Dimethyl Dihydrophenazine: A Highly Conjugated Auxochrome in Fluorophores to Improve Photostability, Red-Shift Wavelength, and Enlarge Stokes Shift.

5,10-Dimethyl-5,10-dihydrophenazine (MP) is utilized as an effective auxochrome, leveraging its highly conjugated structure to enhance the photophysical and photochemical properties of fluorophores. As illustrated in the difluoride-boron complex and coumarin fluorophores, the extensive conjugation of MP auxochrome substantially red-shifts the absorption/emission wavelengths and increases Stokes shift due to the intensified intramolecular charge transfer effect; notably, MP auxochrome effectively improves fluorophores' photostability by mitigating photooxidative reactions through enhanced electron density delocalization on nitrogen atoms and increased ionization potential. Importantly, MP-based fluorophores demonstrate applicability in stimulated emission depletion nanomicroscopy, showcasing their utility in lipid droplet labeling.

Tumor Microenvironment-Activatable Phototheranostic: Leveraging Nitric Oxide and Weak Acidity as Dual Biomarkers for Ratiometric Fluorescence, Photoacoustic Imaging, and Photothermal Therapy.

Tumor microenvironment-responsive phototheranostic agents are highly sought after for their ability to improve diagnostic accuracy and treatment specificity. Here, we introduce a novel single-molecule probe, POZ-NO, which is activated by nitric oxide (NO) and weak acidity, enabling dual-mode imaging and photothermal therapy (PTT) of tumors. In acidic environments with elevated NO levels, POZ-NO exhibits a distinctive ratiometric fluorescence signal shift from the red to near-infrared, accompanied by a 700 nm photoacoustic signal. Additionally, POZ-NO demonstrated potent photothermal effects upon NO and acidity activation, achieving an impressive conversion efficiency of 74.3% under 735 nm laser irradiation. In vivo studies confirm POZ-NO's ability to accurately image tumors through ratiometric fluorescence and photoacoustic modes while selectively treating tumors with PTT.

Design, synthesis, and biological application of A-D-A-type boranil fluorescent dyes.

For the first time, three acceptor-donor-acceptor (A-D-A)-type boranil fluorescent dyes, CSU-BF-R (R = H, CH3, and OCH3), featuring phenothiazine as the donor, were designed and synthesized. CSU-BF-R exhibited remarkable photophysical characteristics, including large Stokes shifts (>150 nm), high fluorescence quantum yields (up to 40%), long-wavelength emissions, and strong red solid-state fluorescence. Moreover, these CSU-BF-R fluorescent dyes were demonstrated to function as highly selective and sensitive ratiometric fluorescent probes for detecting hypochlorous acid (HClO). The preliminary biological applications of CSU-BF-OCH3 for sensing intracellular HClO in living cells and zebrafish were demonstrated. Therefore, CSU-BF-R possess the potential to further explore the physiological and pathological functions associated with HClO and provide valuable insights into the design of high-performance A-D-A-type fluorescent dyes.

Catalase-like pleated niobium carbide MXene loaded with polythiophene for oxygenated sonodynamic therapy in solid tumor.

Sonodynamic therapy (SDT), an emerging treatment for solid tumors, has the advantages of deep tissue penetration, non-invasiveness, low side effects, and negligible drug resistance. However, the hypoxic environment of deep solid tumors can discount the efficacy of oxygenated dependent SDT. Here, we synthesized a polythiophene-based sonosensitizer (PT2) and a two-dimensional pleated niobium carbide (Nb2C) Mxene. PT2 was loaded onto the surface of poly(vinylpyrrolidone) (PVP)-coated Nb2C MXene through electrostatic interaction to obtain Nb2C-PVP-PT2 nanosheets (NSs) with a high loading efficiency of 153.7%. Nb2C MXene exhibited catalase-like activity, which could catalyze hydrogen peroxide (H2O2) to produce O2, in turn alleviating tumor hypoxia and enhancing the efficacy of SDT. The depletion of H2O2 further results in abnormal cellular H2O2 levels and reduced tumor cell activity. Moreover, the decomposed NSs led to the release of the sonosensitizer PT2 that can efficiently generate both singlet oxygen and superoxide anions under ultrasound irradiation. These events led to the inhibition of DNA replication of tumor cells, causing tumor cell death, allowing for enhanced SDT efficacy.

