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Transmissible Spongiform Encephalopathies are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP C ) into its pathological isoform (PrP Sc ). Efficient transmission of PrP Sc occurs within the same species, but a species barrier limits interspecies transmission. While PrP structure is largely conserved among mammals, variations at the β2-α2 loop are observed, and even minor changes in the amino acid sequence of the β2-α2 loop can significantly affect transmission efficiency. The present study shows that the introduction of the elk/deer-specific amino acid substitutions at positions 169 (Ser to Asn) and 173 (Asn to Thr) into the mouse prion protein, which are associated with the structural rigidity of the β2-α2 loop, has a substantial impact on protein dynamics as well as on the misfolding pathways of the protein. Native state hydrogen-deuterium exchange studies coupled with mass spectrometry, show that the rigid loop substitutions stabilize not only the β2-α2 loop but also the C-terminal end of α3, suggesting that molecular interactions between these two segments are strengthened. Moreover, the energy difference between the native state and multiple misfolding-prone partially unfolded forms (PUFs) present at equilibrium, is increased. The decreased accessibility of the PUFs from the native state leads to a slowing down of the misfolding of the protein. The results of this study provide important insights into the early events of conformational conversion of prion protein into β-rich oligomers, and add to the evidence that the β2-α2 loop is a key determinant in prion protein aggregation.

Two-dimensional (2D) transition metal dichalcogenides (TMDs) and perovskites hold substantial promise for various optoelectronic applications such as light emission, photodetection, and energy harvesting. However, each of these materials possesses certain limitations that can be overcome by synergistically combining them to form heterostructures, thereby unveiling intriguing optical properties. In this study, we present an uncomplicated technique for crafting a van der Waals (vdW) heterojunction comprising monolayer WS 2 and a Ruddlesden-Popper (RP) perovskite, namely (TEA) 2 PbI 4 . By utilizing ultrafast transient absorption (TA) spectroscopy, we explored the charge carrier dynamics within the WS 2 /(TEA) 2 PbI 4 heterostructure. Our findings uncover a type-II band alignment in the heterostructure, facilitating rapid (within 260 fs) hole transfer from WS 2 to the perovskite and leading to the formation of interlayer excitons (IXs) with a much longer lifetime (728 ps). This strategic approach has the potential to contribute to the development of hybrid systems aimed at achieving high-performance optoelectronic devices.

Nanoparticles usually enter cells through energy-dependent endocytosis that involves their cytosolic entry via biomembrane-coated endosomes. In contrast, direct translocation of nanoparticles with straight access to cytosol/subcellular components without any membrane coating is limited to very selective conditions/approaches. Here we show that nanoparticles can switch from energy-dependent endocytosis to energy-independent direct membrane penetration once an amphiphile is electrostatically bound to their surface. Compared to endocytotic uptake, this direct cell translocation is faster and nanoparticles are distributed inside the cytosol without any lysosomal trafficking. We found that this direct cell translocation option is sensitive to the charges of both the nanoparticles and the amphiphile. We propose that an electrostatically bound amphiphile induces temporary opening of the cell membrane, which allows direct cell translocation of nanoparticles. This approach can be adapted for efficient subcellular targeting of nanoparticles and nanoparticle-based drug delivery application, bypassing the endosomal trapping and lysosomal degradation.

Nucleic acid nanocapsules (NANs) are enzyme-responsive DNA-functionalized micelles built for the controlled release of DNA-surfactant conjugates (DSCs) that present sequences with demonstrated therapeutic potential. Here, we investigate the mechanisms by which DSCs gain access to intracellular space in vitro and determine the effects of serum on the overall uptake and internalization mechanism of NANs. Using pharmacological inhibitors to selectively block certain pathways, we show, through confocal visualization of cellular distribution and flow cytometry quantification of total cellular association, that scavenger receptor-mediated, caveolae-dependent endocytosis is the major cellular uptake pathway of NANs in the presence and absence of serum. Furthermore, as NANs can be triggered to release DSCs by external stimuli such as enzymes, we sought to examine the uptake profile of particles degraded by enzymes prior to cell-based assays. We found that while scavenger receptor-mediated, caveolae-dependent endocytosis is still at play, energy-independent pathways as well as clathrin-mediated endocytosis are also involved. Overall, this study has helped to elucidate early steps in the cytosolic delivery and therapeutic activity of DSCs packaged into a micellular NAN platform while shedding light on the way in which DNA functionalized nanomaterials in general can be trafficked into cells both as nanostructures and as molecular entities. Importantly, our study also shows that the NAN design in particular is able to stabilize nucleic acids when delivered in the presence of serum, a critical step for effective therapeutic nucleic acid delivery.

