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1.
Dr. Xicheng Liu Xiangdong He Xiaojing Zhang Yongling Wang Jiaying Liu Xiujuan Hao Yue Zhang Dr. Xiang-Ai Yuan Prof. Laijin Tian Prof. Zhe Liu 《Chembiochem : a European journal of chemical biology》2019,20(21):2767-2776
Iridium(III) complexes have attracted more and more attention in the past few years because of their potential antineoplastic activity. In this study, four IrIII complexes of the types [(η5-Cpx)Ir(N^N)Cl]PF6 (complexes 1 and 2 ) and [Ir(Phpy)2(N^N)]PF6 (complexes 3 and 4 ) have been synthesized and characterized. They exhibit potential antineoplastic activity towards A549 cells, especially in the case of complex 1 [IC50=(3.56±0.5) μm ], which was nearly six times as effective as cisplatin [(21.31±1.7) μm ]. Additionally, these complexes show some selectivity towards cancer cells over normal cells. They could be transported by serum albumin (binding constants were changed from 0.37×105 to 81.71×105 m −1). IrIII complexes 1 and 2 could catalyze the transformation of nicotinamide adenine dinucleotide reduced form (NADH) into NAD+ (turnover numbers 43.2, 11.9] and induce the accumulation of reactive oxygen species, thus confirming their antineoplastic mechanism of oxidation, whereas the cyclometalated complexes 3 and 4 were able to target the lysosome [Pearson co-localization coefficient (PCC)=0.73], cause lysosomal damage, and induce apoptosis. Understanding the mechanism of action would help further structure–activity optimization on these IrIII complexes as emerging cancer therapeutics. 相似文献
2.
Considering the high increase in mortality caused by cancer in recent years, cancer drugs with novel mechanisms of anticancer action are urgently needed to overcome the drawbacks of platinum-based chemotherapeutics. Recently, in the area of metal-based cancer drug development research, the concept of catalytic cancer drugs has been introduced with organometallic RuII, OsII, RhIII and IrIII complexes. These complexes are reported as catalysts for many important biological transformations in cancer cells such as nicotinamide adenine dinucleotide (NAD(P)H) oxidation to NAD+, reduction of NAD+ to NADH, and reduction of pyruvate to lactate. These unnatural intracellular transformations with catalytic and nontoxic doses of metal complexes are known to severely perturb several important biochemical pathways and could be the antecedent of next-generation catalytic cancer drug development. In this concept, we delineate the prospects of such recently reported organometallic RuII, OsII, RhIII and IrIII complexes as future catalytic cancer drugs. This new approach has the potential to deliver new cancer drug candidates. 相似文献
3.
Diana R. Melis Chiao-Yu Hsiao Dr. Jill M. Combrinck Prof. Lubbe Wiesner Prof. Gregory S. Smith 《Chembiochem : a European journal of chemical biology》2021,22(9):1568-1572
A fluorescent analogue of a previously synthesised N,N-chelated IrIII complex was prepared by coordination of the organic ligand to an extrinsic bis(2-phenylpyridine)iridium(III) fluorophore. This cyclometallated IrIII complex in itself displays good, micromolar activity against the chloroquine-sensitive NF54 strain of Plasmodium falciparum. Live-cell confocal microscopy found negligible localisation of the fluorescent complex within the digestive vacuole of the parasite. This eliminated the haem detoxification pathway as a potential mechanism of action. Similarly, no localisation of the complex within the parasitic nucleus was found, thus suggesting that this complex probably does not interfere with the DNA replication process. A substantial saturation of fluorescence from the complex was found near phospholipid structures such as the plasma and nuclear membranes but not in neutral lipid bodies. This indicates that an association with these membranes, or organelles such as the endoplasmic reticulum or branched mitochondrion, could be essential to the efficacies of these types of antimalarial compounds. 相似文献
4.
