A Sequential Dual‐Lock Strategy for Photoactivatable Chemiluminescent Probes Enabling Bright Duplex Optical Imaging

Chemiluminescence (CL)‐based technologies have revolutionized in vivo monitoring of biomolecules. However, significant technical hurdles have limited the achievement of trigger‐controlled, bright, and enriched CL signal. Herein, a dual‐lock strategy uses sequence‐dependent triggers for bright optical imaging with real‐time fluorescent signal and ultra‐sensitive CL signal. These probes can obtain an analyte‐triggered accumulation of stable pre‐chemiluminophore with aggregation‐induced emission (AIE), and then the pre‐chemiluminophore exhibits a rapid photooxidation process (1,2‐dioxetane generation) by TICT‐based free‐radical addition, thereby achieving an enrichment and bright CL signal. The dual‐lock strategy expands the in vivo toolbox for highly accurate analysis and has for the first time allowed access to accurately sense and trace biomolecules with high‐resolution, dual‐mode of chemo‐fluoro‐luminescence, and three‐dimensional (3D) imaging in living animals.     

Trajectory surface hopping molecular dynamics on Chemiluminescence of cyclic peroxides

Chemiluminescence (CL) of peroxides is one of the most highly sensitive and most useful analytical techniques. Although the mechanisms of CL were studied experimentally and theoretically in the past decades, the chemiexcitation that a ground-state specie being excited from its electronic ground state to yield excited-state products by a chemical reaction is still not completely understood. Direct dynamics simulation on CL reaction which takes into account the full complexity of the relevant potential energy surface characterizes nonadiabatic processes involved in chemiexcitation and could provide access not only to the available reaction channels but also to statistical quantities such as reaction times and quantum yields. In the last decade, the trajectory surface hopping (TSH) molecular dynamics (MD) which is one of the mixed quantum-classical approaches is hence adopted to simulate the nonadiabatic process in CL of cyclic peroxides. In this article, the basic principle of TSH-MD and the successful applications on the CL reactions were shortly review.     

Controlled kinetics of non-enzymatic chemiluminescence reactions for simple imaging of DNA and protein

A robust and sensitive non-enzymatic chemiluminescence (CL) imaging method is presented. In the method a fast-emitting CL reaction is tuned to furnish a slower-emitting reaction suitable for simple CL imaging. Typically, non-enzymatic CL reactions between luminol or fluorescein and oxygen species generated by KCN as catalyst, were rather fast and unsuitable for CL imaging; the speed of the reactions could, however, be reduced substantially by changing KCN for CH(3)CN or benzonitrile. Light emission from the tuned CL reaction was intense and long-lived, and even with a simple arrangement high sensitivity could be achieved. The maximum CL peak was reached after approximately 1.5 min in the presence of 25% acetonitrile, and as little as 16 fmol commercial isoluminol-labeled streptavidin was detected and visualized on either microplate or membrane. The approach was further illustrated by imaging of DNA on a membrane and of antibody on a microplate by use of biotin-streptavidin chemistry. Overall, this simple, economical, and sensitive CL imaging system is expected to be very useful in biochemical analysis, and greatly complements currently used enzyme-based CL imaging methods, especially in routine applications.     

Highly Bright Near-Infrared Chemiluminescent Probes for Cancer Imaging and Laparotomy

Near-infrared (NIR) chemiluminescence imaging holds potential for sensitive imaging of cancer due to its low background; however, few NIR chemiluminophores are available, which share the drawback of low chemiluminescence quantum yields (Φ_CL). Herein, we report the synthesis of NIR chemiluminophores for cancer imaging and laparotomy. Molecular engineering of the electron-withdrawing group at the para-position of the phenol-dioxetane leads to a highly bright NIR chemiluminophore (DPT), showing the Φ_CL (4.6×10⁻² Einstein mol⁻¹) that is 3 to 5-fold higher than existing NIR chemiluminophores. By caging the phenol group of DPT with a cathepsin B (CatB) responsive moiety, an activatable chemiluminescence probe (DPT_CB) is developed for real-time turn-on detection of deeply buried tumor tissues in living mice. Due to its high brightness, DPT_CB permits accurate chemiluminescence-guided laparotomy.     

