Low Potential CO2 Reduction by Inert Fe(II)-Macrobicyclic Complex: A New Concept of Cavity Assisted CO2 Activation.

The advantage of a pre-organized π-cavity of Fe(II) complex of a newly developed macrobicycle cryptand is explored for CO2 reduction by overcoming the problem of high overpotential associated with the inert nature of the cryptate. Thus, a bipyridine-centered tritopic macrobicycle having a molecular π-cavity capable of forming Fe(II) complex as well as potential for CO2 encapsulation is synthesized. The inert Fe(II)-cryptate shows much lower potential in cyclic voltammetry than the Fe(II)-tris-dimethylbipyridine (Fe-MBP) core. Interestingly, this cryptate shows electrochemical CO2 reduction at a considerably lower potential than the Fe-MBP inert core. Therefore, this study represents that a well-structured π-cavity may generate a new series of molecular catalysts for the CO2 reduction reaction (CO2 RR), even with the inert metal complexes.

PP2A and GSK3 act as modifiers of FUS-ALS by modulating mitochondrial transport.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease which currently lacks effective treatments. Mutations in the RNA-binding protein FUS are a common cause of familial ALS, accounting for around 4% of the cases. Understanding the mechanisms by which mutant FUS becomes toxic to neurons can provide insight into the pathogenesis of both familial and sporadic ALS. We have previously observed that overexpression of wild-type or ALS-mutant FUS in Drosophila motor neurons is toxic, which allowed us to screen for novel genetic modifiers of the disease. Using a genome-wide screening approach, we identified Protein Phosphatase 2A (PP2A) and Glycogen Synthase Kinase 3 (GSK3) as novel modifiers of FUS-ALS. Loss of function or pharmacological inhibition of either protein rescued FUS-associated lethality in Drosophila. Consistent with a conserved role in disease pathogenesis, pharmacological inhibition of both proteins rescued disease-relevant phenotypes, including mitochondrial trafficking defects and neuromuscular junction failure, in patient iPSC-derived spinal motor neurons (iPSC-sMNs). In FUS-ALS flies, mice, and human iPSC-sMNs, we observed reduced GSK3 inhibitory phosphorylation, suggesting that FUS dysfunction results in GSK3 hyperactivity. Furthermore, we found that PP2A acts upstream of GSK3, affecting its inhibitory phosphorylation. GSK3 has previously been linked to kinesin-1 hyperphosphorylation. We observed this in both flies and iPSC-sMNs, and we rescued this hyperphosphorylation by inhibiting GSK3 or PP2A. Moreover, increasing the level of kinesin-1 expression in our Drosophila model strongly rescued toxicity, confirming the relevance of kinesin-1 hyperphosphorylation. Our data provide in vivo evidence that PP2A and GSK3 are disease modifiers, and reveal an unexplored mechanistic link between PP2A, GSK3, and kinesin-1, that may be central to the pathogenesis of FUS-ALS and sporadic forms of the disease.

Variation in Catalytic Efficacies of a 2D pH-Stable MOF by Altering Activation Methods.

Although it is well-known that the Lewis acidity of Metal-Organic Frameworks (MOFs) can effectively enhance their catalytic activity in organic transformations, access to these Lewis-acidic sites remains a key hurdle to widespread applications of Lewis-acidic catalysis by MOFs. Easy accessibility of strong Lewis acidic sites onto 2D MOFs by using proper activation methods can be a cornerstone in attaining desired catalytic performance. Herein, we report a new 2D chemically stable MOF, IITKGP-60, which displayed excellent framework robustness over a wide pH range (2-12). Benefiting from the abundant open metal sites (OMSs) and framework robustness, the catalytic activity of the developed material was explored in one-pot three-component Strecker reaction and Knoevenagel condensation reaction. Moreover, the developed catalyst is superior in catalyzing the reactions involving sterically hindered substrate (1-naphthaldehyde) with high turnover number. A comparative catalytic study was conducted using different activation methods (chloroform and methanol exchanged activated samples), highlighting the significant effect of activation methods on its catalytic performances. The sustainable synthetic pathway under solvent-free conditions for a broad scope of substrates using low catalyst loading and excellent recyclability made the developed pH-stable framework a promising heterogeneous catalyst.

