Band Gap Engineering in Solvochromic 2D Covalent Organic Framework Photocatalysts for Visible Light-Driven Enhanced Solar Fuel Production from Carbon Dioxide.

Solar light-driven fuel production from carbon dioxide using organic photocatalysts is a promising technique for sustainable energy sources. Band gap engineering in sustainable organic photocatalysts for improving efficiency and fulfilling the requirements is highly anticipated. Here, we present a new strategy to engineer the band gap in covalent organic framework (COF) photocatalysts by varying the push-pull electronic effect. To implement this strategy, we have designed and synthesized four different COFs using a tripodal amine 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(([1,1'-biphenyl]-4-amine)) [Ttba] with 1,3,5-triformylbenzene (COF-1), 2,4,6-triformylphloroglucinol (COF-2), 2,4,6-triformylphenol (COF-3), and 2,4,6-triformylresorcinol (COF-4). On varying the number of hydroxyl units in the aldehyde precursor, the resulting COFs allow the fine-tuning of their band gap and band edge positions and result in different morphologies with varying surface areas. The enhanced optical properties of COF-3 and COF-4 with very suitable band gaps of 2.02 and 1.95 eV, respectively, enable them to demonstrate a high-efficiency photobiocatalytic system for NADH photoregeneration and enhanced visible light-driven formic acid production at a rate of 226.3 µmol g-1 in 90 min. The triazine core enables efficient charge separation, while the hydroxyl groups induce an electronic push-pull effect, regulating their photocatalytic efficiency. The results demonstrated the morphology-guided enhanced surface area and dual keto-enol tautomerism-induced push-pull effect in asymmetrical charge distribution as key features in the fine-tuning of the photocatalysts.

Didactic approach recounting advances and limitations in novel glutathione and cysteine detection (reduced GSH probe) with mixed coumarin, aldehyde, and phenyl-selenium chemistry.

We describe the pertinent research steps and analysis, many of which are chemical, to achieve a novel molecular probe for glutathione (GSH) which has been published and patented based on two recent articles: "Exceptional time response, stability and selectivity in doubly-activated phenyl selenium-based glutathione-selective platform" and "Enhanced Doubly Activated Dual Emission Fluorescent Probes for Selective Imaging of Glutathione or Cysteine in Living Systems" (Kim et al., 2015; Mulay et al., 2018). The papers involve coumarin probes. Reaction/detection unfolds with aminothiol attack at an electrophilic ring carbon position. An adjacent -CHO group is heavily involved in resonance aspects of the C-Se position, as well as the binding of the pendant N-group; the coumarin lactone carbonyl also allows for resonance to be achieved (vide infra). The leaving group, -SePh, while precedented in some systems, depends on electronic tuning (Fig. 1). For 1, the response times with GSH was ~100ms; a 100-fold fluorescence increase is observed (Compound 1). The probe also reacts with cysteine (Cys) and homocysteine (Hcy), albeit differently. For glutathione probing, the greater wavelength maxima (1: 550nm, DACP-1: 555nm, DACP-2: 590nm) enabled eventual cell studies (confocal microscopy) and animal studies. The limits of detection (LOD, 1: 270nM DACP-1: 10.1nM DACP-2: 17.0nM), as measured using the 3σ/k method. We provide a didactic presentation from probe conception to probe in vivo testing, etc., with additional considerations presented; a variety of factors/issues (2.1-2.28) help maintain a realistic sequence, a flow from wider to narrower, of the factors that go into developing medical, biological and neurodegenerative disease-related probes, meant to help other researchers follow our intention, gain perspective, and overcome current limitations.

Imaging of Hypochlorous Acid by Fluorescence and Applications in Biological Systems.