Electrochemistry and chemiluminescence techniques compared in the detection of NADPH oxidase activity in phagocyte cells

Several methodologies have been used in clinical chemistry for real-time assessment of NADPH oxidase primary product superoxide anion which dismutases to hydrogen peroxide. Among these methodologies, isoluminol chemiluminescence (CL) is considered to be one of the more sensitive and reliable techniques for the assessment of NADPH oxidase activity in neutrophils. The electrochemical technique was recently designed and also applied for real-time detection of NADPH oxidase activity in neutrophils but its reliability and sensitivity has not been investigated so far. In this study, isoluminol CL and electrochemical techniques were investigated and compared by monitoring the generation of superoxide and hydrogen peroxide in both PLB 985 cell line differentiated into neutrophil-like cells and human neutrophils. The electrochemical technique was shown to be as sensitive as that of CL and able to detect the reactive oxygen species (ROS) release of as low as 500 cells. Thus, the electrochemical technique could be used as an alternative to optical techniques for the evaluation of extracellular ROS in phagocyte cells.     

A Sequential Dual-Lock Strategy for Photoactivatable Chemiluminescent Probes Enabling Bright Duplex Optical Imaging

Chemiluminescence (CL)-based technologies have revolutionized in vivo monitoring of biomolecules. However, significant technical hurdles have limited the achievement of trigger-controlled, bright, and enriched CL signal. Herein, a dual-lock strategy uses sequence-dependent triggers for bright optical imaging with real-time fluorescent signal and ultra-sensitive CL signal. These probes can obtain an analyte-triggered accumulation of stable pre-chemiluminophore with aggregation-induced emission (AIE), and then the pre-chemiluminophore exhibits a rapid photooxidation process (1,2-dioxetane generation) by TICT-based free-radical addition, thereby achieving an enrichment and bright CL signal. The dual-lock strategy expands the in vivo toolbox for highly accurate analysis and has for the first time allowed access to accurately sense and trace biomolecules with high-resolution, dual-mode of chemo-fluoro-luminescence, and three-dimensional (3D) imaging in living animals.     

Electrochemically active–inactive switching molecular beacon for direct detection of DNA in homogenous solution

We report a new kind of electrochemical molecular beacon, termed “electrochemically active–inactive switching molecular beacon”, for direct detection of DNA in homogenous solution. The electrochemical molecular beacon consists of a stable stem-loop oligonucleotide carrying two carminic acid moieties (acting as electrochemical reporter) attached at its termini. In a close form, the electrochemical signal is quenched because two carminic acid moieties are close enough to associate into dimer. In the presence of the complementary DNA target, the electrochemical molecular beacon undergoes a conformational transformation from closed (hairpin) to open (linear) structure, which is associated with an increase in electrochemical signal. We found that the electrochemical molecular beacon is as effective as conventional molecular beacon in signaling the presence of complementary target and discriminating targets that differ by a single nucleotide. The proposed electrochemical molecular beacon has a great potential for investigating the interactions of DNA-protein and developing electrochemical real-time polymerase chain reaction.     

Matrix-assisted laser desorption/ionization mass spectrometry imaging of cardiolipins in rat organ sections

Cardiolipin (CL) is a class of phospholipid tightly associated with the mitochondria functions and a prime target of oxidative stress. Peroxidation of CL dissociates its bound cytochrome C, a phenomenon that reflects oxidative stress sustained by the organ and a trigger for the intrinsic apoptotic pathway. However, CL distribution in normal organ tissues has yet to be documented. Fresh rat organs were snap-frozen, cut into cryosections that were subsequently desalted with ammonium acetate solution, and vacuum-dried. CL distribution in situ was determined using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technique on sections sublimed with 2,5-dihydroxybenzoic acid. CL images in rat cardiac ventricular section showed a homogeneous distribution of a single m/z 1447.9 ion species that was confirmed as the (18:2)₄ CL by tandem mass spectrometry. The presence of low abundant (18:2)₃(18:1) CL with the bulk (18:2)₄ CL in quadriceps femoris rendered the muscle CL exhibiting a slightly deviated isotopic pattern from that of cardiac muscle. In rat liver, MALDI-MSI unveiled three CL-containing mass ranges, each with a unique in situ distribution pattern. Co-registration of the CL ion images with its stained liver section image further revealed the association of CLs in each mass range with the functional zones in the liver parenchyma and suggests the participation of in situ CLs with localized hepatic functions such as oxidation, conjugation, and detoxification. The advances in CL imaging offer an approach with molecular accuracy to reveal potentially dysregulated metabolic machineries in acute and chronic diseased states.     