Pressure Induced Alteration and Stabilization of Intermolecular Stacking in Square-planar Osmium tetracarbonyl.

Osmium carbonyls are well known to form stable 18-electron complexes like Os(CO)5 , Os2 (CO)9 and Os3 (CO)12 having both bridging and terminal carbonyls. For osmium tetra-carbonyl, Os(CO)4 solid-state packing significantly alters the ground-state structure. The gas-phase stable see-saw geometry converts to a square-planar structure in solid state. Highly efficient intermolecular stacking between Os(CO)4 units assists this transformation. Each Os(CO)4 molecule is stacked in a staggered orientation with respect to each other. Pressure induces a [Xe]4f14 5d6 6s2 (S=2)→[Xe]4f14 5d8 (S=0) electronic transition in osmium stabilize a square planar osmium tetra-carbonyl. Under the influence of isotropic pressure, the molecules not only come closer to each other but their relative orientations also get significantly altered. Calculations show that at P=1 GPa and above, the eclipsed orientation for the intermolecular stacking gets preferred over the staggered form. The staggered→eclipsed intermolecular stacking orientation under pressure is shown to be controlled by London dispersion interactions.

Two-Dimensional Cu(II)-MOF with Lewis Acid-Base Bifunctional Sites for Chemical Fixation of CO2 and Bioactive 1,4-DHP Synthesis via Hantzsch Condensation.

Five- and six-membered heterocycles containing nitrogen or oxygen have been considered as privileged scaffolds in organic chemistry and the chemical industry because of their usage in high-value commodities. Herein, we report a two-dimensional (2D) Cu(II)-based MOF catalyst, IITKGP-40, via the strategic employment of ample Lewis acid-base bifunctional sites (open metal nodes and free pyrazine moieties) along the pore wall. IITKGP-40 could convert toxic CO2 to cyclic carbonates in an atom-economical manner under solvent-free conditions and aromatic aldehyde to bioactive 1,4-DHPs via Hantzsch condensation. Exceptional catalytic performance (99%) and turnover number under mild reaction conditions for CO2 fixation using sterically hindered styrene oxide, and good-to-excellent yields for a wide range of aromatic aldehydes toward 1,4-dihydropyridines (1,4-DHPs) make IITKGP-40 promising as a multipurpose heterogeneous catalyst. Moreover, to demonstrate the practical utility of the catalyst, two biologically important drug molecules, diludine and nitrendipine analogue, have also been synthesized. IITKGP-40 is recyclable for at least three consecutive runs without significant loss of activity, making it promising for real-time applications.

First-principles design of heavy-atom-free singlet oxygen photosensitizers for photodynamic therapy.

In photodynamic therapy (PDT) treatment, heavy-atom-free photosensitizers (PSs) are a great source of singlet oxygen photosensitizer. Reactive oxygen species (ROS) are produced by an energy transfer from the lowest energy triplet excited state to the molecular oxygen of cancer cells. To clarify the photophysical characteristics in the excited states of a few experimentally identified thionated (>C=S) molecules and their oxygenated congeners (>C=O), a quantum chemical study is conducted. This study illustrates the properties of the excited states in oxygen congeners that render them unsuitable for PDT treatment. Concurrently, a hierarchy is presented based on the utility of the lowest-energy triplet excitons of thionated compounds. Their non-radiative decay rates are calculated for reverse-ISC and inter-system crossover (ISC) processes. In addition, the vibronic importance of C=O and C=S bonds is clarified by the computation of the Huang-Rhys factor, effective vibrational mode, and reorganization energy inside the Marcus-Levich-Jörtner system. ROS generation in thionated PSs exceeds their oxygen congeners as kf ≪ kISC, where radiative decay rate is designated as kf. As a result, the current work offers a calculated strategy for analyzing the effectiveness of thionated photosensitizers in PDT.

Cell-Type-Dependent Recruitment Dynamics of FUS Protein at Laser-Induced DNA Damage Sites.

