One Stone, Three Birds: Design and Synthesis of "All-in-One" Nanoscale Mn-Porphyrin Coordination Polymers for Magnetic Resonance Imaging-Guided Synergistic Photodynamic-Sonodynamic Therapy.

Multifunctional nanomaterials with potential applications in both bioimaging and photodynamic-sonodynamic therapy have great advantages in cancer theranostic, but the design and preparation of "all-in-one" type of multifunctional nanomaterials with single component remains challenging. Herein the "all-in-one" type of Mn-PpIX (Protoporphyrin IX) coordination polymers (MnPPs) was reported as efficient nano-photo/sonosensitizers. The MnPPs had an average size of âˆ¼ 110 nm. Upon light/US (ultrasound) irradiation for 5 min, 61.8 % (light) and 32.4 % (US) of DPBF (1.3-diphenyl isobenzofuran) was found to be oxidized by MnPPs, which showed effective ROS (reactive oxygen species) generation for photodynamic/sonodynamic therapy (PDT/SDT). In addition, MnPPs revealed excellent biosafety and could be engulfed by cells to produce intracellular ROS under light/US excitation for efficient killing tumor cells. When MnPPs was injected into mice, the tumor could be monitored via MRI (magnetic resonance imaging). In addition, tumor growth could be significantly inhibited by the synergistic PDT-SDT. Therefore, the present study not only represents MnPPs as an "all-in-one" type of multifunctional nanomaterials for MRI-guided PDT-SDT therapy, but also provides some insights for designing other PpIX-related molecules with the similar structure for bioapplication.

From biomaterials to biotherapy: cuttlefish ink with protoporphyrin IX nanoconjugates for synergistic sonodynamic-photothermal therapy.

Biologically produced nanomaterials capable of therapeutic purposes have received increasing interest in tumor therapy because of their intrinsic biocompatibility. In this study, we made cuttlefish ink (extracted from cuttlefish) and protoporphyrin IX (PpIX) nanoconjugates (CIPs) where PpIX was an endogenous organic compound. In the case of CIPs, PpIX could be triggered by ultrasound (US) for sonodynamic therapy (SDT), and the cuttlefish ink could be excited by a near-infrared laser for photothermal therapy (PTT). Thereafter, tumor growth was greatly inhibited through synergistic SDT-PTT in comparison to single SDT or PTT. In addition, in vivo administration of CIPs showed no noticeable side effects for mouse blood and chief organs, providing an effective strategy for developing biologically produced biomaterials and using them for biotherapy.

Design of Stimuli-Responsive Phenothiazine Derivatives with Triplet-Related Dual Emission and High-Contrast Mechanochromism Guided by Polymorph Prediction.

The development of high-contrast stimulus-responsive materials with excited triplet emission is of great significance for anti-counterfeiting, sensor and memory applications, but remains a challenge. Here, we report a strategy for the rational design of stimulus-responsive phenothiazine derivatives with triplet-related dual emissions and high-contrast mechanochromism guided by Polymorph Prediction. The designed phenothiazine derivatives have the characters of simple structures, a facile synthetic procedure, and a good crystalline nature. We found that the crystals of those derivatives with the potential to form both quasi-axial (ax) and quasi-equatorial (eq) conformations could undergo conformation transition and show significant emission difference (Δλem >100 nm) under mechanical force. Meanwhile, all these phenothiazine derivatives exhibit aggregation-induced emission and emit room-temperature phosphorescence or thermally activated delayed fluorescence. The significant luminescent change of these materials under different stimuli gives them promise for applications in encryption and anti-counterfeiting.

Ratiometric fluorescence chemodosimeter for hydrazine in aqueous solution and gas phase based on Quinoline-Malononitrile.

The widespread use of Hydrazine (N2H4) in many areas of the chemical industry, brings potential risks to human health and environmental pollution. To detect N2H4 effectively, a simple ratio fluorescence probe (QMM), designed and synthesized through Vilsmeier reaction and Knoevenagel reaction, was prepared for the specific response of N2H4 based on the irreversible chemical reaction. The ratiometric fluorescence chemodosimeter displayed a response for hydrazine with high selectivity, sensitivity and anti-interference ability. The measured detection limit is 38.30 nm (0.122 ppb), which is far lower than the maximum allowable level of the U.S. Environmental Protection Agency (10 ppb). Moreover, test paper and TLC plates loading QMM had been made, which could be utilized to detect hydrazine both in aqueous solution samples and in gas phase samples. Thus QMM could serve as an easily manufactured, low-cost, efficient and portable solid-state optical probe to detect hydrazine in field measurements.

High-contrast colourimetric probes for fluoride and trace water based on tautomerization of naphthalimide and application in fingerprint imaging.

