Fluorinated Hafnium and Zirconium Coenable the Tunable Biodegradability of Core-Multishell Heterogeneous Nanocrystals for Bioimaging.

Upconversion (UC)/downconversion (DC)-luminescent lanthanide-doped nanocrystals (LDNCs) with near-infrared (NIR, 650-1700 nm) excitation have been gaining increasing popularity in bioimaging. However, conventional NIR-excited LDNCs cannot be degraded and eliminated eventually in vivo owing to intrinsic "rigid" lattices, thus constraining clinical applications. A biodegradability-tunable heterogeneous core-shell-shell luminescent LDNC of Na3HfF7:Yb,Er@Na3ZrF7:Yb,Er@CaF2:Yb,Zr (abbreviated as HZC) was developed and modified with oxidized sodium alginate (OSA) for multimode bioimaging. The dynamic "soft" lattice-Na3Hf(Zr)F7 host and the varying Zr4+ doping content in the outmoster CaF2 shell endowed HZC with tunable degradability. Through elaborated core-shell-shell coating, Yb3+/Er3+-coupled UC red and green and DC second near-infrared (NIR-II) emissions were, respectively, enhanced by 31.23-, 150.60-, and 19.42-fold when compared with core nanocrystals. HZC generated computed tomography (CT) imaging contrast effects, thus enabling NIR-II/CT/UC trimodal imaging. OSA modification not only ensured the exemplary biocompatibility of HZC but also enabled tumor-specific diagnosis. The findings would benefit the clinical imaging translation of LDNCs.

Signal "On-Amplified-Off" Strategy Based on Hafnium Dioxide Nanomaterials as Electrochemiluminescence Emitters for Progesterone Detection.

When consumed, excess progesterone (P4)─found in food and the environment─can lead to severe illnesses in humans. Therefore, quantitative analysis of P4 is critical for identifying its hazardous levels. In this study, a novel signal "on-amplified-off" P4 detection mode was proposed, which was based on the utilization of hafnium oxide (HfO2) as a unique electrochemiluminescence (ECL) emitter, produced by calcining UiO-66(Hf). This is the first time that HfO2 has been used as an ECL emitter. HfO2 displayed excellent conductivity and a high specific surface area, allowing it to connect with numerous aptamers and produce a "signal-on" effect. Ni-doped ZnO (Ni-ZnO) acted as a coreaction accelerator, enhancing the ECL strength of HfO2 by generating more tripropylamine radicals. cDNA was labeled with Ni-ZnO, and Ni-ZnO was linked to the aptamer via base complementary pairing, affording "signal-amplified". The presence of the target molecule P4 instigated a specific binding process with the aptamer, triggering the shedding of cDNA-Ni-ZnO and resulting in "signal-off". This novel "on-amplified-off" strategy effectively improved the sensitivity and specificity of P4 analysis, introducing a practical method for detecting biomolecules beyond the scope of this study, which holds immense potential for future applications.

Harnessing Hafnium-Based Nanomaterials for Cancer Diagnosis and Therapy.

With the rapid development of nanotechnology and nanomedicine, there are great interests in employing nanomaterials to improve the efficiency of disease diagnosis and treatment. The clinical translation of hafnium oxide (HfO2 ), commercially namedas NBTXR3, as a new kind of nanoradiosensitizer for radiotherapy (RT) of cancers has aroused extensive interest in researches on Hf-based nanomaterials for biomedical application. In the past 20 years, Hf-based nanomaterials have emerged as potential and important nanomedicine for computed tomography (CT)-involved bioimaging and RT-associated cancer treatment due to their excellent electronic structures and intrinsic physiochemical properties. In this review, a bibliometric analysis method is employed to summarize the progress on the synthesis technology of various Hf-based nanomaterials, including HfO2 , HfO2 -based compounds, and Hf-organic ligand coordination hybrids, such as metal-organic frameworks or nanoscaled coordination polymers. Moreover, current states in the application of Hf-based CT-involved contrasts for tissue imaging or cancer diagnosis are reviewed in detail. Importantly, the recent advances in Hf-based nanomaterials-mediated radiosensitization and synergistic RT with other current mainstream treatments are also generalized. Finally, current challenges and future perspectives of Hf-based nanomaterials with a view to maximize their great potential in the research of translational medicine are also discussed.

Dimensional Reduction of Metal-Organic Frameworks for Enhanced Cryopreservation of Red Blood Cells.

