Acceptor Function Research Articles

Angiotensin receptor blocker vs ACE inhibitor effects on HDL functionality in patients on maintenance hemodialysis

Background and AimsAngiotensin receptor blockers (ARB) and angiotensin converting enzyme inhibitors (ACEI) reduce cardiovascular events in the general population. Maintenance hemodialysis (MHD) patients are at high cardiovascular risk but few studies have directly addressed the comparative efficacy of these drugs. MHD disrupts the normally atheroprotective actions of high density lipoprotein (HDL), therefore, we compared ACEI or ARB treatment on HDL functions in MHD. Methods and ResultsHDL was isolated at the starting point (pre) and 3–6 months later (post) in 30 MHD randomly assigned to placebo, ramipril or valsartan. Outcomes included cholesterol efflux, inflammatory cytokine response, effects on Toll-like receptors (TLR), superoxide production, methylarginine and serum amyloid A (SAA) levels. HDL from ARB- or ACEI-treated subjects was more effective in maintaining efflux than HDL of placebo. HDL from ARB- or ACEI-treated subjects but not placebo lessened cellular superoxide production. In contrast, neither ARB nor ACEI improved HDL anti-inflammatory effect. Indeed, HDL of ACEI-treated subjects potentiated the cytokine responses in association with activation of TLR but did not alter the HDL content of methylarginines or SAA. ConclusionBoth ACEI and ARB stabilized HDL cholesterol acceptor function and sustained cellular anti-oxidative effects but not anti-inflammatory effects, and ACEI-treatment instead amplified the HDL inflammatory response. The findings reveal possible utility of antagonizing angiotensin actions in MDH and suggest a possible mechanism for superiority of ARB vs ACEI in the setting of advanced kidney disease.

Multifunctional Organosulfonate Anions Self-Assembled with Organic Cations by Charge-Assisted Hydrogen Bonds and the Cooperation of Water

The present study focuses on the assembly of organo-cations with organo-anions in water. The anions, characterized by symmetric moieties (carbon-, adamantane-, or calixarene-based) functionalized with directional hydrogen bond (HB) acceptor functions (tetra-sulfonate moieties), are combined with planar guanidinium or terephtalimidamide cations as hydrogen bond donors, the purpose being to integrate water molecules into the lattice. The imbalance between the charge on the two components, and the considerable number of HB donor and acceptor sites, promotes the insertion of water into the structures. In the reported structures, a part of the water molecules serves as a structural linker between the anions and cations, while the remaining molecules cluster into channels and cavities in a loose association with the supramolecular matrix framework.

Chronic kidney disease alters lipid trafficking and inflammatory responses in macrophages: effects of liver X receptor agonism

BackgroundOur aim was to evaluate lipid trafficking and inflammatory response of macrophages exposed to lipoproteins from subjects with moderate to severe chronic kidney disease (CKD), and to investigate the potential benefits of activating cellular cholesterol transporters via liver X receptor (LXR) agonism.MethodsLDL and HDL were isolated by sequential density gradient ultracentrifugation of plasma from patients with stage 3–4 CKD and individuals without kidney disease (HDLCKD and HDLCont, respectively). Uptake of LDL, cholesterol efflux to HDL, and cellular inflammatory responses were assessed in human THP-1 cells. HDL effects on inflammatory markers (MCP-1, TNF-α, IL-1β), Toll-like receptors-2 (TLR-2) and − 4 (TLR-4), ATP-binding cassette class A transporter (ABCA1), NF-κB, extracellular signal regulated protein kinases 1/2 (ERK1/2) were assessed by RT-PCR and western blot before and after in vitro treatment with an LXR agonist.ResultsThere was no difference in macrophage uptake of LDL isolated from CKD versus controls. By contrast, HDCKD was significantly less effective than HDLCont in accepting cholesterol from cholesterol-enriched macrophages (median 20.8% [IQR 16.1–23.7] vs control (26.5% [IQR 19.6–28.5]; p = 0.008). LXR agonist upregulated ABCA1 expression and increased cholesterol efflux to HDL of both normal and CKD subjects, although the latter continued to show lower efflux capacity. HDLCKD increased macrophage cytokine response (TNF-α, MCP-1, IL-1β, and NF-κB) versus HDLCont. The heightened cytokine response to HDLCKD was further amplified in cells treated with LXR agonist. The LXR-augmentation of inflammation was associated with increased TLR-2 and TLR-4 and ERK1/2.ConclusionsModerate to severe impairment in kidney function promotes foam cell formation that reflects impairment in cholesterol acceptor function of HDLCKD. Activation of cellular cholesterol transporters by LXR agonism improves but does not normalize efflux to HDLCKD. However, LXR agonism actually increases the pro-inflammatory effects of HDLCKD through activation of TLRs and ERK1/2 pathways.