Kelvin K. H. Tong Dr. Muhammad Hanif Dr. Sanam Movassaghi Dr. Matthew P. Sullivan James H. Lovett Dr. Katja Hummitzsch Prof. Tilo Söhnel Dr. Stephen M. F. Jamieson Prof. Suresh K. Bhargava Prof. Hugh H. Harris Prof. Christian G. Hartinger 《ChemMedChem》2021,16(19):3017-3026
We report investigations on the anticancer activity of organometallic [MII/III(η6-p-cymene/η5-pentamethylcyclopentadienyl)] (M=Ru, Os, Rh, and Ir) complexes of N-heterocyclic carbenes (NHCs) substituted with a triazolyl moiety. Depending on the precursors, the NHC ligands displayed either mono- or bidentate coordination via the NHC carbon atom or as N,C-donors. The metal complexes were investigated for their stability in aqueous solution, with the interpretation supported by density functional theory calculations, and reactivity to biomolecules. In vitro cytotoxicity studies suggested that the nature of both the metal center and the lipophilicity of the ligand determine the biological properties of this class of compounds. The IrIII complex 5 d bearing a benzimidazole-derived ligand was the most cytotoxic with an IC50 value of 10 μM against NCI-H460 non-small cell lung carcinoma cells. Cell uptake and distribution studies using X-ray fluorescence microscopy revealed localization of 5 d in the cytoplasm of cancer cells. 相似文献
5.
Prof. Dr. Richard K. Haynes Kwan‐Wing Cheu Dr. Ho‐Wai Chan Dr. Ho‐Ning Wong Ka‐Yan Li Maggie Mei‐Ki Tang Min‐Jiao Chen Dr. Zu‐Feng Guo Prof. Dr. Zhi‐Hong Guo Prof. Dr. Kumar Sinniah Amanda B. Witte Dr. Paolo Coghi Prof. Dr. Diego Monti 《ChemMedChem》2012,7(12):2204-2226
Artemisinins are proposed to act in the malaria parasite cytosol by oxidizing dihydroflavin cofactors of redox‐active flavoenzymes, and under aerobic conditions by inducing their autoxidation. Perturbation of redox homeostasis coupled with the generation of reactive oxygen species (ROS) ensues. Ascorbic acid–methylene blue (MB), N‐benzyl‐1,4‐dihydronicotinamide (BNAH)–MB, BNAH–lumiflavine, BNAH–riboflavin (RF), and NADPH–FAD–E. coli flavin reductase (Fre) systems at pH 7.4 generate leucomethylene blue (LMB) and reduced flavins that are rapidly oxidized in situ by artemisinins. These oxidations are inhibited by the 4‐aminoquinolines piperaquine (PPQ), chloroquine (CQ), and others. In contrast, the arylmethanols lumefantrine, mefloquine (MFQ), and quinine (QN) have little or no effect. Inhibition correlates with the antagonism exerted by 4‐aminoquinolines on the antimalarial activities of MB, RF, and artemisinins. Lack of inhibition correlates with the additivity/synergism between the arylmethanols and artemisinins. We propose association via π complex formation between the 4‐aminoquinolines and LMB or the dihydroflavins; this hinders hydride transfer from the reduced conjugates to the artemisinins. The arylmethanols have a decreased tendency to form π complexes, and so exert no effect. The parallel between chemical reactivity and antagonism or additivity/synergism draws attention to the mechanism of action of all drugs described herein. CQ and QN inhibit the formation of hemozoin in the parasite digestive vacuole (DV). The buildup of heme–FeIII results in an enhanced efflux from the DV into the cytosol. In addition, the lipophilic heme–FeIII complexes of CQ and QN that form in the DV are proposed to diffuse across the DV membrane. At the higher pH of the cytosol, the complexes decompose to liberate heme–FeIII. The quinoline or arylmethanol reenters the DV, and so transfers more heme–FeIII out of the DV. In this way, the 4‐aminoquinolines and arylmethanols exert antimalarial activities by enhancing heme–FeIII and thence free FeIII concentrations in the cytosol. The iron species enter into redox cycles through reduction of FeIII to FeII largely mediated by reduced flavin cofactors and likely also by NAD(P)H–Fre. Generation of ROS through oxidation of FeII by oxygen will also result. The cytotoxicities of artemisinins are thereby reinforced by the iron. Other aspects of drug action are emphasized. In the cytosol or DV, association by π complex formation between pairs of lipophilic drugs must adversely influence the pharmacokinetics of each drug. This explains the antagonism between PPQ and MFQ, for example. The basis for the antimalarial activity of RF mirrors that of MB, wherein it participates in redox cycling that involves flavoenzymes or Fre, resulting in attrition of NAD(P)H. The generation of ROS by artemisinins and ensuing Fenton chemistry accommodate the ability of artemisinins to induce membrane damage and to affect the parasite SERCA PfATP6 Ca2+ transporter. Thus, the effect exerted by artemisinins is more likely a downstream event involving ROS that will also be modulated by mutations in PfATP6. Such mutations attenuate, but cannot abrogate, antimalarial activities of artemisinins. Overall, parasite resistance to artemisinins arises through enhancement of antioxidant defense mechanisms. 相似文献
6.
