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Precise control over the production of carbon monoxide (CO) is essential to exploit the therapeutic potential of this molecule. The development of photoactive CO-releasing molecules (PhotoCORMs) is therefore a promising route for future clinical applications. Herein, a tricarbonyl-rhenium(i) complex (1-TPP), which incorporates a phosphine moiety as ancilliary ligand for boosting the photochemical reactivity, and a pyridyltriazole bidentate ligand with appended 2-phenylbenzoxazole moiety for the purpose of photoluminescence, was synthesized and characterized from a chemical and crystallographic point of view. Upon irradiation in the near-UV range, complex 1-TPP underwent fast photoreaction, which was monitored through changes of the UV-vis absorption and phosphorescence spectra. The photoproducts (i.e. the dicarbonyl solvento complex 2 and one CO molecule) were identified using FTIR, 1H NMR and HRMS. The results were interpreted on the basis of DFT/TD-DFT calculations. The effective photochemical release of CO associated with clear optical variations (the emitted light passed from green to orange-red) could make 1-TPP the prototype of new photochemically-active agents, potentially useful for integration in photoCORM materials.

Based on the recent studies depicting the potential of heterometallic gold complexes as potent antiproliferative agents, herein we first reported the preliminary mechanistic data on the in-vitro antiproliferative activity of tricyclohexylphosphanegold(I) n-mercaptobenzoate, Cy 3 PAu(n-MBA) where n = 2 (1), 3 (2) and 4 (3), and MBA = mercaptobenzoic acid, treated using MCF-7 breast cancer and A2780 ovarian cancer cells, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to assess the cytotoxicity of both cancer cells treated with 1-3, respectively. The IC 50 of 1-3 were applied to the subsequent assays including cell invasion and thioredoxin reductase (TrxR) as well as ubiquitin activities specifically on Lys48 and Lys63-linked polyubiquitin chains via flowcytometric analysis. The mechanistic effect of 1-3 towards both cells were evaluated on human p53 signaling gene expressions via RT 2 profiler Polymerase Chain Reductase (PCR) array. 1-3 were found to be highly cytotoxic towards both MCF-7 and A2780 cancer cell lines with the compounds were more sensitive towards the latter cells. 1-3 also suppressed TrxR and cell invasion activities by modulating p53 related genes related with proliferation, invasion and TrxR activities i.e. CCNB1, TP53, CDK4 etc. 1-3 also regulated Lys48 and Lys63-linked polyubiquitination by reactivation of p53, suggesting the ability of this gene in regulating inhibition of cytoskeletal reorganization via epithelial-mesenchymal transition (EMT), required for tumor progression. Taken together, the overall findings denoted that 1-3 exerted potent antiproliferative activity in MCF-7 and A2780 cells via activation of the p53 signaling pathway.

Dendrimers are hyperbranched macromolecules, which are synthesized step-by-step by the repetition of a series of reactions. While many different types of dendrimers are known, this review focusses on the use of trivalent phosphorus derivatives (essentially phosphines and phosphoramidites) for the synthesis of dendrimers. The first part presents dendrimers constituted of phosphines at each branching point. The other parts display the use of trivalent phosphorus derivatives during the synthesis of dendrimers. Different types of reactions have been applied to phosphines. The very first examples of phosphorus-containing dendrimers were obtained by the alkylation of phosphines. Then, several families of dendrimers were elaborated by reaction of phosphoramidites. Such a type of reaction is the base of the solid phase synthesis of oligonucleotides; it has been applied in particular for the synthesis of dendrimers constituted of oligonucleotides. Finally, the Staudinger reaction between phosphines and azides afforded different families of dendrimers, and was at the origin of accelerated methods of synthesis of dendrimers. Besides, the reactivity of the P=N-P=S linkages created by this reaction led to very original dendritic structures.

Metal-catalyzed asymmetric synthesis is one of the most important methods for the economical and environmentally benign production of useful optically active compounds. The success of the asymmetric transformations is significantly dependent on the structure and electronic properties of the chiral ligands coordinating to the center metals, and hence the development of highly efficient ligands, especially chiral phosphine ligands, has long been an important research subject in this field. This review article describes the synthesis and applications of P-chiral phosphine ligands possessing chiral centers at the phosphorus atoms. Rationally designed P-chiral phosphine ligands are synthesized by the use of phosphine-boranes as the intermediates. Conformationally rigid and electron-rich P-chiral phosphine ligands exhibit excellent enantioselectivity and high catalytic activity in various transition-metal-catalyzed asymmetric reactions. Recent mechanistic studies of rhodium-catalyzed asymmetric hydrogenation are also described.

The preparation of two new Ru(II)/diphosphine complexes containing Lapachol (Lap) and Lawsone (Law): (1) [Ru(Lap)(dppm) 2 ]PF 6 and (2) [Ru(Law)(dppm) 2 ]PF 6 , where dppm = bis(diphenylphosphino)methane, is reported here. The complexes were synthetized and fully characterized by elemental analyses, molar conductivity, UV-Vis, IR, 31 P{ 1 H}, 1 H and 13 C NMR, and the crystal structure of the complex (1) was determined by X-ray diffraction. Complexes (1) and (2) showed high in vitro cytotoxicity against four cancer cells (MDA-MB-231, MCF-7, A549 and DU-145), with IC 50 values in the micromolar range (0.03 to 2.70 μM). Importantly, complexes (1) and (2) were more active than the cisplatin, the drug used as a reference in the cytotoxic assays. Moreover, complex (1) showed high selectivity to triple-negative breast cancer cells (MDA-MB-231). Studies of the mechanism of action in MDA-MB-231 cancer cells showed that complex (1) inhibits cell migration, colony formation, and induces cell cycle arrest and apoptosis by activation of the mitochondrial pathway through the loss of mitochondrial membrane potential (ΔΨm). Furthermore, complex (1) induces ROS (Reactive Oxygen Species) generation in MDA-MB-231 cells, which can cause DNA damage. Finally, complexes (1) and (2) interact with DNA by minor grooves and show a moderate interaction with BSA (Bovine Serum Albumin), with the involvement of hydrophobic interactions. Essentially, Ru(II)/diphosphine-naphthoquinone complexes have remarkable cytotoxic effects with high selectivity to triple-negative breast cancer (MDA-MB-231) and could be promising anticancer candidates for cancer treatment. SYNOPSIS: The naphthoquinones Lapachol and Lawsone can form new ruthenium compounds with promising anticancer properties., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The preparation, characterization and electrochemical and photophysical properties of a series of desymmetrized heteroleptic [Cu(P^P)(N^N)][PF 6 ] compounds are reported. The complexes incorporate the chelating P^P ligands bis(2-(diphenylphosphanyl)phenyl)ether (POP) and (9,9-dimethyl-9 H -xanthene-4,5-diyl)bis(diphenylphosphane) (xantphos), and 6-substituted 2,2'-bipyridine (bpy) derivatives with functional groups attached by -(CH 2 ) n - spacers: 6-(2,2'-bipyridin-6-yl)hexanoic acid ( 1 ), 6-(5-phenylpentyl)-2,2'-bipyridine ( 2 ) and 6-[2-(4-phenyl-1 H -1,2,3,triazol-1-yl)ethyl]-2,2'-bipyridine ( 3 ). [Cu(POP)( 1 )][PF 6 ], [Cu(xantphos)( 1 )][PF 6 ], [Cu(POP)( 2 )][PF 6 ], [Cu(xantphos)( 2 )][PF 6 ], and [Cu(xantphos)( 3 )][PF 6 ] have been characterized in solution using multinuclear NMR spectroscopy, and the single crystal structure of [Cu(xantphos)( 3 )][PF 6 ] . 0.5Et 2 O was determined. The conformation of the 6-[2-(4-phenyl-1 H -1,2,3,triazol-1-yl)ethyl]-substituent in the [Cu(xantphos)( 3 )] + cation is such that the α- and β-CH 2 units reside in the xanthene 'bowl' of the xantphos ligand. The 6-substituent desymmetrizes the structure of the [Cu(P^P)(N^N)] + cation and this has consequences for the interpretation of the solution NMR spectra of the five complexes. The NOESY spectra and EXSY cross-peaks provide insight into the dynamic processes operating in the different compounds. For powdered samples, emission maxima are in the range 542-555 nm and photoluminescence quantum yields (PLQYs) lie in the range 13-28%, and a comparison of PLQYs and decay lifetimes with those of [Cu(xantphos)(6-Mebpy)][PF 6 ] indicate that the introduction of the 6-substituent is not detrimental in terms of the photophysical properties.

