Chemistry - A European Journal最新文献

The arylpyridylmethylamine motif is a privileged scaffold in drug discovery. However, rapidly creating these valuable molecules with structural diversity by directly leveraging readily available, yet simple chemical feedstocks remains a challenge. Herein, we describe a versatile and modular photochemical method for the straightforward construction of arylpyridylmethylamine skeleton utilizing widely accessible starting materials, including amines, aldehydes, and pyridines. This multicomponent coupling proceeds under very mild conditions without the need for any transition-metal catalysts, photocatalysts, and acid additives and displays a broad substrate scope and excellent functional-group tolerance. The potential utility of this methodology in pharmaceutical development is demonstrated through late-stage modification of pharmaceutically relevant compounds, concise synthesis of bioactive compounds, and rapid construction of pyridyl analogue of drug molecules. Combined experimental and computational studies unveiled that this reaction proceeds through radical-radical cross-coupling between persistent pyridylphosphonium radicals and α-amino radicals.

The article describes stepwise oxygenation of the aldimine functions at the backbone of N,N'-bis(pyridin-2-ylmethylene)naphthyl-1,5-diimine (L) in non-interconvertible L-bridged isomeric diruthenium(II)-acac complexes [{RuII(acac)2}2(µ-L)] (cis-1a/trans-1b, acac=acetylacetonate, DFT calculated DEcis-trans = 440 cm-1) via dioxygen activation.. It leads to the formation of the corresponding carboxamido bridged [{RuIII(acac)2}2(µ-Ld2-)] (cis-1ad/ trans-1bd; d denotes doubly-oxygenation) with the concomitant metal oxidation. However, L in doubly oxidized (RuIIIRuIII) congeners i.e. [{RuIII(acac)2}2(µ-L)](ClO4)2 (cis-[1a](ClO4)2/trans-[1b](ClO4)2) as well as electron poor metal fragments derived [{RuII(bpy)2}2(µ-L)]4+ [2](ClO4)4 (bpy=2,2'-bipyridine) and [{RuII(PPh3)2(CO)(H)}2(µ-L)]2+ [3](ClO4)2  failed to undergo the aforestated oxygenation process on purging O2 even at elevated temperature due to the absence of necessary electron exchange between ruthenium and L (i.e. RuII-L-RuII«RuIII-L·--RuII) to initiate the oxygen activation step. Besides structural and spectroscopic characterization of the complexes, oxygenation processes were further monitored through electrochemical, EPR and kinetic experiments in conjunction with DFT calculations, which highlighted mechanistic insights into the reaction sequence.

Short amyloidogenic oligopeptides (APRs) are proposed as early macromolecules capable of forming solvent-separated nanosystems under prebiotic conditions. This study provides experimental evidence that APRs, such as the aggregation-prone oligopeptide A (APR-A), can undergo mutational transitions to form distinct variants, and convert to APR-B, either amyloid-like or water-soluble and non-aggregating. These transitions occur along a spectrum from strongly amyloidogenic (pro-amyloid) to weakly amyloidogenic (anti-amyloid), with the mutation sequence order playing a key role in determining their physicochemical properties. The pro-amyloid pathway facilitates heterogeneous phase separation, leading to amyloid-crystal formation with multiple polymorphs, including the first class 3 amyloid topology. By mapping these transitions, we demonstrate the potential co-evolution of water-soluble miniproteins and insoluble amyloids, both of which could have been pivotal in early bio-nanosystem formation. These insights into amyloid modulation provide a crucial step toward understanding amyloid control mechanisms.

The interaction between apical membrane antigen 1 (PfAMA1) and rhoptry neck protein 2 (PfRON2) is crucial for Plasmodium falciparum red blood cell invasion, making it a key target for anti-malarial drug development strategies. Here, we report the chemical synthesis of PfAMA1 domain-I (PfAMA1-DI) in both linear and backbone-circularized forms, employing a six-segment convergent synthesis approach exploiting one-pot chemistries and solubilizing tags. The chemically synthesized linear PfAMA1-DI construct exhibited incomplete disulfide bond formation during folding, likely due to increased terminal flexibility in the absence of domain-II. To address this, we employed backbone cyclization of the large 180-residue polypeptide chain, with 3-residue linker sequence, as a unique strategy to conformationally restrict its termini and facilitate correct disulfide bond formation. Introducing a multipurpose affinity and solubility tag to the cyclicPfAMA1-DI construct further improved the folding yield by mitigating aggregation. The predicted structure using ColabFold-Alphafold2 indicated that PfRON2 ligand binds within the hydrophobic groove of the cyclicPfAMA1-DI construct similar to the native interactions. These findings underscore the potential of large protein backbone cyclization to stabilize protein structure, offering a compelling strategy for the chemical synthesis of otherwise unstable protein domains with broad applications in miniature protein engineering.

Design of semiconducting materials with facile control of charge transport and the nature of charge carriers is essential for realizing niche applications with organic electronics. Described herein are the synthesis, crystal structure, and analysis of the electronic properties of a four-stage redox amphoteric S-heterocyclic s-indacenodifluorene 6, including the study of its ambipolar charge carrier mobility (μh and μe) in organic field-effect transistor (OFET) devices. Despite being electron-rich, our investigation revealed reversible reduction potentials for 6 in the cyclic voltammetry, which is attributed to the recovery of locally aromatic thiophene and cyclopentadienyl anion units upon electron injection for the two antiaromatic S-heterocyclic as-indacene units in accordance to the Glidewell-Lloyd rule of aromaticity. In line with this, we observed an interesting thermal tunability of the nature of charge carriers from p-type to balanced ambipolar to n-type charge transport with reasonable semiconductor mobility in all regimes of transport. This behaviour is correlated with the modification of the transport levels upon annealing of the semiconductor and possible increase in the extent of π-electron delocalization with temperature. This proof-of-concept tunability of the nature of charge transport indicates the efficacy of our molecular design.

