Photocycloaddition as a Tool for Modulation of the Lower Critical Solution Temperature in a Molecular π-System to Control Transmission of Solar Radiation.

Diels-Alder photocycloaddition, a well-known textbook reaction, has not been explored in materials chemistry. Herein we describe how this classical photochemistry can be used to modulate the lower critical solution temperature (LCST) of a molecular π-system, which can further be exploited for the controlled transmission of solar radiation for the management of indoor heat and light. An amphiphilic anthracene derivative 9-PA-1 exhibited LCST behavior at 27-32 °C with a reversible transition from a transparent to an opaque phase in water (1-5 mM). Irradiation of a toluene solution of 9-PA-1 with 365 nm light resulted in a [4+2] photocycloadduct 9-PA-2, which exhibited a modulated LCST behavior at 25-27 °C, at a concentration as low as 6 µM. The photocycloaddition of 9-PA-1 was significantly retarded in water, making it a stable candidate for the design of sustainable smart windows. We also demonstrated 100 cm2 smart window prototypes (ΔTlum 82 %, ΔTIR 68 %, ΔTsol 73 %) with more than 1000 cycles of stable operation.

Silicon Shadow Mask Technology for Aligning and In Situ Sorting of Semiconducting SWNTs for Sensitivity Enhancement: A Case Study of NO2 Gas Sensor.

Single-walled carbon nanotubes (SWNTs) are incorporated in different device configurations such as chemiresistors and field-effect transistors (FETs) as a sensing element for the fabrication of highly sensitive and specific biochemical sensors. For this purpose, sorting and aligning of semiconducting SWNTs between the electrodes is advantageous. In this work, a silicon shadow mask fabricated using conventional semiconductor processes and silicon bulk micromachining was used to make metal contacts over SWNTs with a minimum feature of 1 µm gap between the electrodes. The developed silicon shadow mask-based metal contact patterning process is cost-effective and free from photoresist (PR) chemical coatings and thermal processing. After a detailed investigation, sodium dodecyl sulfate (SDS), an anionic surfactant, along with ultrasonication process, was found to be effective for the removal of unclamped and metallic SWNTs, resulting in aligned and clamped semiconducting SWNTs between the electrodes. The presence of aligned semiconducting SWNTs was confirmed using atomic force microscopy (AFM), field emission scanning electron microscopy (FESEM), and Raman spectroscopy techniques. The fabricated devices were tested for nitrogen dioxide (NO2) gas sensing as a test case. The sensitivity enhancement of ∼21 to 76% in the 20-80 ppm NO2 concentration range has been observed in the case of aligned semiconducting SWNT devices compared to the random network SWNT-based sensors.

A new pentacyclic pyrylium fluorescent probe that responds to pH imbalance during apoptosis.

Efficient fluorophores with easy synthetic routes and fast responses are of great importance in clinical diagnostics. Herein, we report a new, rigid pentacyclic pyrylium fluorophore, PS-OMe, synthesised in a single step by a modified Vilsmeier-Haack reaction. Insights into the reaction mechanism facilitated a new reaction protocol for the efficient synthesis of PS-OMe which upon demethylation resulted in a "turn-on" pH sensor, PS-OH. This new fluorescent probe has been successfully used to monitor intracellular acidification at physiological pH. From the fluorescence image analysis, we were able to quantify the intracellular dynamic pH change during apoptosis. This new pH probe is a potential chemical tool for screening, drug discovery and dose determination in cancer therapy.

Enzyme-Driven Switchable Fluorescence-SERS Diagnostic Nanococktail for the Multiplex Detection of Lung Cancer Biomarkers.

Comprehensive profiling of multiple protein targets plays a critical role in deeper understanding of specific disease conditions associated with high heterogeneity and complexity. Herein, we present the design and fabrication of smart programmable nanoarchitectures, which could integrate clinically relevant diagnostic modalities for the multiplexed detection of most prevalent panel of disease biomarkers present in lung cancer. The multiplex nanoprobes were prepared by attaching dual-functional Raman-active fluorogens onto spherical gold nanoparticles through a peptide linker, Phe-Lys-Cys (FKC), which is engineered with a cathepsin B (cathB) enzyme cleavage site. The presence of cathB induces the scission of FKC upon homing into the cancer cells, resulting in the release of the initially latent fluorophores with a concomitant quenching of the surface-enhanced Raman signal intensity, thereby realizing an on-off switching between the fluorescence and Raman modalities. The enzyme-triggered switchable nanoprobes were utilized for the simultaneous detection of pathologically relevant lung cancer targets by tethering with specific antibody units. The multiplex-targeted multicolor coded detection capability of the antitags was successfully developed as a valid protein screening methodology, which can address the unmet challenges in the conventional clinical scenario for the precise and early diagnosis of lung cancer.

