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We present a first-principle molecular dynamics study on the uptake and hydration of sulfur dioxide on the dry and wet fully hydroxylated surfaces of (0001) alpha-quartz, which are a proxy for suspended silica dust in atmosphere. The average adsorption energy for SO2 is ~10 kcal/mol on both dry and wet surfaces. The adsorption is driven by hydrogen bonds formation between SO2 and the interfacial hydroxyl groups (on dry silica), or with water molecules (in the wet case). In the dry system, we report an additional electrostatic interaction between the interfacial hydroxyl oxygen and the sulfur atom, which further stabilize the adsorbate. On dry silica, the interfacial hydroxyl group coordinates SO2 yielding to a surface bounded bisulfite (Si-SO3H) complex. On the wet surface, SO2 reacts with water forming bisulfite (HSO3-), and the latter remains solvated inside the adsorbed water layer. The hydration barrier for sulfur oxide is 1 kcal/mol and 3 kcal/mol on the dry and wet silica, respectively, while for the backward reaction (i.e., bisulfite to SO2) the barrier is 6 kcal/mol on both surfaces. The modest backward barrier rationalizes earlier experimental findings showing no SO2 uptake on silicates. These results underline the importance of the surface hydroxylation and/or of adsorbed water layers for the SO2 uptake and its hydration on silica. Moreover, the hydration to bisulfite may prevent direct SO2 photochemistry and be an additional source of sulfate: this is especially relevant in atmosphere subject to high level of suspend mineral dust, intense solar radiation and atmospheric oxidizers.

The stability of the molecular self-assembled monolayers (SAMs) is of vital importance to the performance of the molecular electronics and their integration to the future electronics devices. Here we study the effect of electron irradiation-induced cross-linking on the stability of self-assembled monolayer of aromatic 5,5′-bis(mercaptomethyl)-2,2′-bipyridine [BPD; HS-CH2-(C5H3N)2-CH2-SH] on Au (111) single crystal surface. As a refence, we also study the properties of SAMs of electron saturated 1-dodecanethiol [C12; CH3-(CH2)11-SH] molecules. The stability of the considered SAMs before and after electron-irradiation is studied using low energy Ar+ cluster depth profiling monitored by recording the X-ray photoelectron spectroscopy (XPS) core level spectra and the UV-photoelectron spectroscopy (UPS) in the valance band range. The results indicate a stronger mechanical stability of BPD SAMs than the C12 SAMs. The stability of BPD SAMs enhances further after electron irradiation due to intermolecular cross-linking, whereas the electron irradiation results in deterioration of C12 molecules due to the saturated nature of the molecules. The depth profiling time of the cross-linked BPD SAM is more than 4 and 8 times longer than the profiling time obtained for pristine and BPD and C12 SAMs, respectively. The UPS results are supported by density functional theory calculations, which show qualitative agreement with the experiment and enable us to interpret the features in the XPS spectra during the etching process for structural characterization. The obtained results offer helpful options to estimate the structural stability of SAMs which is a key factor for the fabrication of molecular devices.

The need to chemically convert CO2 at the interface of aqueous amine solutions has become particularly relevant for the development and the broad distribution of cost-effective and near-future devices for direct air capture working at low (e.g., ambient) partial pressure. Here, we have determined the stability of a CO2-monoethanolamine zwitterion and its chemical conversion into carbamate at the vapor/liquid water interface by first-principles molecular dynamics simulations coupled with a recently introduced enhanced sampling technique. Contrary to the bulk water case, our results show that both the zwitterion and carbamate ions are poorly stable at the vapor/amine aqueous interface, further stating the differences between the homogeneous and heterogeneous CO2 chemical conversion. The design of novel and cost-effective capture systems, such as those offered by amine-based scrubbing solutions, working at low (e.g., ambient) CO2 partial pressure should explore the use of novel solvents, different from aqueous mixtures, to overcome the limits of the current absorbents.

Translocations involving Fibroblast Growth Factor Receptor 2 (FGFR2) are found in up to 45% of Intrahepatic Cholangiocarcinoma (ICC). Treatment of patients bearing FGFR2 fusions with FGFR kinase inhibitors induces tumor regressions, though response rate and durability of response appear limited due to the emergence of resistance or to sub-optimal dosing which is limited by drug adverse effects. Thus, therapeutics that drive activity specifically towards FGFR2 are needed to enhance drug efficacy and reduce adverse effects. We first asked whether the extracellular domain (ECD) of FGFR2-BICC1 fusion is functional and important for receptor dimerization and signaling using NanoBiT system and western blotting. FGFR ECD consists of 3 Ig-fold domains D1, D2, and D3. Using focus transformation and viability assays, we found that deletions in D1, D2, D3, and D2-3 ECD FGFR2-BICC1 decreased growth and transformation of FGFR2 fusion driven cells. Next, we sought to investigate if antibodies against the ECD could perturb the growth of FGFR2 fusion transformed cells. We identified six FGFR2 specific antibodies that bind to epitopes in the ECD and confirmed the ligand blocking activity of these bivalent antibodies. In the absence of ligand, however, most of the bivalent antibodies were relatively inactive. As standard bivalent antibodies engage two receptors at a time, they are at risk for agonism or the maintenance of tonic signaling. Thus, to enhance efficacy and prevent the potential agonist or tonic activity of bivalent antibodies, all possible biparatopic antibodies (15), recognizing two distinct epitopes on the FGFR2 ECD, were engineered from the six parental antibodies. The biparatopic antibodies exhibited enhanced efficacies in FGFR2-fusion driven NIH3T3/BaF3 and ICC13-7 cancer cell lines and significantly improved binding affinities (~10-fold) as analyzed by Octet, MSD-SET, and SPR. Two biparatopic antibodies (BpAb-1, BpAb-2) showed the highest antiproliferative activity and induced apoptosis in FGFR2 fusion driven cells. BpAb-1, BpAb-2 were superior to their parental antibodies in reducing FGFR2-fusion driven growth, transformation and downstream signaling (pFGFR2, pFRS) in vitro and in reducing tumor growth in xenograft models. Importantly, BpAb-1 and BpAb-2 significantly induced FGFR2 internalization and lysosomal-mediated degradation as compared to their parental antibodies. Moreover, BpAb-1 and BpAb-2 had anti-growth activities against ICC patient-derived oncogenic FGFR2 ECD in-frame deletions, and FGFR kinase resistance mutations, including the gatekeeper mutation V565F. BpAb-1 and BpAb-2 were also active in FGFR2 WT amplified cells SNU-16. These results suggest that these FGFR2 biparatopic antibodies are a novel treatment option for ICC patients with tumors harboring FGFR2 fusions. Citation Format: Saireudee Chaturantabut, Sydney Oliver, John Kim, Dennie Frederick, Foxy Robinson, Alessandro Sinopoli, Diego J. Rodriguez, Liang Chang, Nabeel Bardeesy, William Sellers. Novel FGFR2 biparatopic antibodies for the treatment of cholangiocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2647.