Utilization of the excess energy of photoexcitation that is otherwise lost as thermal effects can improve the efficiency of next-generation light-harvesting devices. Multiple exciton generation (MEG) in semiconducting materials yields two or more excitons by absorbing a single high-energy photon, which can break the Shockley-Queisser limit for the conversion efficiency of photovoltaic devices. Recently, monolayer transition metal dichalcogenides (TMDs) have emerged as promising light-harvesting materials because of their high absorption coefficient. Here, we report efficient MEGs with low threshold energy and high (86%) efficiency in a van der Waals (vdW) layered material, MoS 2 . Through different experimental approaches, we demonstrate the signature of exciton multiplication and discuss the possible origin of decisive MEG in monolayer MoS 2 . Our results reveal that vdW-layered materials could be a potential candidate for developing mechanically flexible and highly efficient next-generation solar cells and photodetectors.

Perovskite solar cells (PSCs) with superior performance have been recognized as a potential candidate in photovoltaic technologies. However, defects in the active perovskite layer induce nonradiative recombination which restricts the performance and stability of PSCs. The construction of a thiophene-based 2D structure is one of the significant approaches for surface passivation of hybrid PSCs that may combine the benefits of the stability of 2D perovskite with the high performance of three-dimensional (3D) perovskite. Here, a sulfur-rich spacer cation 2-thiopheneethylamine iodide (TEAI) is synthesized as a passivation agent for the construction of a three-dimensional/two-dimensional (3D/2D) perovskite bilayer structure. TEAI-treated PSCs possess a much higher efficiency (20.06%) compared to the 3D perovskite (MA 0.9 FA 0.1 PbI 3 ) devices (17.42%). Time-resolved photoluminescence and femtosecond transient absorption spectroscopy are employed to investigate the effect of surface passivation on the charge carrier dynamics of the 3D perovskite. Additionally, the stability test of TEAI-treated perovskite devices reveals significant improvement in humid (RH ∼ 46%) and thermal stability as the sulfur-based 2D (TEA) 2 PbI 4 material self-assembles on the 3D surface, making the perovskite surface hydrophobic. Our findings provide a reliable approach to improve device stability and performance successively, paving the way for industrialization of PSCs., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Herein, we present a regioselective Pd-catalyzed C-H [4 + 2] benzannulation of N -unprotected 3-arylindoles with external readily available 1,3-dienes via an original sequence involving a Pd-catalyzed domino carbopalladation of 1,3-dienes/direct C 2 -H allylation of an indole ring followed by an oxidation or reduction step. Depending on the nature of the solvent, DCE or CH 3 CN, two consecutive approaches, oxidative or reductive, have been validated and applied to the design of a novel library of C 6 -alkyl or ( E )-C 6 -styryl-benzo[ c ]carbazoles in moderate to good yields.