Increased signs of DNA damage have been associated to aging and neurodegenerative diseases. DNA damage repair mechanisms are tightly regulated and involve different pathways depending on cell types and proliferative vs. postmitotic states. Amongst them, fused in sarcoma (FUS) was reported to be involved in different pathways of single- and double-strand break repair, including an early recruitment to DNA damage. FUS is a ubiquitously expressed protein, but if mutated, leads to a more or less selective motor neurodegeneration, causing amyotrophic lateral sclerosis (ALS). Of note, ALS-causing mutation leads to impaired DNA damage repair. We thus asked whether FUS recruitment dynamics differ across different cell types putatively contributing to such cell-type-specific vulnerability. For this, we generated engineered human induced pluripotent stem cells carrying wild-type FUS-eGFP and analyzed different derivatives from these, combining a laser micro-irradiation technique and a workflow to analyze the real-time process of FUS at DNA damage sites. All cells showed FUS recruitment to DNA damage sites except for hiPSC, with only 70% of cells recruiting FUS. In-depth analysis of the kinetics of FUS recruitment at DNA damage sites revealed differences among cellular types in response to laser-irradiation-induced DNA damage. Our work suggests a cell-type-dependent recruitment behavior of FUS during the DNA damage response and repair procedure. The presented workflow might be a valuable tool for studying the proteins recruited at the DNA damage site in a real-time course.

Electrocatalytic Reduction of Nitrogen to Ammonia Using Tiara-like Phenylethanethiolated Nickel Cluster.

The fixing of N2 to NH3 is challenging due to the inertness of the N≡N bond. Commercially, ammonia production depends on the energy-consuming Haber-Bosch (H-B) process, which emits CO2 while using fossil fuels as the sources of hydrogen and energy. An alternative method for NH3 production is the electrochemical nitrogen reduction reaction (NRR) process as it is powered by renewable energy sources. Here, we report a tiara-like nickel-thiolate cluster, [Ni6 (PET)12 ] (where, PET=2-phenylethanethiol)] as an efficient electro-catalyst for the electrochemical NRR at ambient conditions. Ammonia (NH3 : 16.2±0.8 µg h-1 cm-2 ) was the only nitrogenous product over the potential of -2.3 V vs. Fc + /Fc with a Faradaic efficiency of 25%±1.7. Based on theoretical calculations, NRR by [Ni6 (PET)12 ] proceeds through both the distal and alternating pathways with an onset potential of -1.84 V vs. RHE (i.e., -2.46 V vs. Fc + /Fc ) which corroborates with the experimental findings.

Understanding the Regioselectivity of Ion-Pair-Assisted Meta-Selective C(sp2)-H Activation in Conformationally Flexible Arylammonium Salts.

The lack of directionality and the long-range nature of Coulomb interactions have been a bottleneck to achieve chemically precise C-H activation using ion-pairs. Recent report by Phipps and co-workers of the ion-pair-directed regioselective Iridium-catalyzed borylation opens a new direction toward harnessing noncovalent interactions for C-H activation. In this article, the mechanism and specific role of ion-pairing are investigated using density functional theory (DFT). Computational studies reveal that meta C-H activation is kinetically more favorable than the para analogue due to stronger electrostatic interactions between the ion-pairs in closer proximity [d(NMe3+···SO3-)TSP1m = 3.93 Å versus d(NMe3+···SO3-)TSP1p = 4.30 Å]. The electrostatic interactions overwhelm the Pauli repulsion and distortion interactions incurred in bringing the oppositely charged ions in close contact for the rate-limiting meta transition state (TSP1m). Multiple linear regression shows that the free energies of activation correlate well with descriptors like the charge densities on the meta carbon and Ir atom along with that on the cation and anion with R2 = 0.74. Tuned range-separated DFT calculations demonstrate accurately the localization of charge separation in the reactant complex and transition state for the meta selectivity.

A Highly Selective MOF-Based Probe for Turn-On Luminescent Detection of Al3+, Cr3+, and Fe3+ in Solution and Test Paper Strips through Absorbance Caused Enhancement Mechanism.

