Nitrogen and sulfur co-doped Ti3C2Tx MXenes for high-rate lithium-ion batteries.

The electrification of heavy-duty transport and aviation urgently requires new strategies to develop high-rate lithium-ion batteries (LIBs) whose performance fundamentally relies on electrode materials. However, commercially available graphite anodes still suffer from slow kinetics of lithium-ion diffusion and severe safety concerns of lithium plating when achieving the high-rate use goal. Herein, taking Ti3C2Tx as an example, it is demonstrated that N and S co-doping in Ti3C2Tx results in a high-rate MXene anode for LIBs. Nitrogen doping not only flattens the MXene layers and expands the interlayer spacing but also increases the Ti valence state change ability. As evidenced by density functional theory calculations, the diffusion barriers of S-containing Ti3C2Tx MXenes are lower than those of the S-free counterpart, suggesting that S plays an essential role in achieving high-rate performance. Therefore, the N and S co-doped Ti3C2Tx anode in LIBs exhibited excellent performance with a reversible capacity of 113.8 mA h g-1 at a rate of 3C and ∼89% capacity retention after 1000 charge/discharge cycles. The high capacity is attributed to the change in the oxidation states of both Ti and O elements, and the tiny volume change within ∼0.6% upon the stable charging/discharging process accounts for the good capacity retention. When paired up with a LiFe0.5Mn0.5PO4 cathode, the full cell delivers a reversible capacity of 134 mA h g-1 after 1000 cycles at a high rate of 1C. The demonstration of N and S co-doped Ti3C2Tx MXenes in this work may offer a feasible approach for high-rate intercalation anode materials.

Understanding charge storage in Nb2CTx MXene as an anode material for lithium ion batteries.

MXenes represent an emerging family of two-dimensional materials of transition metal carbides/carbonitrides terminated with functional groups like -O, -OH, and -F on the chemically active surface of MX slabs. As a member of the family, Nb2CTx exhibits superior lithium storage capacity over most of the other MXenes as anode materials in lithium-ion batteries (LIBs). However, an in-depth understanding of the charge storage mechanism is still lacking so far. Here, through combining complementary experiments and density functional theory calculations, we provide insights into the (de)lithiation process. Specifically, Nb2CTx with dominant -O functional groups stores charge as a result of changes in the oxidation states of both transition metals Nb and O, which is supported by Bader charge analysis showing a significant change in the oxidation states of Nb and O upon lithiation. As monitored by ex situ X-ray diffraction, the interlayer spacing of Nb2CTx changes slightly upon lithium ion (de)intercalation, corresponding to a volume change of only 2.3% with a near zero-strain feature. By coupling with a LiFePO4/C cathode, the full cell presents superior rate capability and cycling stability as well. The insights into the charge storage mechanism of Nb2CTx in this work provide useful guidance for the rational design of MXene-based anode materials for high-performance LIBs.

Novel influenza polymerase PB2 inhibitors for the treatment of influenza A infection.

Exploration of the chemical space of known influenza polymerase PB2 inhibitor Pimodivir, was performed by our group. We synthesized and identified compounds 16a and 16b, two novel thienopyrimidine derivatives displaying anti-influenza A activity in the single digit nanomolar range in cell culture. Binding of these unique compounds in the influenza polymerase PB2 pocket was also determined using molecular modeling.

Maximizing Specific Loss Power for Magnetic Hyperthermia by Hard-Soft Mixed Ferrites.

Maximized specific loss power and intrinsic loss power approaching theoretical limits for alternating-current (AC) magnetic-field heating of nanoparticles are reported. This is achieved by engineering the effective magnetic anisotropy barrier of nanoparticles via alloying of hard and soft ferrites. 22 nm Co0.03 Mn0.28 Fe2.7 O4 /SiO2 nanoparticles reach a specific loss power value of 3417 W g-1metal at a field of 33 kA m-1 and 380 kHz. Biocompatible Zn0.3 Fe2.7 O4 /SiO2 nanoparticles achieve specific loss power of 500 W g-1metal and intrinsic loss power of 26.8 nHm2 kg-1 at field parameters of 7 kA m-1 and 380 kHz, below the clinical safety limit. Magnetic bone cement achieves heating adequate for bone tumor hyperthermia, incorporating an ultralow dosage of just 1 wt% of nanoparticles. In cellular hyperthermia experiments, these nanoparticles demonstrate high cell death rate at low field parameters. Zn0.3 Fe2.7 O4 /SiO2 nanoparticles show cell viabilities above 97% at concentrations up to 500 µg mL-1 within 48 h, suggesting toxicity lower than that of magnetite.

Nucleotide Substrate Specificity of Anti-Hepatitis C Virus Nucleoside Analogs for Human Mitochondrial RNA Polymerase.

