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Journal of the American Chemical Society Mar 2022A cobalt-catalyzed intermolecular three-component coupling of arenes, ethylene, and alkynes was developed using the well-defined air-stable cationic bis(phosphine)...
Three-Component Coupling of Arenes, Ethylene, and Alkynes Catalyzed by a Cationic Bis(phosphine) Cobalt Complex: Intercepting Metallacyclopentenes for C-H Functionalization.
A cobalt-catalyzed intermolecular three-component coupling of arenes, ethylene, and alkynes was developed using the well-defined air-stable cationic bis(phosphine) cobalt(I) complex, [(dcype)Co(η-CH)][BAr] (dcype = 1,2-bis(dicyclohexylphosphino)ethane; BAr = B[(3,5-(CF))CH]), as the precatalyst. All three components were required for turnover and formation of -homoallylated arene products. A range of directing groups including amide, ketone, and 2-pyridyl substituents on the arene promoted the reaction. The cobalt-catalyzed method exhibited broad functional group tolerance allowing for the late-stage functionalization of two drug molecules, fenofibrate and haloperidol. A series of control reactions, deuterium labeling studies, resting state analysis, as well as synthesis of substrate- and product-bound η-arene complexes supported a pathway involving C()-H activation from a cobalt(III) metallacycle.
Topics: Alkynes; Catalysis; Cations; Cobalt; Ethylenes; Molecular Structure; Phosphines
PubMed: 35245039
DOI: 10.1021/jacs.1c12646 -
Chimia Apr 2018Reductive stress is a condition present in cells that have an increased concentration of reducing species, and it has been associated with a number of pathologies, such...
Reductive stress is a condition present in cells that have an increased concentration of reducing species, and it has been associated with a number of pathologies, such as neurodegenerative diseases and cancer. The tools available to study reductive stress lack both in selectivity and specific targeting and some of these shortcomings can be addressed by using photoactivatable compounds. We developed a photoactivatable phosphonium probe, which upon irradiation releases a fluorescent molecule and a trialkyphosphine. The probes can permeate through the plasma membrane and the photoreleased phosphine can induce intracellular reductive stress as proven by the detection of protein aggregates.
Topics: Fluorescent Dyes; Glutathione; HeLa Cells; Humans; Oxidation-Reduction; Phosphines
PubMed: 29720317
DOI: 10.2533/chimia.2018.241 -
Journal of the American Chemical Society Oct 2022The dialkyl--biaryl class of phosphines, commonly known as Buchwald-type ligands, are among the most important phosphines in Pd-catalyzed cross-coupling. These ligands...
The dialkyl--biaryl class of phosphines, commonly known as Buchwald-type ligands, are among the most important phosphines in Pd-catalyzed cross-coupling. These ligands have also been successfully applied to several synthetically valuable Ni-catalyzed cross-coupling methodologies and, as demonstrated in this work, are top performing ligands in Ni-catalyzed Suzuki Miyaura Coupling (SMC) and C-N coupling reactions, even outperforming commonly employed bisphosphines like dppf in many circumstances. However, little is known about their structure-reactivity relationships (SRRs) with Ni, and limited examples of well-defined, catalytically relevant Ni complexes with Buchwald-type ligands exist. In this work, we report the analysis of Buchwald-type phosphine SRRs in four representative Ni-catalyzed cross-coupling reactions. Our study was guided by data-driven classification analysis, which together with mechanistic organometallic studies of structurally characterized Ni(0), Ni(I), and Ni(II) complexes allowed us to rationalize reactivity patterns in catalysis. Overall, we expect that this study will serve as a platform for further exploration of this ligand class in organonickel chemistry as well as in the development of new Ni-catalyzed cross-coupling methodologies.
Topics: Phosphines; Nickel; Ligands; Palladium; Molecular Structure; Catalysis
PubMed: 36250758
DOI: 10.1021/jacs.2c09840 -
Chimia Sep 2017Ruthenium(II) complexes of formula [Ru(η6-arene)Cl2 (PTA)] (RAPTA) are potential anticancer drugs with notable antimetastatic and antiangiogenic activity, which are now... (Review)
Review
Ruthenium(II) complexes of formula [Ru(η6-arene)Cl2 (PTA)] (RAPTA) are potential anticancer drugs with notable antimetastatic and antiangiogenic activity, which are now pointing to clinical trials. Following the great interest aroused by these compounds, a variety of RAPTA derivatives, obtained by chloride substitution and/or containing functionalized arene ligands, and complexes resembling the RAPTA structure but bearing different phosphorous ligands have been synthesized and evaluated for their anticancer activity. An overview of all of these biologically relevant complexes will be given, with particular reference to the anticancer behaviour exhibited by the compounds and the possible relationship with structural aspects.
Topics: Antineoplastic Agents; Coordination Complexes; Humans; Ligands; Organometallic Compounds; Phosphines; Phosphorus; Ruthenium
PubMed: 30188287
DOI: 10.2533/chimia.2017.573 -
Journal of the American Chemical Society Jun 2020Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine...
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 SAr 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.
Topics: Bromides; Density Functional Theory; Halogenation; Indicators and Reagents; Iodides; Lithium Chloride; Lithium Compounds; Models, Chemical; Onium Compounds; Phosphines; Pyridines
PubMed: 32469220
DOI: 10.1021/jacs.0c04674 -
Dalton Transactions (Cambridge, England... Feb 2021Precise control over the production of carbon monoxide (CO) is essential to exploit the therapeutic potential of this molecule. The development of photoactive...
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.
Topics: Carbon Monoxide; Coordination Complexes; Density Functional Theory; Ligands; Luminescent Agents; Models, Molecular; Molecular Structure; Phosphines; Photochemical Processes; Rhenium; Triazoles
PubMed: 33404562
DOI: 10.1039/d0dt03577g -
Journal of Biological Inorganic... Dec 2022New mono- and di-nuclear thio-purine and thio-purine nucleoside gold(I) complexes were synthesized, characterized, and evaluated in vitro for biological activities in...