Three probes for fluoride ion and trace water based on naphthalimide were designed and synthesized. A new sensing mechanism based on naphthalimide tautomerization induced by fluoride ion and water was explored in the aprotic organic solvent. In the fluoride ion sensing process, the probes exhibited a remarkable absorption peak centred at 560 nm in the visible range of 400-700 nm. When trace water presented, the newly formed absorption peak centred at 560 nm gradually disappeared. The sensitive colour variation of the probe also was used in fingerprint imaging. Accordingly, the significant changes in chemical shift of dept135 and 1HNMR spectrum confirmed the structural transformation of the probes with high contrast. Furthermore, this work also presented an optimization strategy for the sensitivity of the probe based on regulatory tautomerization.

Retinal-based polyene fluorescent probe for selectively detection of Cu2+ in physiological saline and serum.

Retinal is a flexible natural chromophore and widely present in organisms. The slender conjugated polyene structure retinal is conducive to entering protein structure. In this work, a novel turn-on fluorescent probe for Cu2+ based on retinal and phenylenediamine was designed and synthesized. The probe achieved recognition of copper ions in human serum complex protein environment. Furthermore, the high sensitivity, selectivity for Cu2+ and the sensing mechanism was also investigated.

Aggregation-induced emission enhancement (AIEE)-active boron-difluoride dyes with reversible mechanochromic fluorescence.

A novel class of solid-emissive boron-difluoride derivatives, using phenanthrenequinone hydrazone as ligands, were designed and efficiently synthesized. These dyes exhibit weak fluorescence in dilute solutions, but much higher fluorescence efficiency in aggregate states with a large stokes shift (over 70 nm) due to the their aggregation-induced emission enhancement (AIEE) characteristics. According to their photophysical properties and X-ray single crystal structure analysis, the AIEE was ascribed to the H(J)-aggregate formation aided by multiple intermolecular interactions to restrict intramolecular motion in the solid state. Moreover, their solid emissions could be reversibly tuned between "on" and "off" by mechanical grinding and recrystallization, due to the stacking model transition between H(J)-aggregation with loose molecular packing and J-aggregation with intense intermolecular interactions.

Cyclodextrin-Assisted Two-Component Sonogel for Visual Humidity Sensing.

In this work, two naphthalimide-based compounds, 1a and 1b, have been designed and synthesized. Both compounds can form stable two-component gels in n-propanol or n-butanol upon addition of α-cyclodextrin (α-CD) followed by sonication at room temperature. Interestingly, the 1a/α-CD gel is thixotropic and very sensitive to water. Addition of a small amount of water induces rapid gel collapse, allowing further development of the gel as a visual relative humidity sensor. Specificity of the sensor has been confirmed using several approaches, such as scanning electron microscopy and fluorescence, Fourier transform infrared, and 1H NMR spectroscopy experiments. The results show that α-CD acts as a junction for the assembly of 1a or 1b through hydrogen bonding between hydroxyl and amide groups. Upon addition of water, α-CD interacts with the adamantane group of 1a via an incomplete host-guest encapsulation, resulting in the dissociation of the hydrogen-bonding-assisted two-component assembly, accompanied by gel collapse.

Multicolor imaging of hydrogen peroxide level in living and apoptotic cells by a single fluorescent probe.

To understand the entangled relationship between reactive oxygen species (ROS) and apoptosis, there is urgent need for simultaneous dynamic monitoring of these two important biological events. In this study, we have developed a fluorescent probe, pep4-NP1, which can simultaneously detect H2O2 and caspase 3, the respective markers of ROS and apoptosis. The probe contains a H2O2 fluorescence reporter (NP1) and Cy5 fluorescent chromophore connected by a caspase 3 specific recognition peptide. The detecting strategy was realized through a controllable fluorescence resonance energy transfer (FRET) process between NP1 and Cy5 of pep4-NP1, after reaction with H2O2, which was verified by molecular calculation and in vitro spectral studies. In the absent of caspase 3, the accumulation of H2O2 induces red fluorescence of pep4-NP1 centered at 663nm in living cells due to the existence of FRET. In contrast, FRET is inhibited in apoptotic cells due to cleavage of the peptide spacer of pep4-NP1 by over-expressed caspase 3. Consequently, green fluorescence (555nm) predominated when labelling production of H2O2 in apoptotic cells. Moreover, Pep4-NP1 shows excellent selectivity towards H2O2 and caspase 3 on their respective reaction sites. Therefore, pep4-NP1 can distinguish endogenously generated H2O2 between living cells and apoptotic cells with different fluorescence wavelengths, providing additional information on the ROS production pathways.