Highly conductive materials, with minimal thickness and capable to afford electromagnetic interference (EMI) shielding, are highly advantageous, particularly if they are able to be easily processed into thin films. Here, we demonstrate the potential of a sandwich-like structure of a two-dimensional Ti3C2Tx MXene/Graphene nanoplatelets (GNPs) composites for EMI shielding in the extreme high frequency (EHF) M-band, ranging from 60 to 80 GHz. First, we investigated systematically the microstructural and electrical transport properties of these composites with respect to the GNP contents. After graphene integration, the composite-surface roughness has been found to decrease, while both electrical conductivity and Hall carrier mobility demonstrated a clear trend to increase, reaching the values of ∼105 S/cm and 55 cm2/V, respectively, for only 2.5 wt % of graphene content, reporting thereby one of the most electrically conductive MXene based composite to date. Furthermore, a 1.75 μm-thick Ti3C2Tx MXene/GNP film was found to exhibit an EM absorbance of about 64 dB, which is one of the highest values, normalized to the thickness, among tested materials so far. This remarkable performance could be associated to three key factors, namely the superior transport properties of the composite films, the dominant absorption mechanism, and the multiple internal reflections from Ti3C2Tx and graphene multilayers configuration. These reported results would lead to unprecedented applications in the fields of space, aeronautics, radars, air travels and mobile phones.

Carbon dioxide scrubbing by aqueous amine solution is considered as a promising technology for post-combustion CO2 capture, while mitigating climate change. The lack of physicochemical details for this process, especially at the interface between the gas and the condensed phase, limits our capability in designing novel and more cost-effective scrubbing systems. Here, we present classical and first-principles molecular dynamics results on CO2 capture at the gas/amine solution interfaces using solvents of different polarities. Even if it is apolar, carbon dioxide is absorbed at the gas/monoethanolamine (MEA) aqueous solution interface, forming stable and interfacial [CO2·MEA] complexes, which are the first reaction intermediate toward the chemical conversion of CO2 to carbamate ions. We report that the stability of the interfacial [CO2·MEA] precomplex depends on the nature and polarity of the solution, as well as on the conformer population of MEA. By changing the polarity of the solvent, using chloroform, we observed a shift in the interfacial MEA population toward conformers that form more stable [CO2·MEA] complexes and, at the same time, a further stabilization of the complex induced by the solvent environment. Thus, while lowering the polarity of the solvent could decrease the solubility of MEA, at the same time, it favors conformers that are more prone to CO2 capture and mineralization. The results presented here offer a theoretical framework that helps in designing novel and more cost-effective solvents for CO2 scrubbing systems, while shedding further light on the intrinsic reaction mechanisms of interfacial environments in general.

We report on the optoelectronic characteristics of

Anion exchange membranes (AEMs) are becoming increasingly common in electrochemical energy conversion and storage systems around the world (EES). Proton-/cation-exchange membranes (which conduct positive charged ions such as H+ or Na+) have historically been used in many devices such as fuel cells, electrolysers, and redox flow batteries. High capital costs and the use of noble metal catalysts are two of the current major disadvantages of polymer electrolyte membrane (PEM)-based systems. AEMs may be able to overcome the limitations of conventional PEMs. As a result, polymers with anion exchange properties have recently attracted a lot of attention due to their significant benefits in terms of transitioning from a highly acidic to an alkaline environment, high kinetics for oxygen reduction and fuel oxidation in an alkaline environment, and lower cost due to the use of non-precious metals. The aim of this research was to learn more about the development of a new AEM based on poly tetraarylphosphonium ionomers (pTAP), which has high ionic conductivity, alkaline stability, thermal stability, and good mechanical properties, making it a more cost-effective and stable alternative to conventional and commercial AEMs. A simple solution casting method was used to build novel anion exchange composite membranes with controlled thicknesses using the synthesized pTAP with polysulfone (PS). To ensure their suitability for use as an electrolyte in alkaline electrochemical systems, the composite membranes were characterized using FTIR, XRD, water uptake, ionic conductivity, and alkaline stability. At 40 °C, the PS/pTAP 40/60 percent membrane had a maximum ionic conductivity of 4.2 mS/cm. The thermal and mechanical stability of the composite membranes were also examined, with no substantial weight loss observed up to 150 °C. These findings pave the way for these membranes to be used in a wide variety of electrochemical applications.

