Synthesis and Antitumour Evaluation of Tricyclic Indole-2-Carboxamides against Paediatric Brain Cancer Cells.

Antitumour properties of some cannabinoids (CB) have been reported in the literature as early as 1970s, however there is no clear consensus to date on the exact mechanisms leading to cancer cell death. The indole-based WIN 55,212-2 and SDB-001 are both known as potent agonists at both CB1 and CB2 receptors, yet we demonstrate herein that only the former can exert in vitro antitumour effects when tested against a paediatric brain cancer cell line KNS42. In this report, we describe the synthesis of novel 3,4-fused tricyclic indoles and evaluate their functional potencies at both cannabinoid receptors, as well as their abilities to inhibit the growth or proliferation of KNS42 cells. Compared to our previously reported indole-2-carboxamides, these 3,4-fused tricyclic indoles had either completely lost activities, or, showed moderate-to-weak antagonism at both CB1 and CB2 receptors. Compound 23 displayed the most potent antitumour properties among the series. Our results further support the involvement of non-CB pathways for the observed antitumour activities of amidoalkylindole-based cannabinoids, in line with our previous findings. Transcriptomic analysis comparing cells treated or non-treated with compound 23 suggested the observed antitumour effects of 23 are likely to result mainly from disruption of the FOXM1-regulated cell cycle pathways.

iPSC-derived PSEN2 (N141I) astrocytes and microglia exhibit a primed inflammatory phenotype.

BACKGROUND: Widescale evidence points to the involvement of glia and immune pathways in the progression of Alzheimer's disease (AD). AD-associated iPSC-derived glial cells show a diverse range of AD-related phenotypic states encompassing cytokine/chemokine release, phagocytosis and morphological profiles, but to date studies are limited to cells derived from PSEN1, APOE and APP mutations or sporadic patients. The aim of the current study was to successfully differentiate iPSC-derived microglia and astrocytes from patients harbouring an AD-causative PSEN2 (N141I) mutation and characterise the inflammatory and morphological profile of these cells. METHODS: iPSCs from three healthy control individuals and three familial AD patients harbouring a heterozygous PSEN2 (N141I) mutation were used to derive astrocytes and microglia-like cells and cell identity and morphology were characterised through immunofluorescent microscopy. Cellular characterisation involved the stimulation of these cells by LPS and Aß42 and analysis of cytokine/chemokine release was conducted through ELISAs and multi-cytokine arrays. The phagocytic capacity of these cells was then indexed by the uptake of fluorescently-labelled fibrillar Aß42. RESULTS: AD-derived astrocytes and microglia-like cells exhibited an atrophied and less complex morphological appearance than healthy controls. AD-derived astrocytes showed increased basal expression of GFAP, S100ß and increased secretion and phagocytosis of Aß42 while AD-derived microglia-like cells showed decreased IL-8 secretion compared to healthy controls. Upon immunological challenge AD-derived astrocytes and microglia-like cells showed exaggerated secretion of the pro-inflammatory IL-6, CXCL1, ICAM-1 and IL-8 from astrocytes and IL-18 and MIF from microglia. CONCLUSION: Our study showed, for the first time, the differentiation and characterisation of iPSC-derived astrocytes and microglia-like cells harbouring a PSEN2 (N141I) mutation. PSEN2 (N141I)-mutant astrocytes and microglia-like cells presented with a 'primed' phenotype characterised by reduced morphological complexity, exaggerated pro-inflammatory cytokine secretion and altered Aß42 production and phagocytosis.

The zebrafish paralog six2b is required for early proximal pronephros morphogenesis.