Trivalent metal ions (Cr3+, Al3+, and Fe3+) constitute a major section of the environmental pollutants, and their excess accumulation has a detrimental effect on health, so their detection in trace quantity has been a hot topic of research. A highly scalable 3D porous Zn-based luminescent metal-organic framework (MOF) has been synthesized by exploiting the mixed ligand synthesis concept. The strategic selection of an aromatic π-conjugated organic linker and N-rich spacer containing the azine functionality as metal ion binding sites immobilized across the pore spaces, have made this MOF an ideal turn-on sensor for Al3+, Cr3+, and Fe3+ ions with very high sensitivity, selectivity, and recyclability. An in-depth study revealed absorbance caused enhancement mechanism (ACE) responsible for such turn-on phenomena. In order to make the detection process straightforward, convenient, portable, and economically viable, we have fabricated MOF test paper strips (the MOF could be simply immobilized onto the paper strips) for naked eye visual detection under UV light, which, thus, manifests its potential as a real-time smart sensor for these trivalent ions.

Spin Alternation Rule in USCF for Through-Bond Magnetic Coupling─A New Look: Why and When Does It Arise and How To See It.

This work takes a new look at the spin alternation rule in unrestricted self-consistent-field (USCF) calculations in terms of structural characteristics such as periodicity, impurity location, and Coulomb exchange. For clarity, the systems considered are biradicals produced from linear conjugated hydrocarbons. Both site-parametrized Hamiltonian models for theoretical analysis and spin unrestricted density functional theory (DFT) calculations are used. Theoretical analysis leads to the following conclusions: (1) The diradical state is an excited state of a linear chain of N conjugated carbon atoms (when N is about ≤ 10). Spin alternation is a consequence of the (truncated) periodic symmetry combined with filling each closed-shell pi orbital with two electrons and each singly occupied molecular orbital (SOMO) with one electron. Spin polarization is evident in triplet (T) and broken symmetry (BS) solutions for an odd N and only in the T solution for an even N. Spin alternation is visible in the BS for an odd N and always remains muted in the calculated T. (2) For a doped chain with two radical centers, spin alternation is generally visible in the BS for an odd N. The sign of spin population on the radical centers in the BS indicates the stable spin. For radical centers separated by an odd (even) number of pz electrons, spin alternation favors T (S) state with FM (AFM) interaction. Spin oscillation remains less transparent for an even N without exchange. (3) In an unrestricted treatment with exchange, spin alternation becomes observable. Without SCF iterations, the more stable state can be identified from a clear spin oscillation in the BS. An irregular oscillation indicates a possible singlet ground state. These observations are supported by density functional calculations using the B3LYP functional and the 6-311+g(d,p) basis set on linear decapentaene diradicals with nitronyl nitroxide moieties substituted on two sets of conjugated atoms, (3,9) and (3,10). Because of the SCF procedure, one finds spin alternation in the T (BS) solution and erratic oscillation in the BS (T) solution of the 3,9 (3,10) diradical in respective equilibrium geometries. The ground state is T (S). DFT adiabatic coupling constants, SOMO energies, spin population plots, and SOMO lobe diagrams compare well with molecular electronic characteristics from theoretical analysis using Hamiltonian parameters.

Origin of Intense Luminescence from Supramolecular 2D Molecular Crystals.

Luminescence enhancement in 2D molecular crystals (2D crystals) is promising for a variety of optical applications, yet the availability is limited because of unclear mechanism and inefficient design strategy of luminescence control. Herein, the room temperature phosphorescence from micron long molecular thin free-standing 2D crystals of a mono-cyclometalated Ir(III) complex designed at the water surface is reported. A large luminescence enhancement is observed from the 2D crystals at 300 K, which is comparable with the rigidified solution at 77 K suggesting room temperature phosphorescence origin of the luminescence. In situ synchrotron grazing incidence X-ray diffraction measurements determine the constituent centered rectangular unit cells with precise molecular conformation that promotes the formation of 2D crystals. The molecular crystal design leads to a reduced singlet-triplet energy gap (ΔEST ) and mixing of singlet-triplet states by spin-orbit coupling (SOC) for efficient intersystem crossing, which explains the phosphorescence origin at room temperature and luminescence enhancement. The supramolecular assembly process provides an elegant design strategy to realize room temperature phosphorescence from 2D crystals by rigid intermolecular interactions.