Carbon monoxide (CO) is an important biological gasotransmitter in living cells. Precise spatial and temporal control over release of CO is a major requirement for clinical application. To date, the most reported carbon monoxide releasing materials use expensive fabrication methods and require harmful and poorly designed tissue-penetrating UV irradiation to initiate the CO release precisely at infected sites. Herein, we report the first example of utilizing a green light-responsive CO-releasing polymer P synthesized via ring-opening metathesis polymerization. Both monomer M and polymer P were very stable under dark conditions and CO release was effectively triggered using minimal power and low energy wavelength irradiation (550 nm, ?28 mW). Time-dependent density functional theory (TD-DFT) calculations were carried out to simulate the electronic transition and insight into the nature of the excitations for both L and M. TD-DFT calculations indicate that the absorption peak of M is mainly due to the excitation of the seventh singlet excited state, S7. Furthermore, stretchable materials using polytetrafluoroethylene (PTFE) strips based on P were fabricated to afford P-PTFE, which can be used as a simple, inexpensive, and portable CO storage bandage. Insignificant cytotoxicity as well as cell permeability was found for M and P against human embryonic kidney cells. Copyright - 2019 American Chemical Society. The authors gratefully acknowledge the support of this work from the Qatar National Research Fund project number: NPRP X-095-1-024. Scopus

The electron transfer rate between a donor and an acceptor depends on the free energy change for the reaction as well as differences in structure and electronic coupling between the initial and fin...

The electrochemical reduction of the Mn(bpy)(CO)3X CO2 reduction catalyst is thought to proceed by the initial reduction of MnI to Mn0. We have covalently attached a naphthalenediimide radical anion (NDI•–) chromophore to the 4-, 5-, or 6-position of the bpy via a phenyl bridge to produce Mn(NDI•–-bpy)(CO)3X, where X = Br, CH3CN, or DMF, and have used femtosecond and nanosecond transient IR spectroscopy to directly observe the intermediates produced by two electron-transfer reactions following selective photoexcitation of NDI•– to its lowest excited doublet state, 2*NDI•–. In complexes where NDI•– is attached at the 4- or 5-position of bipyridine, only the reaction Mn(2*NDI•–-bpy)(CO)3X → Mn(NDI-bpy•–)(CO)3X is observed, whereas in the complex where NDI•– is attached to the 6-position of bipyridine, the reaction sequence Mn(2*NDI•–-bpy)(CO)3X → Mn(NDI-bpy•–)(CO)3X → Mn0(NDI-bpy)(CO)3 is observed. Moreover, in the complexes with an NDI•– bound to the 6-position of bipyridine, Mn0(NDI-bpy)(CO)3 exhibits a l...

Introducing redox-active moieties into an ionic liquid (IL) structure is an exciting and attractive approach that has received increasing interest over recent years for a various range of energy applications. The so-called redox-active ionic liquids (RAILs) provide a highly versatile platform to potentially create multifunctional electroactive materials. Ionic liquids are molten salts consisting of ionic species, often having a melting point lower than 100 °C. Such liquids are obtained by combining a bulky asymmetric organic cation and a small anion. Here, we report on the synthesis of a novel RAIL, namely 1-butyl-3-methylimidazolium hydroquinone sulfonate ((BMIM)(HQS)). (BMIM)(HQS) was synthesized in a two-step procedure, starting by the quaternization of methylimidazole using butylchloride to produce 1-butyl-3-methylimidazolium chloride ((BMIM)(Cl)), and followed by the anion exchange reaction, where the chloride anion is exchanged with hydroquinone sulfonate. The resulting product was characterized by 1H NMR, 13C NMR, FT-IR spectroscopy, themogravimetric analysis, and differential scanning calorimetry, and shows a high stability up to 340 °C. Its electrochemical behavior was investigated using cyclic voltammetry at different temperatures and its viscosity analysis was also performed at variable temperatures. The electrochemical response of the presented RAIL was found to be temperature dependent and diffusion controlled. Overall, our results demonstrated that (BMIM)(mix of HQS and HSQ) is redox active and possesses high stability and low volatility, leading to the employment of this RAIL without any additional supporting electrolyte or additives.

The need to chemically convert CO

Carbon dioxide scrubbing by aqueous amine solution is considered as a promising technology for post-combustion CO

We report on the optoelectronic characteristics of p-NiO/n-Si heterojunction photodiode for broadband photodetection, fabricated by depositing a p-type NiO thin film onto a commercial n-type silicon substrate using pulsed laser deposition (PLD) technique. The structural properties of the PLD-grown p-NiO material were analysed by means of x-ray diffraction and x-ray photoelectron spectroscopy, confirming its crystalline nature and revealing the presence of Ni vacancies, respectively. Hall measurements confirmed the p-type semiconducting nature of the NiO thin film having a carrier concentration of 8.4 × 1016 cm−3. The current–voltage (I–V) characteristics of the p-NiO/n-Si heterojunction photodevice were investigated under different wavelengths ranging from UV to NIR. The self-bias properties under different illuminations of light were also explored systematically. Under self-bias condition, the photodiode exhibits excellent responsivities of 12.5 mA W−1, 24.6 mA W−1 and 30.8 mA W−1 with illumination under 365 nm, 485 nm, and 850 nm light, respectively. In addition, the time dependency of the photoresponse of the fabricated photodevice has also been investigated and discussed thoroughly.

The use of fossil fuels will continue to dominate the energy market for the next several decades. To mitigate the large amounts of CO2 released into the atmosphere, it is essential to have clean ways of converting the CO2 back into a high energy density liquid fuel. While still an emerging field, manganese-based catalysts can be successfully integrated into electrochemical and photoelectrochemical devices for CO2 reduction. This review describes the design, feature and efficiency of manganese carbonyl systems reported in literature, for both electro- and photoreduction of CO2. The spectroelectrochemical and spectroscopic techniques used to elucidate the associated catalytic mechanisms and reaction intermediates are also described. The evolution of the reported complexes highlights how progress is being made to eliminate the deficiencies of the early versions of these complexes, and how the future looks bright for their effective use in CO2 reduction.