New mono- and di-nuclear thio-purine and thio-purine nucleoside gold(I) complexes were synthesized, characterized, and evaluated in vitro for biological activities in comparison to related known purine complexes. By combining known anti-tumoral thio-purines with RPAu moieties as present in auranofin, complexes with enhanced effects and selectivities were obtained, which not only act as cytostatics, but also disrupt tumor-specific processes. Their IC values in cytotoxicity test with tumor cell lines ranged from three-digit nanomolar to single-digit micromolar, revealing a tentative structure-activity relationship (SAR). Both the residues R of the phosphane ligand and R at C2 of the pyrimidine ring had a significant impact on the cytotoxicity. In most cases, the introduction of a ribo-furanosyl group at N9 of the purine led to a distinctly more cytotoxic complex. Most complexes were more active against multi-drug-resistant tumor cells or such lacking functional p53 when compared to the respective untreated wild type cell lines. Some nucleoside complexes displayed an interesting dose-dependent dual mode of action regarding cell cycle arrest and DNA repair mechanism. Some phosphane(purine-6-thiolato)gold (I) complexes had a stronger inhibitory effect on the thioredoxin reductase (TrxR) and on the reactive oxygen species (ROS) generation in cancer cells than is typical of other gold complexes. They also led to DNA fragmentation and showed anti-angiogenic effects. Their stability under test conditions was demonstrated by Se NMR monitoring of an exemplary selenopurine complex.
Topics: Gold; Phosphines; Thioredoxin-Disulfide Reductase; Purines; Cell Line, Tumor; Antineoplastic Agents; Coordination Complexes
PubMed: 36244017
DOI: 10.1007/s00775-022-01968-x -
Chembiochem : a European Journal of... Jan 2020The Staudinger reduction and its variants have exceptional compatibility with live cells but can be limited by slow kinetics. Herein we report new small-molecule...
The Staudinger reduction and its variants have exceptional compatibility with live cells but can be limited by slow kinetics. Herein we report new small-molecule triggers that turn on proteins through a Staudinger reduction/self-immolation cascade with substantially improved kinetics and yields. We achieved this through site-specific incorporation of a new set of azidobenzyloxycarbonyl lysine derivatives in mammalian cells. This approach allowed us to activate proteins by adding a nontoxic, bioorthogonal phosphine trigger. We applied this methodology to control a post-translational modification (SUMOylation) in live cells, using native modification machinery. This work significantly improves the rate, yield, and tunability of the Staudinger reduction-based activation, paving the way for its application in other proteins and organisms.
Topics: Animals; HEK293 Cells; Humans; Kinetics; Lysine; Mice; Models, Molecular; Molecular Structure; NIH 3T3 Cells; Optical Imaging; Phosphines; Small Molecule Libraries; Small Ubiquitin-Related Modifier Proteins; Sumoylation
PubMed: 31664790
DOI: 10.1002/cbic.201900464 -
Chemical Research in Toxicology Jun 2019Phosphine (PH) poisoning continues to be a serious problem worldwide, for which there is no antidote currently available. An invertebrate model for examining potential...
Phosphine (PH) poisoning continues to be a serious problem worldwide, for which there is no antidote currently available. An invertebrate model for examining potential toxicants and their putative antidotes has been used to determine if a strategy of using Au(I) complexes as phosphine-scavenging compounds may be antidotally beneficial. When Galleria mellonella larvae (or wax worms) were subjected to phosphine exposures of 4300 (±700) ppm·min over a 20 min time span, they became immobile (paralyzed) for ∼35 min. The administration of Au(I) complexes auro-sodium bisthiosulfate (AuTS), aurothioglucose (AuTG), and sodium aurothiomalate (AuTM) 5 min prior to phosphine exposure resulted in a drastic reduction in the recovery time (0-4 min). When the putative antidotes were given 10 min after the phosphine exposure, all the antidotes were therapeutic, resulting in mean recovery times of 14, 17, and 19 min for AuTS, AuTG, and AuTM, respectively. Since AuTS proved to be the best therapeutic agent in the G. mellonella model, it was subsequently tested in mice using a behavioral assessment (pole-climbing test). Mice given AuTS (50 mg/kg) 5 min prior to a 3200 (±500) ppm·min phosphine exposure exhibited behavior comparable to mice not exposed to phosphine. However, when mice were given a therapeutic dose of AuTS (50 mg/kg) 1 min after a similar phosphine exposure, only a very modest improvement in performance was observed.
Topics: Animals; Antidotes; Larva; Male; Mice; Moths; Organogold Compounds; Phosphines
PubMed: 31070361
DOI: 10.1021/acs.chemrestox.9b00095 -
Journal of the American Chemical Society Jun 2008The selection of rhodium precatalyst and phosphine ligand determines the course of the cycloisomerization of N-allylated bicyclo[1.1.0]butylalkylamines....
The selection of rhodium precatalyst and phosphine ligand determines the course of the cycloisomerization of N-allylated bicyclo[1.1.0]butylalkylamines. Cyclopropane-fused pyrrolidines and azepines are obtained with high levels of stereo- and regiocontrol. Novel azatricyclo[6.1.0.0(1,5)]nonanes are the result of a tandem cycloisomerization-ring closing metathesis sequence. Allylic ethers lead to furans and oxepanes.
Topics: Azepines; Bridged Bicyclo Compounds; Catalysis; Cyclization; Cyclobutanes; Isomerism; Phosphines; Pyrrolidines; Rhodium
PubMed: 18461936
DOI: 10.1021/ja802906k