The transcription factor Six2 plays a crucial role in maintaining self-renewing nephron progenitor cap mesenchyme (CM) during metanephric kidney development. In mouse and human, expression at single-cell resolution has detected Six2 in cells as they leave the CM pool and differentiate. The role Six2 may play in these cells as they differentiate remains unknown. Here, we took advantage of the zebrafish pronephric kidney which forms directly from intermediate mesoderm to test six2b function during pronephric tubule development and differentiation. Expression of six2b during early zebrafish development was consistent with a role in pronephros formation. Using morpholino knock-down and CRISPR/Cas9 mutagenesis, we show a functional role for six2b in the development of proximal elements of the pronephros. By 48 h post-fertilization, six2b morphants and mutants showed disrupted pronephric tubule morphogenesis. We observed a lower-than-expected frequency of phenotypes in six2b stable genetic mutants suggesting compensation. Supporting this, we detected increased expression of six2a in six2b stable mutant embryos. To further confirm six2b function, F0 crispant embryos were analyzed and displayed similar phenotypes as morphants and stable mutants. Together our data suggests a conserved role for Six2 during nephrogenesis and a role in the morphogenesis of the proximal tubule.

Urban and rural male song sparrows (Melospiza melodia) differ in territorial aggression and activation of vasotocin neurons in response to song challenge.

When living in urban habitats, 'urban adapter' species often show greater aggression toward conspecifics, yet we do not understand the mechanisms underlying this behavioral shift. The neuroendocrine system regulates socio-sexual behaviors including aggression and thus could mediate behavioral responses to urbanization. Indeed, urban male song sparrows (Melospiza melodia), which are more territorially aggressive, also have greater abundance of the neuropeptide arginine vasotocin (AVT) in nodes of the brain social behavior network. Higher abundance of AVT could reflect long-term synthesis that underlies baseline territoriality or short-term changes that regulate aggression in response to social challenge. To begin to resolve the timeframe over which the AVT system contributes to habitat differences in aggression we used immediate early gene co-expression as a measure of the activation of AVT neurons. We compared Fos induction in AVT-immunoreactive neurons of the bed nucleus of the stria terminalis (BSTm) and paraventricular nucleus of the hypothalamus (PVN) between urban and rural male song sparrows in response to a short (< 5 min.) or long (> 30 min.) song playback to simulate territorial intrusion by another male. We found that urban males had a higher proportion of Fos-positive AVT neurons in both brain regions compared to rural males, regardless of the duration of song playback. Our results suggest that AVT neurons remain activated in urban males, independently of the duration of social challenge. These findings that Fos induction in AVT neurons differs between rural and urban male song sparrows further implicate this system in regulating behavioral responses to urbanization.

Synthesis and Preclinical Evaluation of Fluorinated 5-Azaindoles as CB2 PET Radioligands.

Several classes of cannabinoid receptor type 2 radioligands have been evaluated for imaging of neuroinflammation, with successful clinical translation yet to take place. Here we describe the synthesis of fluorinated 5-azaindoles and pharmacological characterization and in vivo evaluation of 18F-radiolabeled analogues. [18F]2 (hCB2 Ki = 96.5 nM) and [18F]9 (hCB2 Ki = 7.7 nM) were prepared using Cu-mediated 18F-fluorination with non-decay-corrected radiochemical yields of 15 ± 6% and 18 ± 2% over 85 and 80 min, respectively, with high radiochemical purities (>97%) and molar activities (140-416 GBq/µmol). In PET imaging studies in rats, both [18F]2 and [18F]9 demonstrated specific binding in CB2-rich spleen after pretreatment with CB2-specific GW405833. Moreover, [18F]9 exhibited higher brain uptake at later time points in a murine model of neuroinflammation compared with a healthy control group. The results suggest further evaluation of azaindole based CB2 radioligands is warranted in other neuroinflammation models.

Three-dimensional bioprinting of stem cell-derived central nervous system cells enables astrocyte growth, vasculogenesis, and enhances neural differentiation/function.

