Zhen-Feng Chen

Samarium(III)-catalyzed C(sp3)-H bond activation: synthesis of indolizines via C-C and C-N coupling between 2-alkylazaarenes and propargylic alcohols.

A new rare earth metal and samarium-catalyzed C(sp(3))-H bond activation is reported in which 2-alkylazaarenes and propargylic alcohols were converted to indolizines. This process operates under mild conditions and solvent-free conditions. A broad scope of coupling partners has been established, and a likely mechanism has also been suggested.

Stabilization of G-quadruplex DNA, inhibition of telomerase activity, and tumor cell apoptosis by organoplatinum(II) complexes with oxoisoaporphine.

Two G-quadruplex ligands [Pt(L(a))(DMSO)Cl] (Pt1) and [Pt(L(b))(DMSO)Cl] (Pt2) have been synthesized and fully characterized. The two complexes are more selective for SK-OV-3/DDP tumor cells versus normal cells (HL-7702). It was found that both Pt1 and Pt2 could be a telomerase inhibitor targeting G-quadruplex DNA. This is the first report demonstrating that telomeric, c-myc, and bcl-2 G-quadruplexes and caspase-3/9 preferred to bind with Pt2 rather than Pt1, which also can induce senescence and apoptosis. The different biological behavior of Pt1 and Pt2 may correlate with the presence of a 6-hydroxyl group in L(b). Importantly, Pt1 and Pt2 exhibited higher safety in vivo and more effective inhibitory effects on tumor growth in the HCT-8 and NCI-H460 xenograft mouse model, compared with cisplatin. Taken together, these mechanistic insights indicate that both Pt1 and Pt2 display low toxicity and could be novel anticancer drug candidates.

Coordination polymers constructed by linking metal ions with azodibenzoate anions

Twelve new coordination polymers have been obtained using three different azodibenzoate ligands, 3,3′-azodibenzoic acid (3,3′-ADB), 3,3′-azoxydibenzoic acid (3,3′-AODB) and 4,4′-azodibenzoic acid (4,4′-ADB) in combination with a variety of metal ions and co-ligands. Their crystal structures have been elucidated using single crystal X-ray diffraction analysis and the thermal stabilities of some of the products have been investigated using thermogravimetric analysis. The compounds, [Pb(3,3′-ADB)(phen) ]n (1), [Cu2(3,3′-AODB)(PPh3)2]n (2), [Zn(4,4′-ADB)(Py)2]n (3), [Cd(4,4′-ADB)(H2O)2]n (4), and [Co(4,4′-ADB)(Py)2(H2O)2]n (5), form 1-D chains. Compounds Zn(3,3′-ADB)(CH3CH2OH) (6) and Co3(3,3′-ADB)2(phen)2(CH3COO)2 (7) form 2D sheets which have the (4,4) topology. Two-dimensional sheets are also formed in the case of Cd(4,4′-ADB)(phen)(H2O) (8), Y2(3,3′-ADB)3(phen)2 (9), Sm2(3,3′-ADB)3(phen)2 (10) and Er2(3,3′-ADB)3(phen)2 (11) with 9, 10 and 11 being isomorphous. In the structure of Ba(4,4′-ADB) (12), Ba(II) carboxylate units form 2D sheets which are linked by organic links to form a 3D pillared structure.

Ni2(R*COO)4(H2O)(4,4′-bipy)2—a robust homochiral quartz-like network with large chiral channels

The generation of a chiral network of composition, Ni2(R*COO)4(H2O)(4,4′-bipy)2 (R*COO− = dehydroabietate), was achieved through the deliberate use of enantiomerically pure carboxylic acid, dehydroabietic acid, under hydrothermal conditions.

Intermolecular and Intramolecular Quencher Based Quantum Dot Nanoprobes for Multiplexed Detection of Endonuclease Activity and Inhibition