Dr. Frank Bruchertseifer Prof. Dr. Peter Comba Dr. Bodo Martin Dr. Alfred Morgenstern Dr. Johannes Notni Dr. Miriam Starke Prof. Dr. Hubert Wadepohl 《ChemMedChem》2020,15(16):1591-1600
Hepta- and octadentate bispidines (3,7-diazabicyclo[3.3.1]nonane, diaza-adamantane) with acetate, methyl-pyridine, and methyl-picolinate pendant groups at the amine donors of the bispidine platform have been prepared and used to investigate BiIII coordination chemistry. Crystal structure and solution spectroscopic data (NMR spectroscopy and mass spectrometry) confirm that the rigid and relatively large bispidine cavity with an axially distorted geometry is well suited for BiIII and in all cases forms nine-coordinate complexes; this is supported by an established hole size and shape analysis. It follows that nonadentate bispidines probably will be more suited as bifunctional chelators for 213BiIII-based radiopharmaceuticals. However, two isomeric picolinate-/acetate-based heptadentate ligands already show very efficient complexation kinetics with 213BiIII at ambient temperature and kinetic stability that is comparable with the standard ligands used in this field. The experimentally determined hydrophilicities (log D7.4 values) show that the BiIII complexes reported are relatively hydrophilic and well suited for medicinal applications. We also present a very efficient and relatively accurate method to compute charge distributions and hydrophilicities, and this will help to further optimize the systems reported here. 相似文献
7.
Xiao-Run Wang Xue-Qin Song 《Journal of Inorganic and Organometallic Polymers and Materials》2017,27(4):850-860
Three 2D lanthanide coordination polymers of in situ formed nitrilotriacetic anion (NTA3?) have been hydrothermally synthesized with N-(2-carbamoylmethyl) iminodiacetic acid (H2ADA) as starting material. The photoluminescence properties as well as the energy-transfer behavior of the resulted coordination polymers are studied in detail and the investigations reveal that both EuIII and TbIII complexes show intense emissions characteristic of EuIII and TbIII ion under irradiation of 399 nm. Considering the blue-emission of compound GdIII and the intense emission of EuIII and TbIII compounds, we afforded EuIII and TbIII doped white light emitting materials by the different combination of the doped EuIII and TbIII concentrations. 相似文献
8.
Karen Minori Letícia B. Rosa Dr. Riccardo Bonsignore Prof. Angela Casini Prof. Danilo C. Miguel 《ChemMedChem》2020,15(22):2146-2150
Abstract : A series of mononuclear coordination or organometallic AuI/AuIII complexes ( 1 – 9 ) have been comparatively studied in vitro for their antileishmanial activity against promastigotes and amastigotes, the clinically relevant parasite form, of Leishmania amazonensis and Leishmania braziliensis. One of the cationic AuI bis-N-heterocyclic carbenes ( 3 ) has low EC50 values (ca. 4 μM) in promastigotes cells and no toxicity in host macrophages. Together with two other AuIII complexes ( 6 and 7 ), the compound is also extremely effective in intracellular amastigotes from L. amazonensis. Initial mechanistic studies include an evaluation of the gold complexes′ effect on L. amazonensis’ plasma membrane integrity. 相似文献
9.