Widely Applicable n-Type Molecular Doping for Enhanced Photovoltaic Performance of All-Polymer Solar Cells.

A widely applicable doping design for emerging nonfullerene solar cells would be an efficient strategy in order to further improve device photovoltaic performance. Herein, a family of compound TBAX (TBA= tetrabutylammonium, X = F, Cl, Br, or I, containing Lewis base anions are considered as efficient n-dopants for improving polymer-polymer solar cells (all-PSCs) performance. In all cases, significantly increased fill factor (FF) and slightly increased short-circuit current density (Jsc) are observed, leading to a best PCE of 7.0% for all-PSCs compared to that of 5.8% in undoped devices. The improvement may be attributed to interaction between different anions X- (X = F, Cl, Br, and I) in TBAX with the polymer acceptor. We reveal that adding TBAX at relatively low content does not have a significantly impact on blend morphology, while it can reduce the work function (WF) of the electron acceptor. We find this simple and solution processable n-type doping can efficiently restrain charge recombination in all-polymer solar cell devices, resulting in improved FF and Jsc. More importantly, our findings may provide new protocles and insights using n-type molecular dopants in improving the performance of current polymer-polymer solar cells.

Design, Synthesis, and Antibacterial Evaluation of Oxazolidinones with Fused Heterocyclic C-Ring Substructure.

A series of novel oxazolidinone antibacterials with diverse fused heteroaryl C-rings bearing hydrogen bond donor and hydrogen bond acceptor functionalities were designed and synthesized. The compound with benzoxazinone C-ring substructure (8c) exhibited superior activity compared to linezolid against a panel of Gram-positive and Gram-negative bacteria. Structural modifications at C5-side chain of 8c resulted in identification of several potent compounds (12a, 12b, 12g, and 12h). Selected compounds 8c and 12a showed very good microsomal stability and no CYP450 liability, thus clearing preliminary safety hurdles. A docking model of 12a binding to 23S rRNA suggested that the increased potency of 12a is due to additional ligand-receptor interaction.

Sensitivity of Breakdown Voltage of Power Transistors to Dopant Impurities

The doping sensitivity functions provide a powerful tool to analyze the effects of doping variations on the parameters of power semiconductor devices. They can be coupled with gradient-based optimization algorithms to design the doping profiles in power devices and are instrumental in the statistical analysis of these devices. In this article we discuss about applications of the doping sensitivity functions in power devices. We focus mostly on maximizing the breakdown voltage and minimizing the on-state resistance and on the numerical evaluation of the acceptor and donor sensitivity functions of the breakdown voltage. Simulation results are presented and analyzed for a standard insulated gate bipolar transistor.

Proteorhodopsin Photocycle Kinetics Between pH 5 and pH 9.

The retinal protein proteorhodopsin is a homolog of the well-characterized light-driven proton pump bacteriorhodopsin. Basic mechanisms of proton transport seem to be conserved, but there are noticeable differences in the pH ranges of proton transport. Proton transport and protonation state of a carboxylic acid side chain, the primary proton acceptor, are correlated. In case of proteorhodopsin, the pKa of the primary proton acceptor Asp-97 (pKa ≈7.5) is unexpectedly close to environmental pH (pH≈8). A significant fraction of proteorhodopsin is possibly inactive at natural pH, in contrast to bacteriorhodopsin. We investigated photoinduced kinetics of proteorhodopsin between pH 5 and pH 9 by time resolved UV/vis absorption spectroscopy. Kinetics is inhomogeneous within that pH region and can be considered as a superposition of two fractions. These fractions are correlated with the Asp-97 titration curve. Beside Asp-97, protonation equilibria of other groups influence kinetics, but the observations do not point toward major differences of primary proton acceptor function in proteorhodopsin and bacteriorhodopsin. The pKa of proteorhodopsin and some of its variants is suspected to be an example of molecular adaptation to the physiology of the original organisms.