DNA cleavage by endonucleases plays an important role in many biological events such as DNA replication, recombination, and repair and is used as a powerful tool in medicinal chemistry. However, conventional methods for assaying endonuclease activity and inhibition by gel electrophoresis and chromatography techniques are time-consuming, laborious, not sensitive, or costly. Herein, we combine the high specificity of DNA cleavage reactions with the benefits of quantum dots (QDs) and ultrahigh quenching abilities of inter- and intramolecular quenchers to develop highly sensitive and specific nanoprobes for multiplexed detection of endonucleases. The nanoprobe was prepared by conjugating two sets of DNA substrates carrying quenchers onto the surface of aminated QDs through direct assembly and DNA hybridization. With this new design, the background fluorescence was significantly suppressed by introducing inter- and intramolecular quenchers. When these nanoprobes are exposed to the targeted endonucleases, specific DNA cleavages occur and pieces of DNA fragments are released from the QD surface along with the quenchers, resulting in fluorescence recovery. The endonuclease activity was quantified by monitoring the change in the fluorescence intensity. The detection was accomplished with a single excitation light. Multiplexed detection was demonstrated by simultaneously assaying EcoRI and BamHI (as model analytes) using two different emissions of QDs. The limits of detection were 4.0 × 10(-4) U/mL for EcoRI and 8.0 × 10(-4) U/mL for BamHI, which were at least 100 times more sensitive than traditional gel electrophoresis and chromatography assays. Moreover, the potential application of the proposed method for screening endonuclease inhibitors has also been demonstrated. The assay protocol presented here proved to be simple, sensitive, effective, and easy to carry out.

Potential new inorganic antitumour agents from combining the anticancer traditional Chinese medicine (TCM) matrine with Ga(III), Au(III), Sn(IV) ions, and DNA binding studies.

Three new compounds of Ga(III), Au(III), Sn(IV) with matrine (MT), [H-MT][GaCl(4)] (1), [H-MT][AuCl(4)] (2) and [Sn(H-MT)Cl(5)] (3), have been synthesized and characterized by elemental analysis, IR, ESI-MS and single crystal X-ray diffraction methods. The crystal structural analyses indicate that 1 and 2 are ionic compounds, whereas 3 is a tin(IV) complex formed by the monodentate MT via its carbonyl oxygen atom of MT coordinating to Sn(IV). Their in vitro cytotoxicity towards eight selected tumour cell lines has been evaluated by MTT (3-[4,5-Dimentylthiazole-2-yl]-2,5-diphenpyltetra-zolium bromide) method, and compounds 1 and 2 exhibit enhanced activity, such as 1 to SW480, 2 to HeLa, HepG2 and MCF-7, which exceeds matrine and cisplatin, and display synergistic contribution of their components. The cell cycle analyses show that compounds 1, 3 and MT exhibit cell cycle arrest at the G(2)/M phase. Interactions of these compounds with calf thymus DNA (ct-DNA) have been investigated by spectroscopic analyses. The planar extension of the intercalative metal-matrine compounds increases the interaction of the metal-matrine with DNA, indicating that the cationic metal ions and configuration of the intercalated metal-matrine will affect the extent of interaction. Compound 2, [H-MT][AuCl(4)], exhibits more intensive binding ability to DNA, which may correlate with intercalation and other action mode. The circular dichroism spectra of the ct-DNA bound with metal-MT compounds also suggest that ct-DNA interacted with 1, 2, 3 does not influence its secondary structure. Furthermore, both compounds 1 and 2 exhibit effective inhibition ability to topoisomerase (TOPO I) at concentration of 50 μM, while matrine and compound 3 do not.

Synthesis, characterization and preliminary cytotoxicity evaluation of five Lanthanide(III)–Plumbagin complexes

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone, H-PLN) was isolated from Plumbago zeylanica, the anticancer traditional Chinese medicine (TCM). Five new lanthanide(III) complexes of deprotonated plumbagin: [Y(PLN)(3)(H(2)O)(2)] (1), [La(PLN)(3)(H(2)O)(2)] (2), [Sm(PLN)(3)(H(2)O)(2)]⋅H(2)O (3), [Gd(PLN)(3)(H(2)O)(2)] (4), and [Dy(PLN)(3)(H(2)O)(2)] (5) were synthesized by the reaction of plumbagin with the corresponding lanthanide salts, in amounts equal to ligand/metal molar ratio of 3:1. The PLN-lanthanide(III) complexes were characterized by different physicochemical methods: elemental analyses, UV-visible, IR and (1)H NMR and ESI-MS (electrospray ionization mass spectrum) as well as TGA (thermogravimetric analysis). The plumbagin and its lanthanide(III) complexes 1-5, were tested for their in vitro cytotoxicity against BEL7404 (liver cancer) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The five PLN-lanthanide (III) complexes 1-5 effectively inhibited BEL7404 cell lines growth with IC(50) values of 11.0±3.5, 5.1±1.3, 6.1±1.1, 6.4±1.3, and 9.8±1.5 μM, respectively, and exhibited a significantly enhanced cytotoxicity compared to plumbagin and the corresponding lanthanide salts, suggesting a synergistic effect upon plumbagin coordination to the Ln(III) ion. The lanthanide complexes under investigation also exerted dose- and time-dependent cytotoxic activity. [La(PLN)(3)(H(2)O)(2)] (2) and plumbagin interact with calf thymus DNA (ct-DNA) mainly via intercalation mode, but for [La(PLN)(3)(H(2)O)(2)] (2), the electrostatic interaction should not be excluded; the binding affinity of [La(PLN)(3)(H(2)O)(2)] (2) to DNA is stronger than that of free plumbagin, which may correlate with the enhanced cytotoxicity of the PLN-lanthanide(III) complexes.