Current research tools for preclinical drug development such as rodent models and two-dimensional immortalized monocultures have failed to serve as effective translational models for human central nervous system (CNS) disorders. Recent advancements in the development of induced pluripotent stem cells (iPSCs) and three-dimensional (3D) culturing can improve the in vivo-relevance of preclinical models, while generating 3D cultures though novel bioprinting technologies can offer increased scalability and replicability. As such, there is a need to develop platforms that combine iPSC-derived cells with 3D bioprinting to produce scalable, tunable, and biomimetic cultures for preclinical drug discovery applications. We report a biocompatible poly(ethylene glycol)-based matrix which incorporates Arg-Gly-Asp and Tyr-Ile-Gly-Ser-Arg peptide motifs and full-length collagen IV at a stiffness similar to the human brain (1.5 kPa). Using a high-throughput commercial bioprinter we report the viable culture and morphological development of monocultured iPSC-derived astrocytes, brain microvascular endothelial-like cells, neural progenitors, and neurons in our novel matrix. We also show that this system supports endothelial-like vasculogenesis and enhances neural differentiation and spontaneous activity. This platform forms a foundation for more complex, multicellular models to facilitate high-throughput translational drug discovery for CNS disorders.

What About Females? Urban Female Song Sparrows Elevate Aggressive Signaling Compared to Rural.

The costs and benefits of breeding behaviors are influenced by environmental conditions, and habitat variation can shift the degree to which behaviors are expressed. Novel urban habitats have been shown to differ significantly in disturbances such as noise, light at night, and human presence, as well as resource availability, compared to rural habitats. Perhaps because of these environmental differences, urban males of several species are consistently more aggressive than rural males, raising the hypothesis that greater territorial aggression is beneficial in urban habitats. Though often ignored, female songbirds of many species also perform aggressive territorial behaviors towards conspecifics during the breeding season. For socially monogamous songbirds, this aggression functions to ensure partner fidelity and secure resources for reproduction. Studies of the effects of urbanization on songbird behavior have yet to determine if urban females also express greater territorial aggression. Importantly, energetically demanding behaviors such as territoriality and parental care should constrain one another, leading to behavioral trade-offs during the breeding season. Though territorial aggression and parental care are inversely related in males of several species of songbird, this relationship is understudied in female songbirds, particularly those facing environmental change such as urbanization. In this study, we compared aggressive signaling and a measure of parental care (maternal nest visitation rates) between female song sparrows (Melospiza melodia), living in urban and rural habitats. We hypothesized that female aggressive signaling would be higher in urban environments compared to rural, and negatively correlated with maternal visitation rates. We found that urban females, like males, expressed increased aggressive signaling compared to rural. However, female aggressive signaling was not related to our measure of maternal care, suggesting females aren't facing a trade-off between these two behaviors. Collectively, our results are consistent with the hypothesis that urban habitats promote territorial aggression in female song sparrows. As urbanization continues to spread, understanding the behavioral changes animals employ in urban environments requires studying individuals of different sexes and age classes, and will help us understand how some species are able to cope with human induced rapid environmental change.

Synthesis and antitumour evaluation of indole-2-carboxamides against paediatric brain cancer cells.

Paediatric glioblastomas are rapidly growing, devastating brain neoplasms with an invasive phenotype. Radiotherapy and chemotherapy, which are the current therapeutic adjuvant to surgical resection, are still associated with various toxicity profiles and only marginally improve the course of the disease and life expectancy. A considerable body of evidence supports the antitumour and apoptotic effects of certain cannabinoids, such as WIN55,212-2, against a wide spectrum of cancer cells, including gliomas. In fact, we previously highlighted the potent cytotoxic activity of the cannabinoid ligand 5 against glioblastoma KNS42 cells. Taken together, in this study, we designed, synthesised, and evaluated several indoles and indole bioisosteres for their antitumour activities. Compounds 8a, 8c, 8f, 12c, and 24d demonstrated significant inhibitory activities against the viability (IC50 = 2.34-9.06 µM) and proliferation (IC50 = 2.88-9.85 µM) of paediatric glioblastoma KNS42 cells. All five compounds further retained their antitumour activities against two atypical teratoid/rhabdoid tumour (AT/RT) cell lines. When tested against a medulloblastoma DAOY cell line, only 8c, 8f, 12c, and 24d maintained their viability inhibitory activities. The viability assay against non-neoplastic human fibroblast HFF1 cells suggested that compounds 8a, 8c, 8f, and 12c act selectively towards the panel of paediatric brain tumour cells. In contrast, compound 24d and WIN55,212-2 were highly toxic toward HFF1 cells. Due to their structural resemblance to known cannabimimetics, the most potent compounds were tested in cannabinoid 1 and 2 receptor (CB1R and CB2R) functional assays. Compounds 8a, 8c, and 12c failed to activate or antagonise both CB1R and CB2R, whereas compounds 8f and 24d antagonised CB1R and CB2R, respectively. We also performed a transcriptional analysis on KNS42 cells treated with our prototype compound 8a and highlighted a set of seven genes that were significantly downregulated. The expression levels of these genes were previously shown to be positively correlated with tumour growth and progression, indicating their implication in the antitumour activity of 8a. Overall, the drug-like and selective antitumour profiles of indole-2-carboxamides 8a, 8c, 8f, and 12c substantiate the versatility of the indole scaffold in cancer drug discovery.

