The past 10 years of molecular ferroelectrics: structures, design, and properties.

Ferroelectricity, which has diverse important applications such as memory elements, capacitors, and sensors, was first discovered in a molecular compound, Rochelle salt, in 1920 by Valasek. Owing to their superiorities of lightweight, biocompatibility, structural tunability, mechanical flexibility, etc., the past decade has witnessed the renaissance of molecular ferroelectrics as promising complementary materials to commercial inorganic ferroelectrics. Thus, on the 100th anniversary of ferroelectricity, it is an opportune time to look into the future, specifically into how to push the boundaries of material design in molecular ferroelectric systems and finally overcome the hurdles to their commercialization. Herein, we present a comprehensive and accessible review of the appealing development of molecular ferroelectrics over the past 10 years, with an emphasis on their structural diversity, chemical design, exceptional properties, and potential applications. We believe that it will inspire intense, combined research efforts to enrich the family of high-performance molecular ferroelectrics and attract widespread interest from physicists and chemists to better understand the structure-function relationships governing improved applied functional device engineering.

First Observation of Negative Capacitance in Molecular Ferroelectric Thin Films.

On the path of persisting Moore's Law, one of the biggest obstacles is the "Boltzmann tyranny," which defines the lower limit of power consumption of individual transistors. Negative capacitance (NC) in ferroelectrics could provide a solution and has garnered significant attention in the fields of nanoelectronics, materials science, and solid-state physics. Molecular ferroelectrics, as an integral part of ferroelectrics, have developed rapidly in terms of both performance and functionality, with their inherent advantages such as easy fabrication, mechanical flexibility, low processing temperature, and structural tunability. However, studies on the NC in molecular ferroelectrics are limited. In this study, the focus is centered on the fabricated high-quality thin films of trimethylchloromethyl ammonium trichlorocadmium(II), and a pioneering investigation on their NC responses is conducted. The findings demonstrate that the NC exhibited by molecular ferroelectrics is comparable to that of conventional HfO2 -based ferroelectrics. This underscores the potential of molecular material systems for next-generation electronic devices.

Volume-Confined Fabrication of Large-Scale Single-Crystalline Molecular Ferroelectric Thin Films and Their Applications in 2D Materials.

With outstanding advantages of chemical synthesis, structural diversity, and mechanical flexibility, molecular ferroelectrics have attracted increasing attention, demonstrating themselves as promising candidates for next-generation wearable electronics and flexible devices in the film form. However, it remains a challenge to grow high-quality thin films of molecular ferroelectrics. To address the above issue, a volume-confined method is utilized to achieve ultrasmooth single-crystal molecular ferroelectric thin films at the sub-centimeter scale, with the thickness controlled in the range of 100-1000 nm. More importantly, the preparation method is applicable to most molecular ferroelectrics and has no dependency on substrates, showing excellent reproducibility and universality. To demonstrate the application potential, two-dimensional (2D) transitional metal dichalcogenide semiconductor/molecular ferroelectric heterostructures are prepared and investigated by optical spectroscopic method, proving the possibility of integrating molecular ferroelectrics with 2D layered materials. These results may unlock the potential for preparing and developing high-performance devices based on molecular ferroelectric thin films.

Revealing the Polarizations of Molecular Ferroelectrics via SHG Polarimetry at the Nanoscale.

Multifarious molecular ferroelectrics with multipolar axial characteristics have emerged in recent years, enriching the scenarios for energy harvesting, sensing, and information processing. The increased polar axes have enhanced the urgency of distinguishing different polarization states in material design, mechanism exploration, etc. However, conventional methods hardly meet the requirements of in situ, fast, microscale, contactless, and nondestructive features due to their inherent limitations. Herein, SHG polarimetry is introduced to probe the multioriented polarizations on a nanosized multiaxial molecular ferroelectric, i.e., TMCM-CdCl3 nanoplates, as an example. Combined with the analysis of the second-order susceptibility tensor, SHG polarimetry could serve as an effective method to detect the polarization orders and domain distributions of molecular ferroelectrics. Profiting from the full-optical feature, SHG polarimetry can even be performed on samples covered by transparent mediums, 2D materials, or thin metal electrodes. Our research might spark further fundamental studies and expand the application boundaries of next-generation ferroelectric materials.