To increase the red blood cell (RBC) cryopreservation efficiency by metal-organic frameworks (MOFs), a dimensional reduction approach has been proposed. Namely, 3D MOF nanoparticles are progressively reduced to 2D ultra-thin metal-organic layers (MOLs). We found that 2D MOLs are beneficial for enhanced interactions of the interfacial hydrogen-bonded water network and increased utilization of inner ordered structures, due to the higher surface-to-volume ratio. Specifically, a series of hafnium (Hf)-based 2D MOLs with different thicknesses (monolayer to stacked multilayers) and densities of hydrogen bonding sites have been synthesized. Both ice recrystallization inhibition activity (IRI) and RBCs cryopreservation assay confirm the pronounced better IRI activity and excellent cell recovery efficiency (up to ≈63 % at a very low concentration of 0.7 mg mL-1 ) of thin-layered Hf-MOLs compared to their 3D counterparts, thereby verifying the dimensional reduction strategy to improved cryoprotectant behaviors.

Assessment of the Morphological, Optical, and Photoluminescence Properties of HfO2 Nanoparticles Synthesized by a Sol-Gel Method Assisted by Microwave Irradiation.

In this work, we optimized the synthesis of HfO2 nanoparticles (NPs) with a nonaqueous sol-gel method assisted by microwave heating, with a direct surfactant-free extraction and stabilization in water. To tune the structural, morphological, and photophysical properties, we explored the influence of reaction time, heating temperature, and type and concentration of a salt precursor. The controlled size, shape, crystallinity associated with high stability, a good yield of production, and stabilization in water without any surfactant modification of these HfO2 NPs open possibilities for future optoelectronic and biomedical applications. The investigation of their optical properties, revealed a high absorption in the UV range and the presence of a large band gap, originating in transparency at visible wavelengths. Under UV excitation, photoluminescence (PL) shows three emission bands centered at 305, 381, and 522 nm and are assigned to the vibronic transition of an excited OH•* radical or to a self-trapped exciton, to threefold oxygen vacancies VO3 with recombination to the valence band, and to defect level, respectively. The presence of oxygen vacancies associated with PL properties is particularly attractive for optoelectronic, photocatalysis, scintillator, and UV photosensor applications. Finally, by changing the nature of the hafnium precursor salt, using hafnium ethoxide or hafnium acetylacetonate, low-crystallized and aggregated NPs were obtained, which requires further investigation.

Comparative Studies on the Proton Conductivities of Hafnium-Based Metal-Organic Frameworks and Related Chitosan or Nafion Composite Membranes.

Hafnium (Hf)-based UiO-66 series metal-organic frameworks (MOFs) have been widely studied on gas storage, gas separation, reduction reaction, and other aspects since they were first prepared in 2012, but there are few studies on proton conductivity. In this work, one Hf-based MOF, Hf-UiO-66-fum showing UiO-66 structure, also known as MOF-801-Hf, was synthesized at room temperature using cheap fumaric acid as the bridging ligand, and then imidazole units were successfully introduced into MOF-801-Hf to obatin a doped product, Im@MOF-801-Hf. Note that both MOF-801-Hf and Im@MOF-801-Hf demonstrate excellent thermal, water, and acid-base stabilities. Expectedly, the maximum proton conductivity (σ) of Im@MOF-801-Hf (1.46 × 10-2 S·cm-1) is nearly 4 times greater than that of MOF-801-Hf (3.98 × 10-3 S·cm-1) under 100 °C and 98% relative humidity (RH). To explore their possible practical application value, we doped them into chitosan (CS) or Nafion membranes as fillers, namely, CS/MOF-801-Hf-X, CS/Im@MOF-801-Hf-Y, and Nafion/MOF-801-Hf-Z (X, Y, and Z are the doping percentages of MOF in the membrane, respectively). Intriguingly, it was found that CS/MOF-801-Hf-6 and CS/Im@MOF-801-Hf-4 indicated the highest σ values of 1.73 × 10-2 and 2.14 × 10-2 S·cm-1, respectively, under 100 °C and 98% RH and Nafion/MOF-801-Hf-9 also revealed a high σ value of 4.87 × 10-2 S·cm-1 under 80 °C and 98% RH, which showed varying degrees of enhancement compared to the original MOFs or pure CS and Nafion membranes. Our study illustrates that these Hf-based MOFs and related composite membranes offer great potential in electrochemical fields.