The copper-catalysed cycloaddition of alkynes and azides to form 1,2,3-triazoles has emerged as a powerful tool in ligand design and the synthesis of novel transition metal complexes. In this review we focus on the photophysical properties of metal complexes bearing 1,2,3-triazole-based ligands with a particular emphasis on those of d6 metals including rhenium(I), iron(II), ruthenium(II), osmium(II) and iridium(III). We also highlight key examples of triazole complexes of platinum(II) and palladium(II) as well as the lanthanides and coinage metals.

A series of six homoleptic bis-cyclometalated ruthenium complexes, Ru((NNC)-N-boolean AND-C-boolean AND)(2), is reported where (NNC)-N-boolean AND-C-boolean AND is a 6-(2,4-difluoro-3-R-3-phenyl)-4-R-2-4'-R-1-2,2'-bipyridine with R-3 = -H or -CF3 and R-2 and R-1 = -COOEt or -CF3. An effective synthesis of the ligands and the complexes is described. The UV-visible absorption studies demonstrate that these complexes are panchromatic dyes absorbing up to 900 nm. Importantly, the onset of absorption depends only on the substitution on the metalated phenyl, whereas the intensity of absorption throughout the spectra is a function of substituents on both the phenyl and the bipyridine moieties. The same trend is observed in electrochemistry as the redox gap depends only on the substitution on the metalated phenyl, whereas the oxidation and reduction potentials are a function of substituents on both the phenyl and the bipyridine moieties. Preliminary tests as sensitizer for dye-sensitized solar cells demonstrate that the number of anchoring groups on the dye has a major influence on the device efficiency.

Anthocyanins and anthocyanidins are polyphenolic compounds, responsible for the red and blue colours in several fruits, flowers, and leaves. Their colorant properties, bioavailability and antioxidant activity, made anthocyanins and anthocyanidins largely adopted in food and pharmaceutical industries. In this body of work, we firstly introduced structure, photophysical properties, co-pigmentation, antioxidant properties, glycosylation and complexation of anthocyanins and anthocyanidins. Secondly, we reported the computational methods adopted and the main theoretical results involving either anthocyanins and anthocyanidins, ranging from the first theoretical investigation on the structure of flavylium ions to the most recent studies on anthocyanins adsorbed on TiO2. We reviewed the computational contributions to the description of molecular properties of anthocyanins and anthocyanidins, giving a particular attention to the geometries, the spectroscopic features and the complexation properties of such molecules. Nowadays, theoretical calculations represent an essential methodology to understand and predict the chemical and physical properties of anthocyanins and their derivates.

The preparation and characterisation of a hybrid biscyclometalated coumarin/iridium complex is presented which exhibits intense visible absorption (e ≈ 43800 dm3 mol–1 cm–1) and sensitises both n- and p-type dye-sensitised solar cells (DSSCs).

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of extracellular aggregates of amyloid-b peptides (Ab). Different metal ions accumulate within amyloid deposits, which suggests an involvement of metal ions in AD pathogenesis. Cu(II)-induced Ab neurotoxicity might result from changes in the coordination of the metal ion during Ab oligomerization or from different peptide/ metal ratios. Little is known on the Cu(II) complex with low-molecular-weight Ab species. Here, we report our results on the Cu(II) coordination modes with a synthetic Ab(1-16) dimer where the C-terminal 16Lys residue, of each peptide chain, is linked to a N,N-bis[(3-amino)propyl]glycine bearing a PEG moiety at the C-terminus. The formation of macrochelate complex species with the involvement of imidazole nitrogen donor atoms of His13 and His14, during copper(II) binding at physiological pH and low metal to peptide ratios, is observed.

The synthesis and characterisation of a photoresponsive 3,3-diphenyl-3H-pyrano[3,2-f]quinoline ligand which contains both quinoline and thiazole N-donor moieties is described. This ligand acts as a bidentate N-donor ligand and the solid-state structure of a Ag(I) complex is reported. Whereas the free ligand exhibits typical photochromic behaviour, coordination with Ag(I) results in complete inhibition of the photochromic response. However, excitation wavelength dependent emission spectra demonstrated an increase in fluorescence response of the new Ag(I) complex.

Photocatalytic systems for CO2 reduction represent one of the most important topics within the field of solar fuels. Over last four decades, a great deal of effort has been dedicated to designing such systems, understanding their mechanisms and optimising their components. Together with the more traditional metal complexes, rylenes have recently attracted attention as potential coupled sensitisers for CO2 photoreduction. This chapter provides an overview on the principles of photocatalysis and CO2 photoreduction, with a particular attention to the role and design of the photosensitiser. In addition, we discuss in depth the few examples of rhenium–rylene complexes reported in the literature that explore the current limits of these systems and which could be winning strategies to integrate rylenes in a chromophore–catalyst assembly for photo- or photoelectrochemical CO2 reduction.