Nucleoside analog inhibitors (NAIs) are an important class of antiviral agents. Although highly effective, some NAIs with activity against hepatitis C virus (HCV) can cause toxicity, presumably due to off-target inhibition of host mitochondrial RNA polymerase (POLRMT). The in vitro nucleotide substrate specificity of POLRMT was studied in order to explore structure-activity relationships that can facilitate the identification of nontoxic NAIs. These findings have important implications for the development of all anti-RNA virus NAIs.

Biochemical Characterization of the Active Anti-Hepatitis C Virus Metabolites of 2,6-Diaminopurine Ribonucleoside Prodrug Compared to Sofosbuvir and BMS-986094.

Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on ß-d-2'-C-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhibitor of HCV. DAPN-PD1 is metabolized intracellularly into two distinct bioactive nucleoside triphosphate (TP) analogs. The first metabolite, 2'-C-methyl-GTP, is a well-characterized inhibitor of NS5B polymerase, whereas the second metabolite, 2'-C-methyl-DAPN-TP, behaves as an adenosine base analog. In vitro assays suggest that both metabolites are inhibitors of NS5B-mediated RNA polymerization. Additional factors, such as rNAI-TP incorporation efficiencies, intracellular rNAI-TP levels, and competition with natural ribonucleotides, were examined in order to further characterize the potential role of each nucleotide metabolite in vivo Finally, we found that although both 2'-C-methyl-GTP and 2'-C-methyl-DAPN-TP were weak substrates for human mitochondrial RNA (mtRNA) polymerase (POLRMT) in vitro, DAPN-PD1 did not cause off-target inhibition of mtRNA transcription in Huh-7 cells. In contrast, administration of BMS-986094, which also generates 2'-C-methyl-GTP and previously has been associated with toxicity in humans, caused detectable inhibition of mtRNA transcription. Metabolism of BMS-986094 in Huh-7 cells leads to 87-fold higher levels of intracellular 2'-C-methyl-GTP than DAPN-PD1. Collectively, our data characterize DAPN-PD1 as a novel and potent antiviral agent that combines the delivery of two active metabolites.

Realizing chemical codoping in TiO2.

We demonstrate experimentally a chemical codoping approach that would simultaneously narrow the band gap and control the band edge positions of TiO2 semiconductors. It is shown that a sequential doping scheme with nitrogen (N) leading the way, followed by phosphorus (P), is crucial for the incorporation of both N and P into the anion sites. Various characterization techniques confirm the formation of the N-P bonds, and as a consequence of chemical codoping, the band gap of TiO2 is reduced from 3.2 eV to 1.8 eV. The realization of chemical codoping could be an important step forward in improving the general performance of electronic and optoelectronic materials and devices.

Room temperature ferromagnetic (Fe1-xCox)3BO5 nanorods.

Cobalt-doped ferroferriborate ((Fe1-xCox)3BO5) nanorods (NRs) are synthesized by a one-pot high-temperature organic-solution-phase method. The aspect ratios of the NRs are tuned by the heating rate. These NRs form via anisotropic growth along twin boundaries of the multiply twinned nuclei. Magnetic properties are dramatically modified by Co substitutional doping, changing from antiferromagnetic order at low temperatures to ferromagnetic above room temperature, with a greatly enhanced magnetic ordering temperature. These anisotropic ferromagnetic NRs with a high ordering temperature may provide a new platform for understanding nanomagnetism and for magnetic applications.

Substrate mimicry: HIV-1 reverse transcriptase recognizes 6-modified-3'-azido-2',3'-dideoxyguanosine-5'-triphosphates as adenosine analogs.

ß-D-3'-Azido-2',3'-dideoxyguanosine (3'-azido-ddG) is a potent inhibitor of HIV-1 replication with a superior resistance profile to zidovudine. Recently, we identified five novel 6-modified-3'-azido-ddG analogs that exhibit similar or superior anti-HIV-1 activity compared to 3'-azido-ddG in primary cells. To gain insight into their structure-activity-resistance relationships, we synthesized their triphosphate (TP) forms and assessed their ability to inhibit HIV-1 reverse transcriptase (RT). Steady-state and pre-steady-state kinetic experiments show that the 6-modified-3'-azido-ddGTP analogs act as adenosine rather than guanosine mimetics in DNA synthesis reactions. The order of potency of the TP analogs against wild-type RT was: 3'-azido-2,6-diaminopurine >3'-azido-6-chloropurine; 3'-azido-6-N-allylaminopurine > 2-amino-6-N,N-dimethylaminopurine; 2-amino-6-methoxypurine. Molecular modeling studies reveal unique hydrogen-bonding interactions between the nucleotide analogs and the template thymine base in the active site of RT. Surprisingly, the structure-activity relationship of the analogs differed in HIV-1 RT ATP-mediated excision assays of their monophosphate forms, suggesting that it may be possible to rationally design a modified base analog that is efficiently incorporated by RT but serves as a poor substrate for ATP-mediated excision reactions. Overall, these studies identify a promising strategy to design novel nucleoside analogs that exert profound antiviral activity against both WT and drug-resistant HIV-1.