The mechanism of the carbonylation of diazomethane in the presence of iron-carbonyl-phosphine catalysts has been investigated by means of DFT calculations at the M06/def-TZVP//B97D3/def2-TZVP level of theory, in combination with the SMD solvation method. The reaction rate is determined by the formation of the coordinatively unsaturated doublet-state Fe(CO) 3 (P) precursor followed by the diazoalkane coordination and the N 2 extrusion. The free energy of activation is predicted to be 18.5 and 28.2 kcal/mol for the PF 3 and PPh 3 containing systems, respectively. Thus, in the presence of less basic P-donor ligands with stronger π-acceptor properties, a significant increase in the reaction rate can be expected. According to energy decomposition analysis combined with natural orbitals of chemical valence (EDA-NOCV) calculations, diazomethane in the Fe(CO) 3 (phosphine)( η 1 -CH 2 N 2 ) adduct reveals a π-donor-π-acceptor type of coordination.

Hydroamination of alkenes, the addition of the N-H bond of an amine across an alkene, is a fundamental, yet challenging, organic transformation that creates an alkylamine from two abundant chemical feedstocks, alkenes and amines, with full atom economy 1-3 . The reaction is particularly important because amines, especially chiral amines, are prevalent substructures in a wide range of natural products and drugs. Although extensive efforts have been dedicated to developing catalysts for hydroamination, the vast majority of alkenes that undergo intermolecular hydroamination have been limited to conjugated, strained, or terminal alkenes 2-4 ; only a few examples occur by the direct addition of the N-H bond of amines across unactivated internal alkenes 5-7 , including photocatalytic hydroamination 8,9 , and no asymmetric intermolecular additions to such alkenes are known. In fact, current examples of direct, enantioselective intermolecular hydroamination of any type of unactivated alkene lacking a directing group occur with only moderate enantioselectivity 10-13 . Here we report a cationic iridium system that catalyses intermolecular hydroamination of a range of unactivated, internal alkenes, including those in both acyclic and cyclic alkenes, to afford chiral amines with high enantioselectivity. The catalyst contains a phosphine ligand bearing trimethylsilyl-substituted aryl groups and a triflimide counteranion, and the reaction design includes 2-amino-6-methylpyridine as the amine to enhance the rates of multiple steps within the catalytic cycle while serving as an ammonia surrogate. These design principles point the way to the addition of N-H bonds of other reagents, as well as O-H and C-H bonds, across unactivated internal alkenes to streamline the synthesis of functional molecules from basic feedstocks.

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.)

Complexes with general formula [RuCl(η6-p-cymene)(P-NR-P)]X (R = CH2Py (Py = pyridine) - [1a]+, CH2Ph (Ph = phenyl) - [1b]+, Ph - [1c] and p-tol (p-tol = p-tolyl) - [1d]+; X = PF6- or BF4-) were evaluated as cytotoxic agents against two cancer cell lines (HeLa and MDA-MB-231). All metal complexes are active in the range of concentrations tested (up to 100 μmol L-1). The IC50 (μmol L-1) values for the metal complexes are lower than that found for cisplatin. The activities are up to 6- and 15-fold higher than cisplatin for HeLa and MDA-MB-231 cancer cell lines, respectively. Studies of DNA binding and DNA cleavage were performed. DNA binding studies revealed a modest hypochromic shift in the metal complexes electronic spectra, indicating a weak interaction with Kb values in the range of 1.7 × 103-1.6 × 104. Although the cleavage tests revealed that in the dark DNA is not a biological target for these metal complexes, upon blue light irradiation they are activated causing DNA cleavage. Electrochemical studies showed the presence of two independent redox processes, one attributed to the oxidation process of Ru2+ → Ru3+ (EC process) and the other one to the reduction of Ru2+ → Ru1+, which is further reduced to Ru0 (ECE mechanism). In both processes, coupled chemical reactions were observed. DFT calculations were performed to support the electrochemical/chemical behavior of the complexes. The reactivity of complex [1b]BF4 with CH3CN was evaluated and two complexes were isolated [2b]BF4 and [3b]BF4. The complex mer-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4 ([2b]BF4) was isolated after refluxing the precursor [1b]BF4 in CH3CN. Isomerization of [2b]BF4 in CH3CN resulted in the formation of fac-[RuCl(CH3CN)3(P-NCH2Ph-P)]BF4. An attempt to isolate the fac-isomer by adding diethyl ether was unsuccessful, and the complex [3b]BF4 was observed as the major component. The complex [Ru2(μ-Cl3)(CH3CN)2(P-NCH2Ph-P)2]BF4 ([3b]BF4) proved to be very stable and can be obtained from both the mer- and the fac-isomers. The molecular structures of [1b]BF4 and [3b]BF4 were solved by single-crystal X-ray diffraction.

Gold(i)-phosphine "auranofin-like" compounds have been extensively explored as anticancer agents in the past decade. Although potent cytotoxic agents, the lack of selectivity towards tumorigenic vs. non-tumorigenic cell lines often hinders further application. Here we explore the cytotoxic effects of a series of (R3P)AuL compounds, evaluating both the effect of the basicity and bulkiness of the carrier phosphine (R = Et or Cy), and the leaving group L (Cl-vs. dmap). [Au(dmap)(Et3P)]+ had an IC50 of 0.32 μM against the CEM cell line, with good selectivity in relation to HUVEC. Flow cytometry indicates reduced G1 population and slight accumulation in G2, as opposed to auranofin, which induces a high population of cells with fragmented DNA. Protein expression profile sets [Au(dmap)(Et3P)]+ further apart from auranofin, with proteolytic degradation of caspase-3 and poly(ADP-ribose)-polymerase (PARP), DNA strand-break induced phosphorylation of Chk2 Thr68 and increased p53 ser15 phosphorylation. The cytoxicity and observable biological effects correlate directly with the reactivity trend observed when using the series of gold(i)-phosphine compounds for targeting a model zinc finger, Sp1 ZnF3.