Porous Anionic Co(II) Metal-Organic Framework, with a High Density of Amino Groups, as a Superior Luminescent Sensor for Turn-on Al(III) Detection.

Accumulation of high concentrations of Al(III) in body has a direct impact on health and therefore, the trace detection of Al(III) has been a matter for substantial concern. An anionic metal organic framework ({[Me2 NH2 ]0.5 [Co(DATRz)0.5 (NH2 BDC)] ⋅ xG}n ; 1; HDATRz=3,5-diamino-1,2,4-triazole, H2 NH2 -BDC=2-amino-1,4-benzenedicarboxylic acid, G=guest molecule) composed of two types of secondary building units (SBU) and channels of varying sizes was synthesized by employing a rational design mixed ligand synthesis approach. Free -NH2 groups on both the ligands are immobilized onto the pore surface of the MOF which acts as a superior luminescent sensor for turn-on Al(III) detection. Furthermore, the large channels could allow the counter-ions to pass through and get exchanged to selectively detect Al(III) in presence of other seventeen metal ions with magnificent luminescence enhancement. The observed limit of detection is as low as 17.5 ppb, which is the lowest among the MOF-based sensors achieved so far. To make this detection approach simple, portable and economic, we demonstrate MOF filter paper test for real time naked eye observation.

Tuning of the optoelectronic properties of peptide-appended core-substituted naphthalenediimides: the role of self-assembly of two positional isomers.

This study demonstrates how the self-assembly pattern of two different and isomeric peptide-appended core-substituted naphthalenediimides (NDIs) affects the modulation of their optoelectronic properties. Two isomeric peptide-attached NDIs were synthesized, purified and characterized. Interchanging the position of attachment of the peptide units and the alkyl chains in the NDI has altered the respective self-assembling patterns of these isomeric molecules in the aggregated states. The isomer having a peptide moiety in the core position and the alkyl chain in the imide position (compound N1) forms face to face stacking or 'H' aggregates in aliphatic solvents including n-hexane, and n-decane, whereas compound N2, in which the peptide moiety is at the imide position and the alkyl chain is attached at the core position of NDI exhibits edge to edge stacking or J aggregates under the same conditions as it is evident from their UV-vis studies. The H aggregated species (obtained from N1) show inter-connected nanofibers, whereas the J aggregated species (obtained from N2) exhibit the morphology of helical nanoribbons. FT-IR and X-ray diffraction studies are in favor of the same aggregation behavior. The individual packing patterns of these two peptide-based isomers have a direct impact on their respective electrical conductivity. Interestingly, the H aggregated species shows 100 times greater current conductivity than that of the J aggregate. Moreover, it is only the H aggregated species that exhibits a photocurrent, and no such photocurrent response is observed with the J aggregates. Computational studies also support that different types of aggregation patterns are formed by these two isomeric molecules in the same solvent system. This unique example of tuning of optoelectronic behavior holds future promise for the development of new peptide-conjugated π-functional materials.

Transition-State-like Planar Structures for Amine Inversion with Ultralong C-C Bonds in Diamino-o-carborane and Diamino-o-dodecahedron.

Umbrella-like inversion of pyramidalized amines proceed through a planar transition state (TS). Stabilization of the TS through N(lone-pair) → σ*(C-C) "negative hyperconjugation" in diamino-o-carborane (1) causes rapid inversion in the amine, which results in the observation of a planarized -NH2 from the X-ray crystal structure. This proceeds through quantum mechanical tunneling across the small and narrow barrier (low pyramidalization). Tuning this secondary orbital (donor-acceptor) interaction for various derivatives of 1 and diamino-o-dodecahedron (2) provides a rational approach toward increasing dC-C to as large as 2.001, 2.011, and 1.807 Å for 1b (amino oxide-o-carborane), 1i (di-N,N-dimethylamino-o-carborane), and 2g (di-N,N-diisopropylamino-o-dodecahedron), respectively.

