Juanjuan Li

A neutral molecular-based layered magnet [Fe(C2O4)(CH3OH)]n exhibiting magnetic ordering at TN approximately 23 K.

Solvothermal synthesis of FeCl(2).4H2O and H2C2O(4).2H2O in methanol at 120 degrees C yielded yellow plate-like crystals of [Fe(C2O4)(CH3OH)]n. Each iron atom is in a distorted octahedral environment, being bonded to four oxygen atoms from two bisbidentate oxalate anions, one O atom of a chelating oxalate anion and one O atom from a methanol molecule as an oxalate group bridging ligand in a five-coordination mode. The neutral layer of [Fe(C2O4)(CH3OH)]n with a [4,4] net along the ac plane. There is no interaction between layers. A long range magnetic ordering with spin canting at TN approximately 23 K was observed and confirmed by AC susceptibility measurements.

Half-Sandwich Iridium(III) and Ruthenium(II) Complexes Containing P^P-Chelating Ligands: A New Class of Potent Anticancer Agents with Unusual Redox Features

A series of half-sandwich IrIII pentamethylcyclopentadienyl and RuII arene complexes containing P^P-chelating ligands of the type [(Cpx/arene)M(P^P)Cl]PF6, where M = Ir, Cpx is pentamethylcyclopentadienyl (Cp*), or 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl (CpxbiPh); M = Ru, arene is 3-phenylpropan-1-ol (bz-PA), 4-phenylbutan-1-ol (bz-BA), or p-cymene (p-cym), and P^P is 2,20-bis(diphenylphosphino)-1,10-binaphthyl (BINAP), have been synthesized and fully characterized, three of them by X-ray crystallography, and their potential as anticancer agents explored. All five complexes showed potent anticancer activity toward HeLa and A549 cancer cells. The introduction of a biphenyl substituent on the Cp* ring for the iridium complexes has no effect on the antiproliferative potency. Ruthenium complex [(η6-p-cym)Ru(P^P)Cl]PF6 (5) displayed the highest potency, about 15 and 7.5 times more active than the clinically used cisplatin against A549 and HeLa cells, respectively. No binding to 9-MeA and 9-EtG nucleobases was observed. Although these types of complexes interact with ctDNA, DNA appears not to be the major target. Compared to iridium complex [(η5-Cp*)Ir(P^P)Cl]PF6 (1), ruthenium complex (5) showed stronger ability to interfere with coenzyme NAD+/NADH couple through transfer hydrogenation reactions and to induce ROS in cells, which is consistent with their anticancer activities. The redox properties of the complexes 1, 5, and ligand BINAP were evaluated by cyclic voltammetry. Complexes 1 and 5 arrest cell cycles at the S phase, Sub-G1 phase and G1 phase, respectively, and cause cell apoptosis toward A549 cells.

Mitochondria-targeted half-sandwich rutheniumII diimine complexes: anticancer and antimetastasis via ROS-mediated signalling

Herein we present half-sandwich RuII diimine complexes that combine anticancer and antimetastasis activity into one molecule. Two half-sandwich RuII diimine complexes [(η6-p-cymene)Ru(N^N)Cl]PF6 have been synthesized and characterized. RuII complexes show antiproliferative activity against a wide range of cancer cell lines in vitro. In addition, they exhibit no cross-resistance with cisplatin. The complexes target mitochondria, damage mitochondrial integrity, and induce mitochondrial membrane permeabilization. Further studies show that the complexes can induce activation of caspase 3/PARP. Interestingly, the complexes finally lead to apoptosis and impede cell migration in cancer cells via ROS-mediated signalling.