Hypothalamic-pituitary-adrenal axis regulation and organization in urban and rural song sparrows.

Urban habitats present animals with persistent disturbances and acute stressors not present in rural habitats or present at significantly lower levels. Differences in the glucocorticoid stress response could underlie colonization of these novel habitats. Despite urban habitats characterization as more stressful, previous comparisons of urban and rural birds have failed to find consistent differences in baseline and stress induced glucocorticoid levels. Another aspect of glucocorticoid regulation that could underlie an animal's ability to inhabit novel habitats, but has yet to be well examined, is more efficient termination of the glucocorticoid stress response which would allow birds in urban habitats to recover more quickly after a disturbance. The glucocorticoid stress response is terminated by negative feedback achieved primarily through their binding of receptors in the hippocampus and hypothalamus and subsequent decreased synthesis and release from the adrenals. We investigated if male song sparrows (Melospiza melodia) in urban habitats show more efficient termination of the glucocorticoid stress response than their rural counterparts using two approaches. First, we measured glucocorticoid receptor, mineralocorticoid receptor and 11ß-HSD2 (an enzyme that inactivates corticosterone) mRNA expression in negative feedback targets of the brain (the hippocampus and hypothalamus) as a proxy measure of sensitivity to negative feedback. Second, we measured plasma corticosterone levels after standardized restraint and again following a challenge with the synthetic glucocorticoid, dexamethasone, as a means of assessing how quickly birds decreased glucocorticoid synthesis and release. Though there were no differences in the hypothalamus of urban and rural song sparrows, urban birds had lower glucocorticoid receptor and 11ß-HSD2 mRNA expression in the hippocampus. Further, urban and rural birds had similar reductions in corticosterone following the dexamethasone challenge, suggesting that they do not differ in how quickly they decrease glucocorticoid synthesis and release. Thus, urban and rural song sparrows display similar termination of the glucocorticoid stress response even though urban birds have decreased hippocampal glucocorticoid receptor and 11ß-HSD2 abundance.

Male zebra finches exposed to lead (Pb) during development have reduced volume of song nuclei, altered sexual traits, and received less attention from females as adults.

Lead (Pb) is a pervasive global contaminant that interferes with sensitive windows for neurological development and causes oxidative damage to tissues. The effects of moderate and high exposure to Pb have been well-studied in birds, but whether low-level early-life exposure to Pb influences adult phenotype remains unclear. Female songbirds use a male's song and coloration to discriminate between high- and low-quality males. Therefore, if early-life exposure to Pb disrupts song learning ability or shifts the allocation of antioxidant pigments away from colorful secondary sexual traits, male birds exposed to Pb may be less attractive to females. We exposed developing zebra finches (Taeniopygia guttata) to Pb-contaminated drinking water (100 or 1000 parts per billion [ppb]) after hatching (days 0-100). Once male finches reached adulthood (120-150 days post hatch), we measured song learning ability, coloration of bill and cheek patches, and volume of song nuclei in the brain. We also measured female preference for Pb-exposed males relative to control males. Finally, we measured motoric and spatial cognitive performance in male and female finches to assess whether cognitive traits differed in their sensitivity to Pb exposure. Male zebra finches exposed to 1000 ppb Pb had impaired song learning ability, reduced volume of song nuclei, bills with less redness and received less attention from females. Additionally, Pb exposure impaired motoric performance in both male and female finches but did not affect performance in a spatial cognitive task. Adult finches exposed to Pb-contaminated water had higher blood-Pb levels, though in all cases blood-Pb levels were below 7.0 µg dL-1. This study suggests that low-level exposure to Pb contributes to cognitive deficits that persist into adulthood and may indirectly influence fitness by altering secondary sexual traits and reducing male attractiveness.

The discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine cannabinoid type 2 receptor agonist.

The development of selective CB2 receptor agonists is a promising therapeutic approach for the treatment of inflammatory diseases, without CB1 receptor mediated psychoactive side effects. Preliminary structure-activity relationship studies on pyrazoylidene benzamide agonists revealed the -ylidene benzamide moiety was crucial for functional activity at the CB2 receptor. A small library of compounds with varying linkage moieties between the pyrazole and substituted phenyl group has culminated in the discovery of a potent and selective pyrazolo-[2,3-e]-[1,2,4]-triazine agonist 19 (CB2R EC50 = 19 nM, CB1R EC50 > 10 µM). Docking studies have revealed key structural features of the linkage group that are important for potent functional activity.

Effects of low-density urbanization on genetic structure in the Song Sparrow.

Urbanization fragments landscapes and can impede the movement of organisms through their environment, which can decrease population connectivity. Reduction in connectivity influences gene flow and allele frequencies, and can lead to a reduction in genetic diversity and the fixation of certain alleles, with potential negative effects for populations. Previous studies have detected effects of urbanization on genetic diversity and structure in terrestrial animals living in landscapes that vary in their degree of urbanization, even over very short distances. We investigated the effects of low-intensity urbanization on genetic diversity and genetic structure in Song Sparrows (Melospiza melodia). We captured 208 Song Sparrows at seven sites along a gradient of urbanization in and around Blacksburg, VA, USA, then genotyped them using a panel of fifteen polymorphic microsatellite loci. We found that genetic diversity was comparable among the seven study sites, and there was no evidence of genetic structuring among sites. These findings suggest that over a gradient of urbanization characterized by low density urban development, Song Sparrows likely exist in a single panmictic population.

Strategies to develop selective CB2 receptor agonists from indole carboxamide synthetic cannabinoids.

Activation of the CB2 receptor is an attractive therapeutic strategy for the treatment of a wide range of inflammatory diseases. However, receptor subtype selectivity is necessary in order to circumvent the psychoactive effects associated with activation of the CB1 receptor. We aimed to use potent, non-selective synthetic cannabinoids designer drugs to develop selective CB2 receptor agonists. Simple structural modifications such as moving the amide substituent of 3-amidoalkylindole synthetic cannabinoids to the 2-position and bioisosteric replacement of the indole core to the 7-azaindole scaffold are shown to be effective and general strategies to impart receptor subtype selectivity. 2-Amidoalkylindole 16 (EC50 CB1 > 10 µM, EC50 CB2 = 189 nM) and 3-amidoalkyl-7-azaindole 21 (EC50 CB1 > 10 µM, EC50 = 49 nM) were found to be potent and selective agonists with favourable physicochemical properties. Docking studies were used to elucidate the molecular basis for the observed receptor subtype selectivity for these compounds.

Synthesis and in vitro evaluation of fluorine-18 benzimidazole sulfones as CB2 PET-radioligands.

