Synthesis of Functionalized Organosilicon Compounds/Distal Ketones via Ring-Opening Giese Addition of Cycloalkanols under Organophotocatalytic Conditions.

Visible-light-induced organophotocatalyzed ring-opening followed by remote Giese addition of tertiary cycloalkanols with ß-silylmethylene malonates has been developed under mild reaction conditions for the synthesis of organosilicon compounds, bearing a ketone group distally substituted with a silyl group with an additional dialkyl malonate functional handle in moderate to good yields (34-72%). The protocol also worked well with diverse Michael acceptors, such as alkylidene/benzylidene malonates, trifluoro methylidene malonate, benzylidene malononitrile, α-cyano-enone, and α-cyano vinyl sulfone, and delivered desired valuable distally functionalized ketones. To showcase the potential of the method, various synthetic transformations of the obtained product were also demonstrated.

Selective recognition and extraction of iodide from pure water by a tripodal selenoimidazol(ium)-based chalcogen bonding receptor.

A selenium-based tripodal chalcogen bond (ChB) donor TPI-3Se is demonstrated for the recognition and extraction of I- from 100% water medium. NMR and ITC studies with the halides reveal that the ChB donor selectively binds with the large, weakly hydrated I-. Interestingly, I- crystallizes out selectively in the presence of other halides supporting the superiority of the selective recognition of I-. The X-ray structure of the ChB-iodide complex manifests both the µ1 and µ2 coordinated interactions, which is rare in the C-Se···I chalcogen bonding. Furthermore, to validate the selective I- binding potency of TPI-3Se in pure water, comparisons are made with its hydrogen and halogen bond donor analogs. The computational analysis also provides the mode of I- recognition by TPI-3Se. Importantly, this receptor is capable of extracting I- from pure water through selenium sigma-hole and I- interaction with a high degree of efficiency (∼70%).

Pore-Confined π-Chromophoric Tetracene as a Visible Light Harvester toward MOF-Based Photocatalytic CO2 Reduction in Water.

Integrating photoactive π-chromophoric guest molecules inside the MOF nanopore can result in the emergence of light-responsive features, which in turn can be utilized for developing photoactive materials with inherent properties of MOF. Herein, we report the confining of π-chromophoric tetracene (TET) molecules inside the nanospace of postmodified Zr-MOF-808 (Zr-MOF) with MBA molecules (MBA = 2-(5'-methyl-[2,2'-bipyridine]-5-yl)acetic acid) for effectively utilizing its light-harvesting properties toward photocatalytic CO2 reduction. The confinement of the TET molecules as a photosensitizer and the covalent grafting of a catalytically active [Re(MBA)(CO)3Cl] complex, postsynthetically, result in a single integrated catalytic system named Zr-MBA-TET-Re-MOF. Photoreduction of CO2 over Zr-MBA-TET-Re-MOF showed the evolution of 805 µmol g-1 CO with 99.9% selectivity after 10 h of continuous visible light irradiation in water without any additional sacrificial electron donor and having the apparent quantum efficiency of 1.3%. In addition, the catalyst demonstrated an appreciable activity even under direct sunlight irradiation in aqueous medium with a maximum production of 362.7 µmol g-1 CO, thereby mimicking artificial photosynthesis. Moreover, electron transfer from TET to the catalytic center was supported by the formation of photoinduced TET radical cation, as inferred from in situ UV-vis spectra, electron paramagnetic resonance (EPR) analysis, and transient absorption (TA) studies. Additionally, the in situ diffuse reflectance infrared Fourier transform (DRIFT) measurements support that the photoreduction of CO2 to CO proceeds via *COOH intermediate formation. The close proximity of the light-harvesting molecule and catalytic center facilitated facile electron transfer from the photosensitizer to the catalyst during the CO2 reduction.

Modulated Ultrathin NiCo-LDH Nanosheet-Decorated Zr3+-Rich Defective NH2-UiO-66 Nanostructure for Efficient Photocatalytic Hydrogen Evolution.

