Synthesis,Cytotoxicity, Induction of Apoptosis,and Interaction with DNA of Dinuclear Platinum(II) Complexes

Six dicarboxylato‐bridged dinuclear platinum(II) complexes S1 – S6 , with a newly designed chiral ligand, 2‐{[(1R,2R)‐2‐aminocyclohexyl]amino}propanoic acid ( HL ), were prepared and spectrally characterized. The in vitro cytotoxicity of all resulting platinum(II) complexes was evaluated against human HCT‐116, MCF‐7, and HepG‐2 tumor cell lines. The results show that all compounds exhibit positive biological activity toward HCT‐116 and MCF‐7 cell lines, of which complexes S3 , S4 , and S5 , with succinate and its derivatives as bridges, showing better activity than the positive controls. Moreover, double‐dyeing flow cytometric resection experiments indicate that the target compounds inhibit tumor cell growth by inducing apoptosis; gel electrophoresis experiments demonstrate the compounds′ ability to prompt pET22b plasmid DNA degradation in almost the same way as oxaliplatin.     

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

Osmium compounds are attracting increasing attention as potential anticancer drugs. In this context, a series of bifunctional organometallic osmium(II)‐p‐cymene complexes functionalized with alkyl or perfluoroalkyl groups were prepared and screened for their antiproliferative activity. Three compounds from the series display selectivity toward cancer cells, with moderate cytotoxicity observed against human ovarian carcinoma (A2780) cells, whereas no cytotoxicity was observed on non‐cancerous human embryonic kidney (HEK‐293) cells and human endothelial (ECRF24) cells. Two of these three cancer‐cell‐selective compounds induce cell death largely via apoptosis and were also found to disrupt vascularization in the chicken embryo chorioallantoic membrane (CAM) model. Based on these promising properties, these compounds have potential clinical applications.     

Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents

In the search for alternative chemotherapeutic strategies against leukemia, various 1‐indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1‐indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl^.2M eOH, where L1=1‐indanone thiosemicarbazone, was solved by X‐ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1‐indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies.     

Synthesis, in vitro cytotoxicity, and interaction with DNA of platinum(II) complexes with N-monocycloalkyl derivatives of 1R,2R-diaminocyclohexane as carrier ligands

A series of platinum(II) complexes with N-monocyclopentyl/cyclohexyl derivatives of 1R,2R-diaminocyclohexane as carrier ligands and dicarboxylate anions as leaving groups were synthesized and characterized. All complexes were characterized by elemental analysis, IR, (1)H NMR, and (13)C NMR spectroscopy, as well as ESIMS. The in vitro antiproliferative activities were tested by MTT assay against four human cancer cell lines; breast carcinoma (MCF-7) and colon cancer (HCT-116) cells were particularly sensitive, especially to complexes 1f (IC(50) =9.81 and 1.49 μM) and 2f (IC(50) =4.59 and 0.36 μM). Flow cytometry indicated that representative compounds exert cytotoxicity toward MCF-7 and HCT-116 cells through induction of apoptosis and blockage of cell-cycle progression in the S phase, similar to cisplatin. The interaction between the platinum(II) complexes and pET22b plasmid DNA was observed by agarose gel electrophoresis, revealing that complex 2f has the capacity to distort plasmid DNA in a manner distinct from that of oxaliplatin.     

Bis(dipyridophenazine)(2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Hexafluorophosphate: A Lesson in Stubbornness

Ruthenium complexes are currently considered to be among the most promising alternatives to platinum anticancer drugs. In this work, thirteen structural analogues and organelle/receptor‐targeting peptide bioconjugates of a cytotoxic bis(dppz)‐Ru^II complex [Ru(dppz)₂(CppH)](PF₆)₂ ( 1 ) were prepared, characterized, and assessed for their cytotoxicity and cellular localization (CppH=2‐(2′‐pyridyl)pyrimidine‐4‐carboxylic acid; dppz=dipyrido[3,2‐a:2′,3′‐c]phenazine). It was observed that structural modifications (lipophilicity, charge, and size‐based) result in the cytotoxic potency of 1 being compromised. Confocal microscopy studies revealed that unlike 1 , the screened complexes/bioconjugates do not have a preferential accumulation in mitochondria. The results of this important structure–activity relationship strongly support our initial hypothesis that accumulation in mitochondria is crucial for 1 to exert its cytotoxic action.     