Yunyang Liu Hongding Tang Jingui Qin Makoto Inokuchi Minoru Kinoshita 《Journal of Inorganic and Organometallic Polymers and Materials》2007,17(1):111-119
Two polyferrocenylsilanes (PFSs) 1 and 2 with aniline and carbazolyl as side chains have been prepared by treating silyl-chloride functionalized PFS (PFS-Cl) with hydroxyl-ended aniline and carbazole compounds, respectively, and characterized by NMR, FT-IR, elemental analysis (EA), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and cyclic voltammetry (CV). Both of them could be oxidized by iodine and 2,3-dichloro-5,6-dicyanoquinone (DDQ) to form complexes. PFS 1 could be oxidized by tetracyanoethylene (TCNE) too. The complexes are characterized by FT-IR, EA, Iron-57 Mössbauer spectroscopy. All of them are partially oxidized by the oxidants and both FeII and FeIII coexist in the complexes. Magnetic property measurement by superconducting quantum interference device (SQUID) shows their paramagnetic properties with somewhat antiferromagnetic interaction. Results show that the joint type between PFS backbone and the electron-rich side groups has less direct effect on the exhibition of ferromagnetic interaction in their complexes. 相似文献
10.
Yaqoub Ali Hamam Hasan Moh'd El Ghanem Issam Mahmoud Arafa Moh'd Rida Said Ibrahim Abo aljarayish 《Polymer International》2007,56(3):376-380
FeII, FeIII and mixed‐valence FeII–III chlorides were reacted with poly[N,N′‐bis(dimethylsilyl)ethylenedi‐ amine], [? Si(CH3)2NHCH2CH2NH? ]n, to form the corresponding Fe‐polycarbosilazane macromolecular complexes. The average chain–chain spacing in these materials was estimated from X‐ray diffraction data and found to be 6.94, 7.29, 7.30 and 7.45 Å in metal‐free and FeII? , FeIII? and FeII–III‐containing polycarbosilazanes, respectively. This demonstrates that FeII, FeIII and FeII–III chlorides are encapsulated between the polycarbosilazane chains. The chain–chain expansions in the divalent FeII and trivalent FeIII chloride macromolecular complexes are comparable, but less than that in the FeII–III chloride analog, which suggests that different chain–chain packings exist in the mixed‐valence macromolecular complex. The magnetic properties of the resulting complexes were investigated by measuring the magnetization in magnetic fields up to 8 kOe and in the temperature range from liquid nitrogen temperature to room temperature. Copyright © 2007 Society of Chemical Industry 相似文献
11.
Extended X-ray absorption fine structure (EXAFS) spectroscopy was used to characterize several synthesis stages of hydroxyl-terminated generation four (G4OH) PAMAM dendrimer-derived Ir/γ-Al2O3 catalyst. The EXAFS results indicate that Ir3+ forms complexes with dendrimer functional groups through displacement of two Cl? ion ligands. These complexes are very stable in solution, and no reduction of Ir3+ to Ir nanoparticles or clusters is observed after introduction of reducing agents such as NaBH4 or H2. These Ir3+-dendrimer complexes remain essentially intact after support impregnation. The formation of 1–2 nm particles occurs when the catalysts are treated with O2/H2 or H2, and the dendrimer-derived catalysts exhibit a lower degree of metal support interaction. 相似文献
12.
Dr. Jesica Paola Rada Jéremy Forté Geoffrey Gontard Dr. Vincent Corcé Dr. Michèle Salmain Dr. Nicolás A. Rey 《Chembiochem : a European journal of chemical biology》2020,21(17):2474-2486
This paper reports the design, synthesis and cytotoxicity studies of two new isoxazole-derived aroylhydrazone ligands and their dinuclear copper(II) complexes. Compounds were fully characterized by various spectroscopic and analytical techniques. The molecular structures of four derivatives were confirmed by X-ray crystallography. The stability of the ligands and the complexes in aqueous medium was monitored spectroscopically. Both the ligands and the complexes were shown to interact with calf thymus DNA (ct-DNA). Additionally, structures containing a phenol pendant arm were significantly more cytotoxic than those carrying a pendant pyridine substituent, reaching sub-micromolar IC50 values on the triple-negative human breast cancer cell line MDA-MB-231. The metal chelation and transchelation ability of the compounds towards FeII, FeIII and ZnII ions was explored as a possible mechanism of action of these compounds. 相似文献
13.