Giant electrocaloric effect in a molecular ceramic.

The electrocaloric effect (ECE) is an efficient and environmentally friendly method for solid-state refrigeration driven by an electric field. However, disregarding the ECE performance, the mass of materials also limits the amount of energy transferred in the cooling process. While molecular ECE materials have been attracting intensive attention with their excellent ECE properties, most reported molecular compounds can only be utilized in the form of thin films or single crystals. Unlike inorganic ceramics, molecular thin films and single crystals are very difficult to prepare in a large amount, which greatly restrains the future application of those materials. In this work, we report an excellent molecular ECE material in the form of polycrystalline molecular ceramics. Such molecular ceramics are composed of plastic molecular ferroelectrics, and can fulfil the requirement of large mass, easy processing, excellent performance and low energy consumption. Our molecular ceramic of HQReO4 (HQ: protonated quinuclidine) demonstrates an isothermal entropy change of 5.8 J K-1 kg-1 and an adiabatic temperature change of 3.1 K. Notably, by a simple low-temperature pressing process without added adhesives (about 373 K), an HQReO4 molecular ceramic block can be obtained, and its ECE performance is observed to be comparable to that of single crystals, for the first time. This work proposes a new application form for molecular electrocaloric materials, which opens up new ideas for solid-state refrigeration.

Rational Design of Molecular Ferroelectrics with Negatively Charged Domain Walls.

Ferroelectric domains and domain walls are unique characteristics of ferroelectric materials. Among them, charged domain walls (CDWs) are a special kind of peculiar microstructure that highly improve conductivity, piezoelectricity, and photovoltaic efficiency. Thus, CDWs are believed to be the key to ferroelectrics' future application in fields of energy, sensing, information storage, and so forth. Studies on CDWs are one of the most attractive directions in conventional inorganic ferroelectric ceramics. However, in newly emerged molecular ferroelectrics, which have advantages such as lightweight, easy preparation, simple film fabrication, mechanical flexibility, and biocompatibility, CDWs are rarely observed due to the lack of free charges. In inorganic ferroelectrics, doping is a traditional method to induce free charges, but for molecular ferroelectrics fabricated by solution processes, doping usually causes phase separation or phase transition, which destabilizes or removes ferroelectricity. To realize stable CDWs in molecular systems, we designed and synthesized an n-type molecular ferroelectric, 1-adamantanammonium hydroiodate. In this compound, negative charges are induced by defects in the I- vacancy, and CDWs can be achieved. Nanometer-scale CDWs that are stable at temperatures as high as 373 K can be "written" precisely by an electrically biased metal tip. More importantly, this is the first time that the charge diffusion of CDWs at variable temperatures has been investigated in molecular ferroelectrics. This work provides a new design strategy for n-type molecular ferroelectrics and may shed light on their future applications in flexible electronics, microsensors, and so forth.

Fluorinated 2D Lead Iodide Perovskite Ferroelectrics.