Aerobic Oxidation of Benzylic Alcohols in Water by 2,2,6,6‐Tetramethylpiperidine‐1‐oxyl (TEMPO)/Copper(II) 2‐N‐Arylpyrrolecarbaldimino Complexes

Novel copper(II) 2‐N‐arylpyrrolecarbaldimine‐based catalysts for the aerobic oxidation of benzylic alcohols mediated by the 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) radical are reported. The catalytic activity for both synthesized and in situ made complexes in alkaline water solutions was studied revealing high efficiency and selectivity (according to GC selectivity always >99%) for both of these catalytic systems. For example, quantitative conversion of benzyl alcohol to benzaldehyde can be achieved with the in situ prepared bis[2‐N‐(4‐fluorophenyl)‐pyrrolylcarbaldimide]copper(II) catalysts in 2 h with atmospheric pressure of O₂ at 80 °C. Interestingly, these catalysts can utilize dioxygen as well as air or hydrogen peroxide as the end oxidants, producing water as the only by‐product.     

Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with O,S Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues

(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug development. Over the last few years, classical structure–activity relationships (SAR) have been broken by some promising new compounds based on platinum or other metals. We focus on the synthesis and characterization of 17 different complexes with β-hydroxydithiocinnamic acid esters as O,S bidendate ligands for nickel(II), palladium(II), and platinum(II) complexes. (2) Methods: The bidendate compounds were synthesized and characterized using classical methods including NMR spectroscopy, MS spectrometry, elemental analysis, and X-ray crystallography, and their cytotoxic potential was assessed using in vitro cell culture assays. Data were compared with other recently reported platinum(II), ruthenium(II), and osmium(II) complexes based on the same main ligand system. (3) Results: SAR analyses regarding the metal ion (M), and the alkyl-chain position (P) and length (L), revealed the following order of the effect strength for in vitro activity: M > P > L. The highest activities have Pd complexes and ortho-substituted compounds. Specific palladium(II) complexes show lower IC₅₀ values compared to cisplatin, are able to elude cisplatin resistance mechanisms, and show a higher cancer cell specificity. (4) Conclusion: A promising new palladium(II) candidate (Pd3) should be evaluated in further studies using in vivo model systems, and the identified SARs may help to target platinum-resistant tumors.     

pH‐responsive poly(ethylene glycol)‐poly(ϵ‐caprolactone)‐poly(glutamic acid) polymersome as an efficient doxorubicin carrier for cancer therapy

The synthesis, characterization and potential application in the doxorubicin (Dox) delivery system of a biodegradable polypeptide‐based block copolymer, poly(ethylene glycol)₂₀₀₀‐poly(?‐caprolactone)₆₀₀₀‐poly(glutamic acid)₁₀₀₀ (PEG₂₀₀₀‐PCL₆₀₀₀‐PGA₁₀₀₀), was investigated. The copolymer was synthesized via ring‐opening polymerization and characterized by ¹H NMR and Fourier transform IR. The synthesized copolymer could self‐assemble into aggregates and the critical aggregation concentration was 0.23 mg mL^?1. Transmission electron microscopy indicated that spherical polymersomes formed with a desirable size about 180 nm. Therefore Dox was encapsulated into these polymersomes, and then we investigated its applications in a drug delivery system. These Dox‐loaded polymersomes (PolyDox) were characterized by dynamic light scattering, zeta potential and pH responsiveness measurements. In vitro drug release indicated that the release rate of drug from PolyDox was pH‐responsive and significantly decreased. The drug pharmacokinetic parameters were improved in comparison to the group treated with free Dox, which proved the prolonged Dox release from PolyDox. A WST‐1 assay indicated a low toxicity and good compatibility of copolymer to cells within 48 h. The results also showed that PolyDox appeared to induce a higher anti‐tumor effect. Cell uptake results indicated that PolyDox displayed higher cellular uptake in A549 cells. Endocytosis inhibition results demonstrated that the internalization of PolyDox was mostly mediated by the fluid‐phase endocytosis pathway. © 2017 Society of Chemical Industry     