Novel silver(i) complexes of the type [AgCl(PPh3)2(L)] {PPh3 = triphenylphosphine; L = VTSC = 3-methoxy-4-hydroxybenzaldehyde thiosemicarbazone (1); VMTSC = 3-methoxy-4-[2-(morpholine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (2); VPTSC = 3-methoxy-4-[2-(piperidine-1-yl)ethoxy]benzaldehyde thiosemicarbazone (3)} were synthesized and fully characterized by spectroscopic techniques. The molecular structures of complexes 2 and 3 were determined by single crystal X-ray diffraction. Compounds 1-3 exhibited appreciable cytotoxic activity against human tumor cells (lung A549, breast MDA-MB-231 and MCF-7) with IC50 values in 48 h of incubation ranging from 5.6 to 18 μM. Cellular uptake studies showed that complexes 1-3 were efficiently internalized after 3 hours of treatment in MDA-MB-231 cells. The effects of complex 1 on the cell morphology, cell cycle, induction of apoptosis, mitochondrial membrane potential (Δψm), and reactive oxygen species (ROS) production have been evaluated in triple negative breast cancer (TNBC) cells MDA-MB-231. Our results showed that complex 1 induced typical morphological alterations of cell death, an increase in cells at the sub-G1 phase, apoptosis, and mitochondrial membrane depolarization. Furthermore, DNA binding studies evidenced that 1 can bind to ct-DNA and does so without modifying the B-structure of the DNA, but that the binding is weak compared to that of Hoechst 33258.

Redox-active multimetallic platforms with synthetically addressable and hemilabile active sites are attractive synthetic targets for mimicking the reactivity of enzymatic co-factors toward multielectron transformations. To this end, a family of ternary clusters featuring three edge metal sites anchored on a [Co6Se8] multimetallic support via amidophosphine ligands are a promising platform. In this report, we explore how small changes in the stereoelectronic properties of these ligands alter [Co6Se8] metalloligand formation, but also substrate binding affinity and strength of the edge/support interaction in two new ternary clusters, M3Co6Se8L6 (M = Zn, Fe; L(-) = Ph2PN(-)iPr). These clusters are characterized extensively using a range of methods, including single crystal X-ray diffraction, electronic absorption spectroscopy and cyclic voltammetry. Substrate binding studies reveal that Fe3Co6Se8L6 resists coordination of larger ligands like pyridine or tetrahydrofuran, but binds the smaller ligand CNtBu. Additionally, investigations into the synthesis of new [Co6Se8] metalloligands using two aminophosphines, Ph2PN(H)iPr (LH) and iPr2PN(H)iPr, led to the synthesis and characterization of Co6Se8LH6, as well as the smaller clusters Co4Se2(CO)6LH4, Co3Se(μ2-PPh2)(CO)4LH3, and [Co(CO)3(iPr2PN(H)iPr)]2. Cumulatively, this study expands our understanding on the effect of the stereoelectronic properties of aminophosphine ligands in the synthesis of cobalt chalcogenide clusters, and, importantly on modulating the push-pull dynamic between the [Co6Se8] support, the edge metals and incoming coordinating ligands in ternary M3Co6Se8L6 clusters.

The 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA) derivatives, viz. the already reported 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane 5-oxide (DAPTA=O, 1 ), the novel 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-sulfide (DAPTA=S, 2 ), and 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane-5-selenide (DAPTA=Se, 3 ), have been synthesized under mild conditions. They are soluble in water and most common organic solvents and have been characterized using 1 H and 31 P NMR spectroscopy and, for 2 and 3 , also by single crystal X-ray diffraction. The effect of O, S, or Se at the phosphorus atom on the structural features of the compounds has been investigated, also through the analyses of Hirshfeld surfaces. The presence of 1 - 3 enhances the activity of copper for the catalytic azide-alkyne cycloaddition reaction in an aqueous medium. The combination of cheaply available copper (II) acetate and compound 1 has been used as a catalyst for the one-pot and 1,4-regioselective procedure to obtain 1,2,3-triazoles with high yields and according to 'click rules'.

A series of neutral mixed-ligand [HB(pz) 3 ]Ag(PR 3 ) silver(I) complexes (PR 3 = tertiary phosphine, [HB(pz) 3 ] - = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR 3 ) 4 ]BF 4 compounds have been synthesized and fully characterized. Silver compounds were screened for their antiproliferative activities against a wide panel of human cancer cells derived from solid tumors and endowed with different platinum drug sensitivity. Mixed-ligand complexes were generally more effective than the corresponding homoleptic derivatives, but the most active compounds were [HB(pz) 3 ]Ag(PPh 3 ) ( 5 ) and [Ag(PPh 3 ) 4 ]BF 4 ( 10 ), both comprising the lipophilic PPh 3 phosphine ligand. Detailed mechanistic studies revealed that both homoleptic and heteroleptic silver complexes strongly and selectively inhibit the selenoenzyme thioredoxin reductase both as isolated enzyme and in human ovarian cancer cells (half inhibition concentration values in the nanomolar range) causing the disruption of cellular thiol-redox homeostasis, and leading to apoptotic cell death. Moreover, for heteroleptic Ag(I) derivatives, an additional ability to damage nuclear DNA has been detected. These results confirm the importance of the type of silver ion coordinating ligands in affecting the biological behavior of the overall corresponding silver complexes, besides in terms of hydrophilic-lipophilic balance, also in terms of biological mechanism of action, such as interaction with DNA and/or thioredoxin reductase.

A novel self-healable, fully reprocessable, and inkjet three-dimensional (3D) printable partially biobased elastomer is reported in this work. A long-chain unsaturated diacrylate monomer was first synthesized from canola oil and then cross-linked with a partially oxidized silicon-based copolymer containing free thiol groups and disulfide bonds. The elastomer is fabricated through inkjet 3D printing utilizing the photoinitiated thiol-ene click chemistry and reprocessed by compression molding exploiting the dynamic nature of disulfide bond. Self-healing is enabled by phosphine-catalyzed disulfide metathesis. The elastomer displayed a tensile strength of ∼52 kPa, a breaking strain of ∼24, and ∼86% healing efficiency at 80 °C temperature after 8 h. Moreover, the elastomer showed excellent thermal stability, and the highest thermal degradation temperature was recorded to be ∼524 °C. After reprocessing through compression molding, the elastomer fully recovered its mechanical and thermal properties. These properties of the elastomer yield an ecofriendly alternative of fossil fuel-based elastomers that can find broad applications in soft robotics, flexible wearable devices, strain sensors, health care, and next-generation energy-harvesting and -storage devices.

The introduction of phosphine oxide into a fluorescein scaffold has yielded phospha-fluorescein with bathochromically shifted spectra, reliable photostability and solubility. Moreover, ratiometric and turn-on fluorescence in the decaging process has ensured that the phospha-fluorescein is a unique scaffold for fluorescence bioimaging. Probe DiMe-PF-Gal without further structural decoration was designed for accurately monitoring β-galactosidase in vivo.