Cannabinoid type 2 receptor (CB2) is up-regulated on activated microglial cells and can potentially be used as a biomarker for PET-imaging of neuroinflammation. In this study the synthesis and pharmacological evaluation of novel fluorinated pyridyl and ethyl sulfone analogues of 2-(tert-butyl)-5-((2-fluoropyridin-4-yl)sulfonyl)-1-(2-methylpentyl)-1H-benzo[d]imidazole (rac-1a) are described. In general, the ligands showed low nanomolar potency (CB2 EC50 < 10 nM) and excellent selectivity over the CB1 subtype (>10 000×). Selected ligands 1d, 1e, 1g and 3l showing high CB2 binding affinity (Ki < 10 nM) were radiolabelled with fluorine-18 from chloropyridyl and alkyl tosylate precursors with good to high isolated radioactive yields (25-44%, non-decay corrected, at the end of synthesis). CB2-specific binding of the radioligand candidates [18F]-1d and [18F]-3l was assessed on rat spleen cryosections using in vitro autoradiography. The results warrant further in vivo evaluation of the tracer candidates as prospective CB2 PET-imaging agents.

Photocarrier dynamics in monolayer phosphorene and bulk black phosphorus.

We report a combined theoretical and experimental study on photocarrier dynamics in monolayer phosphorene and bulk black phosphorus. Samples of monolayer phosphorene and bulk black phosphorus were fabricated by mechanical exfoliation, identified according to their reflective contrasts, and protected by covering them with hexagonal boron nitride layers. Photocarrier dynamics in these samples was studied by an ultrafast pump-probe technique. The photocarrier lifetime of monolayer phosphorene was found to be about 700 ps, which is about 9 times longer than that of bulk black phosphorus. This trend was reproduced in our calculations based on ab initio nonadiabatic molecular dynamics combined with time-domain density functional theory in the Kohn-Sham representation, and can be attributed to the smaller bandgap and stronger nonadiabatic coupling in bulk. The transient absorption response was also found to be dependent on the sample orientation with respect to the pump polarization, which is consistent with the previously reported anisotropic absorption of phosphorene. In addition, an oscillating component of the differential reflection signal at early probe delays was observed in the bulk sample and was attributed to the layer-breathing phonon mode with an energy of about 1 meV and a decay time of about 1.35 ps. These results provide valuable information for application of monolayer phosphorene in optoelectronics.

Photocarrier Transfer across Monolayer MoS2-MoSe2 Lateral Heterojunctions.

In-plane heterojuctions formed from two monolayer semiconductors represent the finest control of electrons in condensed matter and have attracted significant interest. Various device studies have shown the effectiveness of such structures to control electronic processes, illustrating their potentials for electronic and optoelectronic applications. However, information about the physical mechanisms of charge carrier transfer across the junctions is still rare, mainly due to the lack of adequate experimental techniques. Here we show that transient absorption measurements with high spatial and temporal resolution can be used to directly monitor such transfer processes. We studied MoS2-MoSe2 in-plane heterostructures fabricated by chemical vapor deposition and lithographic patterning followed by laser-generated vapor sulfurization. Transient absorption measurements in reflection geometry revealed evidence of exciton transfer from MoS2 to MoSe2. By comparing the experimental data with a simulation, we extracted an exciton transfer velocity of 104 m s-1. These results provide valuable information for understanding and controlling in-plane carrier transfer in two-dimensional lateral heterostructures for their electronic and optoelectronic applications.

Charge Transfer Exciton and Spin Flipping at Organic-Transition-Metal Dichalcogenide Interfaces.

Two-dimensional transition-metal dichalcogenides (TMD) can be combined with other materials such as organic small molecules to form hybrid van der Waals heterostructures. Because of different properties possessed by these two materials, the hybrid interface can exhibit properties that cannot be found in either of the materials. In this work, the zinc phthalocyanine (ZnPc)-molybdenum disulfide (MoS2) interface is used as a model system to study the charge transfer at these interfaces. It is found that the optically excited singlet exciton in ZnPc transfers its electron to MoS2 in 80 fs after photoexcitation to form a charge transfer exciton. However, back electron transfer occurs on the time scale of ∼1-100 ps, which results in the formation of a triplet exciton in the ZnPc layer. This relatively fast singlet-triplet transition is feasible because of the large singlet-triplet splitting in organic materials and the strong spin-orbit coupling in TMD crystals. The back electron transfer would reduce the yield of free carrier generation at the heterojunction if it is not avoided. On the other hand, the spin-selective back electron transfer could be used to manipulate electron spin in hybrid electronic devices.