Nanoparticles are widely used in various biomedical applications as drug delivery carriers, imaging probes, single-molecule tracking/detection probes, artificial chaperones for inhibiting protein aggregation, and photodynamic therapy materials. One key parameter of these applications is the ability of the nanoparticles to enter into the cell cytoplasm, target different subcellular compartments, and control intracellular processes. This is particularly the case because nanoparticles are designed to interact with subcellular components for the required biomedical performance. However, cells are protected from their surroundings by the cell membrane, which exerts strict control over entry of foreign materials. Thus, nanoparticles need to be designed appropriately so that they can readily cross the cell membrane, target subcellular compartments, and control intracellular processes.In the past few decades there have been great advancements in understanding the principles of cellular uptake of foreign materials. In particular, it has been shown that internalization of foreign materials (small molecules, macromolecules, nanoparticles) is size-dependent: endocytotic uptake of materials requires sizes greater than 10 nm, and materials with sizes of 10-100 nm usually enter into cells by energy-dependent endocytosis via biomembrane-coated vesicles. Direct access to the cytosol is limited to very specific conditions, and endosomal escape of material appears to be the most practical approach for intracellular processing.In this Account, we describe how cellular uptake and intracellular processing of nanoscale materials can be controlled by appropriate design of size and surface chemistry. We first describe the cell membrane structure and principles of cellular uptake of foreign materials followed by their subcellular trafficking. Next, we discuss the designed surface chemistry of a 5-50 nm particle that offers preferential lipid-raft/caveolae-mediated endocytosis over clathrin-mediated endocytosis with minimum endosomal/lysosomal trafficking or energy-independent direct cell membrane translocation (without endocytosis) followed by cytosolic delivery without endosomal/lysosomal trafficking. In particular, we emphasize that the zwitterionic-lipophilic surface property of a nanoparticle offers preferential interaction with the lipid raft region of the cell membrane followed by lipid raft uptake, whereas a lower number of affinity biomolecules (<25) on the nanoparticle surface offers caveolae/lipid-raft uptake, while an arginine/guanidinium-terminated surface along with a size of <10 nm offers direct cell membrane translocation. Finally, we discuss how nanoprobes can be designed by adapting these surface chemistry and size preference principles so that they can readily enter into the cell, label different subcellular compartments, and control intracellular processes such as trafficking kinetics, exocytosis, autophagy, amyloid aggregation, and clearance of toxic amyloid aggregates. The Account ends with a Conclusions and Outlook where we discuss a vision for the development of subcellular targeting nanodrugs and imaging nanoprobes by adapting to these surface chemistry principles.

Direct membrane translocation of quantum dot for straight access to cytosol is essential for subcellular targeting and intracellular imaging application. However, cellular entry of the quantum dot usually occurs via endocytosis that is associated with vesicular entrapment followed by trafficking to endosome/lysosome. Thus, quantum dots are not freely available in cytosol that restrict their subcellular targeting/labeling. Recent works show that arginine-terminated nanoparticle of <10 nm size (Au-arginine) can enter into cell via direct membrane translocation and delivers protein into subcellular compartments. Here we report Au-arginine as delivery carrier for direct membrane translocation of quantum dot with the straight access to cytosol. The approach involves simple mixing of the colloidal solutions of quantum dot and Au-arginine followed by incubation with cell. We found that quantum dot forms colloidal assembly after binding with Au-arginine, enter into cell with higher efficiency and faster kinetics, distribute homogeneously in cytosol. It has also been observed that the cell uptake mechanism of quantum dot shifts from energy dependent endocytosis to energy independent nonendocytic processes after the binding with Au-arginine. This approach is independent of cell type and can be adapted for direct cytosolic delivery of wide variety of nanoparticles.

Although the piezoelectric property of a BaTiO 3 nanoparticle is routinely used in energy harvesting application, it can also be exploited for wireless cell stimulation and cell therapy. However, such biomedical application is rare due to limited availability of colloidal BaTiO 3 nanoparticles of <100 nm hydrodynamic size with good piezocatalytic property and efficient biolabeling performance. Here, we report a colloidal form of a piezocatalytic BaTiO 3 -based nanorod of <100 nm hydrodynamic size that can offer wireless cell stimulation. The nanorod is prepared using a TiO 2 nanorod as the template, and the resultant TiO 2 -BaTiO 3 -based composite nanorod is coated with a hydrophilic polymer shell. These nanorods can label cells and, under the ultrasound exposure, produce reactive oxygen species inside cells via piezocatalysis, leading to cell death. These nanorods can be used for wireless modulation of intracellular processes.