Small molecular non-fullerene acceptors based on naphthalenediimide and benzoisoquinoline-dione functionalities for efficient bulk-heterojunction devices

Through the conjunction of naphthalenediimide and benzoisoquinoline-dione functionalities, two novel, solution-processable non-fullerene electron acceptors, 2,7-dioctyl-4,9-bis(2-octyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (coded as NDI-N1) and 2,7-dioctyl-4,9-bis(5-(2-octyl-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)thiophen-2-yl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (coded as NDI-N2), were designed, synthesized, and used as active components for bulk-heterojunction photovoltaic devices. The new chromophores were based on the acceptor–acceptor–acceptor module where naphthalenediimide unit served as the central acceptor flanked by terminal benzoisoquinoline-dione acceptor functionality. The optoelectronic and photovoltaic properties of NDI-N1 and NDI-N2 were directly compared. Solution-processable bulk-heterojunction devices were fabricated using NDI-N1 and NDI-N2 as non-fullerene electron acceptor materials. Studies on the photovoltaic properties revealed that the best poly(3-hexylthiophene) (P3HT): NDI-N2-based device showed an impressive enhanced power conversion efficiency of 4.04%, around 40% increase with respect to the efficiency of the best NDI-N1-based device (2.91%). It is justifiable to mention that the device outcome reported herein provides strong support and incentive for the current research strategy, and that the conjoint use of potential acceptor building blocks, such as naphthalenediimide and benzoisoquinoline-dione, can indeed generate efficient non-fullerene acceptors.

Pharmaceutical Crystal Engineering Using Ionic Liquid Anion–Solute Interactions

The main purpose of this work was to investigate the potential of ionic liquids (ILs) in crystal engineering. We have employed ILs with different combinations of cations and anions to study their role in directing crystal structure formation of a nicotinamide (NIC) and oxalic acid (OXA) system. A new crystal form of NIC–OXA salt (2:1) was identified and characterized using standard solid state tools such as powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and Raman and infrared spectroscopy. The crystal structure of the 2:1 salt was elucidated using single-crystal X-ray diffraction. The NIC–OXA 2:1 salt form revealed a two-dimensional layered structure, while the known 1:1 salt had a perpendicular “tape-like” structure. The 2:1 salt form could only be crystallized from the ILs possessing hydrogen bond acceptor functionality. We demonstrated that specific ILs could be selected as solvents for altering the solid-state structure of organic and inorganic materials.

Chemical Synthesis of L‐Fucose Derivatives for Acceptor Specificity Characterisation of Plant Cell Wall Glycosyltransferases

AbstractSeven derivatives of L‐fucose: methyl α‐L‐fucopyranoside, methyl 2‐O‐methyl‐α‐L‐fucopyranoside, methyl 3‐O‐methyl‐α‐L‐fucopyranoside, methyl 4‐O‐methyl‐α‐L‐fucopyranoside, α‐L‐fucopyranosyl‐(1→4)‐α/β‐L‐rhamnopyranose, methyl α‐L‐fucopyranosyl‐(1→4)‐α‐L‐rhamnopyranoside and methyl α‐L‐fucopyranosyl‐(1→4)‐β‐L‐rhamnopyranoside, were chemically synthesized and characterized. The derivatives of L‐fucose were designed to mimic the L‐fucose moieties present in the A‐chain of pectic rhamnogalacturonan‐II and used to investigate the regiospecificity of three heterologously expressed xylosyltransferases from Arabidopsis thaliana. The monosaccharide methyl α‐L‐fucopyranoside was the most efficient acceptor, 30 fold more effective than methyl 4‐O‐methyl‐α‐L‐fucopyranoside. O‐methylation in position 2 or 3 abolished acceptor function. The efficiencies of the disaccharides as acceptors were methyl α‐L‐fucopyranosyl‐(1→4)‐β‐L‐rhamnopyranoside > α‐L‐fucopyranosyl‐(1→4)‐α/β‐L‐rhamnopyranose > methyl α‐L‐fucopyranosyl‐(1→4)‐α‐L‐rhamnopyranoside. These findings demonstrate the utility of acceptor derivatives as probes of glycosyltransferase regiospecificity.