Thioredoxin reductase (TrxR) enzymes are critical in regulating redox homeostasis in cells. We report the first two-photon fluorescent probe of mammalian TrxR (TP-TRFS). TP-TRFS retains high specificity in recognizing TrxR. More importantly, the two-photon absorbing character of TP-TRFS enables it to be used in vivo. With the aid of TP-TRFS, a remarkable decline of the TrxR function was observed in the brain of a mouse model of stroke for the first time, providing a mechanistic link of TrxR dysfunction with stroke.

We report cytotoxic ruthenium(ii) complexes of the general formula [RuCl(cis-tach)(diphosphine)]+ (cis-tach = cis-cis-1,3,5-triaminocyclohexane) that have been characterised by 1H, 13C and 31P{1H} NMR spectroscopy, mass spectrometry, X-ray crystallography and elemental analysis. The kinetics of aquation and stability of the active species have been studied, showing that the chlorido ligand is substituted by water at 298 K with first order rate constants of 10-2-10-3 s-1, ideal for potential clinical use as anti-tumour agents. Strong interactions with biologically relevant duplex and quadruplex DNA models correlate with the activity observed with A549, A2780 and 293T cell lines, and the degree of activity was found to be sensitive to the chelating diphosphine ligand. A label-free ptychographic cell imaging technique recorded cell death processes over 4 days. The Ru(ii) cis-tach diphosphine complexes exhibit anti-proliferative effects, in some cases outperforming cisplatin and other cytotoxic ruthenium complexes.

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.)

A simple preparation of catalysts with high catalytic activity and superior cycling stability is very desirable. In this contribution, magnetic carbon nanotube functionalized by polythiophene (CNT-Fe 3 O 4 -PTh) acts as an efficient and retrievable host for copper nanoparticles to prepare CNT-Fe 3 O 4 -PTh-Cu(I) as a nontoxic and inexpensive catalyst. FT-IR, TGA, EDX, VSM, XRD, FE-SEM, TEM, and AAS techniques were employed to characterize the structure of the synthesized magnetic heterogeneous nanocomposite. Thereafter, the catalytic application of the catalyst was evaluated for the phosphine- and palladium-free Suzuki-Miyaura cross-coupling reaction in water/ethanol as a green media in short reaction times with good to excellent yields. Various derivatives of biaryl compounds were synthesized by reaction of aryl halides and phenylboronic acid. Simple methodology and easy workup, short reaction times, elimination of volatile and toxic solvents, biocompatible reaction conditions, and high yields are some advantages of this protocol. Moreover, the catalyst showed a good reusability owing to its magnetic properties and was recycled several times without appreciable decrease in its catalytic efficiency. Copper(I) nanoparticles supported on magnetic carbon nanotube functionalized by polythiophene (CNT-Fe 3 O 4 -PTh-Cu(I)), was prepared and used for ligand- and palladiumfree Suzuki-Miyaura cross-coupling reaction in water/ethanol as a green media in short reaction times with good to excellent yields. Reusability and stability tests demonstrated that the as prepared catalyst can be recycled with a negligible loss of its activity.

We developed a late-stage modification strategy by a phospha-Michael addition reaction between various functional phosphines and unprotected dehydroalanine (Dha) peptides and proteins under mild conditions. This strategy was applied to generate a staple peptide to enhance its cell membrane penetrability, and it was also able to regulate α-synuclein aggregation properties and morphological characteristics with the addition of different charges.

We report the incorporation of large substituents based on heavy main-group elements that are atypical in ligand architectures to enhance dispersion interactions and, thereby, enhance enantioselectivity. Specifically, we prepared the chiral biaryl bisphosphine ligand (TMG-SYNPHOS) containing 3,5-bis(trimethylgermanyl)phenyl groups on phosphorus and applied this ligand to the challenging problem of enantioselective hydrofunctionalization reactions of 1,1-disubtituted alkenes. Indeed, TMG-SYNPHOS forms a copper complex that catalyzes hydroboration of 1,1-disubtituted alkenes with high levels of enantioselectivity, even when the two substituents are both primary alkyl groups. In addition, copper catalysts bearing ligands possessing germanyl groups were much more active for hydroboration than one derived from DTBM-SEGPHOS, a ligand containing 3,5-di- tert -butyl groups and widely used for copper-catalyzed hydrofunctionalization. This observation led to the identification of DTMGM-SEGPHOS, a bisphosphine ligand bearing 3,5-bis(trimethylgermanyl)-4-methoxyphenyl groups as the substituents on the phosphorus, as a new ligand that forms a highly active catalyst for hydroboration of unactivated 1,2-disubstituted alkenes, a class of substrates that has not readily undergone copper-catalyzed hydroboration previously. Computational studies revealed that the enantioselectivity and catalytic efficiency of the germanyl-substituted ligands is higher than that of the silyl and tert -butyl-substituted analogues because of attractive dispersion interactions between the bulky trimethylgermanyl groups on the ancillary ligand and the alkene substrate and that Pauli repulsive interactions tended to decrease enantioselectivity.

Chemically modified oligonucleotides are being developed as a new class of medicines for curing conditions that previously remained untreatable. Three primary classes of therapeutic oligonucleotides are single-stranded antisense oligonucleotides (ASOs), double stranded small interfering RNAs (siRNAs), and oligonucleotides that induce exon skipping. Recently, ASOs, siRNAs, and exon skipping oligonucleotides have been approved for patients with unmet medical needs, and many other candidates are being tested in late stage clinical trials. In coming years, therapeutic oligonucleotides may match the promise of small molecules and antibodies. Interestingly, in the 1980s when we developed chemical methods for synthesizing oligonucleotides, no one would have imagined that these highly charged macromolecules could become future medicines. Indeed, the anionic nature and poor metabolic stability of the natural phosphodiester backbone provided a major challenge for the use of oligonucleotides as therapeutic drugs. Thus, chemical modifications of oligonucleotides were essential in order to improve their pharmacokinetic properties. Keeping this view in mind, my laboratory has developed a series of novel oligonucleotides where one or both nonbridging oxygens in the phosphodiester backbone are replaced with an atom or molecule that introduces molecular properties that enhance biological activity. We followed two complementary approaches. One was the use of phosphoramidites that could act directly as synthons for the solid phase synthesis of oligonucleotide analogues. This approach sometimes was not feasible due to instability of various synthons toward the reagents used during synthesis of oligonucleotides. Therefore, using a complementary approach, we developed phosphoramidite synthons that can be incorporated into oligonucleotides with minimum changes in the solid phase DNA synthesis protocols but contain a handle for generating appropriate analogues postsynthetically.This Account summarizes our efforts toward preparing these types of analogues over the past three decades and discusses synthesis and properties of backbone modified oligonucleotides that originated from the Caruthers' laboratory. For example, by replacing one of the internucleotide oxygens with an acetate group, we obtained so-called phosphonoacetate oligonucleotides that were stable to nucleases and, when delivered as esters, entered into cells unaided. Alternatively oligonucleotides bearing borane phosphonate linkages were found to be RNase H active and compatible with the endogenous RNA induced silencing complex (RISC). Oligonucleotides containing an alkyne group directly linked to phosphorus in the backbone were prepared as well and used to attach molecules such as amino acids and peptides.