Water-Soluble Ruthenium(II) Complexes with Chiral 4-(2,3-Dihydroxypropyl)-formamide Oxoaporphine (FOA): In Vitro and in Vivo Anticancer Activity by Stabilization of G-Quadruplex DNA, Inhibition of Telomerase Activity, and Induction of Tumor Cell Apoptosis.

Three water-soluble ruthenium(II) complexes with chiral 4-(2,3-dihydroxypropyl)-formamide oxoaporphine (FOA) were synthesized and characterized. It was found that these ruthenium(II) complexes exhibited considerable in vitro anticancer activities and that they were the effective stabilizers of telomeric and G-quadruplex-DNA (G4-DNA) in promoter of c-myc, which acted as a telomerase inhibitor targeting G4-DNA and induced cell senescence and apoptosis. Interestingly, the in vitro anticancer activity of 6 (LC-003) was higher than those of 4 (LC-001) and 5 (LC-002), more selective for BEL-7404 cells than for normal HL-7702 cells, and preferred to activate caspases-3/9. The different biological behaviors of the ruthenium complexes could be correlated with the chiral nature of 4-(2,3-dihydroxypropyl)-formamide oxoaporphine. More significantly, 6 exhibited effective inhibitory on tumor growth in BEL-7402 xenograft mouse model and higher in vivo safety than cisplatin. These mechanistic insights indicate that 6 displays low toxicity and can be a novel anticancer drug candidate.

Nicking enzyme and graphene oxide-based dual signal amplification for ultrasensitive aptamer-based fluorescence polarization assays

In this work, two different configurations for novel amplified fluorescence polarization (FP) aptasensors based on nicking enzyme signal amplification (NESA) and graphene oxide (GO) enhancement have been developed for ultrasensitive and selective detection of biomolecules in homogeneous solution. One approach involves the aptamer-target binding induced the stable hybridization between an aptamer probe and a fluorophore-labeled DNA probe linked to GO, and forms a nicking site-containing duplex DNA region due to the enhancement of base stacking. The second analytical method involves the target induced the assembly of two aptamer subunits into an aptamer-target complex, and then hybridizes with a fluorophore-labeled DNA probe linked to GO, forming a nicking site-containing duplex DNA region. The formation of the duplex DNA region in both methods triggers the NESA process, resulting in the release of many short DNA fragments carrying the fluorophore from GO, generating a significant decrease of the FP value that provides the readout signal for the amplified sensing process. By using the NESA coupled GO enhancement path, the sensitivity of the developed aptasensors can be significantly improved by four orders of magnitude over traditional aptamer-based homogeneous assays. Moreover, these aptasensors also exhibit high specificity for target molecules, which are capable of detecting target molecule in biological samples. Considering these qualities, the proposed FP aptasensors based NESA and GO enhancement can be expected to provide an ultrasensitive platform for amplified analysis of target molecules.

Synthesis, Cytotoxic Activity, and DNA Binding Properties of Copper (II) Complexes with Hesperetin, Naringenin, and Apigenin

Complexes of copper (II) with hesperetin, naringenin, and apigenin of general composition [CuL2(H2O)2] ⋅ nH2O (1–3) have been synthesized and characterized by elemental analysis, UV-Vis, FT-IR, ESI-MS, and TG-DTG thermal analysis. The free ligands and the metal complexes have been tested in vitro against human cancer cell lines hepatocellular carcinoma (HepG-2), gastric carcinomas (SGC-7901), and cervical carcinoma (HeLa). Complexes 1 and 3 were found to exhibit growth inhibition of SGC-7901 and HepG2 cell lines with respect to the free ligands; the inhibitory rate of complex 1 is 43.2% and 43.8%, while complex 3 is 46% and 36%, respectively. The interactions of complex 1 and its ligand Hsp with calf thymus DNA were investigated by UV-Vis, fluorescence, and CD spectra. Both complex 1 and Hsp were found to bind DNA in intercalation modes, and the binding affinity of complex 1 was stronger than that of free ligand.