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While remarkable progress has been made in the development of peptide medicines, many problems related to peptide synthesis remain unresolved. Previously, we reported electrochemical peptide synthesis using a phosphine as a potentially recyclable coupling reagent. However, there was room for improvement from the point of view of reaction efficiency, especially in the carboxylic acid activation step and the peptide bond formation step. To overcome these challenges, we searched for the optimal phosphine. Among phosphines with various electronic properties, we found that electron-rich triaryl phosphines improved the reaction efficiency. Consequently, we successfully performed electrochemical peptide synthesis on sterically hindered and valuable amino acids. We also synthesized oligopeptides that were challenging with our previous method. Finally, we examined the effect of substituents on the phosphine cations, and gained some insights into reactivity, which will aid researchers designing reactions involving phosphine cations., (© 2024 Wiley-VCH GmbH.)

A general method for chemo- and diastereoselective modification of anticancer natural product arglabin with nitrogen- and carbon-centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s-cis-geometry of α-methylene-γ-butyrolactone moiety of arglabin favors for the additional stabilization of the zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly high efficiency of the phosphine-catalyzed Michael additions to this sesquiterpene lactone. Using n-Bu 3 P as the catalyst, pyrazole, phthalimide, 2-oxazolidinone, 4-quinazolinone, uracil, thymine, cytosine, and adenine adducts of arglabin were obtained. The n-Bu 3 P-catalyzed reaction of arglabin with active methylene compounds resulted in the predominant formation of bisadducts bearing a new quaternary carbon center. All synthesized Michael adducts and previously obtained phosphorylated arglabin derivatives were evaluated in vitro against eleven cancer and two normal cell lines, and the results were compared to those of natural arglabin and its dimethylamino hydrochloride salt currently used as anticancer drugs. 2-Oxazolidinone, uracil, diethyl malonate, dibenzyl phosphonate, and diethyl cyanomethylphosphonate derivatives of arglabin exhibited more potent antiproliferative activity towards several cancer cell lines and lower cytotoxicity towards normal cell lines in comparison to the reference compounds, indicating the feasibility of the developed methodology for the design of novel anticancer drugs with better therapeutic potential., (© 2024 Wiley-VCH GmbH.)

The reactions of elemental sulfur (S 8 ) and polysulfides with nucleophiles are relevant to organic synthesis, materials science and biochemistry, but the mechanisms by which they operate are still unknown due to the inherent thermodynamic and kinetic instability of polysulfide intermediates. Using Density Functional Theory (DFT) calculations at the ωB97X-D/aug-cc-pV(T+d)Z/SMD(MeCN) // ωB97X-D/aug-cc-pVDZ/SMD(MeCN) level of theory, we studied the mechanisms behind the reaction of elemental sulfur and polysulfides with cyanide and phosphines, which quantitatively generate the monosulfide products thiocyanate and phosphine sulfides, respectively. All plausible pathways including nucleophilic decomposition, unimolecular decomposition, scrambling reactions, and attack on thiosulfoxides, have been considered to provide the first comprehensive mechanistic picture for this class of reactions. Overall, intramolecular cyclization is identified as the most favorable decomposition pathway for long polysulfides. For short polysulfides, a mixture of unimolecular decomposition, nucleophilic attack, and scrambling pathways can be expected., (© 2023 Wiley-VCH GmbH.)

Addition of the P-H bond in bis(mesitoyl)phosphine, HP(COMes) 2 (BAPH), to a wide variety of activated carbon-carbon double bonds as acceptors was investigated. While this phospha-Michael addition does not proceed in the absence of an additive or catalyst, excellent results were obtained with stoichiometric basic potassium or caesium salts. Simple amine bases can be employed in catalytic amounts, and tetramethylguanidine (TMG) in particular is an outstanding catalyst that allows the preparation of bis(acyl)phosphines, R-P(COMes) 2 , under very mild conditions in excellent yields after only a short time. All phosphines RP(COMes) 2 can subsequently be oxidized to the corresponding bis(acyl)phosphane oxides, RPO(COMes) 2 , a substance class belonging to the most potent photoinitiators for radical polymerizations known to date. Thus, a simple and highly atom economic method has been found that allows the preparation of a broad range of photoinitiators adapted to their specific field of application even on a large scale., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

By applying the potassium salts of cyclopentadienyl-phosphine ligands LK to CoCl 2 , the corresponding cobalt chlorides (1, LCo II Cl) were prepared. By reducing complexes 1 with KHBEt 3 under a N 2 atmosphere, bridging end-on complexes, LCo I -N 2 -Co I L (2 a and 2 b), were successfully obtained. 15 N 2 -labeled [ 15 N 2 ]-2 a was prepared under 15 N 2 / 14 N 2 exchange in THF solution. LCo I -N 2 -Co I L complex 2 a could react with P 4 molecules to release N 2 and generate a Co-P 4 -Co moiety 4. Further reduction of complex 2 b led to cleavage of a P-C bond in the cyclopentadienyl-phosphine ligand to provide novel μ-PCy 2 -bridged Co 0 -N 2 complex 5. DFT calculations confirmed the experimental observations., (© 2022 Wiley-VCH GmbH.)