Luigi Fabbrizzi Maurizio Licchelli Angelo Perotti Antonio Poggi Silvia Soresi 《Israel journal of chemistry》1985,25(2):112-117
The one-electron oxidation of the NiII and CuII complexes with 13- and 14-membered macrocycles 1 and 2 to produce authentic NiIII and CuIII species has been electrochemically investigated and the E1/2 values associated to the reversible MIII/MII redox couple have been determined by means of the Differential Pulse Voltammetry technique. The 13-membered ring favours the attainment of the CuIII state, whereas the 14-membered ring favours the formation of the NiIII complex. This opposite behaviour is satisfactorily interpreted in terms of size of the metal ions and aperture of the macrocyclic cave. Moreover the effect of the concentration of the inert electrolyte (NaClO4, 0.1–7.0 M) on the E1/2(MIII/MII) values has been investigated: the increase of the NaClO4 concentration favours the formation of the CuIII complexes and disfavours the formation of the NiIII species. This behaviour is ascribed to the destabilization of NiIII and CuII complexes induced by perchlorate ion through the formation of hydrogen bonds with water molecules axially coordinated to the metal ions. 相似文献
14.
The polymeric metal complexes of CoII, NiII, CuII, ZnII, CdII , CeIII, LaIII and UO2
II with 1,4-[5-disulphonyl-8-hydroxyquinoline]piperazine have been synthesized. It has been found that the ligand coordinates to the metal ion as a bibasic tetradentate chelating agent and can form polymeric metal complexes. The structure of the isolated metal complexes is supported by chemical analysis, thermoanalytical data, and conductivity measurements, as well as uv-visible, 1H-NMR, and IR spectroscopy. The stoichiometry of these metal complexes is M:L=2:3. A tetrahedral stereochemical configuration is suggested for the polymeric metal complexes with the exception of the CeIII and LaIII complexes, which form six-coordinate polymeric metal complexes. 相似文献
15.
Li An Ma Wen Zong Lai Zhao Hui Wei Yan Bin Chen Hong Xiang Chen 《Journal of the American Ceramic Society》2020,103(9):4742-4747
Novel polycrystalline TiN coated ZnO core-shell heterostructure nanorods have been prepared on carbon paper substrate via a low-temperature hydrothermal and sputtering process. The core-shell emitters exhibit a highly efficient field-emission performance with a low threshold of electric field ∼0.72 V/μm, and a high emission current density ~16.41 mA/cm2, a level that is the highest of ZnO emitters reported to date. The improved field-emission characteristics may be attributed to the unique materials combination of ZnO core and TiN shell, resulting in the conductivity enhancement, emission sites increase, and the work function reduction. Our results demonstrate that ZnO/TiN core-shell emitter will be a distinguished candidate for electronic source devices. 相似文献
16.
Dr. Matthew Allison Daniel Wilson Dr. Christopher M. Pask Prof. Patrick C. McGowan Dr. Rianne M. Lord 《Chembiochem : a European journal of chemical biology》2020,21(14):1988-1996
Herein we present a library of fully characterized β-diketonate and β-ketoiminate compounds that are functionalized with a ferrocenyl moiety. Their cytotoxic potential has been determined by screening against human breast adenocarcinomas (MCF-7 and MDA-MB-231), human colorectal carcinoma p53 wild type (HCT116 p53+/+) and normal human prostate (PNT2) cell lines. The ferrocenyl β-diketonate compounds are more than 18 times more cytotoxic than the ferrocenyl β-ketoiminate analogues. Against MCF-7, compounds functionalized at the meta position are up to nine times more cytotoxic than when functionalized at the para position. The ferrocenyl β-diketonate compounds have increased selectivity towards MCF-7 and MDA-MB-231, with several complexes having selectivity index (SI) values that are more than nine times (MCF-7) and more than six times (MDA-MB-231) that of carboplatin. The stability of these compounds in dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) has been assessed by NMR spectroscopy and mass spectrometry studies, and the compounds show no oxidation of the iron center from FeII to FeIII. Cytotoxicity screening was performed in both DMSO and DMF, with no significant differences observedin their potency. 相似文献
17.