Ultrafast Interlayer Electron Transfer in Incommensurate Transition Metal Dichalcogenide Homobilayers.

Two-dimensional materials, such as graphene, transition metal dichalcogenides, and phosphorene, can be used to construct van der Waals multilayer structures. This approach has shown potentials to produce new materials that combine novel properties of the participating individual layers. One key requirement for effectively harnessing emergent properties of these materials is electronic connection of the involved atomic layers through efficient interlayer charge or energy transfer. Recently, ultrafast charge transfer on a time scale shorter than 100 fs has been observed in several van der Waals bilayer heterostructures formed by two different materials. However, information on the transfer between two atomic layers of the same type is rare. Because these homobilayers are essential elements in constructing multilayer structures with desired optoelectronic properties, efficient interlayer transfer is highly desired. Here we show that electron transfer between two monolayers of MoSe2 occurs on a picosecond time scale. Even faster transfer was observed in homobilayers of WS2 and WSe2. The samples were fabricated by manually stacking two exfoliated monolayer flakes. By adding a graphene layer as a fast carrier recombination channel for one of the two monolayers, the transfer of the photoexcited carriers from the populated to the drained monolayers was time-resolved by femtosecond transient absorption measurements. The observed efficient interlayer carrier transfer indicates that such homobilayers can be used in van der Waals multilayers to enhance their optical absorption without significantly compromising the interlayer transport performance. Our results also provide valuable information for understanding interlayer charge transfer in heterostructures.

Highly Efficient and Anomalous Charge Transfer in van der Waals Trilayer Semiconductors.

Two-dimensional materials, such as graphene and monolayer transition metal dichalcogenides, allow the fabrication of multilayer structures without lattice matching restriction. A central issue in developing such artificial materials is to understand and control the interlayer electron transfer process, which plays a key role in harnessing their emergent properties. Recent photoluminescence and transient absorption measurements revealed that the electron transfer in heterobilayers occurs on ultrafast time scales. However, there is still a lack of fundamental understanding on how this process can be so efficient at van der Waals interfaces. Here we show evidence suggesting the coherent nature of such interlayer electron transfer. In a trilayer of MoS2-WS2-MoSe2, electrons excited in MoSe2 transfer to MoS2 in about one picosecond. Surprisingly, these electrons do not populate the middle WS2 layer during this process. Calculations showed the coherent nature of the charge transfer and reproduced the measured electron transfer time. The hole transfer from MoS2 to MoSe2 is also found to be efficient and ultrafast. The separation of electrons and holes extends their lifetimes to more than one nanosecond, suggesting potential applications of such multilayer structures in optoelectronics.

Type-I van der Waals heterostructure formed by MoS2 and ReS2 monolayers.

We report a van der Waals heterostructure formed by monolayers of MoS2 and ReS2 with a type-I band alignment. First-principle calculations show that in this heterostructure, both the conduction band minimum and the valence band maximum are located in the ReS2 layer. This configuration is different from previously accomplished type-II van der Waals heterostructures where electrons and holes reside in different layers. The type-I nature of this heterostructure is evident by photocarrier dynamics observed by transient absorption measurements. We found that carriers injected in MoS2 transfer to ReS2 in about 1 ps, while no charge transfer was observed when carriers are injected in ReS2. The carrier lifetime in the heterostructure is similar to that in monolayer ReS2, further confirming the lack of charge separation. We attribute the slower transfer time to the incoherent nature of the charge transfer due to the different crystal structures of the two materials forming the heterostructure. The demonstrated type-I semiconducting van der Waals heterostructure provides new ways to utilize two-dimensional materials for light emission applications, and a new platform to study light-matter interaction in atomically thin materials with strong confinement of electrons and holes.