The fine-tuning of metal-phosphine-catalyzed reactions relies largely on accessing ever more precisely tuned phosphine ligands by de-novo synthesis. Late-stage C-H functionalization and diversification of commercial phosphines offers rapid access to entire libraries of derivatives based on privileged scaffolds. But existing routes, relying on phosphorus-directed transformations, only yield functionalization of C sp 2 -H bonds in a specific position relative to phosphorus. In contrast to phosphorus-directed strategies, herein we disclose an orthogonal functionalization strategy capable of introducing a range of substituents into previously inaccessible positions on arylphosphines. The strongly coordinating phosphine group acts solely as a bystander in the sterically controlled borylation of bulky phosphines, and the resulting borylated phosphines serve as the supporting ligands for palladium during diversification through phosphine self-assisted Suzuki-Miyaura reactions., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Diethynyl phosphinates were developed as bisfunctional electrophiles for the site-selective modification of peptides, proteins and antibodies. One of their electron-deficient triple bonds reacts selectively with a thiol and positions an electrophilic moiety for a subsequent intra- or intermolecular reaction with another thiol. The obtained conjugates were found to be stable in human plasma and in the presence of small thiols. We further demonstrate that this method is suitable for the generation of functional protein conjugates for intracellular delivery. Finally, this reagent class was used to generate functional homogeneously rebridged antibodies that remain specific for their target. Their modular synthesis, thiol selectivity and conjugate stability make diethynyl phosphinates ideal candidates for protein conjugation for biological and pharmaceutical applications., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Polyalkyl furans are widespread in nature, often performing important biological roles. Despite a plethora of methods for the synthesis of tetrasubstituted furans, the construction of tetraalkyl furans remains non-trivial. The prevalence of alkyl groups in bioactive furan natural products, combined with the desirable bioactivities of tetraalkyl furans, calls for a general synthetic protocol for polyalkyl furans. This paper describes a Michael-Heck approach, using sequential phosphine-palladium catalysis, for the preparation of various polyalkyl furans from readily available precursors. The versatility of this method is illustrated by the total syntheses of nine distinct polyalkylated furan natural products belonging to different classes, namely the furanoterpenes rosefuran, sesquirosefuran, and mikanifuran; the marine natural products plakorsins A, B, and D and plakorsin D methyl ester; and the furan fatty acids 3D5 and hydromumiamicin., (© 2021 Wiley-VCH GmbH.)

We report the anti-breast cancer stem cell (CSC) properties of a series of Group 10-bis(azadiphosphine) complexes 1-3 under exclusively three-dimensional cell culture conditions. The breast CSC mammosphere potency of 1-3 is dependent on the Group 10 metal present, increasing in the following order: 1 (nickel complex) <2 (palladium complex) <3 (platinum complex). Notably, 3 reduces the formation and size of mammospheres to a greater extent than salinomycin, an established CSC-active compound, or any reported anti-CSC metal complex tested under similar conditions. Mechanistic studies suggest that the most effective complexes 2 and 3 readily penetrate CSC mammospheres, enter CSC nuclei, induce genomic DNA damage, and trigger caspase-dependent apoptosis. To the best of our knowledge, this is the first study to systematically probe the anti-CSC activity of a series of structurally related Group 10 complexes and to be conducted entirely using three-dimensional CSC culture conditions., (© 2020 Wiley-VCH GmbH.)

RNA-RNA interactions are essential for biology, but they can be difficult to study due to their transient nature. While crosslinking strategies can in principle be used to trap such interactions, virtually all existing strategies for crosslinking are poorly reversible, chemically modifying the RNA and hindering molecular analysis. We describe a soluble crosslinker design (BINARI) that reacts with RNA through acylation. We show that it efficiently crosslinks noncovalent RNA complexes with mimimal sequence bias and establish that the crosslink can be reversed by phosphine reduction of azide trigger groups, thereby liberating the individual RNA components for further analysis. The utility of the new approach is demonstrated by reversible protection against nuclease degradation and trapping transient RNA complexes of E. coli DsrA-rpoS derived bulge-loop interactions, which underlines the potential of BINARI crosslinkers to probe RNA regulatory networks., (© 2020 Wiley-VCH GmbH.)

The design of controllable dynamic systems is vital for the construction of organelle-like architectures in living cells, but has proven difficult due to the lack of control over defined topological transformation of self-assembled structures. Herein, we report a DNA based dynamic assembly system that achieves lysosomal acidic microenvironment specifically inducing topological transformation from nanoparticles to organelle-like hydrogel architecture in living cells. Designer DNA nanoparticles are constructed from double-stranded DNA with cytosine-rich stick ends (C-monomer) and are internalized into cells through lysosomal pathway. The lysosomal acidic microenvironment can activate the assembly of DNA monomers, inducing transformation from nanoparticles to micro-sized organelle-like hydrogel which could further escape into cytoplasm. We show how the hydrogel regulates cellular behaviors: cytoskeleton is deformed, cell tentacles are significantly shortened, and cell migration is promoted., (© 2020 Wiley-VCH GmbH.)

