Synthesis and structural characterization of benzyl-functionalized N-heterocyclic carbene platinum complexes: Dramatic substituent effect on anti-cancer activity

International audienceA series of platinum (II) complexes bearing N-heterocyclic carbene NHC ligands functionalized by various benzyl moieties were synthesized and characterized. The molecular structure of two complexes has been confirmed by X-ray diffraction studies on single crystals. Investigation of in vitro cytotoxic activities against various cancer cell lines revealed a strong substituent effect: IC50 as low as 0.005 μM were obtained depending on the substituent on the benzyl moiety

Mono- and dimeric complexes of an asymmetric heterotopic P,CNHC,pyr ligand

An asymmetric heterotopic ligand (S-NMeCP) containing a central bicyclic, expanded-ring NHC with one pyridyl and one phosphine exo-substituent has been synthesised and its coordination chemistry with selected late transition metals investigated. The amidinium precursor [S-NMeCHP]PF6 shows variable coordination modes with Ag(I), Cu(I) and Au(I) depending on the L:M ratio. The reaction of two mols of [S-NMeCHP]PF6 with [Cu(MeCN)4]BF4, AgBF4 or Au(THT)Cl gives the bis-ligand complexes [Cu(κ-P-NMeCHP)2(CH3CN)2]BF4·(PF6)2, 1, and [M(κ-P-NMeCHP)2]X·(PF6)2 (3: M = Ag, X = BF4; 6: M = Au, X = Cl) respectively. The 1:1 reaction of [S-NMeCHP]PF6 with AgOTf gave the head-to-tail dimer H,T-[Ag2(μ-N,P-NMeCHP)2(μ-OTf)2](PF6)2, 2, whereas the analogous reaction with Au(THT)Cl gave monomeric [Au(κ-P-NMeCHP)Cl]PF6, 5. Complex 2 was converted to H,T-[Ag2(μ-C,P-NMeCP)2](PF6)2, 4, upon addition of base, while 6 gave [Au(κ-C-NMeCP)2]Cl, 8, when treated likewise. Reaction of [S-NMeCHP]PF6 with Ni(1,5-COD)2 gave the oxidative addition/insertion product [Ni(κ3-N,C,P-NMeCP)(η3-C8H13)]PF6, 9, which converted to [Ni(κ3-N,C,P-NMeCP)Cl]PF6, 10, upon exposure of a CHCl3 solution to air. Complex 10 showed conformational isomerism that was also present in [Rh(κ3-N,C,P-NMeCP)(CO)]PF6, 14, prepared from the precursor complex [Rh(κ-P-NMeCHP)(acac)(CO)]PF6, 13, upon heating in C6H5Cl. [Pt(κ3-N,C,P-NMeCP)(Cl)]PF6, 12, derived from trans-[Pt(κ-P-NMeCHP)2(Cl)2](PF6)2, 11, was isolated as a single conformer

N-Heterocyclic Carbene-Platinum Complexes Featuring an Anthracenyl Moiety: Anti-Cancer Activity and DNA Interaction

International audienceA platinum (II) complex stabilized by a pyridine and an N-heterocyclic carbene ligand featuring an anthracenyl moiety was prepared. The compound was fully characterized and its molecular structure was determined by single-crystal X-ray diffraction. The compound demonstrated high in vitro antiproliferative activities against cancer cell lines with IC50 ranging from 10 to 80 nM. The presence of the anthracenyl moiety on the N-heterocyclic carbene (NHC) Pt complex was used as a luminescent tag to probe the metal interaction with the nucleobases of the DNA through a pyridine-nucleobase ligand exchange. Such interaction of the platinum complex with DNA was corroborated by optical tweezers techniques and liquid phase atomic force microscopy (AFM). The results revealed a two-state interaction between the platinum complex and the DNA strands. This two-state behavior was quantified from the different experiments due to contour length variations. At 24 h incubation, the stretching curves revealed multiple structural breakages, and AFM imaging revealed a highly compact and dense structure of platinum complexes bridging the DNA strands

Exploring diversity in platinum( iv ) N-heterocyclic carbene complexes: synthesis, characterization, reactivity and biological evaluation

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N-Heterocyclic Carbene Platinum(IV) as Metallodrug Candidates: Synthesis and 195Pt NMR Chemical Shift Trend

A series of octahedral platinum(IV) complexes functionalized with both N-heterocyclic carbene (NHC) ligands were synthesized according to a straightforward procedure and characterized. The coordination sphere around the metal was varied, investigating the influence of the substituted NHC and the amine ligand in trans position to the NHC. The influence of those structural variations on the chemical shift of the platinum center were evaluated by 195Pt NMR. This spectroscopy provided more insights on the impact of the structural changes on the electronic density at the platinum center. Investigation of the in vitro cytotoxicities of representative complexes were carried on three cancer cell lines and showed IC50 values down to the low micromolar range that compare favorably with the benchmark cisplatin or their platinum(II) counterparts bearing NHC ligands

<i>N</i>-Heterocyclic Carbene-Polyethyleneimine (PEI) Platinum Complexes Inducing Human Cancer Cell Death: Polymer Carrier Impact

The high interest in N-Heterocyclic platinum carbene complexes in cancer research stems from their high cytotoxicity to human cancer cells, their stability, as well as their ease of functionalization. However, the development of these new molecules as anticancer agents still faces multiple challenges, in particular solubility in aqueous media. Here, we synthesized platinum-NHC bioconjugates that combine water-solubility and cytotoxicity by using polyethyleneimine as polymer carrier. We showed on 8 different types of cells that the activity of these conjugates is modulated by the size of the polymer and the overall density of metal ions onto polymer chains. Using HCT116 cells, the conjugates displayed an effective activity after only 45 min of exposure in vitro correlated with a quick uptake by the cells as shown by the use of various fluorescent-tagged derivatives

Straightforward Synthesis of L-PEI-Coated Gold Nanoparticles and Their Biological Evaluation

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Synthesis, Structural Characterization and Anti-Proliferative Activity of (κ 1 - C )- and (κ 2 - C , S )-Pt II Complexes Bearing Thioether-Functionalized N-Heterocyclic Carbenes

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