Ruthenium(II) and Platinum(II) Complexes with Biologically Active Aminoflavone Ligands Exhibit In Vitro Anticancer Activity

Continuing our studies on the mechanisms underlying the cytotoxicity of potential drugs, we have described several aspects of the in vitro anticancer activity of ruthenium(II) and platinum(II) complexes with bioactive, synthetic aminoflavone ligands. We examined the mechanism of proapoptotic activity of cis-dichlorobis(3-imino-2-methoxyflavanone)ruthenium(II), cis-dichlorobis(3-imino-2-ethoxyflavanone)ruthenium(II), and trans-dichlorobis(3-aminoflavone)platinum(II). Cisplatin was used as a reference compound. The cytotoxicity was investigated by MTT assay. The mechanism of proapoptotic activity of the tested compounds was investigated by evaluation of caspase-8 activity, cytometric analysis of annexin-V positive cells, and mitochondrial potential loss measurement. The results showed that ruthenium compounds break partially or completely the cisplatin resistance by activating the caspase 8-dependent apoptosis pathway and loss of mitochondrial membrane potential. Platinum compounds also have a cytostatic effect, but their action requires more exposure time. Potential mechanisms underlying drug resistance in the two pairs of cancer cell lines were investigated: total glutathione content, P-glycoprotein activity, and differences in the activity of DNA repair induced by nucleotide excision. Results showed that cisplatin-resistant cells have elevated glutathione levels relative to sensitive cells. Moreover, they indicated the mechanisms enabling cells to avoid apoptosis caused by DNA damage. Pg-P activity has no effect on the development of cisplatin resistance in the cell lines described.     

Platinum(II) as Bifunctional Linker in Antibody–Drug Conjugate Formation: Coupling of a 4‐Nitrobenzo‐2‐oxa‐1,3‐diazole Fluorophore to Trastuzumab as a Model

The potential of platinum(II) as a bifunctional linker in the coordination of small molecules, such as imaging agents or (cytotoxic) drugs, to monoclonal antibodies (mAbs) was investigated with a 4‐nitrobenzo‐2‐oxa‐1,3‐diazole (NBD) fluorophore and trastuzumab (Herceptin?) as a model antibody. The effect of ligand and reaction conditions on conjugation efficiency was explored for [Pt(en)(L‐NBD)Cl](NO₃) (en=ethylenediamine), with L=N‐heteroaromatic, N‐alkyl amine, or thioether. Conjugation proceeded most efficiently at pH 8.0 in the presence of NaClO₄ or Na₂SO₄ in tricine or HEPES buffer. Reaction of N‐coordinated complexes (20 equiv) with trastuzumab at 37 °C for 2 h, followed by removal of weakly bound complexes with excess thiourea, afforded conjugates with an NBD/mAb ratio of 1.5–2.9 that were stable in phosphate‐buffered saline at room temperature for at least 48 h. In contrast, thioether‐coordinated complexes afforded unstable conjugates. Finally, surface plasmon resonance analysis showed no loss in binding affinity of trastuzumab after conjugation.     

Nonionic water‐soluble polymer: Preparation,characterization, and application of poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) as a polychelatogen

The free‐radical copolymerization of water‐soluble poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) was carried out with a feed monomer ratio of 75:25 mol %, and the total monomer concentration was 2.67M. The synthesis of the copolymer was carried out in dioxane at 70°C with benzoyl peroxide as the initiator. The copolymer composition was obtained with elemental analysis and ¹H‐NMR spectroscopy. The water‐soluble polymer was characterized with elemental analysis, Fourier transform infrared, ¹H‐ and ¹³C‐NMR spectroscopy, and thermal analysis. Additionally, viscosimetric measurements of the copolymer were performed. The thermal behavior of the copolymer and its complexes were investigated with differential scanning calorimetry (DSC) and thermogravimetry techniques under a nitrogen atmosphere. The copolymer showed high thermal stability and a glass transition in the DSC curves. The separation of various metal ions by the water‐soluble poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) reagent in the aqueous phase with liquid‐phase polymer‐based retention was investigated. The method was based on the retention of inorganic ions by this polymer in a membrane filtration cell and subsequent separation of low‐molar‐mass species from the polymer/metal‐ion complex formed. Poly(1‐vinyl‐2‐pyrrolidone‐co‐hydroxyethylmethacrylate) could bind metal ions such as Cr(III), Co(II), Zn(II), Ni(II), Cu(II), Cd(II), and Fe(III) in aqueous solutions at pHs 3, 5, and 7. The retention percentage for all the metal ions in the polymer was increased at pH 7, at which the maximum retention capacity could be observed. The interaction of inorganic ions with the hydrophilic polymer was determined as a function of the pH and filtration factor. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 178–185, 2006     