Surfaces that resist nonspecific protein adsorption in a complex biological milieu are required for a variety of applications. However, few strategies can achieve a robust antifouling coating on a surface in an easy and reliable way, regardless of material type, morphology, and shape. Herein, the preparation of an antifouling coating by one-step aqueous supramolecular assembly of bovine serum albumin (BSA) is reported. Based on fast amyloid-like protein aggregation through the rapid reduction of the intramolecular disulfide bonds of BSA by tris(2-carboxyethyl)phosphine, a dense proteinaceous nanofilm with controllable thickness (≈130 nm) can be covered on virtually arbitrary material surfaces in tens of minutes by a simple dipping or spraying. The nanofilm shows strong stability and adhesion with the underlying substrate, exhibiting excellent resistance to the nonspecific adsorption of a broad-spectrum of contaminants including proteins, serum, cell lysate, cells, and microbes, etc. In vitro and in vivo experiments show that the nanofilm can prevent the adhesion of microorganisms and the formation of biofilm. Compared with native BSA, the proteinaceous nanofilm coating exposes a variety of functional groups on the surface, which have more-stable adhesion with the surface and can maintain the antifouling in harsh conditions including under ultrasound, surfactants, organic solvents, and enzymatic digestion., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Reaction of the electrochemically in situ from elemental white phosphorus generated phosphine oxide H 3 PO in a single electrochemical cell, supplied with lead cathode and aluminium anode, with cyclic ketones (cyclopentanone and cyclohexanone) results in formation of secondary phosphine oxides (bis(α-hydroxycyclopentyl)phosphine oxide 2 a, isolated yield 15 %, and bis(α-hydroxycyclohexyl)phosphine oxide 2 b, isolated yield 12 %) with two α-hydroxycycloalkyl substituents at the phosphorus atom. Bis(α-hydroxycyclopentyl)phosphine oxide reacts with [PdCl 2 (COD)] (COD=1,5-cyclooctadiene) to give a new palladium complex trans-[PdCl 2 {P(OH)(cyclo-C 5 H 8 -1-OH) 2 } 2 ] (3 a, isolated yield 11 %) bearing phosphinous acid as a ligand formed via tautomerization of the phosphine oxide. Finally, the cytotoxicity of the synthesized secondary phosphine oxides on tumor and healthy human cell lines was studied. It was found that at a concentration of 10 -6 -10 -4  M, phosphine oxides 2 a,b exhibit similar IC 50 values for the M-Hela cell line (ca. 50 mM), but are non-toxic for MCF-7 cells. For human alveolar adenocarcinoma cells (A-549), only 2 a is active (ca. 35 mM), while 2 b is not toxic., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

A new phosphine is proposed as efficient coinitiator for camphorquinone (CQ)-based photoinitiating systems for the free radical polymerization of (meth)acrylates. Remarkably, this new co-initiator can exhibit two functionalities: a phosphine moiety to overcome oxygen inhibition and an iodonium salt moiety as counter cation to initiate the polymerization process. Excellent polymerization performances in the presence of CQ for the free radical polymerization of methacrylates under blue light are observed, and amine-free systems can be easily developed from the proposed structure. The photopolymerization of composites is also investigated in the presence of the new phosphine (without iodonium counter cation) and very interesting depth of cure can be obtained from the new developed photoinitiating system after only 20 s of irradiation with a blue light-emitting diode., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Catalytic dehydropolymerization of halogen-functionalized phosphine-boranes (4-X-C 6 H 4 )PH 2 ⋅BH 3 (1a: X = Br, 1b: X = I) with [CpFe(CO) 2 (OTf)] at 100 °C provides convenient access to halogen-functionalized polyphosphinoboranes [(4-X-C 6 H 4 )PH-BH 2 ] n (2a: X = Br, 2b: X = I). These polymers are useful precursors for post-polymerization functionalization, which is demonstrated by Sonogashira coupling under mild conditions to yield the alkynyl-functionalized polyphosphinoborane [(4-PhCC-C 6 H 4 )PH-BH 2 ] n (3)., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Transition metal phosphides (TMPs) are regarded as highly active electrocatalysts for the hydrogen evolution reaction (HER). However, traditional synthetic routes usually use expensive and dangerous precursors as P donors. The development of a low-cost and ecofriendly method for the synthesis of TMPs is significant for sustainable energy development. Herein, cobalt phosphides anchored on or embedded in a spirulina-derived porous N-doped carbon matrix (Co 2 P/NC) was fabricated by two-step hydrothermal treatment and carbonization method, which utilized the intrinsic C, N, and P of biomass cleverly as the sources of C, N, and P, respectively. As a result of the high surface area and porosity that enhance the mass-transfer dynamics, Co 2 P/NC shows good electrocatalytic activity at all pH values in the HER. This work not only provides a facile and effective method for the fabrication of TMP nanoparticles loaded onto carbon materials but also opens a new strategy for the utilization of the intrinsic ingredients of biomass for the preparation of other functional electrocatalysts., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A Pd/Pt-Bu 3 catalyst having bulky, electron-rich ligands significantly outperforms conventional "step-growth catalysts" Pd(PPh 3 ) 4 and Pd(Po-Tol 3 ) 3 in the Suzuki polycondensation of the AB-type arylene-based monomers, such as some of the substituted fluorenes, carbazoles, and phenylenes. In the AA+BB polycondensation, Pd/Pt-Bu 3 also performs better under homogeneous reaction conditions, in combination with the organic base Et 4 NOH. The superior performance of Pd/Pt-Bu 3 is discussed in terms of its higher reactivity in the oxidative addition step and inherent advantages of the intramolecular catalyst transfer, which is a key step joining catalytic cycles of the AB-polycondensation. These findings are applied to the synthesis of a carbazole-based copolymer designed for the use as a hole conductor in solution-processed organic light-emitting diodes., (© 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Four cycloaurated phosphine sulfide complexes, [Au{κ 2 -2-C 6 H 4 P(S)Ph 2 } 2 ][AuX 2 ] [X=Cl (2), Br (3), I (4)] and [Au{κ 2 -2-C 6 H 4 P(S)Ph 2 } 2 ]PF 6 (5), have been prepared and thoroughly characterized. The compounds were