Photocontrolled activation of doubly o-nitrobenzyl-protected small molecule benzimidazoles leads to cancer cell death.

Artificial biomimetic chloride anionophores have shown promising applications as anticancer scaffolds. Importantly, stimuli-responsive chloride transporters that can be selectively activated inside the cancer cells to avoid undesired toxicity to normal, healthy cells are very rare. Particularly, light-responsive systems promise better applicability for photodynamic therapy because of their spatiotemporal controllability, low toxicity, and high tunability. Here, in this work, we report o-nitrobenzyl-linked, benzimidazole-based singly and doubly protected photocaged protransporters 2a, 2b, 3a, and 3b, respectively, and benzimidazole-2-amine-based active transporters 1a-1d. Among the active compounds, trifluoromethyl-based anionophore 1a showed efficient ion transport activity (EC50 = 1.2 ± 0.2 µM). Detailed mechanistic studies revealed Cl-/NO3- antiport as the main ion transport process. Interestingly, double protection with photocages was found to be necessary to achieve the complete "OFF-state" that could be activated by external light. The procarriers were eventually activated inside the MCF-7 cancer cells to induce phototoxic cell death.

A Benzohydrazide-Based Artificial Ion Channel that Modulates Chloride Ion Concentration in Cancer Cells and Induces Apoptosis by Disruption of Autophagy.

Fluctuations in the intracellular chloride ion concentration, mediated by synthetic ion transporters, have been known to induce cytotoxicity in cells by disrupting ionic homeostasis. However, the activity of these transporters in modulating autophagy remains largely unexplored. Here, we report a benzoylbenzohydrazide (1c) that self-assembles to form a supramolecular nanochannel lumen that allows selective and efficient transport of chloride ions across the cell membranes, disrupts ion homeostasis, and thus leads to the induction of apoptosis in cancer cells. It is important to note that the transporter was relatively nontoxic to cells of noncancerous origin. 1c was also shown to induce the deacidification of lysosomes, thereby disrupting autophagy in cancer cells. Taken together, these findings provide a rare example of an artificial ion channel that specifically targets cancer cells by induction of apoptosis via disruption of autophagy.

Progress and prospects toward supramolecular bioactive ion transporters.

The majority of cellular physiological processes depend on natural ion channels, which are pore-forming membrane-embedded proteins that let ions flow across the cell membranes selectively. This selective movement of ions across the membranes balances the osmolality within and outside the cell. However, mutations in the genes that encode essential membrane transport proteins or structural reorganisation of these proteins can cause life-threatening diseases like cystic fibrosis. Artificial ion transport systems have opened up a way to replace dysfunctional natural ion channels to cure such diseases through channel replacement therapy. Moreover, recent research has also demonstrated the ability of these systems to kill cancer cells, reigniting interest in the field among scientists. Our contributions to the recent progress in the design and development of artificial chloride ion transporters and their effect on biological systems have been discussed in this review. This review would provide current vistas and future directions toward the development of novel ion transporters with improved biocompatibility and desired anti-cancer properties. Additionally, it strongly emphasises stimuli-responsive ion transport systems, which are crucial for obtaining target-specificity and may speed up the application of these systems in clinical therapeutics.

Discovery of a Magnetic Dirac System with a Large Intrinsic Nonlinear Hall Effect.

Magnetic materials exhibiting topological Dirac fermions are attracting significant attention for their promising technological potential in spintronics. In these systems, the combined effect of the spin-orbit coupling and magnetic order enables the realization of novel topological phases with exotic transport properties, including the anomalous Hall effect and magneto-chiral phenomena. Herein, we report experimental signature of topological Dirac antiferromagnetism in TaCoTe2 via angle-resolved photoelectron spectroscopy and first-principles density functional theory calculations. In particular, we find the existence of spin-orbit coupling-induced gaps at the Fermi level, consistent with the manifestation of a large intrinsic nonlinear Hall conductivity. Remarkably, we find that the latter is extremely sensitive to the orientation of the Néel vector, suggesting TaCoTe2 as a suitable candidate for the realization of non-volatile spintronic devices with an unprecedented level of intrinsic tunability.

Nontoxic Artificial Chloride Channel Formation in Epithelial Cells by Isophthalic Acid-Based Small Molecules.