A "Thermodynamically Stable" 2D Nickel Metal-Organic Framework over a Wide pH Range with Scalable Preparation for Efficient C2 s over C1 Hydrocarbon Separations.

The design and construction of "thermodynamically stable" metal-organic frameworks (MOFs) that can survive in liquid water, boiling water, and acidic/basic solutions over a wide pH range is highly desirable for many practical applications, especially adsorption-based gas separations with obvious scalable preparations. Herein, a new thermodynamically stable Ni MOF, {[Ni(L)(1,4-NDC)(H2 O)2 ]}n (IITKGP-20; L=4,4'-azobispyridine; 1,4-NDC=1,4-naphthalene dicarboxylic acid; IITKGP stands for the Indian Institute of Technology Kharagpur), has been designed that displays moderate porosity with a BET surface area of 218 m2 g-1 and micropores along the [10-1] direction. As an alternative to a cost-intensive, cryogenic, high-pressure distillation process for the separation of hydrocarbons, MOFs have recently shown promise for such separations. Thus, towards an application standpoint, this MOF exhibits a higher uptake of C2 hydrocarbons over that of C1 hydrocarbon under ambient conditions, with one of the highest selectivities based on the ideal adsorbed solution theory (IAST) method. A combination of two strategies (the presence of stronger metal-N coordination of the spacer and the hydrophobicity of the aromatic moiety of the organic ligand) possibly makes the framework highly robust, even stable in boiling water and over a wide range of pH 2-10, and represents the first example of a thermodynamically stable MOF displaying a 2D structural network. Moreover, this material is easily scalable by heating the reaction mixture at reflux overnight. Because such separations are performed in the presence of water vapor and acidic gases, there is a great need to explore thermodynamically stable MOFs that retain not only structural integrity, but also the porosity of the frameworks.

A Phosphate-Based Silver-Bipyridine 1D Coordination Polymer with Crystallized Phosphoric Acid as Superprotonic Conductor.

Phosphate-based silver-bipyridine (Ag-bpy) 1D coordination polymer {[{Ag(4,4'-bpy)}2 {Ag(4,4'-bpy)(H2 PO4 )}]⋅2 H2 PO4 ⋅H3 PO4 ⋅5 H2 O}n (1) with free phosphoric acid (H3 PO4 ), its conjugate base (H2 PO4 - ) and water molecules in its lattice was synthesized by room-temperature crystallization and the hydrothermal method. An XRD study showed that coordinated H2 PO4 - , lattice H2 PO4 - anions, free H3 PO4 and lattice water molecules are interconnected by H-bonding interactions, forming an infinitely extended 2D H-bonded network that facilitates proton transfer. This material exhibits a high proton conductivity of 3.3×10-3  S cm-1 at 80 °C and 95 % relative humidity (RH). Furthermore, synthesis of this material from commercially available starting materials in water can be easily scaled up, and it is highly stable under extreme conditions of conductivity measurements. This report inaugurates the usage and design principle of proton-conducting frameworks based on crystallized phosphoric acid and phosphate.

Two Closely Related Zn(II)-MOFs for Their Large Difference in CO2 Uptake Capacities and Selective CO2 Sorption.