Stabilizing Zn2SiO4 Anode by a Lithium Polyacrylate Binder for Highly Reversible Lithium-Ion Storage.

Binders are crucial for maintaining the mechanical stability of the electrodes. However, traditional binders fail to adequately buffer the volume expansion of Zn2SiO4 anode, causing electrode contact failure and considerable capacity loss during cycling. In this study, we propose a simple and effective solution to address these challenges through a combined strategy of hollow structure design and the introduction of an aqueous lithium poly(acrylic acid) (LiPAA) binder. Hollow structures can shorten ion-transfer distance and accommodate volume change outside. The excellent adhesion of the LiPAA binder created a secure connection between the active Zn2SiO4 particles, conductive additives, and the current collector, which enhanced the mechanical stability and integrity of the electrode. As a result of these positive factors, a Zn2SiO4 electrode using LiPAA as a binder can deliver an excellent capacity of 499 mAh g-1 at a high current density of 5 A g-1 and a long life span of 1000 cycles at 1 A g-1 with a capacity retention of 98%, which significantly outperforms other binders. As demonstrated by ex situ X-ray diffraction and ex situ X-ray absorption spectroscopy, the storage of lithium ions in Zn2SiO4 follows a dual conversion-alloying mechanism, using Zn as the redox center. In this process, Zn is first reduced to metallic Zn and then forms a LiZn alloy upon lithium-ion insertion. This work shows that LiPAA offers a promising approach to improve the cycling longevity of conversion and alloying anodes in Li-ion batteries.

Synthesis and evaluation of Janus type nucleosides as potential HCV NS5B polymerase inhibitors.

The synthesis of new ribo and 2'-ß-C-methyl ribo Janus type nucleosides J-AA, J-AG and J-AU is reported along with their ability to block HCV and HIV replication. Their toxicity was also assessed in Huh7, human lymphocytes, CEM and Vero cells.

Synthesis and evaluation of non-dimeric HCV NS5A inhibitors.

Based on the symmetrical bidentate structure of the NS5A inhibitor BMS-790052, a series of new monodentate molecules were designed. The synthesis of 36 new non-dimeric NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. Among them compound 5a showed picomolar range activity along with an excellent selectivity index (SI > 90,000).

Enhanced Pitting Corrosion Resistance of Nanostructured AISI 304 Stainless Steel via Pipe Inner Surface Grinding Treatment.

By means of a pipe's inner surface grinding, a single-phase nanostructured austenite was formed on the surface of an AISI 304 stainless steel. The electrochemical corrosion behavior was compared with a coarse-grained counterpart of identical surface roughness. Experimental results show that the nanostructured austenite shows a higher pitting potential and a wider passivation interval than those of its coarse-grained counterpart. The enhanced corrosion resistance was attributed to the fast diffusion of Cr within the nanostructure and, hence, the formation of a thicker passive film to efficiently protect the surface against the ion attack. This work provides insights into a simple processing method to improve the surface strength and pitting resistance of stainless steel.

Synthesis and evaluation of novel potent HCV NS5A inhibitors.

Judicious modifications to the structure of the previously reported HCV NS5A inhibitor 1, resulted in more potent anti-HCV compounds with similar and in some cases improved toxicity profiles. The synthesis of 19 new NS5A inhibitors is reported along with their ability to block HCV replication in an HCV 1b replicon system. For the most potent compounds chemical stability, stability in liver microsomes and inhibition of relevant CYP450 enzymes is also presented.

Synthesis and biological evaluation of new potent and selective HCV NS5A inhibitors.

NS5A inhibitors are a new class of direct-acting antiviral agents which display very potent anti-HCV activity in vitro and in humans. Rationally designed modifications to the central biphenyl linkage of a known NS5A series led to selection of several compounds that were synthesized and evaluated in a HCV genotype 1b replicon. The straight triphenyl linked compound 11a showed similar anti-HCV activity to the clinical compound BMS-790052 and a superior cytotoxicity profile in three different cell lines, with an EC(50) value of 26 pM and a therapeutic index of over four million in an HCV replicon assay. This triphenyl analog warrants further preclinical evaluation as an anti-HCV agent.

Scaleable processes for the synthesis of (-)-ß-D-2,6-diaminopurine dioxolane (Amdoxovir, DAPD) and (-)-ß-D-2-aminopurine dioxolane (APD).