Organic lead halide perovskite (OLHP) nanocrystals (NCs) have paved the way to advanced optoelectronic devices through their extraordinary electrical and optical properties. However, understanding of the light-induced complex dynamic phenomena in OLHP NCs remains a subject of debate. Here we used wide field microscopy and time-resolved spectroscopy to correlate the local changes in photophysics and the dynamical behavior of photocarriers. We demonstrate that light-induced brightening of the photoluminescence from the formamidinium lead bromide NC films is related to the film preparation condition and reduction of trap density. The density of trap states is reduced via halide ion migration from interstitial position. Our femtosecond transient absorption study identifies transient Stark effect due to the generation of hot carriers. Because of slow carrier trapping, Auger recombination through many-body carrier-carrier interactions dominates over trion recombination. This work presents unprecedented insights into the light-driven processes enabling better device design in the future.

This work reports a simple and efficient method for the direct phosphorylation of enamide under metal-free conditions. The P-centered radicals, derived from secondary phosphine oxides, are generated under mild reaction conditions in the presence of diphenyliodonium salt and Et 3 N and are introduced onto a range of enamides in good isolated yields. The method features broad substrate scope, good functional group tolerance, and efficient scale-up.

Organometal halide perovskites in the form of nanocrystals (NCs) have attracted enormous attention due to their unique optoelectronic and photoluminescence (PL) properties. Here, we examine the phase composition and the temperature dependence of emission line width broadening in formamidinium lead bromide (FAPbBr 3 ) perovskite nanocrystals (NCs) for light-emitting applications and identify different charge-carrier scattering mechanisms. Our results show most of the emission is from the orthorhombic phase. The PL line width broadening at high temperature is dominated by the Fröhlich interaction between the free charge carriers and the optical phonons. At low temperatures, the peak of the PL spectrum exhibits a continuous red shift indicating an increase of excitons contribution at lower temperatures, and concurrently the line width also narrows down due to the inhibition of the optical phonons. From the temperature-dependent measurements, the coupling strength of both the charge phonon interaction and the exciton phonon interaction have been determined. The obtained results indicate that the charge phonon coupling strengths are higher compared to the exciton phonon coupling.

Nanoparticle-based cellular probes are commonly designed via covalent conjugation with affinity biomolecules. Those nanobioconjugates selectively interact with cell surface receptors and induce endocytosis followed by intracellular trafficking. However, this approach requires functional modification of biomolecules that may alter their biochemical activity. Here, we show that supramolecular host-guest chemistry can be utilized as an alternative approach in nanoparticle functionalization and selective cell labeling. We have used cyclodextrin-conjugated quantum dots (QDs) for supramolecular host-guest interaction-based functionalization with folate (QD-folate) and riboflavin (QD-riboflavin), where cyclodextrin acts as a host for the folate/riboflavin guest. We demonstrate that QD-folate and QD-riboflavin selectively label cells that have over-expressed folate/riboflavin receptors and induce the endocytosis pathway similar to covalently conjugated folate-/riboflavin-based nanoprobes. However, labeling is highly sensitive to the molar ratio of folate/riboflavin to cyclodextrin and incubation time. The presented functionalization/labeling approach is unique as it does not require covalent conjugation and may be extended for in vivo targeting application via simultaneous delivery of host and guest molecules., Competing Interests: The authors declare no competing financial interest.

The heterojunctions of organic/two-dimensional transition metal dichalcogenides (TMDs) have the potential to be used in the next-generation optoelectronic and photonic devices. Herein, we have systemically investigated the temperature-dependent Raman spectroscopy to elucidate the phonon shift and thermal properties of the semiconducting TMD nanosheets grafted by a conjugated polymer (PG-MoS 2 and PG-MoSe 2 ) forming heterojunctions. Our results reveal that softening of Raman modes of PG-TMDs as temperature increases from 77 to 300 K is due to the negative temperature coefficient (TC) and anharmonicity. The TCs of E 1 2g and A 1g modes of PG-MoS 2 nanosheets and A 1g mode of PG-MoSe 2 were found to be -0.015, -0.010, and -0.010 cm -1 K -1 , respectively. The origin of negative TCs is explained on the basis of a double resonance process, which is more active in single- and few-layer MoS 2 and MoSe 2 . Interestingly, the temperature-dependent behavior of the phonon modes of PG-MoS 2 and PG-MoSe 2 is similar to that of pristine nanosheets. Grafting by conjugated polymer does not affect the electron-phonon (e-p) interaction in the semiconducting (2H-phase) TMDs, hinting the application potential of such materials in field-effect electronic devices., Competing Interests: The authors declare no competing financial interest.