Probing a complex of cytochrome c and cardiolipin by magnetic circular dichroism spectroscopy: implications for the initial events in apoptosis

Oxidation of cardiolipin (CL) by its complex with cytochrome c (cyt c) plays a crucial role in triggering apoptosis. Through a combination of magnetic circular dichroism spectroscopy and potentiometric titrations, we show that both the ferric and ferrous forms of the heme group of a CL:cyt c complex exist as multiple conformers at a physiologically relevant pH of 7.4. For the ferric state, these conformers are His/Lys- and His/OH(-)-ligated. The ferrous state is predominantly high-spin and, most likely, His/-. Interconversion of the ferric and ferrous conformers is described by a single midpoint potential of -80 ± 9 mV vs SHE. These results suggest that CL oxidation in mitochondria could occur by the reaction of molecular oxygen with the ferrous CL:cyt c complex in addition to the well-described reaction of peroxides with the ferric form.     

Bioapplications Manipulated by AIEgens with Nonlinear Optical Effect

The modern medicine requires precise diagnostic techniques while the fluorescent imaging shows great potential in such applications due to its excellent sensitivity and high resolution.However,conducting fluorescent imaging in deep-tissue is not so easy because most luminogens show short-wavelength excitation,which may undergo severe light scattering by the bio-tissue.The marriage of fluorescent imaging with nonlinear optical(NLO)effect can alleviate such adverse effects by utilizing NIR laser to reduce light scattering.On the other hand,scientists are enthusiastic in pursuing luminescent materials,which can match well with NLO application.Aggregation-induced emission(AIE)materials exhibit huge advantages in such aspect not only because of its high luminescent efficiency in aggregate state but also due to its excellent photo-stability(a key factor to meet laser application because of its ultrahigh energy density).Inspired by this,many interesting and meaningful works have sprung up based on AIE luminogens with NLO effect in recent years,and for such reason,it motivates us to summarize them to give a systematic presentation.Here,we first give a brief introduction of the principle of NLO effect.Secondly,the strategies for improving the NLO effect of AIE materials,such as increasing molecular conjugation,introduction of donor-acceptor effect,induction of centrally asymmetric array of AIE molecules in crystals and introduction of intermolecular interactions are clarified.In the final part,we also present the multiple applications of AIEgens with NLO effect in cell imaging,deep-tissue tumor and brain blood vessel imaging and photodynamic therapy.We believe,with this review,the topic will attract more attention from the scientists in multi-science field to accelerate the development of AIE materials in biomedical applications.     

Cathodoluminescence Microscopy and Spectroscopy of Opto-Electronic Materials

Cathodoluminescence (CL) microscopy and spectroscopy are enabling techniques for the microcharacterisation of technologically important materials. Recent advances in SEM instrumentation have considerably expanded the microanalytical capabilities of the CL technique. In this paper, following a brief overview of the principles and practice of CL microscopy and spectroscopy, a number of examples are presented that demonstrate the utility of the technique for the microcharacterisation of advanced opto-electronic materials.     

Peroxidatic activity of metalloporphyrin binding to serum albumin: Enhancement effect of serum albumin on metalloporphyrin catalyzed luminol chemiluminescence reaction

The metalloporphyrin (M-P) catalyzed luminol-H₂O₂ chemiluminescence (CL) system can be significantly enhanced in the presence of serum albumins. The enhancement may be explained in terms of the formation of a molecular complex between M-P and serum albumin. The hydrophobic and coordination interactions between M-P and serum albumin were confirmed by comparing the degree of enhancement by the protein on different types of M-P catalyzed CL reactions and by comparing the catalytic activity of M-P/bovine serum albumin (BSA) and M-P/BSA/anti-BSA complexes. Only the non-ionic M-P catalyzed CL reaction was significantly enhanced, and the enhanced CL reaction was inhibited by an immunoreaction. The optimum conditions of the M-P/albumin complex catalyzed CL reaction were evaluated by using a flow-injection system, which was very similar to that using hemoglobin as the catalyst. A brief prospective on the general applicability of the enhanced CL reaction for the determination of serum albumin (2.5–500 μg/ml) is given.     