Staudinger ligation is an attractive bio-orthogonal reaction that has been widely used to tag proteins, carbohydrates, and nucleic acids. Here, we explore the traceless variant of the Staudinger ligation for 3'-end modification of oligoribonucleotides. An azido-containing dinucleotide was used to study the ligation. Nine phosphines containing reactive groups, affinity purification tags, or photoswitch probes have been successfully obtained. The corresponding modified dinucleotides were synthesized and characterized by LC/MS. Mechanistic interpretations of the reaction are proposed, in particular, the unprecedented formation of an oxazaphospholane nucleotide derivative, which was favored by the vicinal position of 2'-N 3 and 3'-OH functional groups on the terminal ribose has been observed. The post-functionalization of a 24-nt RNA with a photoactivable tag is also reported.

The development of both chemotherapeutic drug resistance as well as adverse side effects suggest that the current chemotherapeutic drugs remain ineffective in treating the various types of cancers. The development of new metallodrugs presenting anti-cancer activity is therefore needed. Ruthenium complexes have gained a great deal of interest due to their promising anti-tumour properties and reduced toxicity in vivo. This study highlighted the effective induction of cell death in a malignant melanoma cell by two novel bis-amino-phosphine ruthenium(II) complexes referred to as GA105 and GA113. The IC 50 concentrations were determined for both the complexes, the ligand and cisplatin, for comparison. Both complexes GA105 and GA113 displayed a high anti-cancer selectivity profile as they exhibited low IC 50 values of 6.72 µM and 8.76 µM respectively, with low toxicity towards a non-malignant human cell line. The IC 50 values obtained for both complexes were lower than that of cisplatin. The new complexes were more effective compared to the free ligand, GA103 (IC 50  = >20 µM). Morphological studies on treated cells induced apoptotic features, which with further studies could indicate an intrinsic cell death pathway. Additionally, flow cytometric analysis revealed that the mode of cell death of complex GA113 was apoptosis. The outcomes herein give further insight into the potential use of selected Ru(II) complexes as alternative chemotherapeutic drugs in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Herein, we review developments in synthesis, structure, and biological (anti-cancer) activities of 1,1-bis(diphenylphosphino)methane (dppm) bridged homo- and heterobimetallic systems of the type L m M(μ 2 -dppm)M'L n (M and M' are transition metals which may be different or the same and L n,m are co-ligands) since the first such reported bimetallic system in 1987 until the present time (2020). As the simplest diphosphine, dppm enables facile formation of bimetallic complexes, where, given the short spacer between the PPh 2 groups, close spatial proximity of the metal centres is ensured. We concentrate on complexes bearing no M-M interaction and contrast biological activities of these complexes with mononuclear counterparts and positive control agents such as cisplatin, in an attempt to elucidate patterns in the biological activities of these complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Bulk GaPO 4 is an advanced piezoelectric material operating under high temperatures according to the α-β phase transition at 970 °C. This work presents the technological development of a hydrothermal refluxing method first applied for GaPO 4 single crystal growth. Crystals of 10-20 g were grown in mixtures of aqueous solutions of low- and high-vapor-pressure acids (H 3 PO 4 /HCl) at 180-240 °C (10-20 bars). The principal feature of the refluxing method is a spatial separation of crystal growth and nutrient dissolution zones. This leads to a constant mass transportation of the dissolved nutrient, even for materials with retrograde solubility. Mass transport is carried out by dissolution of GaPO 4 nutrient in a dropping flow of condensed low-vapor-pressure solvent. This method allows an exact saturation at temperature of equilibrium and avoids spontaneous crystallization as well loss of seeds. Grown crystals have a moderate OH - content and reasonable structural uniformity. Moreover, the hydrothermal refluxing method allows a fine defining of GaPO 4 concentration in aqueous solutions of H 3 PO 4 , H 2 SO 4 , HCl and their mixtures at set T-P parameters (T < 250 °C, p = 10-30 bars). The proposed method is relatively simple to use, highly reproducible for crystal growth of GaPO 4 and probably could applied to other compounds with retrograde solubility.

Solid acid catalysts are used extensively in various advanced chemical and petrochemical processes. Their catalytic performance (namely, activity, selectivity, and reaction pathway) mostly depends on their acid properties, such as type (Brønsted versus Lewis), location, concentration, and strength, as well as the spatial correlations of their acid sites. Among the diverse methods available for acidity characterization, solid-state nuclear magnetic resonance (SSNMR) techniques have been recognized as the most valuable and reliable tool, especially in conjunction with suitable probe molecules that possess observable nuclei with desirable properties. Taking 31 P probe molecules as an example, both trimethylphosphine (TMP) and trimethylphosphine oxide (TMPO) adsorb preferentially to the acid sites on solid catalysts and thus are capable of providing qualitative and quantitative information for both Brønsted and Lewis acid sites. This protocol describes procedures for (i) the pretreatment of typical solid acid catalysts, (ii) adoption and adsorption of various 31 P probe molecules, (iii) considerations for one- and two-dimensional (1D and 2D, respectively) NMR acquisition, (iv) relevant data analysis and spectral assignment, and (v) methodology for NMR mapping with the assistance of theoretical calculations. Users familiar with SSNMR experiments can complete 31 P- 1 H heteronuclear correlation (HETCOR), 31 P- 31 P proton-driven spin diffusion (PDSD), and double-quantum (DQ) homonuclear correlation with this protocol within 2-3 d, depending on the complexity and the accessible acid sites of the solid acid samples.

InP QDs have shown a great potential as cadmium-free QDs alternatives in biomedical applications. It is essential to understand the biological fate and toxicity of InP QDs. In this study, we investigated the in vivo renal toxicity of InP/ZnS QDs terminated with different functional groups-hydroxyl (hQDs), amino (aQDs) and carboxyl (cQDs). After a single intravenous injection into BALB/c mice, blood biochemistry, QDs distribution, histopathology, inflammatory response, oxidative stress and apoptosis genes were evaluated at different predetermined times. The results showed fluorescent signals from QDs could be detected in kidneys during the observation period. No obvious changes were observed in histopathological detection or biochemistry parameters. Inflammatory response and oxidative stress were found in the renal tissues of mice exposed to the three kinds of QDs. A significant increase of KIM-1 expression was observed in hQDs and aQDs groups, suggesting hQDs and aQDs could cause renal involvement. Apoptosis-related genes (Bax, Caspase 3, 7 and 9) were up-regulated in hQDs and aQDs groups. The above results suggested InP/ZnS QDs with different surface chemical properties would cause different biological behaviors and molecular actions in vivo. The surface chemical properties of QDs should be fully considered in the design of InP/ZnS QDs for biomedical applications.

We report a proximity-driven crosslinking strategy featuring bioorthogonal cyclopropenones. These motifs react with phosphines to form electrophilic ketene-ylides. Such intermediates can be trapped by neighboring proteins to form covalent adducts. Successful crosslinking was achieved using a model split reporter, and the rate of crosslinking could be tuned using different phosphine triggers. We further demonstrated that the reaction can be performed in cell lysate. Based on these features, we anticipate that cyclopropenones will enable unique studies of protein-protein and other biomolecule interactions.