found to be stable under physiological-like conditions and showed excellent cytotoxicity against a broad range of cancer cell lines and remarkable cytotoxicity in 3D tumor spheroids. Mechanistic studies with cervical cancer (HeLa) cells indicated that the cytotoxic effects of the compounds involve the inhibition of thioredoxin reductase and induction of apoptosis through mitochondrial disruption. In vivo experiments in nude mice bearing HeLa xenografts showed that treatment with compounds 4 and 5 resulted in significant inhibition of tumor growth (35.8 and 46.9 %, respectively), better than that of cisplatin (29 %). The newly synthesized gold complexes were also evaluated for their in vitro and in vivo anti-inflammatory activity through the study of lipopolysaccharide (LPS)-activated macrophages and carrageenan-induced hind paw edema in rats, respectively., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Tertiary allylic alcohols were conveniently converted into either (Z)- or (E)-configured α,β-unsaturated γ-amino acids by treatment with secondary amines under Pd catalysis at ambient conditions. The key to control the stereochemical course of these formal allylic aminations was the presence of a suitable diphosphine ligand, with dppp [1,3-bis(diphenylphosphino)propane, L12] providing high yields and selectivities for the (Z) isomers, whereas the bis[(2-diphenylphosphino)phenyl]ether (DPEPhos) derivative L1' allowed for selective formation of the corresponding (E) isomeric products. This ligand-controlled, stereodivergent protocol thus shows promise for the stereoselective preparation of allylic amine products from a common substrate precursor., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chiral phosphines were found to catalyze the enantioselective asymmetric γ-addition of heteroaromatic compounds to allenoates in good yields with high enantiomeric ratios and regioselectivity in the presence of (S)-BINOL. Both pyrazole and imidazole could be employed in this process. The synthetic value of these γ-addition products was demonstrated by the preparation of biologically relevant molecules and structural scaffolds. Remarkably, the synthetic utility of this strategy was demonstrated through a two-step synthesis of a Janus kinase (JAK) inhibitor., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The stringent reaction conditions for an effective Fenton reaction (pH range of 3-4) hinders its application in cancer therapy. Therefore, how to improve the efficiency of the Fenton reaction in a tumor site has been the main obstacle in chemodynamic therapy (CDT). Herein, we report biocompatible one-dimensional (1D) ferrous phosphide nanorods (FP NRs) with ultrasound (US)- and photothermal (PT)-enhanced Fenton properties and excellent photothermal conversion efficiency (56.6 %) in the NIR II window, showing synergistic therapeutic properties. Additionally, the high photothermal conversion efficiency and excellent traverse relaxivity (277.79 mm -1  s -1 ) of the FP NRs means they are excellent photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) agents. This is the first report on exploiting the response of metallic phosphides to NIR II laser (1064 nm) and ultrasound to improve the CDT effect with a high therapeutic effect and PA/MR imaging., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The organocatalytic properties of unnatural α-amino acids are reviewed. Post-translational derivatives of natural α-amino acids include 4-hydroxy-l-proline and 4-amino-l-proline scaffolds, and also proline homologues. The activity of synthetic unnatural α-amino acid-based organocatalysts, such as β-alkyl alanines, alanine-based phosphines, and tert-leucine derivatives, are reviewed herein. The organocatalytic properties of unnatural monocyclic, bicyclic, and tricyclic proline derivatives are also reviewed. Several families of these organocatalysts permit the efficient and stereoselective synthesis of complex natural products. Most of the reviewed organocatalysts accelerate the reported reactions through covalent interactions that raise the HOMO (enamine intermediates) or lower the LUMO (iminium intermediates)., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The experimental and computational characterization of a series of dialkylterphenyl phosphines, PR 2 Ar' is described. The new P-donors comprise five compounds of general formula PR 2 Ar Dtbp 2 (R=Me, Et, iPr, c-C 5 H 9 and c-C 6 H 11 ); Ar Dtbp 2 = 2,6-C 6 H 3 -(3,5-C 6 H 3 -(CMe 3 ) 2 ) 2 ), and another five PR 2 Ar' phosphines containing the bulky alkyl groups iPr, c-C 5 H 9 or c-C 6 H 11 , in combination with Ar'=Ar Xyl 2 , Ar Xyl ' 2 , or Ar Ph 2 (L1-L10). Steric and electronic parameters have been determined computationally and from IR and X-ray data obtained for the phosphines and for some derivatives, including tricarbonyl and dicarbonyl nickel complexes, Ni(CO) 3 (PR 2 Ar') and Ni(CO) 2 (PR 2 Ar'). In the solid state, the free phosphines PR 2 Ar' adopt one of the three possible structures formally related by rotation around the C ipso -P bond. Details on their relative energies and on the influence of the free phosphine structure on its coordination chemistry towards Ni(CO) n (n = 2, 3) fragments has been obtained by experimental and computational methods., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of 4-ethynylaniline gold(I) complexes containing monophosphane (1,3,5-triaza-7-phosphaadamantane (pta; 2), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (3), and PR 3 , with R=naphthyl (4), phenyl (5), and ethyl (6)) and diphosphane (bis(diphenylphosphino)acetylene (dppa; 7), trans-1,2-bis(diphenylphosphino)ethene (dppet; 8), 1,2-bis(diphenylphosphino)ethane (dppe; 9), and 1,3-bis(diphenylphosphino)propane (dppp; 10)) ligands have been synthesized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2-10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma as well as in normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the cytotoxicity decreasing in the following order 5>6=9=10>8>2>4>7>3. Complex 4 stands out for its very high selectivity towards ovarian carcinoma cells (IC 50 =2.3 μm) compared with colorectal carcinoma and normal human fibroblasts (IC 50 >100 μm), which makes this complex very attractive for ovarian cancer therapy. Its cytotoxicity in these cells correlates with the induction of the apoptotic process and an increase of intracellular reactive oxygen species (ROS). The effects of the nuclearity, rigidity, and solubility