Defect engineering through modification of their surface linkage is found to be an effective pathway to escalate the solar energy conversion efficiency of metal-organic frameworks (MOFs). Herein, defect engineering using controlled decarboxylation on the NH2-UiO-66 surface and integration of ultrathin NiCo-LDH nanosheets synergizes the hydrogen evolution reaction (HER) under a broad visible light regime. Diversified analytical methods including positron annihilation lifetime spectroscopy were employed to investigate the role of Zr3+-rich defects by analyzing the annihilation characteristics of positrons in NH2-UiO-66, which provides a deep insight into the effects of structural defects on the electronic properties. The progressively tuned photophysical properties of the NiCo-LDH@NH2-UiO-66-D-heterostructured nanocatalyst led to an impressive rate of HER (∼2458 µmol h-1 g-1), with an apparent quantum yield of ∼6.02%. The ultrathin NiCo-LDH nanosheet structure was found to be highly favored toward electrostatic self-assembly in the heterostructure for efficient charge separation. Coordination of Zr3+ on the surface of the NiCo-LDH nanosheet support through NH2-UiO-66 was confirmed by X-ray absorption spectroscopy and electron paramagnetic resonance spectroscopy techniques. Femtosecond transient absorption spectroscopy studies unveiled a photoexcited charge migration process from MOF to NiCo-LDH which favorably occurred on a picosecond time scale to boost the catalytic activity of the composite system. Furthermore, the experimental finding and HER activity are validated by density functional theory studies and evaluation of the free energy pathway which reveals the strong hydrogen binding over the surface and infers the anchoring effect of the ultrathin layered double hydroxide (LDH) in the vicinity of the Zr cluster with a strong host-guest interaction. This work provided a novel insight into efficient photocatalysis via defect engineering at the linker modulation in MOFs.

Design and Synthesis of BODIPY-Hetero[5]helicenes as Heavy-Atom-Free Triplet Photosensitizers for Photodynamic Therapy of Cancer.

Designing heavy-atom-free triplet photosensitizers (PSs) is a challenge for the efficient photodynamic therapy (PDT) of cancer. Helicenes are twisted polycyclic aromatic hydrocarbons (PAHs) with an efficient intersystem crossing (ISC) that is proportional to their twisting angle. But their difficult syntheses and weak absorption profile in the visible spectral region restrict their use as heavy-atom-free triplet PSs for PDT. On the other hand, boron-containing PAHs, BODIPYs are highly recognized for their outstanding optical properties. However, planar BODIPY dyes has low ISC and thus they are not very effective as PDT agents. We have designed and synthesized fused compounds containing both BODIPY and hetero[5]helicene structures to develop red-shifted chromophores with efficient ISC. One of the pyrrole units of the BODIPY core was also replaced by a thiazole unit to further enhance the triplet conversion. All the fused compounds have helical structure, and their twisting angles are also increased by substitutions at the boron centre. The helical structures of the BODIPY-hetero[5]helicenes were confirmed by X-ray crystallography and DFT structure optimization. The designed BODIPY-hetero[5]helicenes showed superior optical properties and high ISC with respect to [5]helicene. Interestingly their ISC efficiencies increase proportionally with their twisting angles. This is the first report on the relationship between the twisting angle and the ISC efficiency in twisted BODIPY-based compounds. Theoretical calculations showed that energy gap of the S1 and T1 states decreases in BODIPY-hetero[5]helicene as compared to planar BODIPY. This enhances the ISC rate in BODIPY-hetero[5]helicene, which is responsible for their high generation of singlet oxygen. Finally, their potential applications as PDT agents were investigated, and one BODIPY-hetero[5]helicene showed efficient cancer cell killing upon photo-exposure. This new design strategy will be very useful for the future development of heavy-atom-free PDT agents.

An Isothiazolanthrone-Based Self-Assembling Anticancer Color-Changing Dye for Concurrent Imaging and Monitoring of Cell Viability.

We report the photophysical properties, self-assembly and biological evaluation of an isothiazolanthrone-based dye, 7-amino-6H-anthra[9,1-cd]isothiazol-6-one (AAT), which reveals anticancer properties and can be potentially used as dye for monitoring cell viability. The solvent-dependent photophysical studies suggest that the emission of AAT is sensitive to environment polarity due to which interesting changes in the colored emission may be observed owing to the charge transfer (CT) processes. AAT also self-assembles to tree-like branched morphologies and produce, a greenish emission inside the cells when imaged after short interval (15 mins) of incubation while a red fluorescence could be noted after 24 h. Interestingly, AAT also produce differential emission inside mouse normal cells as compared to its cancer cell lines since it possess anticancer activity. The experimental observations were also validated theoretically via computational modeling.