Nano-sized paramagnetic and fluorescent fluorinated carbon fiber with high NIR absorbance for cancer chemo-photothermal therapy

Nano-sized fluorinated carbon fiber possesses unique charge distribution and special chemical bonds and holds great promise in biomedicine. However, its synthesis remains a big challenge on account of the chemical inertness and strong hydrophobicity of C-F bonds. Herein, an up-bottom method to prepare nano-sized and water-soluble fluorinated carbon fiber oxide (FCO) with tunable lengths and adjustable fluorine levels was first developed. It was found that the effective control over structure and composition endowed the FCO with high photoluminescence (PL) and near-infrared (NIR) light absorbance, which was further employed to monitor the drug loading by turn-off PL and treat cancer by photothermal therapy (PTT). We also reported the first experimental example of paramagnetic FCO, whose novel paramagnetism was generated by point defects from fluorine invasion. Moreover, the FCO was noncovalently functionalized with polyvinylpyrrolidone, loaded with doxorubicin of high capacity (1.15 mg mg-1) and exhibited acid-triggered and photothermally enhanced drug release behavior. The application of FCO in cancer treatment achieved much better therapeutic effects than single chemotherapy or PTT. This work established FCO as a novel nano-carrier with high PL, NIR absorbance, paramagnetism, and drug loading capacity, and demonstrated its first application in cancer chemo-photothermal therapy.

Half-sandwich IridiumIII N-heterocyclic carbene antitumor complexes and biological applications

Series of half-sandwich IrIIIN-heterocyclic carbene (NHC) antitumor complexes [(η5-Cp*)Ir(C^C)Cl] have been synthesized and characterized (Cp* is pentamethyl cyclopentadienyl, and C^C are four NHC chelating ligands containing phenyl rings at different positions). IrIII complexes showed potent antitumor activity with IC50 values ranged from 3.9 to 11.8u202fμM against A549 cells by the MTT assay. Complexes can catalyze the conversion of the coenzyme NADH to NAD+ and induce the production of reactive oxygen species (ROS), and bonding to BSA by static quenching mode. Complexes can arrest the cell cycle in G1 or S phase and reduce the mitochondrial membrane potential. Confocal microscopy test show complexes could target the lysosome and mitochondria in cells with the Pearsons colocalization coefficient of 0.82 and 0.21 after 12u202fh, respectively, and followed by an energy-dependent cellular uptake mechanism.

Lysosome targeted drugs: rhodamine B modified N^N-chelating ligands for half-sandwich iridium(III) anticancer complexes

We designed and synthesized four rhodamine-modified half-sandwich iridium complexes ([(η5-Cpx)Ir(N^N)Cl]PF6). The fluorescence properties of the complexes were studied. Excitingly, the cytotoxicity of the complexes was superior to that of cisplatin for both A549 cells and HeLa cells. In particular, for A549 cells, the cytotoxicity of complexes 2 and 3 was 5 or 6-fold higher than that of cisplatin. Interactions with ctDNA and BSA have been investigated. The results show that the interaction with DNA does not seem to be the main anticancer mechanism. A binding experiment between BSA and complexes was carried out using a UV spectrophotometer and a fluorescence spectrophotometer. The catalytic conversion of the coenzyme NADH to NAD+ has also been investigated for hydrogen transfer of the complexes. In addition, complex 3 was studied in cell experiments because of its good antiproliferative activity. In addition, the cell distribution and targeting mechanisms of these complexes were studied using confocal microscopy. Complex 3 can induce cell death by blocking the G0/G1 phase of the cell cycle, affecting the mitochondrial membrane potential, then entering the cells and specifically targeting lysosomes. These seem to contribute to the anticancer activity of the complexes.

Lysosome-Targeted Chemotherapeutics: Half-Sandwich Ruthenium(II) Complexes That Are Selectively Toxic to Cancer Cells

Poor selectivity between cancer cells and normal cells is one of the major limitations of cancer chemotherapy. Lysosome-targeted ruthenium-based complexes target tumor cells selectively, only displaying rather weak cytotoxicity or inactivity toward normal cells. Confocal microscopy was employed for the first time to determine the cellular localization of the half-sandwich Ru complex.