Synthesis,Structure–Activity Relationship Studies,and ADMET Properties of 3‐Aminocyclohex‐2‐en‐1‐ones as Chemokine Receptor 2 (CXCR2) Antagonists

Herein we describe the synthesis and structure–activity relationships of 3‐aminocyclohex‐2‐en‐1‐one derivatives as novel chemokine receptor 2 (CXCR2) antagonists. Thirteen out of 44 derivatives were found to inhibit CXCR2 downstream signaling in a Tango assay specific for CXCR2, with IC₅₀ values less than 10 μm . In silico ADMET prediction suggests that all active compounds possess drug‐like properties. None of these compounds show significant cytotoxicity, suggesting their potential application in inflammatory mediated diseases. A structure–activity relationship (SAR) map has been generated to gain better understanding of their binding mechanism to guide further optimization of these new CXCR2 antagonists.     

(R)‐α‐Lipoyl‐Glycyl‐L‐Prolyl‐L‐Glutamyl Dimethyl Ester Codrug as a Multifunctional Agent with Potential Neuroprotective Activities

The (R)‐α‐lipoyl‐glycyl‐L ‐prolyl‐L ‐glutamyl dimethyl ester codrug (LA‐GPE, 1 ) was synthesized as a new multifunctional drug candidate with antioxidant and neuroprotective properties for the treatment of neurodegenerative diseases. Physicochemical properties, chemical and enzymatic stabilities were evaluated, along with the capacity of LA‐GPE to penetrate the blood–brain barrier (BBB) according to an in vitro parallel artificial membrane permeability assay for the BBB. We also investigated the potential effectiveness of LA‐GPE against the cytotoxicity induced by 6‐hydroxydopamine (6‐OHDA) and H₂O₂ on the human neuroblastoma cell line SH‐SY5Y by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) reduction assay. Our results show that codrug 1 is stable at both pH 1.3 and 7.4, exhibits good lipophilicity (log P=1.51) and a pH‐dependent permeability profile. Furthermore, LA‐GPE was demonstrated to be significantly neuroprotective and to act as an antioxidant against H₂O₂‐ and 6‐OHDA‐induced neurotoxicity in SH‐SY5Y cells.     

Synthesis of (N,N'-Bis(2-Hydroxyethyl)Ethane-1,2-Diamine)Malonatoplatinum(II) and X-Ray Crystal Structure of the Cis-R,S-Isomer

Hydroxyethyl substituted amineplatinum(II) and (IV) complexes are an interesting class of platinum based antitumour compounds due to their uncoordinated hydroxy groups. These hydroxy groups could play an important role in the mode of action of such complexes with respect to their ability to act as donor or acceptor for hydrogen bonds. Moreover, their chemistry in solution is of interest because it was found that there is the possibility of an intramolecular attack to form ethanolatoamine chelated species which are responsible for very stable monoadducts with 5'-GMP. Furthermore, there is the possibility of derivatisation at the OH site to form a new series of platinum compounds which may be used for a carrier mediated transport to tumour tissues. In this context a series of (N,N'-bis(2-hydroxyethyl)ethane-l,2-diamine)-platinum(II) complexes has been synthesised. During purification of one of the platinum based compounds, it was possible to isolate (SP-4-3)-R,S-(N,N'-bis(2-hydroxyethyl)ethane-l,2-diamine)malonatoplatinum(ll) and to resolve the structure by single crystal structure analysis. Intra- and intermolecular hydrogen bonds have been found which may explain the spontaneous crystallisation of the cis-R,S isomer and the stabilisation of the boat conformation of the malonatoplatinum(II) six-membered ring.     