Real Time Imaging and Dynamics of Hippocampal Zn2+ under Epileptic Condition Using a Ratiometric Fluorescent Probe.

Zinc, the essential trace element in human body exists either in the bound or free state, for both structural and functional roles. Insights on Zn2+ distribution and its dynamics are essential in view of the fact that Zn2+ dyshomeostasis is a risk factor for epileptic seizures, Alzheimer's disease, depression, etc. Herein, a bipyridine bridged bispyrrole (BP) probe is used for ratiometric imaging and quantification of Zn2+ in hippocampal slices. The green fluorescence emission of BP shifts towards red in the presence of Zn2+. The probe is used to detect and quantify the exogenous and endogenous Zn2+ in glioma cells and hippocampal slices. The dynamics of chelatable zinc ions during epileptic condition is studied in the hippocampal neurons, in vitro wherein the translocation of Zn2+ from presynaptic to postsynaptic neuronal bodies is imaged and ratiometrically quantified. Raman mapping technique is used to confirm the dynamics of Zn2+ under epileptic condition. Finally, the Zn2+ distribution was imaged in vivo in epileptic rats and the total Zn2+ in rat brain was quantified. The results favour the use of BP as an excellent Zn2+ imaging probe in biological system to understand the zinc associated diseases and their management.

A Cyclometalated IrIII Complex as a Lysosome-Targeted Photodynamic Therapeutic Agent for Integrated Imaging and Therapy in Cancer Cells.

Organelle-targeted photosensitizers (PSs) having luminescence properties are potential theranostic agents for simultaneous luminescence imaging and photodynamic therapy. Herein, we report a water-soluble luminescent cyclometalated IrIII complex, Ir-Bp-Ly, as a lysosome-targeted theranostic probe. Ir-Bp-Ly exhibits exceptional photophysical properties, with good triplet-state quantum yield (0.90), singlet oxygen generation quantum yield (0.71 at pH 4), and long lifetime (1.47 µs). Interestingly, Ir-Bp-Ly localizes mostly in lysosomes due to the presence of morpholine units, suggesting its potential use as a lyso-tracker. Ir-Bp-Ly displays a notable PDT effect in C6 glioma cells, efficiently generating reactive oxygen species owing to close proximity between the energy levels of its triplet state and those of molecular oxygen (3 O2 ). The mechanism of cell death has been studied through caspase-3/7 and flow cytometry analyses, which clearly established the apoptotic pathway.

A Ratiometric Near-Infrared Fluorogen for the Real Time Visualization of Intracellular Redox Status during Apoptosis.

Direct monitoring of apoptotic progression is a major step forward for the early assessment of therapeutic efficacy of certain treatments and the accurate evaluation of the spread of a disease. Here, the regulatory role of glutathione (GSH) is explored as a potential biomarker for tracking apoptosis. For this purpose, a near- infrared (NIR) squaraine dye is introduced that is capable of sensing GSH in a ratiometric manner by switching its emission from NIR (690 nm) to visible region (560 nm). The favorable biocompatible attributes of the probe facilitated the real-time monitoring of apoptotic process in line with the conventional apoptotic assay. Furthermore, the robust nature of the probe was utilized for the quantitative estimation of GSH during different stages of apoptosis. Through this study, an easy and reliable method of assaying apoptosis is demonstrated, which can provide valuable insights in translational clinical research.

A protein-dye hybrid system as a narrow range tunable intracellular pH sensor.

Accurate monitoring of pH variations inside cells is important for the early diagnosis of diseases such as cancer. Even though a variety of different pH sensors are available, construction of a custom-made sensor array for measuring minute variations in a narrow biological pH window, using easily available constituents, is a challenge. Here we report two-component hybrid sensors derived from a protein and organic dye nanoparticles whose sensitivity range can be tuned by choosing different ratios of the components, to monitor the minute pH variations in a given system. The dye interacts noncovalently with the protein at lower pH and covalently at higher pH, triggering two distinguishable fluorescent signals at 700 and 480 nm, respectively. The pH sensitivity region of the probe can be tuned for every unit of the pH window resulting in custom-made pH sensors. These narrow range tunable pH sensors have been used to monitor pH variations in HeLa cells using the fluorescence imaging technique.

Supercoiled fibres of self-sorted donor-acceptor stacks: a turn-off/turn-on platform for sensing volatile aromatic compounds.