In recent decades, HOCl research has attracted a lot of scientists from around the world. This chemical species is well known as an important player in the biological systems of eukaryotic organisms including humans. In the human body, HOCl is produced by the myeloperoxidase enzyme from superoxide in very low concentrations (20 to 400 µm); this species is secreted by neutrophils and monocytes to help fight pathogens. However, in the condition called "oxidative stress", HOCl has the capability to attack many important biomolecules such as amino acids, proteins, nucleotides, nucleic acids, carbohydrates, and lipids; these reactions could ultimately contribute to a number of diseases such as neurodegenerative diseases (AD, PD, and ALS), cardiovascular diseases, and diabetes. In this review, we discuss recent efforts by scientists to synthesize various fluorophores which are attached to receptors to detect HOCl such as: chalcogen-based oxidation, oxidation of 4-methoxyphenol, oxime/imine, lactone ring opening, and hydrazine. These synthetic molecules, involving rational synthetic pathways, allow us to chemoselectively target HOCl and to study the level of HOCl selectivity through emission responses. Virtually all the reports here deal with well-defined and small synthetic molecular systems. A large number of published compounds have been reported over the past years; this growing field has given scientists new insights regarding the design of the chemosensors. Reversibility, for example is considered important from the stand point of chemosensor reuse within the biological system; facile regenerability using secondary analytes to obtain the initial probe is a very promising avenue. Another aspect which is also important is the energy of the emission wavelength of the sensor; near-infrared (NIR) emission is favorable to prevent autofluorescence and harmful irradiation of tissue; thus, extended applicability of such sensors can be made to the mouse model or animal model to help image internal organs. In this review, we describe several well-known types of receptors that are covalently attached to the fluorophore to detect HOCl. We also discuss the common fluorophores which are used by chemist to detect HOCl, Apart from the chemical aspects, we also discuss the capabilities of the compounds to detect HOCl in living cells as measured through confocal imaging. The growing insight from HOCl probing suggests that there is still much room for improvement regarding the available molecular designs, knowledge of interplay between analytes, biological applicability, biological targeting, and chemical switching, which can also serve to further sensor and theurapeutic agent development alike.

A macrocyclic oligofuran: synthesis, solid state structure and electronic properties.

We report the first π-conjugated macrocyclic system with an oligofuran backbone. The calculated HOMO-LUMO gap is similar to that of the corresponding linear polymer, indicating a remarkable electron delocalization. The X-ray structure reveals a planar conformation, in contrast to the twisted conformation of macrocyclic oligothiophenes. The intermolecular π-π stacking distance is extremely small (3.17 Å), indicating very strong interactions. The macrocycle forms large π-aggregates in solution and shows a tendency toward highly ordered multilayer adsorption at the solid-liquid interface. The face-on orientation of molecules explains the higher hole mobility observed in the out-of-plane direction.

Diels-Alder and Stille Coupling Approach for the Short Protecting-Group-Free Synthesis of Mycophenolic Acid, Its Phenylsulfenyl and Phenylselenyl Analogues, and Reactive Oxygen Species (ROS) Probing Capacity in Water.

A short, protecting-group-free synthesis is achieved. The synthesis is step-efficient and general. A Diels-Alder and Stille cross-coupling approach includes key transformations, allowing for a competitive synthesis which involves a rare halophenol Stille cross-coupling study. The phenylselenyl and phenylsulfenyl analogues were prepared as novel compounds in good overall yield. The applicability of one of the intermediates as a potential probe for reactive oxygen species (ROS) in water is investigated.

Aqueous Red-Emissive Probe for the Selective Fluorescent Detection of Cysteine by Deprotection/Cyclization Cascade Resulting in Large Stokes' Shift.

Cysteine plays a crucial role in cellular functions and in human pathologies. However, the development of cysteine probes with extremely accurate detection is still a key challenge for the field. Herein, we have fully characterized and developed a novel selective fluorescent probe: red emission, aqueous detection and large Stokes' shift for cysteine (Reals-C). Key in the probe synthesis is a Michael addition onto an acroylate group and subsequent intramolecular cyclization. The probe exhibits analyte detection via an intricate role set up by the leaving groups so to discriminate and form the red-emissive analyte sensing platform (λex =471 nm, λem =637 nm) through a chemical cascade pathway. Furthermore, the sensing ability of the probe was demonstrated by both in vitro and in vivo assays. This probe enables for successfully endogenous cysteine sensing in HaCaT human keratinocytes through comparison with a commercial thiol-sensitive probe; Reals-C shows excellent in vivo cysteine detection in a drug-induced animal liver injury model.

Enhanced Doubly Activated Dual Emission Fluorescent Probes for Selective Imaging of Glutathione or Cysteine in Living Systems.

