1,721,042 research outputs found
Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy
Full text linkThe introduction of biologically relevant organic moieties in the coordination sphere of transition metal complexes has recently become a well-established strategy to increase the selectivity and biocompatibility of metallodrugs. In this review, the major advances achieved in this area of research in the last three years are described in detail. Particular attention is given to the metal complexes bearing the main biomolecules of life: carbohydrates, lipids, nucleotides, proteins and vitamins. Each paragraph summarizes the synthetic strategy employed to obtain the complexes of interest as well as the most interesting biological results obtained with these potential metallodrugs. Moreover, the structure–activity relationships observed by the different research groups are described and discussed, with the goal of suggesting to the reader the ligand/metal centre combinations that provide the most promising results in the fight against cancer. Some of the compounds examined in this review as well as other bioconjugated metal complexes published in recent decades exhibit interesting selectivity towards cancer cells over normal ones and a specific mode of action. These latter aspects are the basis of what is commonly known as anticancer target therapy
Synthetic routes to late transition metal-NHC complexes
No full textTransition metal complexes bearing N-heterocyclic carbene ligands (NHCs) have gained a place of crucial importance in numerous areas of research such as medicinal chemistry, material sciences, and homogeneous/heterogeneous catalysis. In the present review, an updated overview of the main synthetic routes used for the preparation of this broad class of compounds along with their main applications are reported. Particular attention will be paid to the synthesis of late transition metal-NHC complexes using weak bases, eco-friendly solvents, and mild operating conditions. This simple synthetic approach, also known as the 'weak base route', represents a recent development with yet unrealized potential
Synthesis of novel olefin complexes of palladium(0) bearing monodentate NHC, phosphine and isocyanide spectator ligands
No full textWe have synthesized and characterized seventeen new bis-NHC, mixed NHC–phosphines or NHC–isocyanides Pd(0) olefin complexes that can potentially act as catalysts. The complexes were characterized by standard spectroscopic methods and elemental analysis and in two cases by SC-XRD technique. We have analyzed with particular care the thermodynamic and kinetic conditions governing the one-pot synthesis of the mixed complexes. In this respect we tried to validate our results by a dedicated computational study on the mutual distribution of the isomers that could be potentially formed. However, the computational result is not clear-cut owing to the not significant value of the calculated ΔG0. Finally, in one case we have measured the rate of the exchange reaction between not particularly encumbered olefins
The importance of the electronic and steric features of the ancillary ligands on the rate of cis–trans isomerization of olefins coordinated to palladium(0) centre. A study involving (Z)-1,2-ditosylethene as olefin model
No full textWith the aim of better understanding the mechanisms governing the spontaneous cis–trans isomerization of the olefins promoted by palladium(0) centers, we have synthesized several novel complexes bearing (Z)- or (E)-1,2-ditosylethene and a combination of other two spectator ligands including phosphines (PPh3 and 1,3,5-triaza-7-phosphaadamantane), isocyanides (i.e. 2,6-dimethylphenylisocyanide) and Nheterocyclic carbenes (NHCs). The nature of ancillary ligands heavily influences the steric and electronic features of the metal centre and consequently its interaction with olefin determines a different capability of supporting the isomerization process. The kinetic analysis and the determination of the rate constants of the isomerization suggested that both the steric and electronic factors play an important role and only an unpredictable combination can guarantee the success of the reaction. The work is completed by the structural characterization of three different Pd(0) complexes
The addition of halogens and interhalogens on palladacyclopentadienyl complexes bearing quinolyl-thioether as spectator ligands. A kinetic and computational study
No full textWe have studied the oxidative addition of halogens (I2 and Br2) and interhalogens (ICl and IBr) on complexes of the type [Pd(thioquinoline)C4(COOMe)4], (thioquinoline = 8-(methylthio)quinoline, 8-(t-butylthioquinoline, 2-methyl-8-(methylthio)quinoline, 2-methyl-8-(t-butylthio)quinoline). The expected palladium(thioquinoline)-σ-butadienyl derivatives have been obtained by the stoichiometric addition of I2 and Br2 to a solution of the starting palladacyclopentadienyl complexes. The bromine in excess induces the extrusion of the di-bromo-(E, E)-σ-butadiene and the formation of the thioquinoline palladium(II) di-bromide species. The kinetics and mechanism of these reactions have been determined. Except for one case which was analyzed in detail by a computational study, the oxidative addition of the interhalogens ICl and IBr yields the species that is less predictable from the thermodynamic point of view. In general the computational approach justifies the reaction progress and allows an interpretative clue suggesting a kinetically governed path to the reaction products. Finally, the solid state structures of two reaction products were resolved and reported