To ensure the comfortable survival of living organisms, detection of different life threatening volatile organic compounds (VOCs) such as biological metabolites and carcinogenic molecules is of prime importance. Herein, we report the use of supercoiled supramolecular polymeric fibres of self-sorted donor-acceptor molecules as "turn-off/turn-on" fluorescent sensors for the detection of carcinogenic VOCs. For this purpose, a C3-symmetrical donor molecule based on oligo(p-phenylenevinylene), C3OPV, and a perylene bisimide based acceptor molecule, C3PBI, have been synthesized. When these two molecules were mixed together in toluene, in contrast to the usual charge transfer (CT) stacking, supramolecular fibres of self-sorted stacks were formed at the molecular level, primarily driven by their distinct self-assembly pathways. However, CT interaction at the macroscopic level allows these fibres to bundle together to form supercoiled ropes. An interfacial photoinduced electron transfer (PET) process from the donor to the acceptor fibres leads to an initial fluorescence quenching, which could be modulated by exposure to strong donor or acceptor type VOCs to regenerate the respective fluorescence of the individual molecular stacks. Thus, strong donors could regenerate the green fluorescence of C3OPV stacks and strong acceptors could reactivate the red fluorescence of C3PBI stacks. These supercoiled supramolecular ropes of self-sorted donor-acceptor stacks provide a simple tool for the detection of donor- or acceptor-type VOCs of biological relevance, using a "turn-off/turn-on" fluorescence mechanism as demonstrated with o-toluidine, which has been reported as a lung cancer marker.

Fluorescence Imaging Assisted Photodynamic Therapy Using Photosensitizer-Linked Gold Quantum Clusters.

Fluorescence imaging assisted photodynamic therapy (PDT) is a viable two-in-one clinical tool for cancer treatment and follow-up. While the surface plasmon effect of gold nanorods and nanoparticles has been effective for cancer therapy, their emission properties when compared to gold nanoclusters are weak for fluorescence imaging guided PDT. In order to address the above issues, we have synthesized a near-infrared-emitting gold quantum cluster capped with lipoic acid (L-AuC with (Au)18(L)14) based nanoplatform with excellent tumor reduction property by incorporating a tumor-targeting agent (folic acid) and a photosensitizer (protoporphyrin IX), for selective PDT. The synthesized quantum cluster based photosensitizer PFL-AuC showed 80% triplet quantum yield when compared to that of the photosensitizer alone (63%). PFL-AuC having 60 µg (0.136 mM) of protoporphyrin IX was sufficient to kill 50% of the tumor cell population. Effective destruction of tumor cells was evident from the histopathology and fluorescence imaging, which confirm the in vivo PDT efficacy of PFL-AuC.

A fluorescent molecular probe for the identification of zinc and cadmium salts by excited state charge transfer modulation.

A fluorescent probe for the identification of a given metal salt is not known. Herein we present a new fluorescent probe 1 for the identification of different zinc and cadmium salts by exploiting the effect of the charge density of counteranions to perturb the excited state solvatochromic behavior of the probe.

Heteroaromatic donors in donor-acceptor-donor based fluorophores facilitate zinc ion sensing and cell imaging.

The excited state intra molecular charge transfer (ICT) property of fluorophores has been extensively used for the design of fluorescent chemosensors. Herein, we report the synthesis and properties of three donor­π-acceptor­π-donor (D­π-A­π-D) based molecular probes BP, BT and BA. Two heteroaromatic rings, pyrrole (BP), and thiophene (BT) and a non-heteroaromatic ring N-alkoxy aniline (BA) were selected as donor moieties which were linked to a bipyridine binding site through a vinylic linkage. The heteroaromatic systems BP and BT perform selective and ratiometric emission signalling for zinc ions whereas the non-heteroaromatic probe BA does not. The advantages of the D­π-A­π-D design strategy in the design of ICT based probes for the selective fluorescent ratiometric signalling of zinc ions in biological media is discussed. Further, the use of BP, BT and BA for imaging Zn(2+) ions from MCF-7 cell lines is demonstrated.

Reversible transformation between rings and coils in a dynamic hydrogen-bonded self-assembly.

Several proteins, such as tobacco mosaic virus coat protein and the beta protein of the bacteriophage lambda, are known to exhibit unique dynamic self-organization processes involving ring-shaped and extended helical nanostructures triggered by chemical stimuli. However, transformation of rings into coils as observed in biological assemblies has never been realized with synthetic molecular building blocks. Oligo(p-phenylenevinylene) functionalized on one end with barbituric acid and on the other end with aliphatic tails self-organizes in aliphatic solvents to form nanorings through hydrogen-bonding and pi-stacking interactions. Upon an increase in concentration, the nanorings transform into rodlike nanostructures, which are considered to be formed through helically coiled objects consisting of quasi-one-dimensional fibers.