Triarylphosphine Ligands with Hemilabile Alkoxy Groups: Ligands for Nickel(II)‐Catalyzed Olefin Dimerization Reactions. Hydrovinylation of Vinylarenes, 1,3‐Dienes,and Cycloisomerization of 1,6‐Dienes

Substitution of one of the phenyl groups of triphenylphosphine with a 2‐benzyloxy‐, 2‐benzyloxymethyl‐ or 2‐benzyloxyethyl‐phenyl moiety results in a set of simple ligands, which exhibit strikingly different behaviour in various nickel(II)‐catalyzed olefin dimerization reactions. Complexes of ligands with 2‐benzyloxyphenyl‐ and 2‐benzyloxymethylphenyldiphenylphosphine ( L5 and L6 , respectively) are most active for hydrovinylation (HV) of vinylarenes, with the former leading to extensive isomerization of the primary 3‐aryl‐1‐butenes into the conjugated 2‐aryl‐2‐butenes even at −55 °C. However, 2‐benzyloxymethyl‐substituted ligand L6 is slightly less active, affording up to quantitative yields of the primary products of HV at ambient temperature with no trace of isomerization, thus providing the best option for a practical synthesis of these compounds. In sharp contrast, hydrovinylation of a variety of 1,3‐dienes is best catalyzed by nickel(II) complexes of 2‐benzyloxyphenyldiphenylphosphine, L5 . The other two ligands, 2‐benzyloxymethyl‐ ( L6 ) and 2‐benzyloxyethyldiphenylphosphine ( L7 ) are much less effective in the HV of 1,3‐dienes. Nickel(II)‐catalyzed cycloisomerization of 1,6‐dienes into methylenecyclopentanes, a reaction mechanistically related to the other hydrovinylation reactions, is also uniquely effected by nickel(II) complexes of L5 , but not of L6 or L7 . In an attempt to prepare authentic samples of the methylencyclohexane products, nickel(II) complexes of N‐heterocyclic carbene ligands were examined. In sharp contrast to the phosphines, which give the methylenecyclopentanes, methylenecyclohexanes are the major products in the (N‐heterocyclic carbene)nickel(II)‐mediated reactions.

     

Cyclometalated N‐Heterocyclic Carbene‐Platinum Catalysts for the Enantioselective Cycloisomerization of Nitrogen‐Tethered 1,6‐Enynes

Platinum(II) complexes which combine six‐membered N‐heterocyclic carbene‐containing metallacyclic units and monodentate chiral phosphines have been prepared. The key step of their synthesis is the intramolecular oxidative addition of N‐2‐iodobenzylimidazolylidene‐platinum(0)‐diene complexes in the presence of the chiral phosphorus ligands. The platinum(II) metallacycles have been used as well‐defined pre‐catalysts for the enantioselective cycloisomerization of nitrogen‐tethered 1,6‐enynes into 3‐azabicyclo[4.1.0]hept‐4‐enes. High enantiomeric excesses have been obtained with either Monophos or phenyl‐Binepine based catalysts (ees=82–96%), although phenyl‐Binepine outperforms Monophos in these reactions. The absolute configuration of the final 3‐azabicyclo[4.1.0.]heptenes has been established by X‐ray diffraction studies. The method has been extended then to the cycloisomerization of dienynes with enantiotopic vinyl groups. An (S)‐phenyl‐Binepine‐platinum(II) complex allows total diastereoselectivity and high enantioselectivity levels to be attained in these reactions (ees up to 95%) which represent the first enantioselective desymetrizations achieved via enyne cycloisomerizations.     

