe(V) nitrido complex. The chemistry toward the iron adamantyl imides was achieved by reacting the Fe(I) precursor [(TIMMNMes)FeI(N2)]+ (1) with 1-adamantyl azide to yield the corresponding trivalent iron imide. Stepwise chemical reduction and oxidation lead to the isostructural series of low-spin [(TIMMNMes)Fe(NAd)]0,1+,2+,3+ (2Ad-5Ad) in oxidation states II to V. The Fe(V) imide [(TIMMNMes)Fe(NAd)]3+ (5Ad) is unstable under ambient conditions and converts to the air-stable nitride [(TIMMNMes)FeV(N)]2+ (6) via N-C bond cleavage. The stability of the pentavalent imide can be increased by derivatizing the nitride [(TIMMNMes)FeIV(N)]+ (7) with an ethyl group using the triethyloxonium salt Et3OPF6. This gives access to the analogous series of ethyl imides [(TIMMNMes)Fe(NEt)]0,1+,2+,3+ (2Et-5Et), including the stable Fe(V) ethyl imide. Iron imido complexes exist in a manifold of different electronic structures, ultimately controlling their diverse reactivities. Accordingly, these complexes were characterized by single-crystal X-ray diffraction analyses, SQUID magnetization, and electrochemical methods, as well as 57Fe Mössbauer, IR vibrational, UV/vis electronic absorption, multinuclear NMR, X-band EPR, and X-ray absorption spectroscopy. Our studies are complemented with quantum chemical calculations, thus providing further insight into the electronic structures of all complexes.