of these complexes on their biological activity were also analyzed. X-ray crystal structure determination allowed the identification of short N-H⋅⋅⋅π contacts as the main driving forces for the three-dimensional packing in these molecules., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Full elucidation of the functions and homeostatic pathways of biological copper requires tools that can selectively recognize and manipulate this trace nutrient within living cells and tissues, where it exists primarily as Cu I . Buffered at attomolar concentrations, intracellular Cu I is, however, not readily accessible to commonly employed amine and thioether-based chelators. Herein, we reveal a chelator design strategy in which phosphine sulfides aid in Cu I coordination while simultaneously stabilizing aliphatic phosphine donors, producing a charge-neutral ligand with low-zeptomolar dissociation constant and 10 17 -fold selectivity for Cu I over Zn II , Fe II , and Mn II . As illustrated by reversing ATP7A trafficking in cells and blocking long-term potentiation of neurons in mouse hippocampal brain tissue, the ligand is capable of intercepting copper-dependent processes. The phosphine sulfide-stabilized phosphine (PSP) design approach, which confers resistance towards protonation, dioxygen, and disulfides, could be readily expanded towards ligands and probes with tailored properties for exploring Cu I in a broad range of biological systems., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

With the global rise of antimicrobial resistance, rapid screening and identification of low concentrations of microorganisms in less than 1 h becomes an urgent technological need for evidence-based antibiotic therapy. Although many commercially available techniques are labeled for rapid microbial detection, they often require 24-48 h of cell enrichment to reach detectable levels. Here, it is shown that the widely used reducing agent tris(2-carboxyethyl)phosphine (TCEP) can also act as a powerful oxidant on gold nanoplates and subsequently lead to a strong catalysis of luminol chemiluminescence. The catalytic reaction results in up to 100-fold signal enhancement and unprecedented stable luminescence for up to 10 min. However, when TCEP is exposed to microorganisms, it is oxidized by the microbial surface proteins and loses its catalytic properties, leading to a decrease in chemiluminescence. The competitive interaction of TCEP with Au nanoplates and microorganisms is used to introduce a homogenous rapid detection method that allows microbial screening in less than 10 min with a limit of detection down to 100 cfu mL -1 . Furthermore, the concept of microbial macromolecular shielding using antibody-conjugated polymers is introduced. The combination of TCEP redox activity and macromolecular shielding enables specific microbial identification within 1 h, without preconcentration, cell enrichment, or heavy equipment other than a hand-held luminometer. The technique is demonstrated by specific detection of methicillin-resistant Staphylococcus aureus in environmental and urine samples containing a mixture of microorganisms., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Developing nonprecious, highly active, and stable catalysts is essential for efficient electrocatalytic hydrogen evolution reaction in water splitting. In this study, the facile synthesis of a 3D flower-like Co x P/carbon architecture is proposed composed of an assembly of nanosheets interconnected by silk fibroin that acts as 3D scaffolds and a carbon source. This unique 3D architecture coupled with a carbon matrix enhances catalytic activity by exposing more active sites and increasing charge transport. The flower-like Co x P/carbon can facilitate a lower overpotential, Tafel slope, charge transfer resistance, and a higher electrochemically active surface than carbon-free and silk-free Co x P. The nanostructured architecture exhibits excellent catalytic performance with low overpotentials of 109 and 121 mV at 10 mA cm -2 and Tafel slopes of 55 and 62 mV dec -1 in acidic and alkaline media, respectively. Furthermore, it minimally degrades the overpotential and current density after long-term stability tests 10 000 cyclic voltammetry cycles and a chronoamperometric test over 40 h, respectively, in acidic media, which confirms the high durability and stability of the flower-like Co x P/carbon., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Nitrogenases catalyse nitrogen fixation to ammonia on a multinuclear Fe-Mo centre, but their mechanism and particularly the order of proton and electron transfer processes that happen during the catalytic cycle is still unresolved. Recently, a unique biomimetic mononuclear iron model was developed using tris(phosphine)borate (TPB) ligands that was shown to convert N 2 into NH 3 . Herein, we present a computational study on the [(TPB)FeN 2 ] - complex and describe its conversion into ammonia through the addition of electrons and protons. In particular, we tested the consecutive proton transfer on only the distal nitrogen atom or alternated protonation of the distal/proximal nitrogen. It is found that the lowest energy pathway is consecutive addition of three protons to the same site, which forms ammonia and an iron-nitrido complex. In addition, the proton transfer step of complexes with the metal in various oxidation and spin states were tested and show that the pK a values of biomimetic mononuclear nitrogenase intermediates vary little with iron oxidation states. As such, the model gives several possible NH 3 formation pathways depending on the order of electron/proton transfer, and all should be physically accessible in the natural system. These results may have implications for enzymatic nitrogenases and give insight into the catalytic properties of mononuclear iron centres., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