Alessandro Sinopoli, a Michael Wasielewski, b Muhammad Sohail. a aQatar Environment & Energy Research Institute, Hamad Bin Khalifa University, PO Box 5825, Doha, Qatar; bDepartment of Chemistry and Argonne-Northwestern Solar Energy Research (ANSER) Center, Northwestern University, Evanston, Illinois 60208-3113, USA. The use of fossil fuels, especially natural gas, which has a lower carbon burden than oil or coal, will continue to dominate the energy market for the next several decades. In order to mitigate the large amounts of CO2 released into the atmosphere, it is essential to have clean ways of converting the CO2 back into a high energy density liquid fuel. Benchmark catalysts for CO2 reduction typically employ second and third row transition metals like palladium, iridium, and rhenium. The rarity, cost, and environmental ramifications of mining large quantities of such precious metals deter scaling up the usage of such catalysts. Developing a CO2 catalytic system that uses earth abundant first row transition metals like manganese, will push the field away from rare earth metal catalysts. While still an emerging field, transition metal-based catalysts can be successfully integrated in electrochemical and photoelectrochemical devices for CO2 reduction. Inside this class of compounds, developing manganese-based systems remains an extremely promising strategy for the advent of low cost but at the same time efficient molecular systems for CO2 reduction. We will therefore investigate Mn(bpy)(CO)3Br and its related derivatives that have recently been shown to efficiently reduce CO2 to CO. More importantly, none of these Mn-bipyridine complexes have yet been integrated with a covalent photo-driven source of electrons and this will be the main synthetic and experimental challenge within this project. Aromatic organic anions (radical anions or closed shell dianions) are reactive species involved in various chemical transformations. The photochemistry and photophysics of these species have been the subject of extensive study since they have been implicated in many photo-induced electron transfer processes, and are suggested to be powerful reducing agents. Such properties were substantiated by the observation of rapid electron ejection to give solvated electrons, electron-cation pairs, or reduced electron acceptors upon photolysis of aromatic anions (e.g. sodium pyrenide or biphenylide). We envision that the high reducing power (up to − 3 V vs. SCE) of excited monoanions or dianions of aromatic diimides can be exploited for CO2 reduction catalysis. In particular, the anions of PDI perylene-3,4:9,10-bis(dicarboximide) and its homolog naphthalene-1,8:4,5-bis(dicarboximide) (NDI) will be used as the primary photosensitizers in this study. These planar, chemically robust, redox-active compounds are widely used as industrial pigments, supramolecular building blocks, photooxidants, and n-type semiconducting materials. In the effort of integrating NDI and PDI units in the design and development of manganese based photocatalysts, experiments will be carried out in two stages. In the first stage, we will synthesise photosensitizer systems designed specifically to act as catalysts, so that their structures and properties can be determined. Figure 1. Examples of Mn-based catalysts designed for this project. The structures depicted in Figure 1 are examples of PDI and NDI photosensitizer systems designed for this project. For example, in the molecule on the left (Figure 1), two easily reducible PDI molecules are covalently attached to the bpy ligand. One-electron reduction of PDI will produce the stable PDI-• radical anion. The structure of the designed manganese complexes, the dynamics of CO2 binding, and subsequent protonation of the bound Mn carboxylate will be studied using femtosecond transient absorption spectroscopies with both UV-Vis and mid-IR probing as well as and femtosecond stimulated Raman spectroscopy (FSRS). The second stage of the experiments will study the laser-generated Mn(0)(bpy)-1(CO)3-based catalyst followed by CO2 binding and protonation. For this we will perform steady-state photolysis experiments on the systems in DMF with varying amounts of HBF4 and CO2 up to the limit of a saturated solution of CO2 in DMF at 25 °C and 1 atm, which is about 0.14 M. These studies will look for products generated following one-electron reduction of the Mn catalysts. We will quantitate the yield of CO produced by the overall photoreaction using a 16-sample parallel system in which the samples are illuminated using filtered LEDs and a parallel, continuous gas sampling system connected to a gas chromatograph. The system will be calibrated with appropriate standard gas mixtures, and a full range of conditions and appropriate control experiments will be performed by varying the concentrations of catalyst, CO2, HBF4, and sodium ascorbate in the solution. Solar energy, an abundant resource in Qatar, can drive CO2 reduction to produce both liquid solar fuels and potentially high value chemicals. In this regard, our study will represent the birth of a new generation of efficient photocatalytic systems for CO2 reduction by coupling robust light harvesting molecules with earth abundant transition metals like manganese.

Surface-enhanced Raman spectroscopy has emerged as a widely used tool in the identification of organic dyes in works of art. Indigo is among the most used organic pigment, its identification can therefore give important information about the provenience and the making of the investigated work of art. In this work, we combine Surface Enhanced Raman Spectroscopy (SERS) experiments with density functional theory (DFT) computations of the Raman frequencies of indigo and an indigo molecule adsorbed onto a silver surface made of 16 silver atoms. The SERS spectrum of a molecule adsorbed on a metallic surface, in fact, can differ from the corresponding Raman one. The knowledge and the comprehension of the SERS spectrum then are mandatory in dyes identification. Experimental SERS spectra were acquired using ad hoc SERS active substrates consisting of pulsed laser ablated silver nanoparticles deposited onto a polishing sheet. The polishing sheet surface roughness is able to remove some pigments grains from the surface of a work of art without damage. OFT calculations provide a good description of the observed SERS spectra, in particular, the indigo-Ag-16 structure gives a better description with respect to structures where only one or two silver atoms attached to the indigo molecule are considered. (C) 2018 Elsevier B.V. All rights reserved.

Monoamine oxidase (MAO) enzymes play a central role in the pathogenesis of Alzheimer's disease (AD) and MAO inhibitors (MAOIs) are antidepressant drugs currently studied for theft neuroprotective properties in neurodegenerative disorders. In the present work MAOIs such as tranylcypromine [trans(+)-2-phenylcyclopropanamine, TCP] and its amide derivatives, TCP butyramide (TCP-But) and TCP acetamide (TCP-Ac), were tested for their ability to protect cortical neurons challenged with synthetic amyloid-beta (A beta)-(1-42) oligomers (100 nM) for 48 h. TCP significantly prevented A beta-induced neuronal death in a concentration-dependent fashion and was maximally protective only at 10 mu M. TCP-But was maximally protective in mixed neuronal cultures at 10 mu M, a lower concentration compared to TCP, whereas the new derivative, TCP-Ac, was more efficacious than TCP and TCP-But and significantly protected cortical neurons against A beta toxicity at nanomolar concentrations (100 nM). Experiments carried out with the Thioflavin-T (Th-T) fluorescence assay for fibril formation showed that TCP and its amide derivatives influenced the early events of the A beta aggregation process in a concentration-dependent manner. TCP-Ac was more effective than TCP-But and TCP in slowing down the A beta (1-42) aggregates formation through a lengthening at the lag phase. In our experimental model coincubation of A beta(1-42) oligomers with TCP-Ac was able to almost completely prevent A beta-induced neurodegeneration. These results suggest that inhibition of A beta oligomenmediated aggregation significantly contributes to the overall neuroprotective activity of TCP-Ac and also raise the possibility that TCP, and in particular the new compound TCP-Ac, might represent new pharmacological tools to yield neuroprotection in AD. (C) 2015 Elsevier B.V. All rights reserved.