Naphthalene diimide-based non-fullerene acceptors flanked by open-ended and aromatizable acceptor functionalities.

Herein we present the design, synthesis and characterization of two novel, naphthalene diimide (NDI) core-based non-fullerene acceptors, N5 and N6, comprising respectively 2-methoxyethyl-2-cyanoacetate and cyanopyridone acceptor functionalities at the terminals. The influence of terminal units on optoelectronic and photovoltaic properties was studied. The target chromophore bearing cyanopyridone acceptor units (N6) afforded a power conversion efficiency of 6.10% when paired with the conventional donor polymer poly(3-hexylthiophene), a result that is the highest for the NDI core-based non-fullerene acceptors.

Biocombinatorial Synthesis of Novel Lipopeptides by COM Domain-Mediated Reprogramming of the Plipastatin NRPS Complex.

Both donors and acceptors of communication-mediating (COM) domains are essential for coordinating intermolecular communication within nonribosomal peptides synthetases (NRPSs) complexes. Different sets of COM domains provide selectivity, allowing NRPSs to utilize different natural biosynthetic templates. In this study, novel lipopeptides were synthesized by reprogramming the plipastatin biosynthetic machinery. A Thr-to-Asp point mutation was sufficient to shift the selectivity of the donor COM domain of ppsB toward that of ppsD. Deletion and/or interchangeability established donor and acceptor function. Variations in acceptor COM domain did not result in novel product formation in the presence of its partner donor, whereas plipastatin formation was completely abrogated by altering donor modules. Five novel lipopeptides (cyclic pentapeptide, linear hexapeptide, nonapeptide, heptapeptide, and cyclic octapeptide) were identified and verified by high-resolution LC-ESI-MS/MS. In addition, we demonstrated the potential to generate novel strains with the antimicrobial activity by selecting compatible COM domains, and the novel lipopeptides exhibited antimicrobial activity against five of the fungal species at a contention of 31.25–125 μg/ml.

Electrocatalytic investigation on the water oxidation ability of a hangman complex based on the [Ru(tpy)(bpy)(OH2)]2+ motif

Many known single-site ruthenium complexes used in the catalytic water oxidation reaction react according to the WNA mechanism (WNA=water nucleophilic attack). During catalysis, a nucleophilic attack of a water molecule on a high-valent metal oxo species occurs and the efficiency is positively influenced by beneficial hydrogen-bonding interactions utilizing an external acid or base. Thus, installing a proton‐donor/acceptor functionality in proximity to the catalytic site should have a dramatic influence on the catalytic activity. We recently prepared a “hangman” version of the known [Ru(tpy)(bpy)(OH2)]2+ complex (bpy=2,2′-bipyridine, tpy=2,2′;6′,2″-terpyridine) in which a carboxylic functional group is placed close to the ruthenium center. This catalyst was initially investigated in homogeneous catalysis using cerium (IV) ammonium nitrate as sacrificial electron acceptor. Unfortunately, due to the acidic conditions used, the positive effect on the catalytic performance according to the base-assisted WNA mechanism was in fact hampered. Further investigations on heterogenized systems are presented herein and reveal a clear dependence of the catalytic activity on the solution pH.