This article presents the synthesis and characterization of a series of robust high-valent organometallic nickel complexes stabilized by a functionalized PC(sp³)P pincer ligand. Notably, the nickel center, covalently confined within the three-dimensional ligand framework, exhibits predictable coordination and redox behavior, coupled with remarkable stability across oxidation states +2, +3, and +4. These states were found to interconvert via one-electron transfer reactions. Among these complexes, the Ni(III)-PC(sp³)P species was identified as an efficient catalyst for the mild and selective hydrosilylation of alkenes, operating through a non-oxidative mechanism that, in some cases, leads to the formation of vinyl silanes and polysilylated products. We demonstrated that, contrary to a widely accepted concept, high-valent metals can serve as viable candidates for hydrogenation catalysts.

A series of Ir(III) complexes, [Ir(C^N)2(en)]+ (where C^N = 2-phenyl-benzo[d]thiazolyl cyclometalating ligand; en = ethylene diamine), are reported with structural variation via a substituent (H, Me, OMe, Cl, OCF3) at the coordinated phenyl ring.  The complexes were soluble in aqueous buffer, with solubility limits correlating inversely with the predicted logP. The complexes display efficient visible absorption at 400-500 nm (e ~ 5000 M-1 cm-1) due to charge-transfer transitions and are triplet emitters in aerated buffer (lem = 529-540 nm; lifetimes up to 0.763 ms; Fem £ 12 %). Each complex was investigated, via computational and biophysical experiments, in the context of DNA binding. According to UV-visible titrations, the cationic complexes bind to DNA with apparent affinities ranging from 6´104 to 5´105 M-1 with apparent binding site sizes between 0.4 and 1.0 base pairs.Isothermal titration calorimetry (ITC) showed that complexes [Ir(L1-3)2(en)]Cl bind to DNA in two types of binding sites, viz. a high affinity (107-108 M-1) binding site with characteristics of major groove binding and a low affinity binding site (105 M-1)  with characteristics of non-specific binding to negatively charged DNA, with binding supported by hydrophobic interactions between complexes.

Electrocatalytic splitting of H2O into H2 and O2 is one of the potential ways to develop clean and storable energy. In this study, the self-supporting Ni0.85Se-Ni foam (Ni0.85Se-NF) hybrid electrode was modified with Ni3Fe (Ni3Fe/Ni0.85Se-NF) via facile selenization and electrochemical deposition method. The Ni3Fe/Ni0.85Se-NF hybrid electrode exhibited excellent performance of electrocatalytic overall water splitting in an alkaline solution (1 M KOH, pH = 13.9), which is much more active than the individual Ni0.85Se-NF and Ni3Fe/NF. In particular, the Ni3Fe/Ni0.85Se-NF hybrid electrode generated 10 mA cm-2 cathodic current at an overpotential of 81 mV, and 10 mA cm-2 anodic current at an overpotential of 209 mV in KOH solution (1 M, pH = 13.9), respectively. In addition, only 1.68 V potential was required to generate 12 mA cm-2 current in a two-electrode system for overall water splitting in an alkaline aqueous solution using the Ni3Fe/Ni0.85Se-NF working as the anode and cathode, respectively. The TEM images and Raman spectra results indicated that the microstructure reconstruction happened on the surface of the Ni3Fe/Ni0.85Se-NF electrode after the HER or OER test. Some Ni and Fe species were found to convert to the NixFe1-xOOH during water electrocatalysis.

Multistate switches are interesting systems for a plethora of potential applications, such as for data storage involving many different states or for logic operations characterized by specific outputs. The main challenge is to achieve a precise control of accessibility to a specific state via a given sequence of multiple stimuli. Here we have connected dihydroazulene (DHA) and spiropyran (SP) photoswitches in dyads to elucidate differences in optical and switching properties between ortho-, meta-, and para-phenylene bridged dyads. Dyads were prepared by Suzuki and Sonogashira coupling reactions and photoisomerizations studied in detail by stationary and ultrafast spectroscopies. Moreover, the kinetics of thermal back-reactions of meta-stable states were studied. The results show path-dependent switchings of the dyads using light in combination with other stimuli (acid/base/heat), allowing access to eight distinct states. The accessibility to some specific states via only one sequence of external stimuli provides an additional degree of data storage - information is not only stored as the state itself but also as the unique sequence of stimuli required to reach this state. By changing the bridging unit between the photoswitches, various properties (outputs) were finely tuned such as absorption and fluorescence behaviors, lifetime of meta-stable state, and photoisomerization dynamics.

Birefringence, a vital property of anisotropic crystals, is indispensable for advanced optical technologies. Quasi-one-dimensional (quasi-1D) structures, with their inherent structural anisotropy, offer fertile ground for discovering materials with exceptional optical anisotropy. In this work, we report four metal-free quasi-1D crystals-(C5H6NO)+(NO3)- (4HPN), (C5H6NO)+(HC2O4)- (4HPO), (C4N3H6)+(NO3)- (2APMN), and (C4N3H6)+(HC2O4)-·H2O (2APMO)-designed to feature pseudo-chain structures and grown as centimeter-scale crystals via a facile aqueous-solution method. These crystals display wide bandgaps (3.40-4.48 eV) and exceptional birefringence, with calculated values up to 0.555@546 nm and an experimental maximum of 0.597@546 nm for 4HPN. The giant birefringence stems from their quasi-1D architectures, high spatial density, and optimal arrangement of the birefringence-active groups (BAGs). This study highlights the promise of metal-free quasi-1D materials for next-generation miniaturized polarization optics and laser-driven applications.