Half-Sandwich Iridium and Ruthenium Complexes: Effective Tracking in Cells and Anticancer Studies

Half-sandwich metal-based anticancer complexes suffer from uncertain targets and mechanisms of action. Herein we report the observation of the images of half-sandwich iridium and ruthenium complexes in cells detected by confocal microscopy. The confocal microscopy images showed that the cyclopentadienyl iridium complex 1 mainly accumulated in nuclei in A549 lung cancer cells, whereas the arene ruthenium complex 3 is located in mitochondria and lysosomes, mostly in mitochondria, although both complexes entered A549 cells mainly through energy-dependent active transport. The nuclear morphological changes caused by Ir complex 1 were also detected by confocal microscopy. Ir complex 1 is more potent than cisplatin toward A549 and HeLa cells. DNA binding studies involved interaction with the nucleobases 9-ethylguanine, 9-methyladenine, ctDNA, and plasmid DNA. The determination of bovine serum albumin binding was also performed. Hydrolysis, stability, nucleobase binding, and catalytic NAD+/NADH hydride transfer tests for complexes 1 and 3 were also carried out. Both complexes activated depolarization of mitochondrial membrane potential and intracellular ROS overproduction and induced cell apoptosis. Complex 3 arrested the cell cycle at the G0/G1 phase by inactivation of CDK 4/cyclin D1. This work paves the way to track and monitor half-sandwich metal complexes in cells, shines a light on understanding their mechanism of action, and indicates their potential application as theranostic agents.

Highly potent half-sandwich iridium and ruthenium complexes as lysosome-targeted imaging and anticancer agents

In this study, six half-sandwich luminescent iridium (Ir) and ruthenium (Ru) anticancer complexes bearing P^P-chelating ligands 1,2-bis(diphenylphosphino)benzene (dppbz) and 1,8-bis(diphenylphosphino)naphthalene (dppn) were synthesized and characterized via1H-NMR spectroscopy, 31P-NMR spectroscopy, mass spectrometry, elemental analysis and X-ray crystallography. All the complexes displayed more potent anticancer activity than cisplatin towards A549 lung cancer cells and HeLa cervical cancer cells, especially the most potent iridium complex Ir3, which was 73 times more potent than cisplatin against A549 cells. Different from cisplatin, no nucleobase adducts of Ir3 were detected. With the help of the self-luminescence of complex Ir3 and confocal microscopy, it was observed that Ir3 efficiently penetrated into the A549 cells via energy-dependent active transport, and specifically accumulated in lysosomes, affected the permeabilization of the lysosomal membranes and induced caspase-dependent cell death through lysosomal damage. Both apoptosis and autophagy of the A549 cells were observed. The reactive oxygen species (ROS) elevation, reduction of the mitochondrial membrane potential and cell cycle arrest at the G0/G1 phase also contributed to the observed cytotoxicity of Ir3. We demonstrate that these half-sandwich Ir and Ru anticancer complexes have different anticancer mechanism of action from that of cisplatin, which can be developed as potential multifunctional theranostic platforms that combine bioimaging and anticancer capabilities.

Half-sandwich Iridium(III) Benzimidazole-Appended Imidazolium-Based N-heterocyclic Carbene Complexes and Antitumor Application

A series of half-sandwich iridium(III) benzimidazole-appended imidazolium-based N-heterocyclic carbene (NHC) antitumor complexes [(η5 -Cpx )Ir(C^N)Cl]Cl, where Cpx is pentamethylcyclopentadienyl (Cp*) or its biphenyl derivative (Cpxbiph ) and C^N is a NHC chelating ligand, were successfully synthesized and characterized. The IrIII complexes showed potential antitumor activity against A549 cells, at most three times more potent than cis-platin under the same conditions. Complexes could bind to BSA by a static quenching mode, catalyzing the change of NADH to NAD+ and inducing the production of reactive oxygen species (maximum turnover number, 9.8), which play an important role in regulating cell apoptosis. Confocal microscopy showed that the complexes could specifically target lysosomes in cells with a Pearsons co-localization coefficient 0.76 and 0.72 after 1u2005h and 6u2005h, respectively, followed an energy-dependent cellular uptake mechanism and damaged the integrity of lysosomes. At the same time, complexes caused a marked loss of mitochondrial membrane potential.