Coupling Sr-Nd-Hf Isotope Ratios and Elemental Analysis to Accurately Quantify North African Dust Contributions to PM2.5 in a Complex Urban Atmosphere by Reducing Mineral Dust Collinearity.

Tracking Saharan-Sahelian dust across the globe is essential to elucidate its effects on Earth's climate, radiation budget, hydrologic cycle, nutrient cycling, and also human health when it seasonally enters populated/industrialized regions of Africa, Europe, and North America. However, the elemental composition of mineral dust arising locally from construction activities and aeolian soil resuspension overlaps with African dust. Therefore, we derived a novel "isotope-resolved chemical mass balance" (IRCMB) method by employing radiogenic strontium, neodymium, and hafnium isotopes to accurately differentiate and quantitatively apportion collinear proximal and synoptic-scale crustal and anthropogenic mineral dust sources. IRCMB was applied to two air masses that transported African dust to Barbados and Texas to track particulate matter (PM) spikes at both locations. During Saharan-Sahelian intrusions, the radiogenic content of urban PM2.5 increased with respect to 87Sr/86Sr and 176Hf/177Hf but decreased in terms of 143Nd/144Nd, demonstrating the ability of these isotopes to sensitively track African dust intrusions even in complex metropolitan atmospheres. The principal aerosol strontium, neodymium, and hafnium end members were concrete dust and soil, soil and motor vehicles, and motor vehicles and North African dust, respectively. IRCMB separated and quantified local soil and distal crustal dust even when PM2.5 concentrations were low, opening a promising source apportionment avenue for urbanized/industrialized atmospheres.

Recovery of 177Lu from Irradiated HfO2 Targets for Nuclear Medicine Purposes.

A new method of production of one of the most widely used isotopes in nuclear medicine, 177Lu, with high chemical purity was developed; this method includes irradiation of the HfO2 target with bremsstrahlung photons. The irradiated target was dissolved in HF and then diluted and placed onto a column filled with LN resin. Quantitative sorption of 177Lu could be observed during this process. The column later was rinsed with the mixture of 0.1 M HF and 1 M HNO3 and then 2 M HNO3 to remove impurities. Quantitative desorption of 177Lu was achieved by using 6 M HNO3. The developed method of 177Lu production ensures high purification of this isotope from macroquantities of hafnium and zirconium and radioactive impurities of carrier-free yttrium. The content of 177mLu in 177Lu in photonuclear production was determined. Due to high chemical and radionuclide purity, 177Lu obtained by the developed method can be used in nuclear medicine.

A Metal-Phenolic Nanosensitizer Performs Hydrogen Sulfide-Reprogrammed Oxygen Metabolism for Cancer Radiotherapy Intensification and Immunogenicity.

Radiotherapy (RT) is hampered by the limited oxygen in tumors, which could be potentiated via reprogramming the oxygen metabolism and increasing the oxygen utilization efficiency. Herein, a metal-phenolic nanosensitizer (Hf-PSP-DTC@PLX) was integrated via an acid-sensitive hydrogen sulfide (H2 S) donor (polyethylene glycol-co-polydithiocarbamates, PEG-DTC) and a hafnium-chelated polyphenolic semiconducting polymer (Hf-PSP) in an amphiphilic polymer (poloxamer F127, PLX). Hf-PSP-DTC@PLX elicited a high imaging performance for precise RT and generated H2 S to reduce the cellular oxygen consumption rate via mitochondrial respiration inhibition, which reprogrammed the oxygen metabolism for improvement of the tumor oxygenation. Then, Hf-sensitization could fully utilize the well-preserved oxygen to intensify RT efficacy and activate immunogenicity. Such a synergistic strategy for improvement of oxygenation and oxygen utilization would have great potential in optimizing oxygen-dependent therapeutics.

Spectroelectrochemical Properties and Catalytic Activity in Cyclohexane Oxidation of the Hybrid Zr/Hf-Phthalocyaninate-Capped Nickel(II) and Iron(II) tris-Pyridineoximates and Their Precursors.