Superiority of the Supramolecular Halogen Bond Receptor over Its H-Bond Analogue toward the Efficient Extraction of Perrhenate from Water.

A halogen bond-based water-soluble tetrapodal iodoimidazolium receptor, (L-I)(4Br), exhibited a high degree of efficiency (∼96%) in extracting ReO4- from 100% aqueous medium within a wide range of concentrations and of pH values along with excellent reusability. The solid-state X-ray diffraction study showed the trapping of ReO4- by (L-I)(4Br) via the Re-O····I halogen bonding interaction. XPS studies also suggested the interaction between I and ReO4- through polarization of the electron density of I atoms by ReO4-. (L-I)(4Br) is found to be capable of retaining its high extraction efficiency in the presence of competing anions such as F-, Cl-, I-, SO42-, H2PO4-, CO32-, NO3-, BF4-, ClO4-, Cr2O72-, and a mixture of these anions. Interestingly, (L-I)(4Br) was found to be superior in ReO4- extraction as compared to its hydrogen-bond donor analogue, (L-H)(4Br), as confirmed by a series of control experiments and theoretical calculations. Our synthesized dipodal and tripodal halogen bond donor receptors and their H-analogues validated the superiority of these classes of supramolecular halogen bond donor receptors over their hydrogen-bond analogues. (L-I)(4Br) also showed superior practical applicability in terms of the removal of ReO4- at anion concentrations as low as ∼100 ppm, which was a major shortcoming of (L-H)(4Br).

The discovery of potent small molecule cyclic urea activators of STING.

STING mediates innate immune responses that are triggered by the presence of cytosolic DNA. Activation of STING to boost antigen recognition is a therapeutic modality that is currently being tested in cancer patients using nucleic-acid based macrocyclic STING ligands. We describe here the discovery of 3,4-dihydroquinazolin-2(1H)-one based 6,6-bicyclic heterocyclic agonists of human STING that activate all known human variants of STING with high potency.

Integrated non-volatile plasmonic switches based on phase-change-materials and their application to plasmonic logic circuits.

Integrated photonic devices or circuits that can execute both optical computation and optical data storage are considered as the building blocks for photonic computations beyond the von Neumann architecture. Here, we present non-volatile hybrid electro-optic plasmonic switches as well as novel architectures of non-volatile combinational and sequential logic circuits. The electro-optic switches consist of a plasmonic waveguide having a thin layer of a phase-change-material (PCM). The optical losses in the waveguide are controlled by changing the phase of the PCM from amorphous to crystalline and vice versa. The phase transition process in the PCM can be realized by electrical threshold switching or thermal conduction heating via external electrical heaters or the plasmonic waveguide metal itself as an integrated heater. We have demonstrated that all logic gates, a half adder circuit, as well as sequential circuits can be implemented using the plasmonic switches as the active elements. Moreover, the designs of the plasmonic switches and the logic operations show minimum extinction ratios greater than 20 dB, compact designs, low operating power, and high-speed operations. We combine photonics, plasmonics and electronics on the same platform to design an effective architecture for logic operations.

Natural DNA assisted white light generation and stimuli responsive colour tuning.

The unique structure of a natural nucleic acid, calf thymus DNA, which can provide an appropriate scaffold for an efficient cascaded energy transfer among organic chromophores, has been used for the generation of bright and pure white light on UV light excitation. Two most commonly used DNA stains, 4',6-diamidino-2-phenylindole (DAPI) and ethidium bromide (EB) have been used as a part of the donor-acceptor pairs. We have judiciously selected 10-anthracene-10-yl-3-methylbenzothiazol-3-ium chloride (AnMBTZ), an ultrafast molecular rotor, to act as a bridge between DNA bound DAPI and EB for the cascaded flow of energy. The unique molecular rotor properties of AnMBTZ and its exceptional binding ability with natural DNA help to form a distinct tri-chromophoric system in DNA template which can produce bright and pure white light on UV excitation. Detailed flow of energy from photoexcited DAPI to EB via AnMBTZ has been explored using steady state and time-resolved emission spectroscopy. Further, unique binding nature of AnMBTZ with DNA molecules has been used to modulate the colour of the emission from the present tri-chromophoric system by external stimuli, like salt and temperature. Such unique stimuli responsive multi-chromophoric system in a bio-template has great potential for different lightening applications.