Two azo functionalized Zn(II)-based MOFs, {[Zn(SDB)(3,3'-L)0.5]·xG}n, IITKGP-13A, and {[Zn2(SDB)2(4,4'-L)]·xG}n, IITKGP-13B (IITKGP stands for Indian Institute of Technology Kharagpur), have been constructed through the self-assembly of isomeric N,N'-donor spacers (3,3'-L = 3,3'-azobispyridine and 4,4'-L = 4,4'-azobispyridine) with organic ligand 4,4'-sulfonyldibenzoic acid (SDBH2) and Zn(NO3)2·6H2O (G represents disordered solvent molecules). Single-crystal X-ray diffraction studies reveal the 2D structure with sql topology for both MOFs. However, the subtle change in positions of coordinating N atoms of spacers makes IITKGP-13A noninterpenetrated, while IITKGP-13B bears a 2-fold interpenetrated structure. IITKGP-13A exhibits higher uptake of CO2 over CH4 and N2 with high IAST selectivities for mixed CO2/CH4 (50:50, biogas) and CO2/N2 (15:85, flue gas) gas systems. In contrast, IITKGP-13B takes up very low amount of CO2 gas (0.4 mmol g-1) compared to IITKGP-13A (1.65 mmol g-1) at 295 K. Density functional theory (DFT)-based electronic structure calculations have been performed to explain the origin of the large differences in CO2 uptake capacity between the two MOFs at the atomistic level. The results show that the value of the change in enthalpy (ΔH) at 298 K temperature and 1 bar pressure for the CO2 adsorption is more negative in IITKGP-13A as compared to that in IITKGP-13B, thus indicating that CO2 molecules are more favored to get adsorbed in IITKGP-13A than in IITKGP-13B. The computed values for the Gibbs' free energy change (ΔG) for the CO2 adsorption are positive for both of the MOFs, but a higher value is observed for the IITKGP-13B. The noncovalent types of interactions are the main contribution toward the attractive energies between the host MOF frameworks and guest CO2 molecules, which has been studied with the help of energy decomposition analysis (EDA).

Polymorphism Dependent 9-Phosphoanthracene Derivative Exhibiting Thermally Activated Delayed Fluorescence: A Computational Investigation.

Polymorphs of anthracene derivatives exhibit diverse photophysical properties that can help to develop efficient organic-based photovoltaic devices. 10-Anthryl-9-phosphoanthracene (10-APA) shows different photophysical behaviors for the solid state due to its variety in crystalline arrangement. Herein, we investigate the ground and excited-state properties of the monomer and two different polymorphs of 10-APA from first-principles. Calculations reveal that strong spin-orbit coupling (SOC) between first excited singlet state (S1) and triplet manifolds at their S1-optimized geometries enabling the reverse intersystem crossing (RISC). The electron-vibration coupling (Huang-Rhys factor) in the excited state is the most relevant factor here. For both ISC and RISC, a similarity in Huang-Rhys factors for the molecular vibration along the π···π stacking at low-frequency region makes the rates effective. On the other side, the nonvanishing vibronic relaxation modes provide a relatively slower RISC rate in the red crystal. However, for the red crystal, small reorganization energy (λ) and large Huang-Rhys factor toward S1 → S0 conversion reduce nonradiative decay, leading to a prompt fluorescence. As the feasibility of S1 ↔ T1 conversion increases in the yellow dimer, it allows a delay in fluorescence emission, leading to thermally activated delayed fluorescence (TADF).

Combined Dendritic and Axonal Deterioration Are Responsible for Motoneuronopathy in Patient-Derived Neuronal Cell Models of Chorea-Acanthocytosis.

Chorea acanthocytosis (ChAc), an ultra-rare devastating neurodegenerative disease, is caused by mutations in the VPS13A gene, which encodes for the protein chorein. Affected patients suffer from chorea, orofacial dyskinesia, epilepsy, parkinsonism as well as peripheral neuropathy. Although medium spinal neurons of the striatum are mainly affected, other regions are impaired as well over the course of the disease. Animal studies as well as studies on human erythrocytes suggest Lynkinase inhibition as valuable novel opportunity to treat ChAc. In order to investigate the peripheral neuropathy aspect, we analyzed induced pluripotent stem cell derived midbrain/hindbrain cell cultures from ChAc patients in vitro. We observed dendritic microtubule fragmentation. Furthermore, by using in vitro live cell imaging, we found a reduction in the number of lysosomes and mitochondria, shortened mitochondria, an increase in retrograde transport and hyperpolarization as measured with the fluorescent probe JC-1. Deep phenotyping pointed towards a proximal axonal deterioration as the primary axonal disease phenotype. Interestingly, pharmacological interventions, which proved to be successful in different models of ChAc, were ineffective in treating the observed axonal phenotypes. Our data suggests that treatment of this multifaceted disease might be cell type and/or neuronal subtype specific, and thus necessitates precision medicine in this ultra-rare disease.