We describe a selective and mild chemical approach for controlling RNA hybridization, folding, and enzyme interactions. Reaction of RNAs in aqueous buffer with an azide-substituted acylating agent (100-200 mm) yields several 2'-OH acylations per RNA strand in as little as 10 min. This poly-acylated ("cloaked") RNA is strongly blocked from hybridization with complementary nucleic acids, from cleavage by RNA-processing enzymes, and from folding into active aptamer structures. Importantly, treatment with a water-soluble phosphine triggers a Staudinger reduction of the azide groups, resulting in spontaneous loss of acyl groups ("uncloaking"). This fully restores RNA folding and biochemical activity., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Proton conducting polymeric membranes are highly searched in many different technologies ranging from energy to biosensing. Protic ionic liquids and their polymeric version represent a new family of proton conducting molecules with relatively facile synthesis and excellent properties. In this work, protic poly(ionic liquids) having the most popular phosphonium counter-cations are presented for the first time. The synthesis is carried out through proton transfer reactions or through ion exchange reactions by using commercially available tertiary phosphines. Tributyl-, trioctyl-, and tricyclohexyl-phosphine are selected to form the desired cations. Polystyrene sulfonic acid, poly(2-acrylamido-2-methyl-1-propanesulfonic acid), and lithium poly[(4-styrenesulfonyl) (trifluoromethanesulfonyl)imide] polymers are used to form the polymeric anions. The chemical structure of the protic poly(ionic liquids) is confirmed by spectroscopic characterizations such as Fourier transform infrared and nuclear magnetic resonance spectroscopies. Thermal properties of the polymer are characterized by means of differential scanning calorimetry and thermogravimetric analysis. Polymers exhibit good membrane forming ability as well as high ionic conductivities in the range of 10 -8 to 10 -3 S cm -1 from 30 to 90 °C., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A series of 21 novel, structurally diverse ω-(isothiocyanato)alkylphosphinates and phosphine oxides (ITCs) were designed and synthesized in moderate to good yields. The synthesized compounds were evaluated for in vitro antiproliferative activity using LoVo and LoVo/DX cancer cell lines. The biological activity of the synthesized compounds was higher than that of natural isothiocyanates such as benzyl isothiocyanate or sulforaphane. The antiproliferative activity of selected ITCs was also tested on selected cancer cell lines: A549, MESSA and MESSA/DX-5, HL60 and HL60MX2, BALB/3T3, and 4T1. These compounds were assessed for their mechanism of action as inducers of cell-cycle arrest and apoptosis. Ethyl (6-isothiocyanatohexyl)(phenyl)phosphinate (71) was tested in vivo on the 4T1 cell line and demonstrated moderate antitumor activity, similar to that benzyl isothiocyanate and cyclophosphamide., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A controllable method for the functionalization of XantPhos Pd-G3 precatalyst with thiosugars and thiols has been established. Under mild and operationally simple reaction conditions through just mixing of precatalyst and thiosugars (α- or β-mono-, di- and poly-thiosugar derivatives) in water at 25 °C for 20 min, a series of 1-aminobiphenyl thioglycosides that are difficult to synthesize by classical methods has been synthesized in very high yields., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Artificial metalloenzymes (ArMs) are hybrid catalysts that offer a unique opportunity to combine the superior performance of natural protein structures with the unnatural reactivity of transition-metal catalytic centers. Therefore, they provide the prospect of highly selective and active catalytic chemical conversions for which natural enzymes are unavailable. Herein, we show how by rationally combining robust site-specific phosphine bioconjugation methods and a lipid-binding protein (SCP-2L), an artificial rhodium hydroformylase was developed that displays remarkable activities and selectivities for the biphasic production of long-chain linear aldehydes under benign aqueous conditions. Overall, this study demonstrates that judiciously chosen protein-binding scaffolds can be adapted to obtain metalloenzymes that provide the reactivity of the introduced metal center combined with specifically intended product selectivity., (© 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Macromolecular crystallization has many implications in biological and materials science. Similar to the crystallization of other molecules, macromolecular crystallization conventionally considers a critical nucleus, followed by crystallographic packing of macromolecules to drive further crystal growth. Herein, we discover a distinctive macromolecular crystallization pathway by developing the concept of a macromolecular mesocrystal. This nonclassical polymer crystallization occurs through the mesoscale self-assembly of (bio)macromolecular nanocrystals. The new concept for macromolecular crystallization presented herein is fundamental and relevant to many fields, including materials science, chemistry, biomimetics, nanoscience, and structural biology., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One of the obstacles towards efficient radiative recombination in hybrid perovskites is a low exciton binding energy, typically in the orders of tens of meV. It has been shown that the use of electron-donor additives can lead to a substantial reduction of the non-radiative recombination in perovskite films. Herein, the approach using small molecules with semiconducting properties, which are candidates to be implemented in future optoelectronic devices, is presented. In particular, highly luminescent perovskite-organic semiconductor composite thin films have been developed, which can be processed from solution in a simple coating step. By tuning the relative concentration of methylammonium lead bromide (MAPbBr 3 ) and 9,9spirobifluoren-2-yl-diphenyl-phosphine oxide (SPPO1), it is possible to achieve photoluminescent quantum yields (PLQYs) as high as 85 %. This is attributed to the dual functions of SPPO1 that limit the grain growth while passivating the perovskite surface. The electroluminescence of these materials was investigated by fabricating multilayer LEDs, where charge injection and transport was found to be severely hindered for the perovskite/SPPO1 material. This was alleviated by partially substituting SPPO1 with a hole-transporting material, 1,3-bis(N-carbazolyl)benzene (mCP), leading to bright electroluminescence. The potential of combining perovskite and organic semiconductors to prepare materials with improved properties opens new avenues for the preparation of simple lightemitting devices using perovskites as the emitter., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a fast Staudinger reaction between perfluoroaryl azides (PFAAs) and aryl phosphines, which occurs readily under ambient conditions. A rate constant as