Artificial channels capable of facilitating the transport of Cl- ions across cell membranes while being nontoxic to the cells are rare. Such synthetic ion channels can mimic the functions of membrane transport proteins and, therefore, have the potential to treat channelopathies by replacing defective ion channels. Here we report isophthalic acid-based structurally simple molecules 1 a and 2 a, which self-assemble to render supramolecular nanochannels that allow selective transport of Cl- ions. As evident from the single-crystal X-ray diffraction analysis, the self-assembly is governed by intermolecular hydrogen bonding and π-π stacking interactions. The MD simulation studies for both 1 a and 2 a confirmed the formation of stable Cl- channel assembly in the lipid membrane and Cl- transport through them. The MQAE assay showed the efficacy of the compounds in delivering Cl- ions into cells, and the MTT assays proved that the compounds are nontoxic to cells even at a concentration of 100 µM.

The C-SHIFT Algorithm for Normalizing Covariances.

Omics technologies are powerful tools for analyzing patterns in gene expression data for thousands of genes. Due to a number of systematic variations in experiments, the raw gene expression data is often obfuscated by undesirable technical noises. Various normalization techniques were designed in an attempt to remove these non-biological errors prior to any statistical analysis. One of the reasons for normalizing data is the need for recovering the covariance matrix used in gene network analysis. In this paper, we introduce a novel normalization technique, called the covariance shift (C-SHIFT) method. This normalization algorithm uses optimization techniques together with the blessing of dimensionality philosophy and energy minimization hypothesis for covariance matrix recovery under additive noise (in biology, known as the bias). Thus, it is perfectly suited for the analysis of logarithmic gene expression data. Numerical experiments on synthetic data demonstrate the method's advantage over the classical normalization techniques. Namely, the comparison is made with Rank, Quantile, cyclic LOESS (locally estimated scatterplot smoothing), and MAD (median absolute deviation) normalization methods. We also evaluate the performance of C-SHIFT algorithm on real biological data.

Formation of supramolecular channels by reversible unwinding-rewinding of bis(indole) double helix via ion coordination.

Stimulus-responsive reversible transformation between two structural conformers is an essential process in many biological systems. An example of such a process is the conversion of amyloid-ß peptide into ß-sheet-rich oligomers, which leads to the accumulation of insoluble amyloid in the brain, in Alzheimer's disease. To reverse this unique structural shift and prevent amyloid accumulation, ß-sheet breakers are used. Herein, we report a series of bis(indole)-based biofunctional molecules, which form a stable double helix structure in the solid and solution state. In presence of chloride anion, the double helical structure unwinds to form an anion-coordinated supramolecular polymeric channel, which in turn rewinds upon the addition of Ag+ salts. Moreover, the formation of the anion-induced supramolecular ion channel results in efficient ion transport across lipid bilayer membranes with excellent chloride selectivity. This work demonstrates anion-cation-assisted stimulus-responsive unwinding and rewinding of artificial double-helix systems, paving way for smart materials with better biomedical applications.

Selective and rapid water transportation across a self-assembled peptide-diol channel via the formation of a dual water array.

Achieving superfast water transport by using synthetically designed molecular artifacts, which exclude salts and protons, is a challenging task in separation science today, as it requires the concomitant presence of a proper water-binding site and necessary selectivity filter for transporting water. Here, we demonstrate the water channel behavior of two configurationally different peptide diol isomers that mimic the natural water channel system, i.e., aquaporins. The solid-state morphology studies showed the formation of a self-assembled aggregated structure, and X-ray crystal structure analysis confirmed the formation of a nanotubular assembly that comprises two distinct water channels. The water permeabilities of all six compounds were evaluated and are found to transport water by excluding salts and protons with a water permeability rate of 5.05 × 108 water molecules per s per channel, which is around one order of magnitude less than the water permeability rate of aquaporins. MD simulation studies showed that the system forms a stable water channel inside the bilayer membrane under ambient conditions, with a 2 × 8 layered assembly, and efficiently transports water molecules by forming two distinct water arrays within the channel.

Disentangling Structural and Electronic Properties in V2O3 Thin Films: A Genuine Nonsymmetry Breaking Mott Transition.