Remarkably Selective Binding, Behavior Modification, and Switchable Release of (Bipyridine)3Ru(II) vis-à-vis (Phenanthroline)3Ru(II) by Trimeric Cyclophanes in Water.

A recurring dream of molecular recognition is to create receptors that distinguish between closely related targets with sufficient accuracy, especially in water. The more useful the targets, the more valuable the dream becomes. We now present multianionic trimeric cyclophane receptors with a remarkable ability to bind the iconic (bipyridine)3Ru(II) (with its huge range of applications) while rejecting the nearly equally iconic (phenanthroline)3Ru(II). These receptors not only selectively capture (bipyridine)3Ru(II) but also can be redox-switched to release the guest. 1D- and 2D(ROESY)-NMR spectroscopy, luminescence spectroscopy, and molecular modeling enabled this discovery. This outcome allows the control of these applications, e.g., as a photocatalyst or as a luminescent sensor, by selectively hiding or exposing (bipyridine)3Ru(II). Overall, a 3D nanometric object is selected, picked-up, and dropped-off by a discrete molecular host. The multianionic receptors protect excited states of these metal complexes from phenolate quenchers so that the initial step in photocatalytic phenolate oxidation is retarded by nearly 2 orders of magnitude. This work opens the way for (bipyridine)3Ru(II) to be manipulated in the presence of other functional nano-objects so that many of its applications can be commanded and controlled. We have a cyclophane-based toolkit that can emulate some aspects of proteins that selectively participate in cell signaling and metabolic pathways by changing shape upon environmental commands being received at a location remote from the active site.

Vascular disruption agent and phototherapeutic assembled nanoparticles for enhanced tumor inhibition.

Vascular disruption agent (combretastatin A-4 phosphate) and phototherapeutic (IEICO-4F) assembled nanoparticles (IFC NPs) were prepared for the first time. The IFC NPs have a high photo energy utilization efficiency of up to 96.1%, and could significantly inhibit tumor growth by photodynamic and photothermal therapy enhanced tumor vascular disruption.

A Tool, an App and a Field: Fluorescent PET Sensors, Blood Electrolyte Analysis and Molecular Logic as Products of Supramolecular Photoscience from Northern Ireland and Sri Lanka.

The general tool of fluorescent PET (photoinduced electron transfer) sensors/switches - a molecular design principle with engineering features - is outlined, with the aid of frontier orbital energy diagrams. Fluorophores such as anthracene, 1,3-diaryl-Δ2 -pyrazolines and 4-amino-1,8-naphthalimides are employed within this system, alongside receptors such as amines, carboxylates, crown ethers and amino acids. This tool appealed to a multinational corporation for building a medical analyzer for electrolytes such as Na+ , K+ , Ca2+ and gases like CO2 , which became a commercially successful application. Finally, the tool was a springboard for chemistry to cross into computer science. The field of molecular logic can elucidate how molecules inside us handle information. Molecular examples of the simplest logic gates such as YES, NOT, OR, AND are described. A case of a human-level computation - visual edge detection - is also included.

Multiple molecular logic gate arrays in one system of (2-(2'-pyridyl)imidazole)Ru(ii) complexes and trimeric cyclophanes in water.