The synthesis, physico-chemical characterization and cytotoxicity of two di-iron(III) complexes toward three human leukemia cell lines (THP-1, U937 and Molt-4) are reported: [(Cl2)FeIII(μ-HL1)2FeIII(Cl2)]·3H2O (1) and [(Cl2)FeIII(μ-HL2)2FeIII(Cl2)] (2), where HL1 and HL2 are isomers and contain pyridine, phenol, amine and alcohol moieties with a naphthyl pendant unit. These compounds were characterized by a range of physico-chemical methods. Electrochemical studies reveal the maintenance of the dinuclear arrangement in solution, which is supported by ESI(+)-MS studies. Mossbauer spectra consist of a unique doublet indicating equivalent iron centers in the whole sample. The hyperfine parameters are typical of high-spin iron(III). Complex (1) is more active than complex (2), showing an effect of the isomerism on the antitumoral activity. The comparison between these data and those obtained for complexes containing copper and cobalt reveals that the isomerism of the ligand, the nature of the metal centers, the nuclearity and the kind of cell line exert a great influence on the biological activity. 相似文献
18.
Sahand Razzaghi Evan K. Brooks Dr. Enrica Bordignon Prof. Dr. Wayne L. Hubbell Dr. Maxim Yulikov Prof. Dr. Gunnar Jeschke 《Chembiochem : a European journal of chemical biology》2013,14(14):1883-1890
Lanthanide‐induced enhancement of the longitudinal relaxation of nitroxide radicals in combination with orthogonal site‐directed spin labeling is presented as a systematic distance measurement method intended for studies of bio‐macromolecules and bio‐macromolecular complexes. The approach is tested on a water‐soluble protein (T4‐lysozyme) for two different commercially available lanthanide labels, and complemented by previously reported data on a membrane‐inserted polypeptide. Single temperature measurements are shown to be sufficient for reliable distance determination, with an upper measurable distance limit of about 5–6 nm. The extracted averaged distances represent the closest approach in LnIII–nitroxide distance distributions. Studies of conformational changes and of bio‐macromolecule association‐dissociation are proposed as possible application area of the relaxation‐enhancement‐based distance measurements. 相似文献
19.
Recent Advances in the Design of Targeted Iridium(III) Photosensitizers for Photodynamic Therapy
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Dr. Huaiyi Huang Dr. Samya Banerjee Prof. Dr. Peter J. Sadler 《Chembiochem : a European journal of chemical biology》2018,19(15):1574-1589
Photodynamic therapy (PDT) is a noninvasive treatment for certain types of cancer, bacterial, fungal and viral infections, and skin diseases. In recent years, adaptation of this treatment so as to achieve more specific targeted cancer therapy in particular has attracted significant attention. We focus herein on the design of novel iridium‐based photosensitizers (PSs) with tunable photophysical and photobiological properties as efficient PDT agents. We highlight the ability of some IrIII photosensitizers to target specific cellular components, including their activation by one‐ and two‐photon irradiation. 相似文献
20.
Liladhar B. Kumbhare Amey P. Wadawale Vimal K. Jain Monika Sieger Wolfgang Kaim 《Inorganic chemistry communications》2010,13(4):475-478
Monoselenocarboxylate–bridged binuclear complexes of RhIII and IrIII, [(Cp1MCl)2(μ-SeCOAr)2] (1) (M = Rh or Ir; Cp1 = pentamethylcyclopentadienyl; Ar = Ph, C6H4Me–4), have been isolated either by the reaction between [Cp12M2(μ-Cl)2Cl2] with KSeCOAr in acetonitrile or by treatment of [Cp1MCl(solvent)2][PF6] with KSeCOAr in acetone. The novel binuclear complexes, [Cp1IrCl(μ-SeCOAr)(κ2-SeCOC6H3R–)IrCp1] (2) (R = H or Me-4) with ortho-metallation at one of the iridium centres have been isolated following the use of excess AgPF6. The single crystal structure of [Cp1IrCl(μ-SeCOC6H5)(κ2-SeCOC6H4–)IrCp1] (2a) exhibits two phenylcarboselenolate moieties situated in syn fashion with respect to the “Ir2Se2” plane, one of which leans towards the metal centre in order to undergo ortho-metallation after iridium–chlorine bond dissociation. 相似文献