Analysis of the Cleavage Mechanism by Protein-Only RNase P Using Precursor tRNA Substrates with Modifications at the Cleavage Site

Ribonuclease P (RNase P) is the enzyme that endonucleolytically removes 5′-precursor sequences from tRNA transcripts in all domains of life. RNase P activities are either ribonucleoprotein (RNP) or protein-only RNase P (PRORP) enzymes, raising the question about the mechanistic strategies utilized by these architecturally different enzyme classes to catalyze the same type of reaction. Here, we analyzed the kinetics and cleavage-site selection by PRORP3 from Arabidopsis thaliana (AtPRORP3) using precursor tRNAs (pre-tRNAs) with individual modifications at the canonical cleavage site, with either Rp- or Sp-phosphorothioate, or 2′-deoxy, 2′-fluoro, 2′-amino, or 2′-O-methyl substitutions. We observed a small but robust rescue effect of Sp-phosphorothioate-modified pre-tRNA in the presence of thiophilic Cd2+ ions, consistent with metal-ion coordination to the (pro-)Sp-oxygen during catalysis. Sp-phosphorothioate, 2′-deoxy, 2′-amino, and 2′-O-methyl modification redirected the cleavage mainly to the next unmodified phosphodiester in the 5′-direction. Our findings are in line with the 2′-OH substituent at nucleotide −1 being involved in an H-bonding acceptor function. In contrast to bacterial RNase P, AtPRORP3 was found to be able to utilize the canonical and upstream cleavage site with similar efficiency (corresponding to reduced cleavage fidelity), and the two cleavage pathways appear less interdependent than in the bacterial RNA-based system.

Aluminum and Gallium Hydrazides as Active Lewis Pairs: Cooperative C–H Bond Activation with H–C≡C–Ph and Pentafluorobenzene

Hydroalumination or hydrogallation of a sterically encumbered hydrazone, H10C5N–N═C(C9H14) (NC5H10 = piperidine, C(C9H14) = 2-adamantdiyl), afforded hydrazides that, depending on the steric shielding by the substituents at the metal atoms, had different molecular structures. While both di(tert-butyl)metal derivatives (1a, 1b) are monomeric in the solid state with highly strained MN2 heterocycles (M = Al, Ga), the dimethylmetal compounds (1c, 1d) are dimeric with M2N2 heterocycles and exocyclic N–N bonds. The latter compounds are highly dynamic in solution. 1d crystallized as a mixture of cis- and trans-isomers as detected by crystal structure determinations. These compounds react as active Lewis pairs by their specific donor–acceptor functionality and are able to activate C–H bonds of moderately acidic substrates. Reaction of 1a (M = Al) with H–C≡C–C6H5 afforded by C–H bond activation and release of H–CMe3 trialkynyl compound 4, in which three alkynyl groups and a neutral hydrazine ligand are bound to Al....

Enhancing the efficiency of solution-processable bulk-heterojunction devices via a three-dimensional molecular architecture comprising triphenylamine and cyanopyridone

Through the employment of a three-dimensional molecular geometry, a novel, solution-processable small molecular organic chromophore was designed, synthesized and characterized for application in bulk-heterojunction solar cells. The new chromophore, [(5Z,5′Z,5″Z)-5,5′,5″-(((nitrilotris(benzene-4,1-diyl))tris(thiophene-5,2-diyl))tris(methanylylidene))tris(1-(2-ethylhexyl)-4-methyl-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile)] (coded as 3D), was based on a donor–acceptor (D–A) module where a simple triphenylamine unit served as an electron donor, cyanopyridone as an electron acceptor, and a thiophene unit as π-bridge embedded between the donor and acceptor functionalities. The optoelectronic and photovoltaic properties of 3D were directly compared with those of a structural analogue, [(Z)-5-((5-(4-(diphenylamino)phenyl)thiophen-2-yl)methylene)-1-(2-ethylhexyl)-4-methyl-2,6-dioxo-1,2,5,6-tetrahydropyridine-3-carbonitrile)], namely 1D. The three-dimensional (otherwise termed as non-linear) design, compared to one-dimensional (or linear) design, demonstrated (1) an enhancement of light-harvesting ability by about 50%; (2) an increase in wavelength of the longest wavelength absorption maximum of thin film (633 nm vs. 581 nm) and (3) a narrower optical band-gap (1.53 eV vs. 1.65 eV). Solution-processable bulk-heterojunction devices were fabricated with 3D and 1D as donor materials. Studies on the photovoltaic and hole charge mobility properties revealed that the best 3D- [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM)-based device showed an impressive enhanced power conversion efficiency of 4.76%, an increase of greater than two-fold with respect to the efficiency of the best 1D-based device (2.11%), and a higher hole mobility of the order of 3.4 × 10−4 cm2 V−1 s−1. Not only is 3D the first reported example in the literature where cyanopyridone acceptor functionality has been used to generate a three-dimensional donor molecule but the power conversion efficiency reported here is the highest value reported so far for non-linear, star-shaped molecular architectures. These results clearly illustrated that the use of a three-dimensional geometry helped to extend molecular conjugation, thus enhancing the light-harvesting ability and short-circuit current density, while further improving the bulk-heterojunction device performance.