Superiority of a polymeric scavenger over its hexapodal monomer towards efficient ReO4- removal in water.

A new imidazolium functionalized hexapodal polymeric receptor, [PHIm-Br], showed selective and efficient removal (>99%) of perrhenate (ReO4-), from 100% aqueous medium via solid-liquid extraction, which was 13% higher as compared to its monomeric analouge [HIm-Br]. Most importantly, [PHIm-Br] overcomes the drawback of [HIm-Br] in terms of removal of ReO4- at lower anion concentration of ∼100 ppm along with excellent radiation resistivity and reusability within a wide pH range, which implies its potential towards practical applications.

The discovery of potent small molecule activators of human STING.

The adaptor protein STING plays a major role in innate immune sensing of cytosolic nucleic acids, by triggering a robust interferon response. Despite the importance of this protein as a potential therapeutic target for serious unmet medical conditions including cancer and infectious disease there remains a paucity of STING ligands. Starting with a benzothiazinone series of weak STING activators (human EC50 ∼10 µM) we identified several chemotypes with sub-micromolar STING activity across all the major protein polymorphs. An example compound 53 based on an oxindole core structure demonstrated robust on-target functional activation of STING (human EC50 185 nM) in immortalised and primary cells and a cytokine induction fingerprint consistent with STING activation. Our study has identified several related series of potent small molecule human STING activators with potential to be developed as immunomodulatory therapeutics.

G10 is a direct activator of human STING.

The cGAS/STING pathway initiates an innate immune response when DNA is detected in the cytosol. DNA bound cGAS synthesizes cyclic dinucleotides which bind and activate the adaptor STING, leading to downstream secretion of Type I interferons and other pro-inflammatory NFκB pathway cytokines. In the mouse, the STING driven innate immune response is central to immune based clearance of various tumors and this has triggered a significant effort focused on the discovery of human STING agonists for the treatment of cancer. This report uses an in vitro kinase assay to show that G10, a previously identified STING pathway activator is actually a weak but direct STING agonist and identifies other more potent leads.

Selective and efficient removal of perrhenate by an imidazolium based hexapodal receptor in water medium.

This work reports a new cationic imidazolium based hexapodal receptor, [L.6Br], for selective and efficient removal of perrhenate (ReO4-) as [L.6ReO4] from 100% aqueous medium via extraction through precipitation. Selective removal of ReO4- even in the presence of common anions such as halides and oxyanions in excess within a wide range of pH values from 1 to 14 by this receptor is also demonstrated. Importantly, [L.6Br] could easily be recovered upon heating [L.6ReO4] with tetrabutylammonium bromide (TBABr) in acetonitrile at 60 °C and recycled as a fresh extractant for ReO4-.

SOX2Mediates Carbon Nanotube-Induced Fibrogenesis and Fibroblast Stem Cell Acquisition.

Certain nanosized particles like carbon nanotubes (CNTs) are known to induce pulmonary fibrosis, but the underlying mechanisms are unclear, and efforts to prevent this disease are lacking. Fibroblast-associated stem cells (FSCs) have been suggested as a critical driver of fibrosis induced by CNTs by serving as a renewable source of extracellular matrix-producing cells; however, a detailed understanding of this process remains obscure. Here, we demonstrated that single-walled CNTs induced FSC acquisition and fibrogenic responses in primary human lung fibroblasts. This was indicated by increased expression of stem cell markers (e.g., CD44 and ABCG2) and fibrogenic markers (e.g., collagen and α-SMA) in CNT-exposed cells. These cells also showed increased sphere formation, anoikis resistance, and aldehyde dehydrogenase (ALDH) activities, which are characteristics of stem cells. Mechanistic studies revealed sex-determining region Y-box 2 (SOX2), a self-renewal associated transcription factor, as a key driver of FSC acquisition and fibrogenesis. Upregulation and colocalization of SOX2 and COL1 were found in the fibrotic lung tissues of CNT-exposed mice via oropharyngeal aspiration after 56 days. The knockdown of SOX2 by gene silencing abrogated the fibrogenic and FSC-inducing effects of CNTs. Chromatin immunoprecipitation assays identified SOX2-binding sites on COL1A1 and COL1A2, indicating SOX2 as a transcription factor in collagen synthesis. SOX2 was also found to play a critical role in TGF-ß-induced fibrogenesis through its collagen- and FSC-inducing effects. Since many nanomaterials are known to induce TGF-ß, our findings that SOX2 regulate FSCs and fibrogenesis may have broad implications on the fibrogenic mechanisms and treatment strategies of various nanomaterial-induced fibrotic disorders.