Shape-switchable cyclophane hosts allow the controlled capture and release of reactive polypyridineRu(ii) complexes in water. This gives rise to a network of host-guest binding, acid-base reactions in ground and excited states, and chemical redox interconversions. In the case of (2-(2'-pyridyl)imidazole)Ru(ii) complexes, several molecular logic gate arrays of varying complexity emerge as a result. Cyclophane-induced 'off-on' switching of luminescence in neutral solution is found to originate from two features of these aromatic hosts: enhancement of radiative decay by the polarizable host and the suppression of nonradiative decay involving deprotonation by reducing the water content within the deep host cavity. These are examples of nanometric coordination chemistry/physics being controlled by inclusion in an open box. The aromatic units of the macrocycle are also responsible for the shape-switching mechanism of wall collapse/erection.

Recent advances in NIR-II fluorescence based theranostic approaches for glioma.

Gliomas are among the most common malignant tumors in the central nervous system and lead to poor life expectancy. However, the effective treatment of gliomas remains a considerable challenge. The recent development of near infrared (NIR) II (1000-1700 nm) theranostic agents has led to powerful strategies in diagnosis, targeted delivery of drugs, and accurate therapy. Because of the high capacity of NIR-II light in deep tissue penetration, improved spatiotemporal resolution can be achieved to facilitate the in vivo detection of gliomas via fluorescence imaging, and high contrast fluorescence imaging guided surgery can be realized. In addition to the precise imaging of tumors, drug delivery nano-platforms with NIR-II agents also allow the delivery process to be monitored in real-time. In addition, the combination of targeted drug delivery, photodynamic therapy, and photothermal therapy in the NIR region significantly improves the therapeutic effect against gliomas. Thus, this mini-review summarizes the recent developments in NIR-II fluorescence-based theranostic agents for glioma treatment.

Taming Tris(bipyridine)ruthenium(II) and Its Reactions in Water by Capture/Release with Shape-Switchable Symmetry-Matched Cyclophanes.

Electron/proton transfers in water proceeding from ground/excited states are the elementary reactions of chemistry. These reactions of an iconic class of molecules─polypyridineRu(II)─are now controlled by capturing or releasing three of them with hosts that are shape-switchable. Reversible erection or collapse of the host walls allows such switchability. Some reaction rates are suppressed by factors of up to 120 by inclusive binding of the metal complexes. This puts nanometric coordination chemistry in a box that can be open or shut as necessary. Such second-sphere complexation can allow considerable control to be exerted on photocatalysis, electrocatalysis, and luminescent sensing involving polypyridineRu(II) compounds. The capturing states of hosts are symmetry-matched to guests for selective binding and display submicromolar affinities. A perching complex, which is an intermediate state between capturing and releasing states, is also demonstrated.

Fluorescent Molecular Logic Gates Driven by Temperature and by Protons in Solution and on Solid.

Temperature-driven fluorescent NOT logic is demonstrated by exploiting predissociation in a 1,3,5-trisubstituted Δ2 -pyrazoline on its own and when grafted onto silica microparticles. Related Δ2 -pyrazolines become proton-driven YES and NOT logic gates on the basis of fluorescent photoinduced electron transfer (PET) switches. Additional PASS 1 and YES+PASS 1 logic gates on silica are also demonstrated within the same family. Beside these small-molecule systems, a polymeric molecular thermometer based on a benzofurazan-derivatized N-isopropylacrylamide copolymer is attached to silica to produce temperature-driven fluorescent YES logic.

A Colorimetric Method for Quantifying Cis and Trans Alkenes Using an Indicator Displacement Assay.

A colorimetric indicator displacement assay (IDA) amenable to high-throughput experimentation was developed to determine the percentage of cis and trans alkenes. Using 96-well plates two steps are performed: a reaction plate for dihydroxylation of the alkenes followed by an IDA screening plate consisting of an indicator and a boronic acid. The dihydroxylation generates either erythro or threo vicinal diols from cis or trans alkenes, depending upon their syn- or anti-addition mechanisms. Threo diols preferentially associate with the boronic acid due to the creation of more stable boronate esters, thus displacing the indicator to a greater extent. The generality of the protocol was demonstrated using seven sets of cis and trans alkenes. Blind mixtures of cis and trans alkenes were made, resulting in an average error of ±2 % in the percentage of cis or trans alkenes, and implementing E2 and Wittig reactions gave errors of ±3 %. Furthermore, we developed variants of the IDA for which the color may be tuned to optimize the response for the human eye.