The in situ spectroelectrochemical cyclic voltammetric studies of the antimony-monocapped nickel(II) and iron(II) tris-pyridineoximates with a labile triethylantimony cross-linking group and Zr(IV)/Hf(IV) phthalocyaninate complexes were performed in order to understand the nature of the redox events in the molecules of heterodinuclear zirconium(IV) and hafnium(IV) phthalocyaninate-capped derivatives. Electronic structures of their 1e-oxidized and 1e-electron-reduced forms were experimentally studied by electron paramagnetic resonance (EPR) spectroscopy and UV-vis-near-IR spectroelectrochemical experiments and supported by density functional theory (DFT) calculations. The investigated hybrid molecular systems that combine a transition metal (pseudo)clathrochelate and a Zr/Hf-phthalocyaninate moiety exhibit quite rich redox activity both in the cathodic and in the anodic region. These binuclear compounds and their precursors were tested as potential catalysts in oxidation reactions of cyclohexane and the results are discussed.

Hafnium (IV) oxide obtained by atomic layer deposition (ALD) technology promotes early osteogenesis via activation of Runx2-OPN-mir21A axis while inhibits osteoclasts activity.

BACKGROUND: Due to increasing aging of population prevalence of age-related disorders including osteoporosis is rapidly growing. Due to health and economic impact of the disease, there is an urgent need to develop techniques supporting bone metabolism and bone regeneration after fracture. Due to imbalance between bone forming and bone resorbing cells, the healing process of osteoporotic bone is problematic and prolonged. Thus searching for agents able to restore the homeostasis between these cells is strongly desirable. RESULTS: In the present study, using ALD technology, we obtained homogeneous, amorphous layer of hafnium (IV) oxide (HfO2). Considering the specific growth rate (1.9Å/cycle) for the selected process at the temperature of 90 °C, we performed the 100 nm deposition process, which was confirmed by measuring film thickness using reflectometry. Then biological properties of the layer were investigated with pre-osteoblast (MC3T3), pre-osteoclasts (4B12) and macrophages (RAW 264.7) using immunofluorescence and RT-qPCR. We have shown, that HfO2 (i) enhance osteogenesis, (ii) reduce osteoclastogenesis (iii) do not elicit immune response and (iv) exert anti-inflammatory effects. CONCLUSION: HfO2 layer can be applied to cover the surface of metallic biomaterials in order to enhance the healing process of osteoporotic bone fracture.

Structural Evolution and Magnetic Properties of Gd2Hf2O7 Nanocrystals: Computational and Experimental Investigations.

Structural evolution in functional materials is a physicochemical phenomenon, which is important from a fundamental study point of view and for its applications in magnetism, catalysis, and nuclear waste immobilization. In this study, we used x-ray diffraction and Raman spectroscopy to examine the Gd2Hf2O7 (GHO) pyrochlore, and we showed that it underwent a thermally induced crystalline phase evolution. Superconducting quantum interference device measurements were carried out on both the weakly ordered pyrochlore and the fully ordered phases. These measurements suggest a weak magnetism for both pyrochlore phases. Spin density calculations showed that the Gd3+ ion has a major contribution to the fully ordered pyrochlore magnetic behavior and its cation antisite. The origin of the Gd magnetism is due to the concomitant shift of its spin-up 4f orbital states above the Fermi energy and its spin-down states below the Fermi energy. This picture is in contrast to the familiar Stoner model used in magnetism. The ordered pyrochlore GHO is antiferromagnetic, whereas its antisite is ferromagnetic. The localization of the Gd-4f orbitals is also indicative of weak magnetism. Chemical bonding was analyzed via overlap population calculations: These analyses indicate that Hf-Gd and Gd-O covalent interactions are destabilizing, and thus, the stabilities of these bonds are due to ionic interactions. Our combined experimental and computational analyses on the technologically important pyrochlore materials provide a basic understanding of their structure, bonding properties, and magnetic behaviors.

Hf(OTf)4 as a Highly Potent Catalyst for the Synthesis of Mannich Bases under Solvent-Free Conditions.

Hf(OTf)4 was identified as a highly potent catalyst (0.1-0.5 mol%) for three-component Mannich reaction under solvent-free conditions. Hf(OTf)4-catalyzed Mannich reaction exhibited excellent regioselectivity and diastereoselectivity when alkyl ketones were employed as substrates. 1H NMR tracing of the H/D exchange reaction of ketones in MeOH-d4 indicated that Hf(OTf)4 could significantly promote the keto-enol tautomerization, thereby contributing to the acceleration of reaction rate.