Energy transfer-mediated white light emission from Nile red-doped 9,10-diphenylanthracene nanoaggregates upon excitation with near UV light.

The low cost, ease of preparation, colour tunability and wide application range garnered huge research interest on organic light emitting diode materials (OLED). The development of white light-emitting organic diode materials is mostly targeted for this. Anthracene derivatives have recently emerged as low-cost and efficient blue light-emitting diodes. However, developing efficient organic diode materials that cover the entire visible spectrum is very challenging. Herein, we demonstrated that Nile red (NR)-doped 9,10-diphenylanthracene (DPA) nanoaggregates provided strong white light emission upon excitation with near UV light. The dual emissions of the DPA nanoaggregates covering the blue and green regions were exploited and combined with the controlled red emission of the properly doped NR dye to cover the full visible spectrum, rendering white light emission with a quantum yield of >0.4. The fluorescence spectra of the DPA nanoaggregates doped with NR at various concentrations were monitored and their CIE coordinates were followed to evaluate the proper doping ratio for equal-energy white-light emission. Concurrent time-resolved emission studies provided mechanistic insights into the energy transfer from the exciton and excimer states of DPA to NR. It was revealed that the energy transfer from the singlet excitonic state of DPA followed the diffusion-assisted resonance energy transfer (RET) model. On the other hand, the excimer state showed negligible diffusion and energy transfer from this state found to follow the single-step Förster resonance energy transfer mechanism. The observation of efficient white light emission in the doped DPA nanoaggregates was proposed to have prospective applications in OLED devices, given the fact that triplet excitons may be exploited for emission through the efficient triplet-triplet annihilation contribution to fluorescence enhancement.

Anthryl Benzothiazolium Molecular Rotor-Based Turn-On DNA Probe: Detailed Mechanistic Studies.

An efficient turn-on fluorescence probe for biomolecules not only helps in its sensitive detection but is also useful to understand the different interactions that are operating between biomolecules and probes. Polycyclic aromatic molecules are known to be strong interacting ligand for DNA and extensively studied as a model cancer drug. However, these molecules show large decrease in their emission intensity, i.e., a turn-off probe for DNA. In the present work, we have synthesized a benzothiazole-based anthracene derivative and studied its interaction with a natural DNA with the aim of having a turn-on DNA probe with a polycyclic aromatic moiety. Our detailed spectroscopic studies show that the new probe strongly interacts with DNA molecules and results in a significant increase in its emission yield. Time-resolved studies show a large increase in probe's excited-state lifetime in DNA solution. Detailed experiments have been performed to understand its mode of interaction with DNA molecules. The mode of interaction has also been supported by the blind molecular docking studies. Further, the viscosity-dependent photophysical properties and detailed quantum chemical calculations confirm that the new probe belongs to molecular rotor class of molecules. Association with DNA molecules results in a significant retardation in the nonradiative deactivation process due to the torsional motion in the excited state of the probe and leads to a significant increase in its emission yield. Thus, due its molecular rotor nature, despite with a turn-off fluorophore unit, anthracene, the new probe, acts as a sensitive turn-on fluorescence probe for DNA molecules.

Acquisition of Cancer Stem Cell-like Properties in Human Small Airway Epithelial Cells after a Long-term Exposure to Carbon Nanomaterials.