The development of novel fluorescent probes for monitoring the concentration of various biomolecules in living systems has great potential for eventual early diagnosis and disease intervention. Selective detection of competitive species in biological systems is a great challenge for the design and development of fluorescent probes. To improve on the design of fluorescent coumarin-based biothiol sensing technologies, we have developed herein an enhanced dual emission doubly activated system (DACP-1 and the closely related DACP-2) for the selective detection of glutathione (GSH) through the use of one optical channel and the detection of cysteine (Cys) by another channel. A phenylselenium group present at the 4-position completely quenches the fluorescence of the probe via photoinduced electron transfer to give a nonfluorescent species. Probes are selective for glutathione (GSH) in the red region and for cysteine/homocysteine (Cys/Hcy) in the green region. When they were treated with GSH, DACP-1 and DACP-2 showed strong fluorescence enhancement in comparison to that for closely related species such as amino acids, including Cys/Hcy. Fluorescence quantum yields (ΦF) increased for the red channel (<0.001 to 0.52 (DACP-1) and 0.48 (DACP-2)) and green channel (Cys) (<0.001 to 0.030 (DACP-1) and 0.026 (DACP-2)), respectively. Competing fluorescent enhancements upon addition of closely related species were negligible. Fast responses, improved water solubility, and good cell membrane permeability were all properly established with the use of DACP-1 and DACP-2. Live human lung cancer cells and fibroblasts imaged by confocal microscopy, as well as live mice tumor model imaging, confirmed selective detection.

Thiomaleimide Functionalization for Selective Biological Fluorescence Detection of Peroxynitrite as Tested in HeLa and RAW 264.7 Cells.

The role of fluorescent molecules in diagnosis, treatment as well as in biomedical research has great current medicinal significance and is the focus of concentrated effort across the scientific research spectrum. Related research continues to reveal new practical sensing systems that bear enhanced features for interfacing of substituted molecules with biological systems. As part of an effort to better understand chalcogenide systems, a new dithiomaleimide BODIPY (BDP-NGM) probe has been designed, synthesized and characterized. The fluorescence of BDP-NGM was quenched by the incorporation of [3,4-bis(phenylthio)] on the maleimide-4-phenyl moiety which is, in turn, placed at the meso-position of the BODIPY system. The probe shows a turn-on fluorescence response upon reaction with ONOO- ; mass spectral evidence reveals peaks in agreement with products involving oxidation of the sulfur groups to sulfone groups. An about 18.0-fold emission intensity enhancement was found. By comparison, the emission signal from another ROS/RNS, superoxide, gave a modest turn on signal (≈5.0-fold). The reaction is complete within 10 min, judging from the monitoring of the turn-on fluorescence process; the detection limit was found to be 0.4 µm. BDP-NGM can be used for the detection of ONOO- under both acidic and basic conditions. Live cell imaging showed that the current probe can be used for the selective detection of ONOO- in living systems.

Novel intramolecular π-π-interaction in a BODIPY system by oxidation of a single selenium center: geometrical stamping and spectroscopic and spectrometric distinctions.

A new BODIPY system displaying an intramolecular π-π-interaction was synthesized and studied. When the selenium center was oxidized, the substituted phenyl group undergoes π-π stacking with one side of the BODIPY core. The oxidized form showed, not only a down-field shift in the NMR peak, but also splitting due to geometrical changes that arise when going from Cs to C1. The compound was characterized by X-ray diffraction; DFT methods helped elucidate the influence of the unexpected π-π stack and its connection to the photophysical properties imparted by the Se oxidation.

Fluorescent Sensing of a Nerve Agent Simulant with Dual Emission over Wide pH Range in Aqueous Solution.

A new 1,8-naphthalimide-based fluorescent probe for the detection of diethyl cyanophosphonate, a very common nerve agent simulant, is designed, synthesized, and characterized fully. The probe shows around 50-fold enhancement of fluorescence intensity over other nerve agent simulants. Importantly, the probe is able to work under aqueous conditions in a wide pH range. Two reactive groups, the oxime and the phenol, allow a dual emission with different kinetic reactions. The reaction of diethyl cyanophosphonate with the oxime group occurs in advance; the resulting time response of the fluorescence enhancement is observed within approximately 30 s. After the oxime reaction, then phenol also undergoes a substitution reaction with diethyl cyanophosphonate, resulting in a blue emission. The real application of this new probe is demonstrated through the use of silica plate assays for the detection of diethyl cyanophosphonate in both gas and liquid phases through dual emission channels.