Hybrid perovskite materials are famous for their great application potential in photovoltaics and optoelectronics. Among them, lead-iodide-based perovskites receive great attention because of their good optical absorption ability and excellent electrical transport properties. Although many believe the ferroelectric photovoltaic effect (FEPV) plays a crucial role for the high conversion efficiency, the ferroelectricity in CH3 NH3 PbI3 is still under debate, and obtaining ferroelectric lead iodide perovskites is still challenging. In order to avoid the randomness and blindness in the conventional method of searching for perovskite ferroelectrics, a design strategy of fluorine modification is developed. As a demonstration, a nonpolar lead iodide perovskite is modified and a new 2D fluorinated layered hybrid perovskite material of (4,4-difluorocyclohexylammonium)2 PbI4 , 1, is obtained, which possesses clear ferroelectricity with controllable spontaneous polarization. The direct bandgap of 2.38 eV with strong photoluminescence also guarantees the direct observation of polarization-induced FEPV. More importantly, the 2D structure and fluorination are also expected to achieve both good stability and charge transport properties. 1 is not only a 2D fluorinated lead iodide perovskite with confirmed ferroelectricity, but also a great platform for studying the effect of ferroelectricity and FEPV in the context of lead halide perovskite solar cells and other optoelectronic applications.

A Nickel(II) Nitrite Based Molecular Perovskite Ferroelectric.

The X-site ion in organic-inorganic hybrid ABX3 perovskites (OHPs) varies from halide ion to bridging linkers like HCOO- , N3 - , NO2 - , and CN- . However, no nitrite-based OHP ferroelectrics have been reported so far. Now, based on non-ferroelectric [(CH3 )4 N][Ni(NO2 )3 ], through the combined methodologies of quasi-spherical shape, hydrogen bonding functionality, and H/F substitution, we have successfully synthesized an OHP ferroelectric, [FMeTP][Ni(NO2 )3 ] (FMeTP=N-fluoromethyl tropine). As an unprecedented nitrite-based OHP ferroelectric, the well-designed [FMeTP][Ni(NO2 )3 ] undergoes the ferroelectric phase transition at 400 K with an Aizu notation of 6/mmmFm, showing multiaxial ferroelectric characteristics. This work is a great step towards not only enriching the molecular ferroelectric families but also accelerating the potential practical applications.

The functional and mechanistic relatedness of EZH2 and menin in hepatocellular carcinoma.

BACKGROUND & AIMS: The alterations of histone modification may serve as a promising diagnostic biomarker of hepatocellular carcinoma (HCC), but the clinical and mechanistic relatedness of the histone H3 lysine 27 and 4 trimethylation (H3K27me3 and H3K4me3) in HCC remains poorly understood. Here we propose that the combination of H3K27me3 and H3K4me3 is a more precise predictive/prognostic value for outcome of HCC patients. METHODS: We used chromatin immunoprecipitation (ChIP) assays and a ChIP-on-chip screen to analyse HCC. RESULTS: We found that the EZH2 occupancy coincides with the H3K27me3 at promoters and directly silences the transcription of target genes in HCC. The H3K27me3-related gene network of EZH2 contains well-established genes, such as CDKN2A, as well as previously unappreciated genes, including FOXO3, E2F1, and NOTCH2, among others. We further observed independently increasing profiles of H3K27me3 and H3K4me3 at the promoters of certain target genes in HCC specimens. Importantly, Kaplan-Meier analysis reveals that 3-year overall and tumour-free survival rates are dramatically reduced in patients that simultaneously express EZH2 and menin, compared to rates in the EZH2 or menin under expressing patients. Furthermore, an inhibitor of H3K27me3 alone, or in combination with an H3K4me3 inhibitor, effectively blocked the aggressive phenotype of HCC cells. CONCLUSIONS: Our results indicate that a combined analysis of both H3K27me3 and H3K4me3 may serve as powerful diagnostic biomarkers of HCC, and targeting both might benefit anti-HCC therapy.

Menin promotes hepatocellular carcinogenesis and epigenetically up-regulates Yap1 transcription.