The present work introduces a surface plasmon resonance-based method for the discrimination of direct competition and allosteric effects that occur in ternary systems comprising a receptor protein and two small-molecular-weight ligands that bind to it. Fatty acid binding protein 4, fructose-1,6-bisphosphatase and human serum albumin were used as model receptor molecules to demonstrate the performance of the method. For each of the receptor molecules, pairs of ligand molecules were selected for which either direct competition or an allosteric effect had already been determined by other methods. The method of discrimination introduced here is based on the surface plasmon resonance responses observed at equilibrium when an immobilized receptor protein is brought into contact with binary mixtures of interacting ligands. These experimentally determined responses are compared with the responses calculated using a theoretical model that considers both direct competition and allosteric ligand interaction modes. This study demonstrates that the allosteric ternary complex model, which enables calculation of the fractional occupancy of the protein by each ligand in such ternary systems, is well suited for the theoretical calculation of these types of responses. For all of the ternary systems considered in this work, the experimental and calculated responses in the chosen concentration ratio range were identical within a five-σ confidence interval when the calculations considered the correct interaction mode of the ligands (direct competition or different types of allosteric regulation), and in case of allosteric modulation, also the correct strength of this effect. This study also demonstrates that the allosteric ternary complex model-based calculations are well suited to predict the ideal concentration ratio range or even single concentration ratios that can serve as hot spots for discrimination, and such hot spots can drastically reduce the numbers of measurements needed for discrimination between direct competition and distinct modulation modes (neutral, positive or negative allostery).

Pancreatic islets in type 2 diabetesmellitus (T2DM) patients are characterized by reduced ?-cells mass, increased ?-cells apoptosis, and diffuse extracellular amyloidosis.Amyloid deposition involves the aggregation of the islet amyloid polypeptide (IAPP) which is a neuropancreatic hormone cosecreted with insulin by ?-cells. IAPP is physiologically involved in glucose homeostasis, but it may turn toxic to ?-cells owing to its tendency to misfold giving rise to oligomers and amyloid fibrils. Despitemany studies dealing with this issue, the process by which the natively unfolded IAPP starts to self-assemble and the overall factors promoting this conversion are still poorly understood. The process of IAPP aggregation in vivo is harmful to pancreatic ?-cells but the nature of the IAPP toxic species, what exactly causes ?-cell damage and how ?-cells die, remains elusive. Over the last decades, there has been growing consensus about the notion that early stage molecular assemblies, notably small hIAPP oligomers, are the culprit of ?-cells decline. Some studies have pointed out how numerous environmental factors might affect "in vivo" the conformational features, as well as the aggregation and the cytotoxic properties of IAPP. Herein we review recent progress in the field, focusing our attention on the influences that membranes, pH, and metal ions may have on the conformational conversion and cytotoxicity of full-length IAPP as well as some peptide fragments. Thereafter, current theories proposed for the mechanisms of toxicity will be also summarized together with an outline of the underlying molecular links between IAPP and amyloid beta (A?) misfolding.

A novel anchoring ligand for dye-sensitised solar cell chromophoric complexes, 1-(2,2′-bipyrid-4-yl)-1,2,3-triazole-4,5-dicarboxylic acid (dctzbpy), is described. The new dye complexes [Ru(bpy)2(dctzbpy)][PF6]2 (AS16), [Ir(ppy)2(dctzbpy)][PF6] (AS17) and [Re(dctzbpy)(CO)3Cl] (AS18) were prepared in a two stage procedure with intermediate isolation of their diester analogues, AS16-Et2, AS17-Et2 and AS18-Et2 respectively. Electrochemical analysis of AS16-Et2, AS17-Et2 and AS18-Et2 reveal reduction potentials in the range −1.50 to −1.59 V (vs. Fc+/Fc) which are cathodically shifted with respect to that of the model complex [Ru(bpy)2(dcbH2)]2+ (1) (Ered = −1.34 V, dcbH2 = 2,2′-bipyridyl-4,4′-dicarboxylic acid). This therefore demonstrates that the LUMO of the complex is correctly positioned for favourable electron transfer into the TiO2 conduction band upon photoexcitation. The higher energy LUMOs for AS16 to AS18 and a larger HOMO–LUMO gap result in blue-shifted absorption spectra and hence reduced light harvesting efficiency relative to their dcbH2 analogues. Preliminary tests on TiO2 n-type and NiO p-type DSSCs have been carried out. In the cases of the Ir(III) and Re(I) based dyes AS17 and AS18 these show inferior performance to their dcbH2 analogues. However, the Ru(II) dye AS16 (η = 0.61%) exhibits significantly greater efficiency than 1 (η = 0.1%). In a p-type cell AS16 shows the highest photovoltaic efficiency (η = 0.028%), almost three times that of cells incorporating the benchmark dye coumarin C343.