Phase transitions are key in determining and controlling the quantum properties of correlated materials. Here, by using the combination of material synthesis and photoelectron spectroscopy, we demonstrate a genuine Mott transition undressed of any symmetry breaking side effects in the thin films of V2O3. In particular and in contrast with the bulk V2O3, we unveil the purely electronic dynamics approaching the metal-insulator transition, disentangled from the structural transformation that is prevented by the residual substrate-induced strain. On approaching the transition, the spectral signal evolves slowly over a wide temperature range, the Fermi wave-vector does not change, and the critical temperature is lower than the one reported for the bulk. Our findings are fundamental in demonstrating the universal benchmarks of a genuine nonsymmetry breaking Mott transition, extendable to a large array of correlated quantum systems, and hold promise of exploiting the metal-insulator transition by implementing V2O3 thin films in devices.

Chloride Transport across Liposomes and Cells by Nontoxic 3-(1H-1,2,3-Triazol-1-yl)benzamides.

Synthetic anion transmembrane transporters are adding new aspirations for treating channelopathies by replacing defective ion channels. The availability of such suitable candidates is still infrequent due to the associated toxicity. Here, we report 3-(1H-1,2,3-triazol-1-yl)benzamides as transmembrane anion carriers, nontoxic to cells. The selective and electrogenic chloride transport activity was established by fluorescence and ion selective electrode-based assays. MQAE assay confirmed the chloride uptake into the cells by the nontoxic compounds.

Evidence of magnetism-induced topological protection in the axion insulator candidate EuSn2P2.

We unravel the interplay of topological properties and the layered (anti)ferromagnetic ordering in EuSn2P2, using spin and chemical selective electron and X-ray spectroscopies supported by first-principle calculations. We reveal the presence of in-plane long-range ferromagnetic order triggering topological invariants and resulting in the multiple protection of topological Dirac states. We provide clear evidence that layer-dependent spin-momentum locking coexists with ferromagnetism in this material, a cohabitation that promotes EuSn2P2 as a prime candidate axion insulator for topological antiferromagnetic spintronics applications.

Anion Recognition through Multivalent C-H Hydrogen Bonds: Anion-Induced Foldamer Formation and Transport across Phospholipid Membranes.

A series of triazole-cyanostilbene receptors were designed and synthesized. The receptor binds with the anions through various CH···anion hydrogen bonding interactions, where strong binding was observed for SO42- anions followed by Cl-, Br-, NO3-, and I-, calculated from the 1H NMR titration experiment. The NOESY NMR experiment of the receptor confirmed the formation of anion-induced folded conformation. The CH···anion hydrogen bonding interaction-mediated anion recognition and foldamer formation were further confirmed from geometry optimization studies of the anion-bound complex. The receptor transports Cl- anions efficiently compared to SO42- anions across the lipid bilayer membrane via a mobile carrier mechanism.

Stimuli-Responsive Anion Transport through Acylhydrazone-Based Synthetic Anionophores.

Photoswitchable acylhydrazone-based synthetic anionophores are reported. Single-crystal X-ray structure and 1H NMR titration studies confirmed the chloride binding in solid and solution states. The ion transport activity of 1a was greatly attenuated through a phototriggered E to Z photoisomerization process, and the photoisomerized deactivated state showed high kinetic stability due to an intramolecular hydrogen bond. Switchable "OFF-ON" transport activity was achieved by the application of light and acid-catalyzed reactivation process.

Mitrofanovite Pt3Te4: A Topological Metal with Termination-Dependent Surface Band Structure and Strong Spin Polarization.

Due to their peculiar quasiparticle excitations, topological metals have high potential for applications in the fields of spintronics, catalysis, and superconductivity. Here, by combining spin- and angle-resolved photoemission spectroscopy, scanning tunneling microscopy/spectroscopy, and density functional theory, we discover surface-termination-dependent topological electronic states in the recently discovered mitrofanovite Pt3Te4. Mitrofanovite crystal is formed by alternating, van der Waals bound layers of Pt2Te2 and PtTe2. Our results demonstrate that mitrofanovite is a topological metal with termination-dependent (i) electronic band structure and (ii) spin texture. Despite their distinct electronic character, both surface terminations are characterized by electronic states exhibiting strong spin polarization with a node at the Γ point and sign reversal across the Γ point, indicating their topological nature and the possibility of realizing two distinct electronic configurations (both of them with topological features) on the surface of the same material.

High-frequency rectifiers based on type-II Dirac fermions.