high as 18 m -1  s -1 was obtained between methyl 4-azido-2,3,5,6-tetrafluorobenzoate and methyl 2-(diphenylphosphanyl)benzoate in CD 3 CN/D 2 O. Furthermore, the iminophosphorane product was stable toward hydrolysis and aza-phosphonium ylide reactions. This PFAA Staudinger reaction proved to be an excellent bioothorgonal reaction. PFAA-derivatized mannosamine and galactosamine were successfully transformed into cell-surface glycans and efficiently labeled with phosphine-derivatized fluorophore-conjugated bovine serum albumin., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The design and development of earth-abundant electrocatalysts for efficient full water splitting under mild conditions are highly desired, yet remain a challenging task. A homologous Fe-doped Co-based nanoarray incorporating complementary catalysts is shown to effect high-performance and durable water splitting in near-neutral media. Iron-doped cobalt phosphate borate nanoarray on carbon cloth (Fe-Co-Pi-Bi/CC) derived from iron-doped cobalt phosphide on CC (Fe-CoP/CC) through oxidative polarization behaves as a highly active bimetallic electrocatalyst for water oxidation with an overpotential of 382 mV to afford a catalytic current density of 10 mA cm -2 in 0.1 m potassium borate (K-Bi, pH 9.2). Fe-CoP/CC is also highly active for the hydrogen evolution reaction, capable of driving 10 mA cm -2 at an overpotential of only 175 mV in 0.1 m K-Bi. A two-electrode water electrolyzer incorporating Fe-Co-Pi-Bi/CC as anode and Fe-CoP/CC as cathode achieves 10 mA cm -2 water-splitting current at a cell voltage of 1.95 V with strong long-term electrochemical durability., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Prolinol-phosphine chiral ligands enabled highly enantioselective copper-catalyzed intermolecular alkyne-nitrone coupling (Kinugasa reaction) to produce 1,3,4-trisubstituted chiral β-lactams. A high level of enantiocontrol was achieved not only with aryl- or alkenylacetylenes but also with alkylacetylenes, which were important but unfavorable substrates in the previously reported protocols. Two-point hydrogen bonding between the chiral ligand and the nitrone oxyanion consisting of O-H⋅⋅⋅O and C(sp 3 )-H⋅⋅⋅O hydrogen bonds is proposed., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Ultra-broadband light-absorbing materials are highly desired for effective solar-energy harvesting. Herein, novel cobalt phosphide double-shelled nanocages (CoP-NCs) are synthesized. Uniquely, these CoP-NCs are able to nonselectively absorb light spanning the full solar spectrum, benefiting from its electronic properties and hollow nanostructure. They promise a wide range of applications involving solar energy utilization. As proof-of-concept demonstrations, CoP-NCs are employed here as effective photothermal agents to ablate cancer cells by utilizing their ability of near-infrared heat conversion, and as photoactive material for self-powered photoelectrochemical sensing by taking advantage of their ability of photon-to-electricity conversion., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO 4 ] (tht=tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a zebrafish model. Their cytotoxicity and their mechanisms of action are different and involve apoptosis, necrosis, and DNA damage. The compounds presented herein are potent metal-based cytostatics displaying LD 50 values from 3.5-38 μm in different tumor cell lines and induce double-strand DNA breaks (DSB) as shown by H2AX phosphorylation (γH2AX) at foci of DSBs., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A mild and effective method is described for 11 C-labeling of peptides selectively at the N-terminal nitrogen or at internal lysine positions. The presented method relies on the use of specific biphosphine palladium-methyl complexes and their high reactivity towards amino-carbonylation of amine groups in the presence [ 11 C]carbon monoxide. The protocol facilitates the production of native N- 11 C-acetylated peptides, without any structural modifications and has been applied to a selection of bioactive peptides., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A highly active, durable, and low-cost hydrogen evolution reaction (HER) catalyst is desirable for energy storage through water splitting but its fabrication presents great challenges. Herein, mediated by dynamically self-assembled graphene quantum dots (GQDs), small, uniform, high-density, and well-dispersed CoP nanoparticles were grown in situ on pristine graphene for the first time. This hybrid nanostructure was then employed as HER electrocatalyst, showing an onset potential of 7 mV, an overpotential of 91.3 mV to achieve 10 mA cm -2 , a Tafel slope of 42.6 mV dec -1 , and an exchange current density of 0.1225 mA cm -2 , all of which compare favorably to those of most reported non-noble-metal catalysts. The developed catalyst also exhibits excellent durability with negligible current loss after 2000 cyclic voltammetry cycles (+0.01 to -0.17 V vs. RHE) or 34 h of chronoamperometric measurement at an overpotential of 91.3 mV. This work not only develops a new strategy for the fabrication of high-performance and inexpensive electrocatalysts for HER but also provides scientific insight into the mechanism of the dynamically self-assembled GQDsmediated synthesis process., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A general procedure for the catalytic hydrogenation of nitriles to primary amines by using a non-noble metal-based system is presented. Co(acac) 3 in combination with tris[2-(dicyclohexylphosphino)ethyl]phosphine efficiently catalyzes the selective hydrogenation of a wide range of (hetero)aromatic and aliphatic nitriles to give the corresponding amines., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Efficient delivery of biomacromolecules (e.g., proteins, nucleic acids) into cell cytosol remains a critical challenge for the development of macromolecular therapeutics or diagnostics. To date, most common approaches to assess cytosolic delivery rely on fluorescent labeling of macromolecules with an "always on" reporter and subcellular imaging of endolysosomal escape by confocal microscopy. This strategy is limited by poor signal-to-noise ratio and only offers low throughput, qualitative information. Herein we describe a quantitative redox-activatable sensor (qRAS) for the real-time monitoring of cytosolic delivery of macromolecules. qRAS-labeled macromolecules are silent (off) inside the intact endocytic