Protein biochemistry protocols typically include disulfide bond reducing agents to guard against unwanted thiol oxidation and protein aggregation. Commonly used disulfide bond reducing agents include dithiothreitol, β-mercaptoethanol, glutathione, and the tris(alkyl)phosphine compounds tris(2-carboxyethyl)phosphine (TCEP) and tris(3-hydroxypropyl)phosphine (THPP). While studying the catalytic activity of the NAD(P)H-dependent enzyme Δ 1 -pyrroline-5-carboxylate reductase, we unexpectedly observed a rapid non-enzymatic chemical reaction between NAD + and the reducing agents TCEP and THPP. The product of the reaction exhibits a maximum ultraviolet absorbance peak at 334 nm and forms with an apparent association rate constant of 231-491 M -1 s -1 . The reaction is reversible, and nuclear magnetic resonance characterization ( 1 H, 13 C, and 31 P) of the product revealed a covalent adduct between the phosphorus of the tris(alkyl)phosphine reducing agent and the C4 atom of the nicotinamide ring of NAD + . We also report a 1.45 Å resolution crystal structure of short-chain dehydrogenase/reductase with the NADP + -TCEP reaction product bound in the cofactor binding site, which shows that the adduct can potentially inhibit enzymes. These findings serve to caution researchers when using TCEP or THPP in experimental protocols with NAD(P) + . Because NAD(P) + -dependent oxidoreductases are widespread in nature, our results may be broadly relevant.

Methacrylated lignin was reacted with PH 3 (g) to prepare a phosphorus rich bio-based polymer containing PH/PH 2 functional groups, which were converted to tertiary phosphine units via the phosphane-ene reaction. This represents a straightforward method for the upconversion of low-value biomass waste to useful inorganic polymer with potential utility in metal scavenging applications.

Current methods for Suzuki-Miyaura couplings of nontriflate phenol derivatives are limited by their intolerance of halides including aryl chlorides. This is because Ni(0) and Pd(0) often undergo oxidative addition of organohalides at a similar or faster rate than most Ar-O bonds. DFT and stoichiometric oxidative addition studies demonstrate that small phosphines, in particular PMe 3 , are unique in promoting preferential reaction of Ni(0) with aryl tosylates and other C-O bonds in the presence of aryl chlorides. This selectivity was exploited in the first Ni-catalyzed C-O-selective Suzuki-Miyaura coupling of chlorinated phenol derivatives where the oxygen-containing leaving group is not a fluorinated sulfonate such as triflate. Computational studies suggest that the origin of divergent selectivity between PMe 3 and other phosphines differs from prior examples of ligand-controlled chemodivergent cross-couplings. PMe 3 effects selective reaction at tosylate due to both electronic and steric factors. A close interaction between nickel and a sulfonyl oxygen of tosylate during oxidative addition is critical to the observed selectivity.

We have developed a new dialkylbiaryl monophosphine ligand, GPhos, that supports a palladium catalyst capable of promoting carbon-nitrogen cross-coupling reactions between a variety of primary amines and aryl halides; in many cases, these reactions can be carried out at room temperature. The reaction development was guided by the idea that the productivity of catalysts employing BrettPhos-like ligands is limited by their lack of stability at room temperature. Specifically, it was hypothesized that primary amine and N-heteroaromatic substrates can displace the phosphine ligand, leading to the formation of catalytically dormant palladium complexes that reactivate only upon heating. This notion was supported by the synthesis and kinetic study of a putative off-cycle Pd complex. Consideration of this off-cycle species, together with the identification of substrate classes that are not effectively coupled at room temperature using previous catalysts, led to the design of a new dialkylbiaryl monophosphine ligand. An O t -Bu substituent was added ortho to the dialkylphosphino group of the ligand framework to improve the stability of the most active catalyst conformer. To offset the increased size of this substituent, we also removed the para i -Pr group of the non-phosphorus-containing ring, which allowed the catalyst to accommodate binding of even very large α-tertiary primary amine nucleophiles. In comparison to previous catalysts, the GPhos-supported catalyst exhibits better reactivity both under ambient conditions and at elevated temperatures. Its use allows for the coupling of a range of amine nucleophiles, including (1) unhindered, (2) five-membered-ring N-heterocycle-containing, and (3) α-tertiary primary amines, each of which previously required a different catalyst to achieve optimal results.