Menin is a scaffold protein encoded by the multiple endocrine neoplasia type 1 (MEN1) gene in humans, and it interacts with a variety of transcriptional proteins to control active or repressive cellular processes. Here, we show that heterozygous ablation of Men1 in female mice reduces chemical carcinogen-induced liver carcinogenesis and represses the activation of the inflammation pathway. Using ChIP-on-chip screens and ChIP assays, we find that menin occupancy frequently coincides with H3K4me3 at the promoter of many liver cancer-related genes, such as Yes-associated protein (Yap1). Increased menin and Yap1 expression in human hepatocellular carcinoma specimens was associated with poor prognosis. Our findings reveal that menin plays an important epigenetic role in promoting liver tumorigenesis, and support the notion that H3K4me3, which is regulated by the menin-mixed-lineage leukemia complex, is a potential therapeutic target in hepatocellular carcinoma.

SUMO modification of menin.

Menin acts as contextual a tumor suppressor and a tumor promoter, partly via epigenetic regulation of gene transcription. While menin is phosphorylated, it remains unclear whether wild type menin has other post-translational modifications. Here, we report that menin is SUMOylated by SUMO1 in vivo and in vitro, and the SUMOylation is reduced by a SUMO protease. Lysine 591 of menin was covalently modified by SUMO1 and K591R mutation in menin blocked SUMOylation of the C-terminal part of menin in transfected cells. Full-length menin with K591 mutation was still SUMOylated in vivo, suggesting the existence of multiple SUMOylation sites. Menin K591R mutant or menin-SUMO fusion protein still retains the ability to regulate cell proliferation and the expression of the examined menin target genes.

Interplay between menin and K-Ras in regulating lung adenocarcinoma.

MEN1, which encodes the nuclear protein menin, acts as a tumor suppressor in lung cancer and is often inactivated in human primary lung adenocarcinoma. Here, we show that the inactivation of MEN1 is associated with increased DNA methylation at the MEN1 promoter by K-Ras. On one hand, the activated K-Ras up-regulates the expression of DNA methyltransferases and enhances the binding of DNA methyltransferase 1 to the MEN1 promoter, leading to increased DNA methylation at the MEN1 gene in lung cancer cells; on the other hand, menin reduces the level of active Ras-GTP at least partly by preventing GRB2 and SOS1 from binding to Ras, without affecting the expression of GRB2 and SOS1. In human lung adenocarcinoma samples, we further demonstrate that reduced menin expression is associated with the enhanced expression of Ras (p < 0.05). Finally, excision of the Men1 gene markedly accelerates the K-Ras(G12D)-induced tumor formation in the Men1(f/f);K-Ras(G12D/+);Cre ER mouse model. Together, these findings uncover a previously unknown link between activated K-Ras and menin, an important interplay governing tumor activation and suppression in the development of lung cancer.

Menin represses malignant phenotypes of melanoma through regulating multiple pathways.

Substantial genetic evidence suggests that chromosome 11q is involved in regulating initiation and progression of malignant melanomas. Mutations of the MEN1 gene, located in chromosome 11q13, predispose individuals to the multiple endocrine neoplasia type 1 (MEN1) familial syndrome. MEN1 patients develop primary malignant melanoma, suggesting a potential link between MEN1 syndrome and development of melanomas, but the precise molecular mechanism is poorly understood. Here we show that the MEN1 gene suppresses malignant phenotypes of melanoma cells through multiple signalling pathways. Ectopic expression of menin, the product of MEN1 gene, significantly inhibited melanoma cell proliferation and migration in vitro and in vivo. The inhibition was partly achieved through suppressing expression of growth factor pleiotrophin (PTN) and receptor protein tyrosine phosphatase (RPTP) ß/ζ, accompanied with the reduced expression of phosphatidylinositol 3-kinase (pI3K) and decreased phosphorylation of focal adhesion kinase (FAK) and extracellular signal regulated kinase (ERK1/2). Interestingly, reduced expression of menin was associated with hypermethylation of the CpG islands of the MEN1 promoter in melanoma cells. Taken together, these findings suggest a previously unappreciated function for menin in suppressing malignant phenotypes of melanomas and unravel a novel mechanism involving in regulating PTN signalling by menin in development and progression of melanomas.