organelles, but can be turned on by redox activation after endolysosomal disruption and delivery into the cytosol, thereby greatly improving the detection accuracy. In addition to confocal microscopy, this quantitative sensing technology allowed for a high-throughput screening of a panel of polymer carriers toward efficient cytosolic delivery of model proteins on a plate reader. The simple and versatile qRAS design offers a useful tool for the investigation of new strategies for endolysosomal escape of biomacromolecules to facilitate the development of macromolecular therapeutics for a variety of disease indications., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photoactivatable phosphines that induce intracellular reductive stress are reported. The design of these probes takes advantage of the conjugate addition of trialkylphosphines to carbocyanine dyes, which can be reverted photochemically to produce the trialkylphosphine and a fluorescent reporter. The photochemical release depends on the efficiency of photoinduced electron transfer from the indolenine arm of the probe to the coumarin acceptor. These probes readily permeate the mammalian plasma membrane and can be photoactivated in live cells. Upon irradiation of the probe, the released trialkylphosphine induces intracellular reductive stress, which ultimately leads to formation of thioflavin-positive intracellular protein aggregates. These effects could be induced in individual cells within a monolayer, with minimal disturbance of neighboring cells., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of non-precious-metal hydrogen evolution reaction (HER) electrocatalysts with high activity and excellent durability in acidic media is of significant importance for renewable energy research. We report a novel electrocatalyst based on a three-dimensional (3D) graphene aerogel decorated with cobalt phosphide nanoparticles (CoP/GA). The material has a unique hierarchical porous structure with CoP nanoparticles encapsulated uniformly within the graphene sheets. The optimized catalyst shows superior activity, with an overpotential of only 121 mV at 10 mA cm -2 , a Tafel slope of 50 mV dec -1 , and an exchange current density of 0.105 mA cm -2 , and it maintains its catalytic activity for at least 13 h. More importantly, this work provides a versatile way for the rational design and fabrication of 3D graphene-based multifunctional composite materials., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, we report unusual four-center interactions in the novel cage-like phosphane, 1,4,7-triaza-9-phosphatricyclo[5.3.2.1(4,9) ]tridecane (CAP). This water-soluble ligand, the first example of a tris(homoadamantane) ring system, can be considered a macrocyclic homologue of the well-known PTA (1,3,5-triaza-7-phosphaadamantane). However, (31) P NMR spectroscopic anomalies of CAP follow those typical for the bi-/tricyclic atrane systems. Another atrane-like feature of CAP is the ability of one nitrogen atom to undergo out-in pyramidal inversion. The latter is associated with a substantial decrease in the intracage N-N and P-N distances. Analysis of electron density distribution [molecular electrostatic potential (MESP) and atoms-in-molecules (AIM) approaches] suggests that the P and N atoms in the pyramidally inverted CAP derivatives are involved in interactions resulting in accumulation of electron density at the center of the phosphane cage. The latter can reliably explain the stereoelectronic and NMR anomalies of the new ligand. The semi-flexible CAP cage populates the structural niche between the rigid adamantine skeleton of PTA and flexible atrane systems and can be regarded as an alternative to PTA in aqueous coordination chemistry., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A multifunctional copolymer (PyPPh2 -SO3 H@porous organic polymers, POPs) was prepared by combining acidic groups and heterogeneous P,N ligands through the copolymerization of vinyl-functionalized 2-pyridyldiphenylphosphine (2-PyPPh2 ) and p-styrene sulfonic acid under solvothermal conditions. The morphology and chemical structure of the copolymer were evaluated using a series of characterization techniques. Compared with traditional homogeneous Pd(OAc)2 /2-PyPPh2 / p-toluenesulfonic acid catalyst, the copolymer supported palladium catalyst (Pd-PyPPh2 -SO3 H@POPs) exhibited higher activity for alkoxycarbonylation of terminal alkynes under the same conditions. This phenomenon could be attributed to the synergistic effect between the single-site Pd centers, 2-PyPPh2 ligands, and SO3 H groups, the outstanding swelling properties as well as the high enrichment of the reactant concentration by the porous catalyst. In addition, the catalyst could be reused at least 4 times without any apparent loss of activity. The excellent catalytic reactivity and good recycling properties make it an attractive catalyst for industrial applications. This work paves the way for advanced multifunctional porous organic polymers as a new type of platform for heterogeneous catalysis in the future., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The third generation of aminobiphenyl palladacycle pre-catalyst "G3-Xantphos" enables functionalization of peptides containing cysteine in high yields. The conjugation (bioconjugation) occurs chemoselectively at room temperature under biocompatible conditions. Extension of the method to protein functionalization allows selective bioconjugation of the trastuzumab antibody., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Inspired by the active-site structure of the [NiFe] hydrogenase, we have computationally designed the iron complex [P(tBu) 2 N(tBu) 2 )Fe(CN)2 CO] by using an experimentally ready-made diphosphine ligand with pendant amines for the hydrogenation of CO2 to methanol. Density functional theory calculations indicate that the rate-determining step in the whole catalytic reaction is the direct hydride transfer from the Fe center to the carbon atom in the formic acid with a total free energy barrier of 28.4 kcal mol(-1) in aqueous solution. Such a barrier indicates that the designed iron complex is a promising low-cost catalyst for the formation of methanol from CO2 and H2 under mild conditions. The key role of the diphosphine ligand with pendent amine groups in the reaction is the assistance of the cleavage of H2 by forming a Fe-H(δ-) ⋅⋅⋅H(δ+) -N dihydrogen bond in a fashion of frustrated Lewis pairs., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)