Substituent Effects in BODIPY in Live Cell Imaging.

Small-molecule organoselenium-based fluorescent probes possess great capacity in understanding biological processes through the detection of various analytes such as reactive oxygen/nitrogen species (ROS/RNS), biothiols (cysteine, homocysteine and glutathione), lipid droplets, etc. Herein, we present how substituents on the BODIPY system play a significant part in the detection of biologically important analytes for in vitro conditions and live cell imaging studies. The fluorescence of the probe was quenched by 2-chloro and 6-phenyl selenium groups; the probe shows high selectivity with NaOCl among other ROS/RNS, and gives a turn-on response. The maximum fluorescence intensity is attained within ≈1-2 min with a low detection limit (19.6 nm), and shows a ≈110-fold fluorescence enhancement compared to signals generated for other ROS/RNS. Surprisingly, in live cell experiments, the probe specifically located and accumulated in lipid droplets, and showed a fluorescence turn-on response. We believe this turn-on response occurred because of aggregation-induced emission (AIE), which surprisingly occurred only by introducing one lipophilic mesityl group at the meso position of the BODIPY.

Enhanced Fluorescence Turn-on Imaging of Hypochlorous Acid in Living Immune and Cancer Cells.

Two closely related phenyl selenyl based boron-dipyrromethene (BODIPY) turn-on fluorescent probes for the detection of hypochlorous acid (HOCl) were synthesized for studies in chemical biology; emission intensity is modulated by a photoinduced electron-transfer (PET) process. Probe 2 intrinsically shows a negligible background signal; however, after reaction with HOCl, chemical oxidation of selenium forecloses the PET process, which evokes a significant increase in fluorescence intensity. The fluorescence intensity of probes 1 and 2 with HOCl involves an ∼18 and ∼50-fold enhancement compared with the respective responses from other reactive oxygen/nitrogen species (ROS/RNS) and low detection limits (30.9 nm for 1 and 4.5 nm for 2). Both probes show a very fast response with HOCl; emission intensity reached a maximum within 1 s. These probes show high selectivity for HOCl, as confirmed by confocal microscopy imaging when testing with RAW264.7 and MCF-7 cells.

Synthetic studies on actinorhodin and γ-actinorhodin: synthesis of deoxyactinorhodin and deoxy-γ-actinorhodin/crisamicin†A isomer.

A strategy based on bidirectional Dötz benzannulation and the oxa-Pictet-Spengler reaction toward the synthesis of actinorhodin and γ-actinorhodin has been explored. This work has resulted in the synthesis of deoxyactinorhodin and deoxy-γ-actinorhodin. The latter is a regioisomer of crisamicin A (which has 10,10'-dihydroxy groups).

Exceptional time response, stability and selectivity in doubly-activated phenyl selenium-based glutathione-selective platform.

A phenyl-selenium-substituted coumarin probe was synthesized for the purpose of achieving highly selective and extremely rapid detection of glutathione (GSH) over cysteine (Cys)/homocysteine (Hcy) without background fluorescence. The fluorescence intensity of the probe with GSH shows a ∼100-fold fluorescent enhancement compared with the signal generated for other closely related amino acids, including Cys and Hcy. Importantly, the substitution reaction with the sulfhydryl group of GSH at the 4-position of the probe, which is doubly-activated by two carbonyl groups, occurs extremely fast, showing subsecond maximum fluorescence intensity attainment; equilibrium was reached within 100 ms (UV-vis). The probe selectivity for GSH was confirmed in Hep3B cells by confocal microscopy imaging.

A chiron approach to the total synthesis of (-)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin.

A general, efficient, and common strategy for the synthesis of (-)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin is reported here. The strategy involves the synthesis of a key building block alkyne from a cheap chiral pool material, D-glucono-δ-lactone, Dötz benzannulation, oxa-Pictet-Spengler reaction, and H(2)SO(4)-mediated epimerization.

Total synthesis of (+)-demethoxycardinalin 3.

The total synthesis of (+)-demethoxycardinalin 3 is described. The synthetic strategy features the synthesis of dimeric Fischer carbene and its use in a bidirectional Dötz benzannulation reaction to set the dimeric structure of the cardinalins. The oxa-Pictet-Spengler reaction was used to construct the pyran rings. The synthesis is completed in seven steps and an overall yield of 7%.