Biological activity against reference and multi-drug resistant (MDR) clinical strains of fluoroquinolones (FQs): ciprofloxacin (HCp), norfloxacin (HNr), lomefloxacin (HLm) and sparfloxacin (HSf), phosphine ligands derived from those antibiotics and 14 phosphino copper(I) and copper(II) complexes with 2,9-dimethyl-1,10-phenanthroline, 1,10-phenanthroline or 2,2'-biquinoline have been determined. Almost all phosphines showed excellent antibacterial activity relative to reference strains (S. aureus ATCC 6538, E. coli ATCC 25922, K. pneumoniae ATCC 4352, and P. aeruginosa ATCC 27853). In rare cases P. aeruginosa rods showed natural insensitivity to oxides, and their copper(II) complexes. Most of the studied compounds showed weak antibacterial activity against clinical multi-drug resistant strains (MDR P. aeruginosa 16, 46, 325, 355, MRD A. baumanii 483 and MDR S. aureus 177). However, phosphines Ph 2 PCH 2 Sf (PSf), Ph 2 PCH 2 Lm (PLm) and their copper(I) complexes were characterized by the best antibacterial activity. In addition, PSf compounds, in which the activities relative to P. aeruginosa MDRs were relatively diverse, paid particular attention in our studies. Genetic and phenotypic studies of these strains showed significant differences between the strains, indicating different profiles of FQs resistance mechanisms. This may prove that a change in the spatial conformation of the PSf derivatives relative to the native form of HSf increased its affinity for the target site of action in gyrase, leading to selective inhibition of the multiplication of MDR strains. In conclusion, differences in PSf activity within closely related P. aeruginosa strains may indicate its diagnostic and therapeutic potential., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aiming at obtaining new copper complexes with good cytotoxicity against cancer cells, triphenylphosphine (TPP) was introduced to obtain insight into the influence of the co-ligands. In this paper, two copper complexes, Cu(2-pbmq)(CH 3 OH)Br 2 (1) and [Cu(2-pbmq)(TPP)Br] 2 (2) were designed, synthesized, and characterized by X-ray crystallography, 2-((2-(pyrazin-2-yl)-1H-benzo[d]imidazol-1-yl)methyl))quinolone (2-pbmq), to investigate the influence of the TPP group on the anticancer activity of the metal complex. Although the presence of the TPP group diminished the intensity of the interaction properties of the complex with DNA, the in vitro anticancer activity and cellular uptake of the TPP-containing complex were markedly superior to those of its TPP-lacking counterpart. Detailed studies on the more potently cytotoxic complex 2 revealed that it accumulated in nucleus, arrested the cell cycle at the G0-G1 phase, causing mitochondrial dysfunction, involving the potential simultaneous mitochondrial membrane collapse, cellular ATP level depletion, and Ca 2+ leakage, eventually inducing cell apoptosis. In summary, the introduction of a TPP group enhances the biological activity and cytotoxicity of the complex., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To further develop the biomimetic chemistry of [FeFe]- and [NiFe]-hydrogenases for catalytic proton reduction to hydrogen (H 2 ), two serials of dinuclear diiron and trinuclear NiFe 2 dithiolate complexes with chelating PCNCP ligands, namely, Fe 2 (μ-edt)(CO) 4 {κ 2 -(Ph 2 PCH 2 ) 2 NR} (1a-1c) and Fe 2 (CO) 6 (μ 3 -S) 2 Ni{(Ph 2 PCH 2 ) 2 NR} (2a-2c) where edt = SCH 2 CH 2 S and PCNCP = (Ph 2 PCH 2 ) 2 NR [R = Bu i (CH 2 CHMe 2 ), Bu t (CMe 3 ), and Bu n (CH 2 CH 2 CH 2 Me)], have been synthesized in moderate yields. All the new complexes 1a-1c and 2a-2c have been fully characterized by elemental analysis, FT-IR, NMR spectroscopy, and single-crystal X-ray diffraction analysis. More importantly, to explore the influence of transition metal cores (i.e., nickel and iron) on the electrochemical and electrocatalytic properties of hydrogenase-inspired molecular catalysts for H 2 evolution, the cyclic voltammetries (CVs) of 1a-1c and 2a-2c are studied and compared in n Bu 4 NPF 6 /DMF solution without and with acetic acid (HOAc) as a proton source. This finding suggests that (i) complexes 1a-1c and 2a-2c are all found to be active for electrocatalytic H 2 evolution, but (ii) they display the distinct redox behaviors and electrocatalytic proton reduction abilities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Several propargyl functionalised substrates with different heteroatoms (N, O or S) have been used for the preparation of propargyl gold(i) phosphine complexes. The complexes were prepared in high yields either by reaction of the substrate with [Au(acac)PPh3] or by reaction of [AuCl(PPh3)] with potassium hydroxide and the substrate in methanol. Several of the complexes have been characterised by X-ray diffraction showing the presence of secondary bonds such as π-stacking and aurophilic interactions. The reaction of the propargyl gold(i) phosphine complexes with [Cu(NO3)(PPh3)2] or [Ag(OTf)(PPh3)2] afforded heterobimetallic complexes with π-coordination of {Cu(PPh3)2} or {Ag(PPh3)2} to the alkyne bond. When the substituent of the propargyl unit contained more strongly coordinating pyridine moieties, [(PyCH2)2NCH2C[triple bond, length as m-dash]CAuPPh3], coordination of the heterometal to the pyridine units occurred, displacing the phosphine groups and giving rise to a dimeric structure. The antiproliferative activity of the complexes against cisplatin resistant lung cancer cell line A549 was determined by MTT assay. The mononuclear gold complexes showed excellent activities with IC50 values < 14 μM. Coordination of copper of silver to the alkynyl fragment resulted in a significant increase in activity suggesting a synergistic effect between the two metal centres.

Bioorthogonal reactions including the bioorthogonal ligations and cleavages have become an active field of research in chemical biology, and they play important roles in chemical modification and functional regulation of biomolecules. This review summarizes the developments and applications of the representative bioorthogonal reactions including the Staudinger reactions, the metal-mediated bioorthogonal reactions, the strain-promoted cycloadditions, the inverse electron demand Diels-Alder reactions, the light-triggered bioorthogonal reactions, and the reactions of chloroquinoxalines and ortho -dithiophenols., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley-VCH GmbH.)

A series of silver(I) camphorsulfonato complexes containing various phosphine ligands having the stoichiometry [Ag(camphSO 3 )(PR 3 )] [PR 3 = PTA (1,3,5-triaza-7-phosphaadamantane), PASO 2 (2-thia-1,3,5-triaza-7-phosphaadamantane-2,2-dioxide), PPh 3 , PCy 3 , P(CH 2 CH 2 CN) 3 , PPyPh 2 , or P( o -tol) 3 ] were prepared and fully characterized by NMR spectroscopic methods and X-ray crystallography. Depending on the nature of the phosphine, a variety of different supramolecular structures, including dimers, macrocycles, and coordination polymers, were observed in the solid state. The in vitro antimicrobial activity in seven different pathogens ( Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Acinetobacter baumannii , Candida albicans , and Cryptococcus neoformans var. grubii ) as well as toxicity in human cells was also examined. While all compounds show some activity against the bacteria, they were especially active against the fungus C. neoformans . The most active and at the same time least toxic compound was found to be the water-soluble complex [Ag(camphSO 3 )(PTA) 2 ].

This work reports a straightforward regioselective synthetic methodology to prepare α-aminophosphine oxides and phosphonates through the addition of oxygen and sulfur nucleophiles to the C-N double bond of 2 H -azirine derivatives. Determined by the nature of the nucleophile, different α-aminophosphorus compounds may be obtained. For instance, aliphatic alcohols such as methanol or ethanol afford α-aminophosphine oxide and phosphonate acetals after N-C3 ring opening of the intermediate aziridine. However, addition of 2,2,2-trifluoroethanol, phenols, substituted benzenthiols or ethanethiol to 2 H -azirine phosphine oxides or phosphonates yields allylic α-aminophosphine oxides and phosphonates in good to high general yields. In some cases, the intermediate aziridine attained by the nucleophilic addition of O - or S -nucleophiles to the starting 2 H -azirine may be isolated and characterized before ring opening. Additionally, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549) and non-malignant cells (MCR-5) was also screened. Some α-aminophosphorus derivatives exhibited very good activity against the A549 cell line in vitro. Furthermore, selectivity towards cancer cell (A549) over non-malignant cells (MCR-5) has been detected in almost all compounds tested.

An improved protocol for the Pd-catalyzed C-O cross-coupling of secondary alcohols is described. The use of biaryl phosphine L2 as the ligand was key to achieving efficient cross-coupling of (hetero)aryl chlorides with only a 20% molar excess of the alcohol. Additionally, we observed an unusual reactivity difference between an electron-rich aryl bromide and the analogous aryl chloride, and deuterium-labeling suggested that currently unidentified pathways for reduction play an important role in explaining this disparity.

Phosphine oxides and related phosphorus-containing functional groups such as phosphonates and phosphinates are established structural motifs that are still underrepresented in today's drug discovery projects, and only few examples can be found among approved drugs. In this account, the physicochemical and in vitro properties of phosphine oxides and related phosphorus-containing functional groups are reported and compared to more commonly used structural motifs in drug discovery. Furthermore, the impact on the physicochemical properties of a real drug scaffold is exemplified by a series of phosphorus-containing analogs of imatinib. We demonstrate that phosphine oxides are highly polar functional groups leading to high solubility and metabolic stability but occasionally at the cost of reduced permeability. We conclude that phosphine oxides and related phosphorus-containing functional groups are valuable polar structural elements and that they deserve to be considered as a routine part of every medicinal chemist's toolbox.