Highly Fluorescent Non-Conventional Boron-Difluoride-Based π Organogel with Gelation-Assisted Piezochromism.

Triphenylamine-functionalized boron 2-(2'-pyridyl)imidazole complex bearing no alkyl chains or H-bond unit was found to be able to gelate a series of solvents, and the balanced intermolecular π-π interactions play an important role in its supramolecular self-assembly. The gelator molecule is piezochromic, and the dried gel responded to pressure more sensitively than regular crystalline powder.

A spiropyran-based fluorescent probe for the specific detection of ß-amyloid peptide oligomers in Alzheimer's disease.

We report a new spiropyran-based fluorescent probe that exhibits high affinity and specificity towards Aß oligomers both in vitro and in vivo. This probe can penetrate the blood brain barrier and specifically target Aß oligomers in the brains of transgenic mice in models for Alzheimer's disease.

White light emission from a two-component hybrid gel via an energy transfer process.

A two-component light-harvesting organogel containing a naphthalimide-based gelator (1) as a donor and a phosphorescent Ir(III) complex [Ir(bt)2(acac)] (bt = 2-phenylbenzothiazole and acac = acetylacetone) (Ir) as an acceptor was used to produce white-light-emitting organogels. The addition of complex Ir to the gel 1 had a certain effect on the self-assembly behaviour of molecule 1, but did not affect the gelation ability, mechanical strength and structure surface wettability of the gel. The optical properties of the two-component gel 1-Ir could be tuned via high intermolecular energy transfer efficiency between 1 and complex Ir, which was confirmed by geometry optimizations and harmonic vibrational analyses. The white-light-emitting organogel was obtained with the molar ratio of complex Ir in the range of 0.3-1.0. In particular, the gel 1-Ir with the addition of 0.5 equivalent of Ir could emit white-light with the Commission Internationale de L' eclairage (CIE) coordinates of 0.33 and 0.31 under the excitation of 374 nm light.

Tunable and Switchable Control of Luminescence through Multiple Physical Stimulations in Aggregation-Based Monocomponent Systems.

This report describes how the luminescence of naphthalimide could be tuned by various physical stimuli, including heat, sonication, and grinding. Herein, instant and switchable control of color and fluorescent emissions has been achieved by the sonication-triggered gelation of an organic liquid with naphthalimide-based organogelators (N3-N7). Green emissive suspensions of the gelators in organic liquids are transformed into orange emissive gels upon brief irradiation with ultrasound with an emission wavelength red-shift of approximately 60 nm and fluorescence intensity quenching by a factor of 20, which can subsequently be reversed by heating. When sonication-triggered S-gels are evaporated to S-xerogels, the solid state xerogels (N3, N4, N6, N7) exhibit mechanochromism, the color of which changes from red to yellow and the emission color of which changes from orange to green with enhanced intensity by grinding. This mechanochromic property can be reversed through a regelation process. The mechanochromic character of the S-xerogel of N3 is thus applied to quantitatively sense the mechanical pressure range from 2 to 40 MPa through fluorescence changes, reflecting a new type of application for gelation assembly. The physical stimuli triggered fluorescence changes of these compounds strongly depend on the molecular structure and solvent. The results demonstrate that the different aggregation modes and long-range order arrangement of the molecules regulated by the stimulus may affect the internal charge transfer (ICT) process of the naphthalimide groups, resulting in the tunability of the photophysical properties of the gelators. This report provides a new strategy for tunable and switchable control of luminescence through nonchemical stimuli in aggregation-based monocomponent systems.

Photoisomerization-induced morphology and transparency transition in an azobenzene based two-component organogel system.

A two-component gel containing long chain alkylated gallic acid (GA) and photochromic phenazopyridine (PAP) was prepared. The gel was thoroughly characterized by UV-visible and IR spectra, SEM and POM images, XRD diffraction and dynamic oscillatory measurements. The structure and transparency of the two-component gel can be reversibly changed by alternative UV light irradiation and warming in the palm of the hand. This kind of soft material has potential application in upscale surface functional materials.

Visual Recognition of Aliphatic and Aromatic Amines Using a Fluorescent Gel: Application of a Sonication-Triggered Organogel.