// Fulvio Florenzano 1,* , Corsetti Veronica 2,* , Gabriele Ciasca 3,* , Maria Teresa Ciotti 4 , Anna Pittaluga 5 , Gunedalina Olivero 5 , Marco Feligioni 1,6 , Filomena Iannuzzi 1 , Valentina Latina 2 , Michele Francesco Maria Sciacca 7 , Alessandro Sinopoli 7 , Danilo Milardi 7 , Giuseppe Pappalardo 7 , De Spirito Marco 3 , Massimiliano Papi 3 , Anna Atlante 8,9 , Antonella Bobba 8,9 , Antonella Borreca 4 , Pietro Calissano 1 and Giuseppina Amadoro 1,2 1 European Brain Research Institute, Rome, Italy 2 Institute of Translational Pharmacology, CNR, Rome, Italy 3 Institute of Physics, Catholic University of the Sacred Heart, Largo F Vito 1, Rome, Italy 4 Institute of Cellular Biology and Neuroscience, CNR, IRCSS Santa Lucia Foundation, Rome, Italy 5 Department of Pharmacy, Pharmacology and Toxicology Section, University of Genoa, Genoa, Viale Cembrano, Italy 6 Department of Neurorehabilitation Sciences, Casa Cura Policlinico, Milan, Italy 7 Institute of Biostructures and Bioimaging, CNR, Catania, Italy 8 Institute of Biomembranes and Bioenergetics, CNR, Bari, Italy 9 Center of Excellence for Biomedical Research, University of Genoa, Genoa, Viale Benedetto XV, Italy * These authors have equally contributed to this work Correspondence to: Giuseppina Amadoro, email: // Keywords : extracellular tau, tau cleavage, Alzheimer’s disease, neurodegeneration, synapse(s), Gerotarget Received : March 07, 2017 Accepted : April 11, 2017 Published : April 22, 2017 Abstract The largest part of tau secreted from AD nerve terminals and released in cerebral spinal fluid (CSF) is C-terminally truncated, soluble and unaggregated supporting potential extracellular role(s) of NH 2 -derived fragments of protein on synaptic dysfunction underlying neurodegenerative tauopathies, including Alzheimer’s disease (AD). Here we show that sub-toxic doses of extracellular-applied human NH 2 tau 26-44 (aka NH 2 htau) -which is the minimal active moiety of neurotoxic 20-22kDa peptide accumulating in vivo at AD synapses and secreted into parenchyma- acutely provokes presynaptic deficit in K + -evoked glutamate release on hippocampal synaptosomes along with alteration in local Ca 2+ dynamics. Neuritic dystrophy, microtubules breakdown, deregulation in presynaptic proteins and loss of mitochondria located at nerve endings are detected in hippocampal cultures only after prolonged exposure to NH 2 htau. The specificity of these biological effects is supported by the lack of any significant change, either on neuronal activity or on cellular integrity, shown by administration of its reverse sequence counterpart which behaves as an inactive control, likely due to a poor conformational flexibility which makes it unable to dynamically perturb biomembrane-like environments. Our results demonstrate that one of the AD-relevant, soluble and secreted N-terminally truncated tau forms can early contribute to pathology outside of neurons causing alterations in synaptic activity at presynaptic level, independently of overt neurodegeneration.

The five naturally most abundant anthocyanidins (delphinidin, cyanidin, pelargonidin, malvidin and peonidin) were investigated experimentally and theoretically for dye sensitised solar cell (DSSC) applications. The five dyes were characterised by UV-Vis absorption spectroscopy and cyclic voltammetry, revealing ideal photophysical and electrochemical properties for their final DSSC application. The molecular geometries, electronic structures, vertical transitions and proton affinity of these molecules were investigated with DFT and TDDFT calculations. All of the studied dyes show photo-energy conversion activity, with efficiencies up to eta = 1.4% for pelargonidin. The experimental characterisation together with the computational analysis were fundamental tools in order to better understand the obtained photovoltaic performances and after two decades stopping the cyanidin hegemony in the field of natural dyes for DSSC applications. (C) 2017 Elsevier Ltd. All rights reserved.

We report the unprecedented observation and unequivocal crystallographic characterization of the meta-stable ligand loss intermediate solvento complex trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+ (1 a) that contains a monodentate chelate ligand. This and analogous complexes can be observed during the photolysis reactions of a family of complexes of the form [Ru(equation image)(btz)2]2+ (1 a–d: btz=1,1′-dibenzyl-4,4′-bi-1,2,3-triazolyl; equation image=a) 2,2′-bipyridyl (bpy), b) 4,4′-dimethyl-2,2′-bipyridyl (dmbpy), c) 4,4′-dimethoxy-2,2′-bipyridyl (dmeobpy), d) 1,10-phenanthroline (phen)). In acetonitrile solutions, 1 a–d eventually convert to the bis-solvento complexes trans-[Ru(equation image)(btz)(NCMe)2]2+ (3 a–d) along with one equivalent of free btz, in a process in which the remaining coordinated bidentate ligands undergo a new rearrangement such that they become coplanar. X-ray crystal structure of 3 a and 3 d confirmed the co-planar arrangement of the equation image and btz ligands and the trans coordination of two solvent molecules. These conversions proceed via the observed intermediate complexes 2 a–d, which are formed quantitatively from 1 a–d in a matter of minutes and to which they slowly revert back on being left to stand in the dark over several days. The remarkably long lifetime of the intermediate complexes (>12 h at 40 °C) allowed the isolation of 2 a in the solid state, and the complex to be crystallographically characterized. Similarly to the structures adopted by complexes 3 a and d, the bpy and κ2-btz ligands in 2 a coordinate in a square-planar fashion with the second monodentate btz ligand coordinated trans to an acetonitrile ligand.