EFFECT OF IRON(III) ON CHEMILUMINESCENCE FROM THE NEUTRALIZATION REACTION OF NITRIC ACID and POTASSIUM HYDROXIDE

Low levels (around 90 μM) of iron(III) caused an increase in chemiluminescence (CL) from the neutralization reaction involving nitric acid and potassium hydroxide without use of any luminescent reagent. When oxygen was excluded from the reaction, a significant decrease in the CL emission was observed. This suggests that molecular oxygen present in the solutions may play an important role in the process of the iron-catalyzed CL induced by the neutralization reaction, which liberates a sufficient energy. Other experimental parameters like the influence of several other metal ions, counteranions and acid media were also examined. The results showed that the observed CL enhancement by iron(III) proved to become most remarkable under sporadical conditions alone, and the presence of small amounts (less than 0.20 mM) of sulfate ion increase the catalytic activity of iron(III). A possible mechanism involving transient formation of iron–radical complexes upon neutralization and subsequent reaction of the complexes with molecular oxygen is considered for the present CL reaction.     

Molecular Basis of the Chemiluminescence Mechanism of Luminol

Light emission from luminol is probably one of the most popular chemiluminescence reactions due to its use in forensic science, and has recently displayed promising applications for the treatment of cancer in deep tissues. The mechanism is, however, very complex and distinct possibilities have been proposed. By efficiently combining DFT and CASPT2 methodologies, the chemiluminescence mechanism has been studied in three steps: 1) luminol oxygenation to generate the chemiluminophore, 2) a chemiexcitation step, and 3) generation of the light emitter. The findings demonstrate that the luminol double-deprotonated dianion activates molecular oxygen, diazaquinone is not formed, and the chemiluminophore is formed through the concerted addition of oxygen and concerted elimination of nitrogen. The peroxide bond, in comparison to other isoelectronic chemical functionalities (−NH−NH−, −N⁻−N⁻−, and −S−S−), is found to have the best chemiexcitation efficiency, which allows the oxygenation requirement to be rationalized and establishes general design principles for the chemiluminescence efficiency. Electron transfer from the aniline ring to the OO bond promotes the excitation process to create an excited state that is not the chemiluminescent species. To produce the light emitter, proton transfer between the amino and carbonyl groups must occur; this requires highly localized vibrational energy during chemiexcitation.     

Calixarenes,Macrocycles with (Almost) Unlimited Possibilities

The condensation reaction between p-tert-butylphenol and formaldehyde leads in a single step to good yields of cyclic oligomers in which, depending on the reaction conditions, either four, six, or eight phenol units are joined by methylene bridges. The beakerlike shape of the most stable conformation of the tetramer has led to their being given the name “calixarenes” (calix = chalice). Resorcinol can undergo condensation in a similar manner with a variety of aldehydes to afford cyclic tetramers with the same basic structure (the resorcarenes). In both cases the reaction does not require the use of dilution techniques, so that large quantities of product can be readily obtained. In addition, the parent compounds can be modified in various ways, in particular at the phenolic hydroxy groups or the phenyl residues; these approaches can be used separately or in combination. Calixarenes are thus ideal starting materials for the synthesis of various types of host molecules and can also act as building blocks for the construction of larger molecular systems with defined structures and functions. Their potential applications range from use as highly specific ligands for analytical chemistry, sensor techniques and medical diagnostics to their use in the decontamination of waste water and the construction of artificial enzymes and the synthesis of new materials for non-linear optics or for ultrathin layers and sieve membranes with molecular pores.     

聚ε-己内酯的微米硅球固定化猪胰脂肪酶促合成

本文采用微米硅球固定化猪胰脂肪酶为催化剂合成聚ε-己内酯, 以期获得具有较高分子量、 良好生物相容性和使用安全性的生物可降解医用高分子材料.     