A naphthalimide-based fluorescent gelator (N1) containing an alkenyl group has been designed and characterized. This material is able to gelate alcohols via a precipitate-to-gel transformation when triggered with ultrasound for less than 2 min (S-gel). The gelation process in n-propanol was studied by means of absorption, fluorescence, and IR spectra, scanning electron microscopy (SEM) images, and X-ray diffraction patterns. The fluorescence intensity of N1 decreased during the gelation process in a linear relationship with the sonication time. The S-gel of N1 could be used to sense aliphatic and aromatic amines by measuring the change in the signal output. For example, the addition of propylamine to the S-gel of N1 resulted in a dramatic enhancement of the fluorescence intensity, accompanied by a gel-to-sol transition. On the contrary, when the S-gel of N1 was treated with aromatic amines such as aniline, fluorescence was quenched and there was no gel collapse. The sensing mechanisms were studied by (1)H NMR, small-angle X-ray scattering, SEM and spectroscopic experiments. It is proposed that isomerization of the alkenyl group of N1 from the trans to cis form occurs when the S-gel is treated with propylamine, resulting in a gel-sol transition. However, the aromatic aniline molecules prefer to insert into the gel networks of N1 via hydrogen-bonding and charge-transfer interactions, maintaining the gel state. As potential applications, testing strips of N1 were prepared to detect aniline.

CB[8] gated photochromism of a diarylethene derivative containing thiazole orange groups.

Photochromism in a diarylethene derivative (1O) can be gated by a host-guest interaction where the thiazole orange groups are bound into the hydrophobic cavity of CB[8] in water. The closed-ring isomer (1C), which cannot be obtained freely in aqueous solution, survives even when the complex is dissociated by displacement from CB[8] by competition with 1-adamantanamine hydrochloride.

Sugar based nanotube assembly for the construction of sonication triggered hydrogel: an application of the entrapment of tetracycline hydrochloride.

A sugar functionalized naphthalimide derivative (H1) self-assembles into supramolecular nanotubes (25 nm pore diameter) by the reaction of 4-N-ethylaminenaphthalimide-N-propinyl and delta-gluconolactone in refluxed ethanol. The suspension of the tube assembly in water can directly form hydrogels when triggered by sonication, without change in morphology or molecular aggregates in the pH range of 5-8. Modified with aminocarproic acid, H2 with more hydrogen bonding sites can form pH tolerant hydrogels in the widest range of pH values from 1-14 accelerated by sonication. The gelation mechanism was studied in detail. To the best of our knowledge, this is the first paradigm wherein hydrogels were constructed from naphthalimide derivatives. Finally, the potential of the hydrogel as a drug delivery and release system for hydrophilic medicine was explored.

Diarylethene based fluorescent switchable probes for the detection of amyloid-ß pathology in Alzheimer's disease.

Two fluorescent switchable diarylethene derivatives which exhibit high affinity for amyloid-ß aggregates with the increase of fluorescence intensity were reported. Moreover, the probes show excellent photochromic and anti-photobleaching properties both in vitro and in vivo.

Large red-shifted fluorescent emission via intermolecular π-π stacking in 4-ethynyl-1,8-naphthalimide-based supramolecular assemblies.

Two low molecular weight gelators containing 4-ethynyl-1,8-naphthalimide groups with large conjugated structure via different length of alkyl chains were synthesized and fully characterized. The gelation properties, structural character, and fluorescence of the gels were investigated via methods of scanning electron microscopy, X-ray diffraction, and spectral studies. The gelators have high fluorescence quantum yields in both solution and solid state. Interestingly, the wavelength of the fluorescent emission in the reversible sol-gel transition process of the gels has a large red-shift of 80 nm in DMF, which is extremely sparse for 1,8-naphthalimide derivatives in the literature. The intermolecular π-π stacking between naphthalimide is suggested to be the main driving force for the gel formation and fluorescent variation by means of temperature-dependent (1)H NMR study and theoretical calculation.

A highly sensitive ratiometric fluorescent probe for the detection of cytoplasmic and nuclear hydrogen peroxide.

As a marker for oxidative stress and a second messenger in signal transduction, hydrogen peroxide (H2O2) plays an important role in living systems. It is thus critical to monitor the changes in H2O2 in cells and tissues. Here, we developed a highly sensitive and versatile ratiometric H2O2 fluorescent probe (NP1) based on 1,8-naphthalimide and boric acid ester. In response to H2O2, the ratio of its fluorescent intensities at 555 and 403 nm changed 1020-fold within 200 min. The detecting limit of NP1 toward H2O2 is estimated as 0.17 µM. It was capable of imaging endogenous H2O2 generated in live RAW 264.7 macrophages as a cellular inflammation response, and especially, it was able to detect H2O2 produced as a signaling molecule in A431 human epidermoid carcinoma cells through stimulation by epidermal growth factor. This probe contains an azide group and thus has the potential to be linked to various molecules via the click reaction. After binding to a Nuclear Localization Signal peptide, the peptide-based combination probe (pep-NP1) was successfully targeted to nuclei and was capable of ratiometrically detecting nuclear H2O2 in living cells. These results indicated that NP1 was a highly sensitive ratiometric H2O2 dye with promising biological applications.