Fluorescent molecular logic gates based on photoinduced electron transfer (PET) driven by a combination of atomic and biomolecular inputs.

Molecular AND logic gates 1, 3, 5 and 7, which are designed according to principles of photoinduced electron transfer (PET) switching, respond to co-existing Candida antarctica lipase B and H+ (and Na+).

A Personal Journey across Fluorescent Sensing and Logic Associated with Polymers of Various Kinds.

Our experiences concerning fluorescent molecular sensing and logic devices and their intersections with polymer science are the foci of this brief review. Proton-, metal ion- and polarity-responsive cases of these devices are placed in polymeric micro- or nano-environments, some of which involve phase separation. This leads to mapping of chemical species on the nanoscale. These devices also take advantage of thermal properties of some polymers in water in order to reincarnate themselves as thermometers. When the phase separation leads to particles, the latter can be labelled with identification tags based on molecular logic. Such particles also give rise to reusable sensors, although molecular-scale resolution is sacrificed in the process. Polymeric nano-environments also help to organize rather complex molecular logic systems from their simple components. Overall, our little experiences suggest that researchers in sensing and logic would benefit if they assimilate polymer concepts.

Population analysis to increase the robustness of molecular computational identification and its extension into the near-infrared for substantial numbers of small objects.

The first population analysis is presented for submillimetric polymer beads which are tagged with five multi-valued logic gates, YES, 2YES + PASS 1, YES + PASS 1, YES + 2PASS 1 and PASS 1 with H+ input, 700 nm near-infrared fluorescence output and 615 nm red excitation light as the power supply. The gates carry an azaBODIPY fluorophore and an aliphatic tertiary amine as the H+ receptor where necessary. Each logic tag has essentially identical emission characteristics except for the H+-induced fluorescence enhancement factors which consistently map onto the theoretical predictions, after allowing for bead-to-bead statistical variability for the first time. These enhancement factors are signatures which identify a given bead type within a mixed population when examined with a 'wash and watch' protocol under a fluorescence microscope. This delineates the scope of molecular computational identification (MCID) for encoding objects which are too small for radiofrequency identification (RFID) tagging.

Molecular memory with downstream logic processing exemplified by switchable and self-indicating guest capture and release.

Molecular-logic based computation (MLBC) has grown by accumulating many examples of combinational logic gates and a few sequential variants. In spite of many inspirations being available in biology, there are virtually no examples of MLBC in chemistry where sequential and combinational operations are integrated. Here we report a simple alcohol-ketone redox interconversion which switches a macrocycle between a large or small cavity, with erect aromatic walls which create a deep hydrophobic space or with collapsed walls respectively. Small aromatic guests can be captured or released in an all or none manner upon chemical command. During capture, the fluorescence of the alcohol macrocycle is quenched via fluorescent photoinduced electron transfer switching, meaning that its occupancy state is self-indicated. This represents a chemically-driven RS Flip-Flop, one of whose outputs is fed into an INHIBIT gate. Processing of outputs from memory stores is seen in the injection of packaged neurotransmitters into synaptic clefts for onward neural signalling. Overall, capture-release phenomena from discrete supermolecules now have a Boolean basis.

Consolidating Molecular Logic with New Solid-Bound YES and PASS†1 Gates and Their Combinations.

Proton-driven YES and PASS 1 molecular logic tags based on anthracene and 4-aminonaphthalimide fluorophores, emitting blue and green, respectively, are employed on amino-terminated polyethylene glycol-polystyrene and aminopropyl silica particles. The (YES+PASS 1) logic combination is also a distinguishable tag in both colours. The scope of such tags is delineated.