Unsaturated and Benzannulated N-Heterocyclic Carbene Complexes of Titanium and Hafnium: Impact on Catalysts Structure and Performance in Copolymerization of Cyclohexene Oxide with CO2.

Tridentate, bis-phenolate N-heterocyclic carbenes (NHCs) are among the ligands giving the most selective and active group 4-based catalysts for the copolymerization of cyclohexene oxide (CHO) with CO2. In particular, ligands based on imidazolidin-2-ylidene (saturated NHC) moieties have given catalysts which exclusively form polycarbonate in moderate-to-high yields even under low CO2 pressure and at low copolymerization temperatures. Here, to evaluate the influence of the NHC moiety on the molecular structure of the catalyst and its performance in copolymerization, we extend this chemistry by synthesizing and characterizing titanium complexes bearing tridentate bis-phenolate imidazol-2-ylidene (unsaturated NHC) and benzimidazol-2-ylidene (benzannulated NHC) ligands. The electronic properties of the ligands and the nature of their bonds to titanium are studied using density functional theory (DFT) and natural bond orbital (NBO) analysis. The metal-NHC bond distances and bond strengths are governed by ligand-to-metal σ- and π-donation, whereas back-donation directly from the metal to the NHC ligand seems to be less important. The NHC π-acceptor orbitals are still involved in bonding, as they interact with THF and isopropoxide oxygen lone-pair donor orbitals. The new complexes are, when combined with [PPN]Cl co-catalyst, selective in polycarbonate formation. The highest activity, albeit lower than that of the previously reported Ti catalysts based on saturated NHC, was obtained with the benzannulated NHC-Ti catalyst. Attempts to synthesize unsaturated and benzannulated NHC analogues based on Hf invariably led, as in earlier work with Zr, to a mixture of products that include zwitterionic and homoleptic complexes. However, the benzannulated NHC-Hf complexes were obtained as the major products, allowing for isolation. Although these complexes selectively form polycarbonate, their catalytic performance is inferior to that of analogues based on saturated NHC.

In vivo measurement of pre-operational spallation source workers: baseline body burden levels and detection limits of relevant gamma emitters using high-resolution gamma spectrometry.

As a measure to prepare for long-term internal dose monitoring of workers at the European Spallation Source (ESS) in Lund, Sweden, operated by the European Research Infrastructure Consortium (ERIC), as well as to enhance emergency preparedness against accidental releases, a series of in vivo measurements were conducted using a high-resolution HPGe detector with a 123% relative efficiency (1.332 MeV). This study describes the whole-body counting set-up, calibration procedure, and subsequent validation measurements using conventional NaI(Tl)-scanning-bed geometry on a selection of workers from the ESS. Detection limits for the relevant gamma emitters 7Be, 172Hf, and 182Ta were determined to be 65 Bq, 130 Bq, and 22 Bq, respectively, using a 2400 s acquisition time. The baseline measurements suggest that care must be taken to ensure that the fluctuations in the presence of radon daughters 214Bi and 214Pb are minimised by, for example, ensuring a minimum air exchange between the measuring room and the ambient air, and by demanding that the measured subjects change clothes and shower before measurement. Furthermore, in a monitoring program for internal doses to spallation source workers, the presence of radionuclides originating from non-work-related sources (such as 226Ra from private water wells or 137Cs from intakes of Chernobyl contaminated foodstuffs), or radionuclides from previous work history (such as 60Co within the nuclear power industry), must be considered.

Discrete Hf18 Metal-oxo Cluster as a Heterogeneous Nanozyme for Site-Specific Proteolysis.

The selective hydrolysis of proteins by non-enzymatic catalysis is difficult to achieve, yet it is crucial for applications in biotechnology and proteomics. Herein, we report that discrete hafnium metal-oxo cluster [Hf18 O10 (OH)26 (SO4 )13 ⋅(H2 O)33 ] (Hf18 ), which is centred by the same hexamer motif found in many MOFs, acts as a heterogeneous catalyst for the efficient hydrolysis of horse heart myoglobin (HHM) in low buffer concentrations. Among 154 amino acids present in the sequence of HHM, strictly selective cleavage at only 6 solvent accessible aspartate residues was observed. Mechanistic experiments suggest that the hydrolytic activity is likely derived from the actuation of HfIV Lewis acidic sites and the Brønsted acidic surface of Hf18 . X-ray scattering and ESI-MS revealed that Hf18 is completely insoluble in these conditions, confirming the HHM hydrolysis is caused by a heterogeneous reaction of the solid Hf18 cluster, and not from smaller, soluble Hf species that could leach into solution.

NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial.

BACKGROUND: Pathological complete response to preoperative treatment in adults with soft-tissue sarcoma can be achieved in only a few patients receiving radiotherapy. This phase 2-3 trial evaluated the safety and efficacy of the hafnium oxide (HfO2) nanoparticle NBTXR3 activated by radiotherapy versus radiotherapy alone as a pre-operative treatment in patients with locally advanced soft-tissue sarcoma. METHODS: Act.In.Sarc is a phase 2-3 randomised, multicentre, international trial. Adults (aged ≥18 years) with locally advanced soft-tissue sarcoma of the extremity or trunk wall, of any histological grade, and requiring preoperative radiotherapy were included. Patients had to have a WHO performance status of 0-2 and a life expectancy of at least 6 months. Patients were randomly assigned (1:1) by an interactive web response system to receive either NBTXR3 (volume corresponding to 10% of baseline tumour volume at a fixed concentration of 53·3 g/L) as a single intratumoural administration before preoperative external-beam radiotherapy (50 Gy in 25 fractions) or radiotherapy alone, followed by surgery. Randomisation was stratified by histological subtype (myxoid liposarcoma vs others). This was an open-label study. The primary endpoint was the proportion of patients with a pathological complete response, assessed by a central pathology review board following European Organisation for Research and Treatment of Cancer guidelines in the intention-to-treat population full analysis set. Safety analyses were done in all patients who received at least one puncture and injection of NBTXR3 or at least one dose of radiotherapy. This study is registered with ClinicalTrials.gov, number NCT02379845, and is ongoing for long-term follow-up, but recruitment is complete. FINDINGS: Between March 3, 2015, and Nov 21, 2017, 180 eligible patients were enrolled and randomly assigned and 179 started treatment: 89 in the NBTXR3 plus radiotherapy group and 90 in the radiotherapy alone group. Two patients in the NBTXR3 group and one patient in the radiotherapy group were excluded from the efficacy analysis because they were subsequently discovered to be ineligible; thus, a total of 176 patients were analysed for the primary endpoint in the intention-to-treat full analysis set (87 in the NBTXR3 group and 89 in the radiotherapy alone group). A pathological complete response was noted in 14 (16%) of 87 patients in the NBTXR3 group and seven (8%) of 89 in the radiotherapy alone group (p=0·044). In both treatment groups, the most common grade 3-4 treatment-emergent adverse event was postoperative wound complication (eight [9%] of 89 patients in the NBTXR3 group and eight [9%] of 90 in the radiotherapy alone group). The most common grade 3-4 adverse events related to NBTXR3 administration were injection site pain (four [4%] of 89) and hypotension (four [4%]) and the most common grade 3-4 radiotherapy-related adverse event was radiation skin injury in both groups (five [6%] of 89 in the NBTXR3 group and four [4%] of 90 in the radiotherapy alone group). The most common treatment-emergent grade 3-4 adverse event related to NBTXR3 was hypotension (six [7%] of 89 patients). Serious adverse events were observed in 35 (39%) of 89 patients in the NBTXR3 group and 27 (30%) of 90 patients in the radiotherapy alone group. No treatment-related deaths occurred. INTERPRETATION: This trial validates the mode of action of this new class of radioenhancer, which potentially opens a large field of clinical applications in soft-tissue sarcoma and possibly other cancers. FUNDING: Nanobiotix SA.

RRAM-based synapse devices for neuromorphic systems.