Structural, electronic, and optical properties of a new coumarin dye, zinc oxide (ZnO) nanoclusters of varying sizes, and their complexes have been investigated using density functional theory (DFT). The band gap of oxide nanoclusters varies with size validating quantum confinement effect in small particles. Energy level diagrams of dye, ZnO nanoclusters, and redox electrolyte are in favor of efficient electron injection from dye to nanocluster and regeneration of the ionized dye. The adsorption of the organic dye to nanocluster is tested for anchoring through three different functional groups (cyano, carbonyl, and hydroxyl) of the dye. We have compared simulated absorption spectra of the dye, nanoclusters, and dye functionalized nanoclusters and discussed the matching with the solar irradiance spectrum. A strong new band appeared in the low energy side of the absorption spectra for dye adsorbed nanoclusters. Frontier molecular orbital calculations reveal that the first absorption band of dye-ZnO complexes is charge transfer (CT) in character. Excitation of this band leads to direct electron transfer to the conduction band (CB) of the nanocluster, making dye-ZnO complexes suitable for type II DSSCs as well.

A chemosensor having a bipodal thiocarbamate scaffold attached to histidine moieties senses Hg(2+) with a remarkable selectivity. The binding results in a 50 nm blue shift in the fluorescence spectra and a 19-fold enhancement of the fluorescence quantum yield of the ligand. In addition to the detection of Hg(2+) visually under UV light in solution, the chemosensor was used for fabrication of paper strips that detected Hg(2+) in aqueous samples. The sensor was also used for imaging Hg(2+) in adult zebrafish and in human epithelial carcinoma HeLa S3 cells.

Ultrafast transient absorption spectra in the deep to near UV range (212-384 nm) were measured for the [Cu(II)(MeOH)(5)Cl](+) complexes in methanol following 255-nm excitation of the complex into the ligand-to-metal charge-transfer excited state. The electronically excited complex undergoes sub-200 fs radiationless decay, predominantly via back electron transfer, to the hot electronic ground state followed by fast vibrational relaxation on a 0.4-4 ps time scale. A minor photochemical channel is Cu-Cl bond dissociation, leading to the reduction of copper(II) to copper(I) and the formation of MeOH·Cl charge-transfer complexes. The depletion of ground-state [Cu(II)(MeOH)(5)Cl](+) perturbs the equilibrium between several forms of copper(II) complexes present in solution. Complete re-equilibration between [Cu(II)(MeOH)(5)Cl](+) and [Cu(II)(MeOH)(4)Cl(2)] is established on a 10-500 ps time scale, slower than methanol diffusion, suggesting that the involved ligand exchange mechanism is dissociative., (© 2011 American Chemical Society)

We have studied the influence of three different fullerene derivatives on the charge generation and recombination dynamics of polymer/fullerene bulk heterojunction (BHJ) solar cell blends. Charge generation in APFO3/[70]PCBM and APFO3/[60]PCBM is very similar and somewhat slower than charge generation in APFO3/[70]BTPF. This difference qualitatively matches the trend in free energy change of electron transfer estimated from the LUMO energies of the polymer and fullerene derivatives. The first order (geminate) charge recombination rate is significantly different for the three fullerene derivatives studied and increases in the order APFO3/[70]PCBM < APFO3/[60]PCBM < APFO3/[70]BTPF. The variation in electron transfer rate cannot be explained from the LUMO energies of the fullerene derivatives and single-step electron transfer in the Marcus inverted region and simple considerations of expected trends for the reorganization energy and free energy change. Instead we suggest that geminate charge recombination occurs from a state where electrons and holes have separated to different distances in the various materials because of an initially high charge mobility, different for different materials. In a BHJ thin film this charge separation distance is not sufficient to overcome the electrostatic attraction between electrons and holes and geminate recombination occurs on the nanosecond to hundreds of nanoseconds time scale. In a BHJ solar cell, we suggest that the internal electric field in combination with polarization effects and the dynamic nature of polarons are key features to overcome electron-hole interactions to form free extractable charges.