Background: Hemophilia A is caused by deficiency of factor VIII (F.VIII), an essential blood-clotting cofactor. The current standard of care involves prophylactic or on-demand use of F.VIII. However, approximately 30% of severe hemophilia A patients develop inhibitory antibodies against the replacement factor VIII. Additionally, venous infusion of F.VIII is burdensome especially in pediatric patients. Hemlibra®, a humanized bispecific antibody (BiAb) that mimics the action of factor VIII, has been developed and approved for treating hemophilia A patients with or without inhibitors. Using Kymab's IntelliSelect® Bispecific antibody discovery platform, a fully human common light chain (CLC) bispecific antibody was developed and optimized to mimic the function of F.VIII. The biological activity of the CLC bispecific antibody was characterized using clinically relevant hemostatic assays. Methods: Kymab IntelliSelect® Transgenic mice were immunized with human factor IX (F.IX) or factor X (F.X). Isolated F.IX and F.X arms were combinatorially expressed as 2-heavy-2-light (2H2L) BiAbs. Light chain of a biologically active F.IX arm was chosen to generate CLC transgenic mice. CLC transgenic mice were immunized with F.X to identify F.X heavy chains pairing with CLC. The isolated F.X heavy chains were co-expressed with the heavy and light chains of the selected F.IX arm as CLC BiAbs and re-screened by functional assays. Biologically active BiAbs were further optimized to generate a lead BiAb, KY1049. KY1049 heterodimer was purified by a two-step method using Protein A and cation ion exchange chromatography (cIEX). The purified BiAb was analyzed by analytical HPLC and mass spectrometry (MS). The purified BiAb was also characterized using a combination of in vitro and ex vivo hemostatic assays including chromogenic FXase (FXase), activated partial thromboplastin time (aPTT) and thrombin generation assay (TGA). Binding of KY1049 to F.IX and F.X was studied using surface plasmon resonance (SPR). Results: More than 8,000 2H2L BiAbs were first screened by high-throughput chromogenic FXase assay. Functionally active 2H2L BiAbs were identified, consisting of one F.IX arm and different F.X arms. The light chain of this promiscuous F.IX arm was chosen to generate CLC transgenic mice expressing the light chain exclusively. More than 400 F.X heavy chains isolated from the CLC transgenic mice were screened to identify functionally active CLC BiAbs. Further work to iteratively and combinatorially optimize the variable domains resulted in KY1049, a lead BiAb which demonstrates robust hemostatic activity. KY1049 demonstrates a dose-dependent reduction in clotting time and a dose-dependent increase in thrombin burst, thereby functionally restoring the hemostatic activity of F.VIII-depleted plasma. Compared with a sequence identical analog (SIA) of Hemlibra®, KY1049 shows comparable efficacy in a range of concentration of IgG (0.1 to 300 nM). Importantly, KY1049 can be purified using a routine purification process. The purity and the identity of KY1049 was confirmed by mass spectrometry. KY1049 was shown to simultaneously bind F.IX and F.X using SPR in confirmation of its mode of action. Summary/conclusions: KY1049, developed using Kymab's IntelliSelect® Bispecific platform, is a potent F.VIII mimetic bispecific antibody with activities comparable to a SIA of Hemlibra®. This fully human CLC bispecific antibody can potentially provide a new treatment option for hemophilia A patients. Disclosures Wang: Kymab Ltd.: Employment, Equity Ownership, Patents & Royalties. Blackwood:Kymab Ltd.: Employment, Equity Ownership, Patents & Royalties. Magliozzi:Kymab Ltd.: Employment, Equity Ownership, Patents & Royalties. Moraes:Kymab Ltd.: Employment, Equity Ownership. Hollins:Kymab Ltd.: Employment, Equity Ownership. Sinopoli:Kymab Ltd.: Employment, Equity Ownership. Chi:Kymab Ltd.: Employment, Equity Ownership. Mitchell:Kymab Ltd.: Employment, Equity Ownership. Sellick:Kymab Ltd.: Employment, Equity Ownership. Pearce:Kymab Ltd.: Employment, Equity Ownership. Theurl:Kymab Ltd.: Consultancy, Equity Ownership; Sierra Oncoloy: Research Funding. Germaschewski:Kymab Ltd.: Employment, Equity Ownership. Galson:Kymab Ltd.: Employment, Equity Ownership. Badiali:Kymab Ltd.: Employment, Equity Ownership. Dickson:Kymab Ltd.: Employment, Equity Ownership. Bradley:Kymab Ltd.: Employment, Equity Ownership, Patents & Royalties. Lee:Kymab Ltd.: Employment, Equity Ownership, Patents & Royalties.

The 2D transition metal carbides (MXenes) are increasingly considered among of the most promising 2D nanomaterials, because of their unique properties such as hydrophilic nature, metallic conductivity, large surface-area-to-volume ratio, and active surface functionalities. This has led to their growing utilization in water/wastewater treatment and environmental remediation applications, including water purification membranes, heavy metal removal, capacitive deionization, and bactericidal agents. This account will focus on the key characteristic properties of MXenes such as high metallic/electronic conductivity, and catalytic activity, and their utilization for the electrocatalytic and photocatalytic-based environmental remediation applications. We will also address the key challenges facing MXene-based materials in aqueous media and possible mitigation routs.

The inhibition of amyloid formation is a promising therapeutic approach for the treatment of neurodegenerative diseases. Peptide-based inhibitors, which have been widely investigated, are generally derived from original amyloid sequences. Most interestingly, trehalose, a nonreducing disaccharide of ?-glucose, is effective in preventing the aggregation of numerous proteins. We have determined that the development of hybrid compounds could provide new molecules with improved properties that might synergically increase the potency of their single moieties. In this work, the ability of Ac-LPFFD-Th, a C-terminally trehalose-conjugated derivative, to slow down the A? aggregation process was investigated by means of different biophysical techniques, including thioflavin T fluorescence, dynamic light scattering, ESI-MS, and NMR spectroscopy. Moreover, we demonstrate that Ac-LPFFD-Th modifies the aggregation features of A? and protects neurons from A? oligomers' toxic insult.

We present the photoelectrochemical properties of dye-sensitized solar cells using natural pigments containing betalains and anthocyanins as sensitizers. The dyes extracted from grape, mulberry, blackberry, red Sicilian orange, Sicilian prickly pear, eggplant and radic-chio have shown a monochromatic incident photon to current efficiency (IPCE) ranging from 40% to 69%. Short circuit photocurrent densities (J(sc)) up to 8.8 mA/cm(2), and open circuit voltage (V-oc) ranging from 316 to 419 mV, were obtained from these natural dyes under 100 mW/cm(2) (AM 1.5) simulated sunlight. The best solar conversion efficiency of 2.06% was achieved with Sicilian prickly pear fruits extract. The influence of pH and co-absorbers on natural sensitizers, were investigated and discussed. (C) 2012 Elsevier Ltd. All rights reserved.