An efficient and scalable synthesis of (-)-DAPD and (-)-APD has been developed. We discovered that t-butyl cyanoacetate can be used as a new additive for the sugar nucleoside base coupling step en route to DAPD with improved ß-selectivity and an isolated yield four fold greater than the original process scale method. Using this new process, (-)-DAPD has been prepared on greater than 20 g scale. In the synthesis of (-)-APD, a key enzyme-catalyzed hydrolysis reaction afforded the water-soluble deprotected α-anomer while leaving the ß-anomer completely untouched.

Diastereoselective Synthesis of 2'-Dihalopyrimidine Ribonucleoside Inhibitors of Hepatitis C Virus Replication.

We present a newly developed synthetic route to 2-bromo-2-fluoro ribolactone based on our published 2-chloro-2-fluoro ribolactone synthesis. Stereoselective fluorination is key to controlling the 2-diastereoselectivity. We also report a substantially improved glycosylation reaction with both the 2-bromo-2-fluoro and 2-chloro-2-fluoro sugars. These improvements allowed us to prepare 2'-dihalo nucleosides 13 and 14 in an overall 15-20% yield.

Patterning of Wafer-Scale MXene Films for High-Performance Image Sensor Arrays.

As a rapidly growing family of 2D transition metal carbides and nitrides, MXenes are recognized as promising materials for the development of future electronics and optoelectronics. So far, the reported patterning methods for MXene films lack efficiency, resolution, and compatibility, resulting in limited device integration and performance. Here, a high-performance MXene image sensor array fabricated by a wafer-scale combination patterning method of an MXene film is reported. This method combines MXene centrifugation, spin-coating, photolithography, and dry-etching and is highly compatible with mainstream semiconductor processing, with a resolution up to 2 µm, which is at least 100 times higher than other large-area patterning methods reported previously. As a result, a high-density integrated array of 1024-pixel Ti3 C2 Tx /Si photodetectors with a detectivity of 7.73 × 1014 Jones and a light-dark current ratio (Ilight /Idark ) of 6.22 × 106 , which is the ultrahigh value among all reported MXene-based photodetectors, is fabricated. This patterning technique paves a way for large-scale high-performance MXetronics compatible with mainstream semiconductor processes.

The base component of 3'-azido-2',3'-dideoxynucleosides influences resistance mutations selected in HIV-1 reverse transcriptase.

We recently reported that HIV-1 resistant to 3'-azido-3'-deoxythymidine (AZT) is not cross-resistant to 3'-azido-2',3'-dideoxypurines. This finding suggested that the nucleoside base is a major determinant of HIV-1 resistance to nucleoside analogs. To further explore this hypothesis, we conducted in vitro selection experiments by serial passage of HIV-1(LAI) in MT-2 cells in increasing concentrations of 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG), 3'-azido-2',3'-dideoxycytidine (3'-azido-ddC), or 3'-azido-2',3'-dideoxyadenosine (3'-azido-ddA). 3'-Azido-ddG selected for virus that was 5.3-fold resistant to 3'-azido-ddG compared to wild-type HIV-1(LAI) passaged in the absence of drug. Population sequencing of the entire reverse transcriptase (RT) gene identified L74V, F77L, and L214F mutations in the polymerase domain and K476N and V518I mutations in the RNase H domain. However, when introduced into HIV-1 by site-directed mutagenesis, these 5 mutations only conferred ∼2.0-fold resistance. Single-genome sequencing analyses of the selected virus revealed a complex population of mutants that all contained L74V and L214F linked to other mutations, including ones not identified during population sequencing. Recombinant HIV-1 clones containing RT derived from single sequences exhibited 3.2- to 4.0-fold 3'-azido-ddG resistance. In contrast to 3'-azido-ddG, 3'-azido-ddC selected for the V75I mutation in HIV-1 RT that conferred 5.9-fold resistance, compared to the wild-type virus. Interestingly, we were unable to select HIV-1 that was resistant to 3'-azido-ddA, even at concentrations of 3'-azido-ddA that yielded high intracellular levels of 3'-azido-ddA-5'-triphosphate. Taken together, these findings show that the nucleoside base is a major determinant of HIV-1 resistance mechanisms that can be exploited in the design of novel nucleoside RT inhibitors.

Synthesis of purine modified 2'-C-methyl nucleosides as potential anti-HCV agents.

Based on the anti-hepatitis C activity of 2'-C-methyl-adenosine and 2'-C-methyl-guanosine, a series of new modified purine 2'-C-methyl nucleosides was prepared as potential anti-hepatitis C virus agents. Herein, we report the synthesis of both 6-modified and 2-modified purine 2'-C-methyl-nucleosides along with their anti-HCV replication activity and cytotoxicity in different cells.