A critically important process in catalysis is the formation of an active catalyst from the combination of a metal precursor and a ligand, as the efficacy of this reaction governs the amount of active catalyst. This Review is a comprehensive overview of reactions catalyzed by nickel and an added bidentate phosphine, focusing on the steps transforming the combination of precatalyst and ligand into an active catalyst and the potential effects of this transformation on nickel catalysis. Reactions covered include common cross-coupling reactions, such as Suzuki, Heck, Kumada, and Negishi couplings, addition reactions, cycloadditions, C-H functionalizations, polymerizations, hydrogenations, and reductive couplings, among others. Overall, the most widely used nickel precatalyst with free bidentate phosphines is Ni(cod) 2 , which accounts for ∼50% of the reports surveyed, distantly followed by Ni(acac) 2 and Ni(OAc) 2 , which account for ∼10% each. By compiling the reports of these reactions, we have calculated statistics of the usage and efficacy of each ligand with Ni(cod) 2 and other nickel sources. The most common bidentate phosphines are simple, relatively inexpensive ligands, such as DPPE, DCPE, DPPP, and DPPB, along with others with more complex backbones, such as DPPF and Xantphos. The use of expensive chiral phosphines is more scattered, but the most common ligands include BINAP, Me-Duphos, Josiphos, and related analogs.

The search for new antifungals is very important because the large genetic variation of pathogenic organisms has resulted in the development of increasingly effective defense mechanisms by microorganisms. Metal complexes as potential drugs are nowadays gaining interest, because they are characterized by accessible redox states of metal centers and a plethora of easily modifiable geometries. In this work we present two new copper(i) iodide or thiocyanide complexes with 2,9-dimethyl-1,10-phenanthroline (dmp) and a diphenylphosphane derivative of ketoconazole (KeP), where a ketoconazole acetyl group is replaced by the -CH 2 PPh 2 unit, [CuI(dmp)KeP] (1-KeP) and [CuNCS(dmp)KeP] (2-KeP) - their synthesis and structural characteristics. The analysis of the intrinsic fluorescence of the ketoconazole moiety in the coordinated KeP molecule revealed that the copper(i) central atom does not act as a quencher and the observed decrease of fluorescence intensity is a result of a strong inner filter effect caused by the presence of the CuXdmp unit. Moreover, the complexes exhibit a remarkable MLCT (metal-ligand charge transfer) based phosphorescence with the emission maximum at 600-615 nm in aqueous media, which probably results from the formation of dimers and higher order oligomers in the most polar solutions. Both complexes proved to be promising antifungal agents towards Candida albicans, showing a relatively high efficiency towards the fluconazole resistant strains with -CDR1 and CDR2 or MDR1 efflux pump overexpression, which suggests that they overcome at least partially these defense mechanisms. Simulations of docking to the cytochrome P450 14α-demethylase (the azoles' primary molecular target) suggested that the compounds studied were rather incapable of competitively inhibiting this enzyme, unlike ketoconazole and the KeP ligand. On the other hand, the phosphorescence in aqueous solutions allowed recording the confocal micrographs of the complexes which showed that both of them are situated in spherical structures inside the cells, most likely in the vacuoles.

Industrial and agricultural goods are fumigated in transport containers in order to control pest infestations and to avoid the transmission of alien species. Phosphine is increasingly used prior to the export as fumigant for table grapes, fruit cultures and dried fruits to control active table grapevine insect pests. Less knowledge exists for fumigants about the desorption time of toxic gases and factors that affect the composition of the fumigated good. Therefore, red and white table grapes (´Thompson seedless´, ´Scarlotta´ and ´Flame seedless´) were chosen to represent the allowed group of phosphine fumigated foods and were treated with a concentration of 2000 vpm phosphine (PH 3 ) at different temperatures. In the present study, sorption and desorption behavior of PH 3 by table grapes and possible changes in their VOC (volatile organic compounds) profiles were investigated. The PH 3 concentration was monitored before and after the fumigation process and was determined under the maximum residue level 0.005 ppm after 35 days. The adsorbed amount of PH 3 was not influenced by fumigation parameters. For analysis of the influences on the volatile profile after fumigation, a headspace solid-phase micro-extraction coupled to gas chromatography mass spectrometry (HS-SPME-GC/MS) was used. Small differences in volatile profiles of fumigated and subsequently outgassed table grapes compared to non-fumigated table grapes could be observed. A slight influence on the aldehyde group directly after fumigation could be perceived by a decrease of hex-2-en-1-ol and 1- hexanol in PH 3 -treated table grapes. The concentrations of both compounds increase again after completion of the desorption process. On the other hand terpenes are not significantly influenced by the fumigation process. Overall these changes are likely to affect table grape aroma characteristics directly after a treatment with PH 3 and it could be demonstrated that phosphine alters the volatile profile of fumigated table grapes qualitatively and quantitatively., Competing Interests: Declaration of Competing Interest For this publication there is no conflict of interest on the authors' side., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational studies indicate that C-halogen bond formation occurs via an S N Ar pathway, and phosphine elimination is the rate-determining step. Steric interactions during C-P bond cleavage account for differences in reactivity between 2- and 3-substituted pyridines.

This work describes the synthesis of the gold(i) complexes of phosphine sulphides. The formation of these new derivatives has been confirmed by X-ray crystallography. The coordination of gold(i) with the sulphur atom of the phosphine sulphides favors the inhibition of topoisomerase I as well as a high cytotoxicity of the gold(i)-complexed compounds against the cancer line A549 with IC 50 values in the nanomolar range and IC 50 values below 5 μM against the SKOV3 cell line. It should be noted that the cytotoxicities observed for the new gold(i) complexes are higher than those observed for phosphine sulphide ligands before binding to gold. Furthermore, the results also indicate that the presence of a nitrogenated heterocycle, such as tetrahydroquinoline or quinoline, is also necessary for the TopI inhibition to be maintained. In addition, no toxicity was observed when the non-cancerous lung fibroblast cell line (MRC5) was treated with the new phosphine sulphide gold(i) complexes prepared.

The crystal structure of 4-(2,3,5,6-tetrafluoropyridyl)diphenylphosphine oxide ( 1 ) contains two independent molecules in the asymmetric unit. Although the molecules are virtually identical in all other aspects, the P=O bond distances differ by ca. 0.02 Å. In contrast, although tris(pentafluorophenyl)phosphine oxide ( 2 ) has a similar crystal structure, the P=O bond distances of the two independent molecules are identical. To investigate the reason for the difference, a density functional theory study was undertaken. Both structures comprise chains of molecules. The attraction between molecules of 1 , which comprises lone pair-π, weak hydrogen bonding and C-H∙∙∙arene interactions, has energies of 70 and 71 kJ mol -1 . The attraction between molecules of 2 comprises two lone pair-π interactions, and has energies of 99 and 100 kJ mol -1 . There is weak hydrogen bonding between molecules of adjacent chains involving the oxygen atom of 1 . For one molecule, this interaction is with a symmetry independent molecule, whereas for the other, it also occurs with a symmetry related molecule. This provides a reason for the difference in P=O distance. This interaction is not possible for 2 , and so there is no difference between the P=O distances of 2 .