Cancer stem cells (CSCs) are a key driver of tumor formation and metastasis, but how they are affected by nanomaterials is largely unknown. The present study investigated the effects of different carbon-based nanomaterials (CNMs) on neoplastic and CSC-like transformation of human small airway epithelial cells and determined the underlying mechanisms. Using a physiologically relevant exposure model (long-term/low-dose) with system validation using a human carcinogen, asbestos, we demonstrated that single-walled carbon nanotubes, multi-walled carbon nanotubes, ultrafine carbon black, and crocidolite asbestos induced particle-specific anchorage-independent colony formation, DNA-strand break, and p53 downregulation, indicating genotoxicity and carcinogenic potential of CNMs. The chronic CNM-exposed cells exhibited CSC-like properties as indicated by 3D spheroid formation, anoikis resistance, and CSC markers expression. Mechanistic studies revealed specific self-renewal and epithelial-mesenchymal transition (EMT)-related transcription factors that are involved in the cellular transformation process. Pathway analysis of gene signaling networks supports the role of SOX2 and SNAI1 signaling in CNM-mediated transformation. These findings support the potential carcinogenicity of high aspect ratio CNMs and identified molecular targets and signaling pathways that may contribute to the disease development.

Ultrafast Conformational Relaxation Dynamics in Anthryl-9-benzothiazole: Dynamic Planarization Driven Delocalization and Protonation-Induced Twisting Dynamics.

Conformational motion in the excited state of fluorophores critically governs their photophysical properties. Unveiling controlling parameters of photoinduced molecular motion in organic dyes is essential for optimization of light-triggered processes. Herein, we present ultrafast dynamics of conformational relaxation controlled photophysical properties of anthryl-9-benzthiazole (AnBT). The title compound is a bichromophore, consists of anthracene (AN) and benzothiazole (BT) units connected by a single bond, and exists in out of plane ground state conformation (dihedral angle of about 65?). Vibronic resolved structured absorption feature of anthracene localized excitation is lost in first excited singlet state displaying large Stokes-shifted fluorescence, characteristics of delocalized state involving both AN and BT unit. Ultrafast transient absorption spectroscopic studies revealed evolution of anthracene-localized Franck?Condon state to a delocalized excited state in a few picosecond time scale depending on solvent viscosity. A planarized motion of AN and BT units is proposed to be involved in excited state relaxation. However, protonation of BT unit is shown to induce significant intramolecular charge transfer facilitated by ultrafast torsional relaxation promoting nonradiative deactivation. Thus, depending upon protonation state, AnBT is shown to undergo either ultrafast planarized motion facilitating delocalized emissive excited state or perpendicular torsion rendering nonemissive twisted intramolecular charge transfer state. Experimental results were corroborated by quantum chemical calculation.

Disentangling Time Scales of Vibrational Cooling, Solvation, and Hydrogen Bond Reorganization Dynamics Using Ultrafast Transient Infrared Spectroscopy of Formylperylene.

Unraveling dynamics of solvation and hydrogen bond (H-bond) reorganization between a solute and solvent is crucial to understand the importance of specific and nonspecific interactions in a solution-phase chemical reaction. Ultrafast time-resolved infrared (TRIR) spectroscopy provides direct opportunity to monitor site-specific intermolecular dynamics on a real-time scale by probing vibrational marker bands in the excited state of a solute. Herein, we report the real-time dynamics of vibrational cooling, solvation, and hydrogen bond reorganization of formylperylene (FPe) through TRIR spectroscopy of carbonyl (C═O) stretching mode in nonpolar, polar aprotic, and polar protic solvents. High sensitivity of the C═O stretch frequency (υ̅C═O) to photoinduced intramolecular charge transfer processes induced by specific and nonspecific solvent interactions led us to monitor the dynamics of dipolar solvation, site-specific H-bond formation, and reorganization processes by the TRIR method. In nonpolar cyclohexane, the υ̅C═O stretch band appears at 1610 cm-1 and exhibits negligible spectral shift over several tens of picoseconds. In acetonitrile, the υ̅C═O peak shifts to 1594 cm-1 and exhibits a further temporal red shift of about 5 cm-1 with a characteristic solvation time scale of acetonitrile (τ ∼ 0.5 ps). In methanol, υ̅C═O exhibits two bands corresponding to free and H-bonded FPe in early time scale. The free FPe population converts to the hydrogen-bonded population with a lifetime of about 10 ps. Vibrational cooling (τvc ∼ 12-20 ps) in the excited electronic state of FPe could independently be monitored from the temporal dynamics of the ring vibration mode, which is less sensitive to solvation and hydrogen bonding. The present study provides insight into the specific and nonspecific solvation-controlled charge transfer dynamics in aprotic and protic solvents using FPe as a probe.