Reactions of proteins with a few organopalladium compounds of medicinal interest
No full textPd compounds form a promising class of experimental anticancer drug candidates whose mechanism of action is still largely unknown; in particular, a few organopalladium compounds seem very attractive. To gain mechanistic insight into medicinal palladium compounds, we have explored here - through ESI MS analysis - the interactions of four organopalladium agents (1-4) - showing remarkable in vitro antiproliferative properties - with a few representative model proteins, i.e., lysozyme (HEWL), ribonuclease A (RNase), and carbonic anhydrase (hCAI). The tested panel included three Pd allyl compounds with one or two carbene ligands and a palladacyclopentadienyl complex. Notably, the Pd allyl compounds turned out to manifest, on the whole, a modest tendency to react with the above proteins. Only complex 3 produced small amounts of characteristic adducts with hCAI bearing either one or two Pd allyl groups. In contrast, the palladacyclopentadienyl complex 4 manifested a greater and peculiar reactivity with all the above proteins generating invariably protein adducts with a mass increase of +256 Da where a butadienyl group - with no associated Pd - is attached to the proteins. Afterwards, we extended our investigations to the C-terminal dodecapeptide of thioredoxin reductase bearing the -Cys-Sec- reactive motif. In this latter case adducts were formed with all tested Pd compounds; however, complex 4 manifested towards this dodecapeptide a type of reactivity deeply different from that observed with HEWL, RNase A and hCAI. The mechanistic implications of these findings are discussed
Flow chemistry of main group and transition metal complexes
No full textContinuous flow reactors have earned their place as an important technology in organic synthesis, receiving increased interest in the past decade. The favorable heat and mass transfer capabilities, combined with the ease of scale-up, have not only made it a safer option in many cases, but often the only option when dealing with highly reactive, short-lived intermediates. In this review, an overview is given of the most recent advances made in the flow synthesis of organometallic compounds. This includes both main group and transition metal applications
Allyl palladium complexes bearing carbohydrate-based N-heterocyclic carbenes: Anticancer agents for selective and potent in vitro cytotoxicity
No full textNovel allyl palladium compounds stabilized by carbohydrate-based N-heterocyclic carbenes (NHCs) were prepared and characterized by nuclear magnetic resonance, high-resolution mass spectrometry and elemental analysis. The antiproliferative activity of the compounds was tested on a panel of different tumor lines, especially ovarian cancer and MRC-5 human lung fibroblasts (nontumor cells). These experiments showed that both mixed NHC/PPh3 and NHC/PTA (PTA = 1,3,5-triaza-7-phosphaadamantane) allyl complexes have IC50 (half maximal inhibitory concentration) values comparable and sometimes even significantly lower than cisplatin. Moreover, the mixed NHC/PTA allyl complexes exhibit good activity toward the seven tumor lines tested with a substantial inactivity against normal cells, a necessary condition to avoid the general cytotoxicity of a metallo-drug. Furthermore, this subclass of compounds proved particularly active on the A549 lung cancer tumor line (up to 100-fold more cytotoxic than cisplatin) and exhibited satisfactory cytotoxicity against KURAMOCHI and OVCAR3 cell lines, which are currently considered the best in vitro models for serous ovarian cancer, the most lethal tumor for women worldwide
Measuring the Olefin-to-Pd(0) Bond Strength: A Kinetic Study Involving Olefin Exchange Reactions on Palladium(0) Complexes Bearing Isocyanide Ligands
No full textIn this article, the synthesis and characterization of new palladium(η2-olefin) complexes bearing isocyanides as spectator ligands are described. These derivatives have been tested on olefin exchange reactions, allowing to define a scale of strength of the palladium(0)-olefin bond. In this way we have proved that dimethyl fumarate can be released by the metal center much more easily than the other olefins and that (Z)-1,2-ditosylethene is by far the most firmly anchored to palladium. When the sterically encumbered tetramethylethene-1,1,2,2-tetracarboxylate (tmetc) is involved in the olefin exchange, the reaction kinetics can be monitored by UV-Vis spectrophotometry, showing that the process follows a second-order rate law. This response indicates that the reaction mechanism is associative, as is also confirmed by a DFT study
The unexpected case of reactions of halogens and interhalogens with halide substituted Pd(II) σ-butadienyl complexes
No full textWe have experimentally studied and theoretically interpreted the addition under stoichiometric conditions of halogens or interhalogens to σ-butadienyl palladium complexes bearing the heteroditopic thioquinolines as spectator ligands. The observed reactions do not involve the expected extrusion of the butadienyl fragment but rather the unpredictable substitution of the halide coordinated to palladium and in some cases also of that bound to the terminal butadienyl carbon. We have explained this peculiar reactivity with a mechanistic hypothesis based on a sequence of selective processes of oxidative addition and reductive elimination involving Pd(iv) intermediates
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