Colloid chemistry of nanocatalysts: a molecular view

Recent advances of a colloidal chemistry can offer great opportunities to fabricate and design nanocatalysts. Comprehensive understanding of a basic concept and theory of the colloidal synthetic chemistry facilitates to engineer elaborate nano-architectures such as bi- or multi-metallic, heterodimers, and core/shell. This colloidal solution technique not only enables to synthesize high surface mesoporous materials, but also provides a versatile tool to incorporate nanoparticles into mesoporous materials or onto substrates. For green chemistry, catalysis research has been pursued to design and fabricate a catalyst system that produces only one desired product (100% selectivity) at high turnover rates to reduce the production of undesirable wastes. Recent studies have shown that several molecular factors such as the surface structures, composition, and oxidation states affect the turnover frequency and reaction selectivity depending on the size, morphology, and composition of metal nanoparticles. Multipath reactions have been utilized to study the reaction selectivity as a function of size and shape of platinum nanoparticles. In the past, catalysts were evaluated and compared with characterizations before and after catalytic reaction. Much progress on in situ surface characterization techniques has permitted real-time monitoring of working catalysts under various conditions and provides molecular information during the reaction.     

飞秒激光烧蚀含能材料的分子动力学模拟

为了得到飞秒激光侵蚀(FLA)1, 3二硝基甲苯(简称DNB,分子式：C₆H₄N₂O₄),六硝基六氮杂异伍兹烷(简称CL20,分子式：C₆H₆N₁₂O₁₂)和CL20/DNB共晶系统的物理和化学响应过程,本文采用ReaxFF/lg反应力场对其过程进行模拟。计算结果表明,CL20/DNB系统的温度和压力在飞秒激光加载过程中出现阶跃,激光加载过程后系统有一个冷却过程,然后系统的温度和压力逐渐升高达到最大值并维持平衡。研究发现,在此过程中CL20和CL20/DNB系统触发反应均为CL20分子中的N―NO₂断裂。CL20系统的分解速率大于CL20/DNB共晶系统,这可能是因为共晶系统在反应初期具有大量的DNB分子以及分解产物中含有比较稳定的苯环减少了CL20及其产物之间的有效碰撞。     

Single and multiplexed immunoassays for the chemiluminescent imaging detection of animal glues in historical paint cross-sections

The characterization of the organic components in a complex, multilayered paint structure is fundamental for studying painting techniques and for authentication and restoration purposes. Proteinaceous materials, such as animal glue, are of particular importance since they are widely used as binders, adhesives and for gilding. Even though proteins are usually detected by chromatographic and proteomic techniques, immunological methods represent an alternative powerful approach to protein analysis thanks to the high specificity of antigen–antibody reactions. Our previous studies demonstrated that ovalbumin and casein could be localized in paint cross-sections with high sensitivity and good spatial resolution (i.e. within the single painting layers) by using chemiluminescent (CL) immunochemical microscope imaging. In the present research work, we describe for the first time the immunolocalization of collagen (the main protein of animal glue) in paint cross-sections by CL imaging microscopy. Two different analytical protocols have been developed, allowing either the detection of collagen or the simultaneous detection of collagen and ovalbumin in the same paint sample. The assays were used to detect collagen and ovalbumin in cross-sections from model samples and historical paintings (a wall painting dated to 1773–1774 and a painted wood panel of the Renaissance period) in order to achieve information on paint techniques and past restoration interventions.

Molecular recognition of mono- and disaccharides through interaction with p-iodophenylboronic acid in capillary electrophoresis with a chemiluminescence detection system

Molecular recognition of mono- and disaccharides was performed making use of the interaction between their diol groups and p-iodophenylboronic acid in capillary electrophoresis (CE) with a chemiluminescence (CL) detection system. p-Iodophenylboronic acid acted as an enhancer for luminol-horseradish peroxidase-hydrogen peroxide CL reaction. p-Iodophenylboronic acid was injected as a sample into the present system to give a CL peak on the electropherogram. The CL intensities were examined using running buffers including mono- and disaccharides. The CL intensities with 1-methyl-D-glucoside, D-saccharose, D-maltose, D-glucose, and D-fructose decreased in this order. The decrease in CL intensity was based on the formation by p-iodophenylboronic acid of cyclic esters with mono- and disaccharides, particularly with those including cis-diol groups. That is, the decrease in CL intensity affected the specific complexation between p-iodophenylboronic acids and saccharides, leading to the molecular recognition of saccharides. We also report separation of a mixture of p-iodophenol and p-iodophenylboronic acid as well as estimation of the apparent binding constant between p-iodophenylboronic acid and saccharides taking advantage of their molecular recognition behavior.