Hardware artificial neural network (ANN) systems with high density synapse array devices can perform massive parallel computing for pattern recognition with low power consumption. To implement a neuromorphic system with on-chip training capability, we need to develop an ideal synapse device with various device requirements, such as scalability, MLC characteristics, low power operation, data retention, and symmetric/linear conductance changes under potentiation/depression modes. Although various devices have been proposed for synapse applications, they have limitations for application in neuromorphic systems. In this paper, we will cover various RRAM synapse devices, such as filamentary switching RRAM (HfOx, TaOx, Cu-CBRAM) and analog RRAM devices, based on interface resistive switching (Pr0.7Ca0.3MnOx and TiOx) and ferroelectric polarization (HfZrOx). By optimizing potentiation/depression conditions, we could improve the conductance linearity and MLC characteristics of filamentary synapse devices. Interface RRAM has better MLC characteristics with limited retention and conductance linearity. By controlling the reactivity of metal electrodes and the oxygen concentration in oxides, we can modulate the synapse characteristics. Metal-Ferroelectric-Insulator-Semiconductor (MFIS) FET devices exhibit good retention characteristics and analog memory characteristics due to polarization. Based on various synapse device characteristics, we have estimated the pattern recognition accuracy of MNIST handwritten digits and CIFAR-10 datasets. We have confirmed that synapse device characteristics directly affect the pattern recognition accuracy of ANNs. In order to simultaneously satisfy all the requirements of synapse devices, it is necessary to develop new technology capable of controlling the movement of oxygen vacancies and metal ions at the atomic scale. Considering the limited synapse characteristics of current 2-terminal RRAM devices, hardware ANNs capable of only off-chip training can be constructed by optimizing the current RRAM devices by limiting the bit number. A 3-terminal synapse device or a device based on a new operation principle should be developed as an alternative for on-chip training applications.

Preparation of Pincer Hafnium Complexes for Olefin Polymerization.

Pincer-type [Cnaphthyl, Npyridine, Namido]HfMe2 complex is a flagship among the post-metallocene catalysts. In this work, various pincer-type Hf-complexes were prepared for olefin polymerization. Pincer-type [Namido, Npyridine, Namido]HfMe2 complexes were prepared by reacting in situ generated HfMe4 with the corresponding ligand precursors, and the structure of a complex bearing 2,6-Et2C6H3Namido moieties was confirmed by X-ray crystallography. When the ligand precursors of [(CH3)R2Si-C5H3N-C(H)PhN(H)Ar (R = Me or Ph, Ar = 2,6-diisopropylphenyl) were treated with in situ generated HfMe4, pincer-type [Csilylmethyl, Npyridine, Namido]HfMe2 complexes were afforded by formation of Hf-CH2Si bond. Pincer-type [Cnaphthyl, Sthiophene, Namido]HfMe2 complex, where the pyridine moiety in the flagship catalyst was replaced with a thiophene unit, was not generated when the corresponding ligand precursor was treated with HfMe4. Instead, the [Sthiophene, Namido]HfMe3-type complex was obtained with no formation of the Hf-Cnaphthyl bond. A series of pincer-type [Cnaphthyl, Npyridine, Nalkylamido]HfMe2 complexes was prepared where the arylamido moiety in the flagship catalyst was replaced with alkylamido moieties (alkyl = iPr, cyclohexyl, tBu, adamantyl). Structures of the complexes bearing isopropylamido and adamantylamido moieties were confirmed by X-ray crystallography. Most of the complexes cleanly generated the desired ion-pair complexes when treated with an equivalent amount of [(C18H37)2N(H)Me]+[B(C6F5)4]-, which showed negligible activity in olefin polymerization. Some complexes bearing bulky substituents showed moderate activities, even though the desired ion-pair complexes were not cleanly afforded.

Highly Efficient Synthesis of Substituted 3,4-Dihydropyrimidin-2-(1H)-ones (DHPMs) Catalyzed by Hf(OTf)4: Mechanistic Insights into Reaction Pathways under Metal Lewis Acid Catalysis and Solvent-Free Conditions.

In our studies on the catalytic activity of Group IVB transition metal Lewis acids, Hf(OTf)4 was identified as a highly potent catalyst for "one-pot, three-component" Biginelli reaction. More importantly, it was found that solvent-free conditions, in contrast to solvent-based conditions, could dramatically promote the Hf(OTf)4-catalyzed formation of 3,4-dihydro-pyrimidin-2-(1H)-ones. To provide a mechanistic explanation, we closely examined the catalytic effects of Hf(OTf)4 on all three potential reaction pathways in both "sequential bimolecular condensations" and "one-pot, three-component" manners. The experimental results showed that the synergistic effects of solvent-free conditions and Hf(OTf)4 catalysis not only drastically accelerate Biginelli reaction by enhancing the imine route and activating the enamine route but also avoid the formation of Knoevenagel adduct, which may lead to an undesired byproduct. In addition, ¹H-MMR tracing of the H-D exchange reaction of methyl acetoacetate in MeOH-d4 indicated that Hf(IV) cation may significantly accelerate ketone-enol tautomerization and activate the ß-ketone moiety, thereby contributing to the overall reaction rate.