Molecular Design Principles for Near-Infrared Absorbing and Emitting Indolizine Dyes.

Desirable components for dye-sensitzed solar cell (DSC) sensitizers and fluorescent imaging dyes include strong donating building blocks coupled with well-balanced acceptor functionalities for absorption beyond the visible range. We have evaluated the effects of increasing acceptor strengths and incorporation of dye morphology controlling groups on molar absorptivity and absorption breadth with indolizine donor-based dyes. Indolizine-based D-A and D-π-A sensitizers incorporating bis-rhodanine, tricyanofuran (TCF), and cyanoacrylic acid functionalities were analyzed for performance in DSC devices. The TCF derivatives were also evaluated as near-infrared (NIR)-emissive materials with the AH25 emissions extending past 1000 nm.

ChemInform Abstract: Coordination‐ and Redox‐Noninnocent Behavior of Ambiphilic Ligands Containing Antimony

AbstractReview: 46 refs.

Rational Tuning of AIEE Active Coumarin Based α-Cyanostilbenes toward Far-Red/NIR Region Using Different π-Spacer and Acceptor Units

A series of cyanostilbene based D−π–A derivatives, comprising 6-(diethylamino)coumarin as a donor and benzene and benzothiazole as acceptors bridged by different π-spacers (benzene, thiophene), have been synthesized and characterized. The influence of π-spacer and acceptor units on the photophysical, electrochemical, and thermal properties of the dyes was investigated in detail. The incorporation of coumarin donor results in a significant increase of the fluorescence quantum yield. In the solution phase, the absorption and emission of the dye TB show a bathochromic shift (TB > BBT) indicating dominant dynamic intramolecular rotations (IMR) behavior of cyano group over the acceptor functionality. On the other hand, the emission is reversed (BBT > TB) in the case of aggregates. The synergistic combination of intramolecular planarization and torsional alleviation around cyanostilbenes induced by strong electron withdrawing benzothiazole unit in BBT enabled pronounced bathochromic shift upon aggregation. Upon...

Beyond the top of the volcano? – A unified approach to electrocatalytic oxygen reduction and oxygen evolution

We study the oxygen reduction (ORR) and the oxygen evolution reaction (OER) and based on previous obtained mechanistic insight we provide a unified general analysis of the two reactions simultaneously. The analysis shows that control over at least two independent binding energies is required to obtain a reversible perfect catalyst for both ORR and OER. Often only the reactivity of the surface is changed by changing from one material to another and all binding energies scale with the reactivity. We investigate the limitation in efficiency imposed by these linear scaling relations. This analysis gives rise to a double volcano for ORR and OER, with a region in between, forbidden by the scaling relations. The reversible perfect catalyst for both ORR and OER would fall into this “forbidden region”. Previously, we have found that hydrogen acceptor functionality on oxide surfaces can improve the catalytic performance for OER beyond the limitations originating from the scaling relations. We use this concept to search for promising combinations of binding sites and hydrogen donor/acceptor sites available in transition metal doped graphene, which can act as a catalyst for ORR and OER. We find that MnN4-site embedded in graphene by itself or combined with a COOH is a promising combination for a great combined ORR/OER catalyst.