The advent of topological semimetals enables the exploitation of symmetry-protected topological phenomena and quantized transport. Here, we present homogeneous rectifiers, converting high-frequency electromagnetic energy into direct current, based on low-energy Dirac fermions of topological semimetal-NiTe2, with state-of-the-art efficiency already in the first implementation. Explicitly, these devices display room-temperature photosensitivity as high as 251 mA W-1 at 0.3 THz in an unbiased mode, with a photocurrent anisotropy ratio of 22, originating from the interplay between the spin-polarized surface and bulk states. Device performances in terms of broadband operation, high dynamic range, as well as their high sensitivity, validate the immense potential and unique advantages associated to the control of nonequilibrium gapless topological states via built-in electric field, electromagnetic polarization and symmetry breaking in topological semimetals. These findings pave the way for the exploitation of topological phase of matter for high-frequency operations in polarization-sensitive sensing, communications and imaging.

Estimation of long-range dependence in gappy Gaussian time series.

Knowledge of the long range dependence (LRD) parameter is critical to studies of self-similar behavior. However, statistical estimation of the LRD parameter becomes difficult when the observed data are masked by short range dependence and other noise, or are gappy in nature (i.e., some values are missing in an otherwise regular sampling). Currently there is a lack of theory for spectral- and wavelet-based estimators of the LRD parameter for gappy data. To address this, we estimate the LRD parameter for gappy Gaussian semiparametric time series based upon undecimated wavelet variances. We develop estimation methods by using novel estimators of the wavelet variances, providing asymptotic theory for the joint distribution of the wavelet variances and our estimator of the LRD parameter. We introduce sandwich estimators to compute standard errors for our estimates. We demonstrate the efficacy of our methods using Monte Carlo simulations, and provide guidance on practical issues such as how to select the range of wavelet scales. We demonstrate the methodology using two applications: one for gappy Arctic sea-ice draft data, and another for gap free and gappy daily average temperature data collected at 17 locations in south central Sweden.

Tripodal cyanurates as selective transmembrane Cl- transporters.

Tris-carboxyamide and tris-sulfonamide-based anion transporters with a cyanuric acid core are reported. Interestingly, Cl- ion binding and transmembrane transport properties of carboxyamides are better compared to those of their tris-sulfonamide analogs. The carboxyamide derivatives act as mobile carriers of Cl- and exchange anions via antiport mechanism.

Evidence of Systematic Triggering at Teleseismic Distances Following Large Earthquakes.

Earthquakes are part of a cycle of tectonic stress buildup and release. As fault zones near the end of this seismic cycle, tipping points may be reached whereby triggering occurs and small forces result in cascading failures. The extent of this effect on global seismicity is currently unknown. Here we present evidence of ongoing triggering of earthquakes at remote distances following large source events. The earthquakes used in this study had magnitudes ≥M5.0 and the time period analyzed following large events spans three days. Earthquake occurrences display increases over baseline rates as a function of arc distance away from the epicenters. The p-values deviate from a uniform distribution, with values for collective features commonly below 0.01. An average global forcing function of increased short term seismic risk is obtained along with an upper bound response. The highest magnitude source events trigger more events, and the average global response indicates initial increased earthquake counts followed by quiescence and recovery. Higher magnitude earthquakes also appear to be triggered more often than lower magnitude events. The region with the greatest chance of induced earthquakes following all source events is on the opposite side of the earth, within 30 degrees of the antipode.

Wavelet variance analysis for random fields on a regular lattice.

There has been considerable recent interest in using wavelets to analyze time series and images that can be regarded as realizations of certain 1-D and 2-D stochastic processes on a regular lattice. Wavelets give rise to the concept of the wavelet variance (or wavelet power spectrum), which decomposes the variance of a stochastic process on a scale-by-scale basis. The wavelet variance has been applied to a variety of time series, and a statistical theory for estimators of this variance has been developed. While there have been applications of the wavelet variance in the 2-D context (in particular, in works by Unser in 1995 on wavelet-based texture analysis for images and by Lark and Webster in 2004 on analysis of soil properties), a formal statistical theory for such analysis has been lacking. In this paper, we develop the statistical theory by generalizing and extending some of the approaches developed for time series, thus leading to a large-sample theory for estimators of 2-D wavelet variances. We apply our theory to simulated data from Gaussian random fields with exponential covariances and from fractional Brownian surfaces. We demonstrate that the wavelet variance is potentially useful for texture discrimination. We also use our methodology to analyze images of four types of clouds observed over the southeast Pacific Ocean.