New low bandgap conjugated polymer derived from 2, 7‐carbazole and 5, 6‐bis(octyloxy)‐4, 7‐di(thiophen‐2‐yl) benzothiadiazole: Synthesis and photovoltaic properties

To develop conjugated polymers with low bandgap, deep HOMO level, and good solubility, a new conjugated alternating copolymer PC‐DODTBT based on N‐9′‐heptadecanyl‐2,7‐carbazole and 5, 6‐bis(octyloxy)‐4,7‐di(thiophen‐2‐yl)benzothiadiazole was synthesized by Suzuki cross‐coupling polymerization reaction. The polymer reveals excellent solubility and thermal stability with the decomposition temperature (5% weight loss) of 327°C. The HOMO level of PC‐DODTBT is ‐5.11 eV, indicating that the polymer has relatively deep HOMO level. The hole mobility of PC‐DODTBT as deduced from SCLC method was found to be 2.03 × 10^?4 cm²/Versus Polymer solar cells (PSCs) based on the blends of PC‐DODTBT and [6,6]‐phenyl‐C₇₁‐butyric acid methyl ester (PC₇₁BM) with a weight ratio of 1:2.5 were fabricated. Under AM 1.5 (AM, air mass), 100 mW/cm^?2 illumination, the devices were found to exhibit an open‐circuit voltage (V_oc) of 0.73 V, short‐circuit current density (J_sc) of 5.63 mA/cm^?2, and a power conversion efficiency (PCE) of 1.44%. This photovoltaic performance indicates that the copolymer is promising for polymer solar cells applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Conjugation of Cisplatin Analogues and Cyclooxygenase Inhibitors to Overcome Cisplatin Resistance

Cyclooxygenase (COX) is an enzyme involved in tumorigenesis and is associated with tumor cell resistance against platinum‐based antitumor drugs. Cisplatin analogues were conjugated with COX inhibitors (indomethacin, ibuprofen) to study the synergistic effects that were previously observed in combination treatments. The conjugates ensure concerted transport of both drugs into cells, and subsequent intracellular cleavage enables a dual‐action mode. Whereas the platinum(II) complexes showed cytotoxicities similar to those of cisplatin, the platinum(IV) conjugates revealed highly increased cytotoxic activities and were able to completely overcome cisplatin‐related resistance. Although some of the complexes are potent COX inhibitors, the conjugates appear to execute their cytotoxic action via COX‐independent mechanisms. Instead, the increased lipophilicity and kinetic inertness of the conjugates seem to facilitate cellular accumulation of the platinum drugs and thus improve the efficacy of the antitumor agents. These conjugates are important tools for the elucidation of the direct influence of COX inhibitors on platinum‐based anticancer drugs in tumor cells.     

Hyperbranched PEI grafted by hydrophilic amino acid segment poly[N‐(2‐hydroxyethyl)‐L‐glutamine] as an efficient nonviral gene carrier

A polyethylenimine‐poly(hydroxyethyl glutamine) copolymer (PEI‐PHEG) was designed and synthesized as a gene delivery system. The molecular structure of PEI‐PHEG was characterized using nuclear magnetic resonance. Moreover, PEI‐PHEG/pDNA complexes were fabricated and characterized by gel retardation assay, particle size analysis, and zeta potential analysis. The transfection efficiency and cytotoxicity of PEI‐PHEG were evaluated using human cervical carcinoma (HeLa), human embryonic kidney (HEK293), and murine colorectal adenocarcinoma (CT26) cells in vitro. The results show that PEI‐PHEG could effectively form positively charged nano‐sized particles with pDNA; the particle size was in a range of 130.2 to 173.0 nm and the zeta potential was in a range of 27.6 to 41.0 mV. PEI‐PHEG exhibited much lower cytotoxicity and higher gene transfection efficiency than PEI‐25K with different cell lines in vitro. An animal test was also conducted on a Lewis Lung Carcinoma tumor model in C57/BL6 mice by using subcutaneous intratumoral administration. The results show that in vivo transfection efficiency of PEI‐PHEG was improved greatly compared with that of commercial PEI‐25K. These results demonstrate that PEI‐PHEG can be a potential nonviral vector for gene delivery systems both in vitro and in vivo. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

A novel polymer chemodosimeter for the detection of mercury ions: Synthesis and fluorescence “turn‐on” responses of fluorene‐based conjugated polymer with reactive pendent N,N‐diethyl‐2‐(4‐phenoxy)‐thioacetamide

A novel conjugating polyfluorene bearing N,N‐diethyl‐2‐(4‐phenoxy)‐thioacetamide as side chain was designed for the detection of Hg(II) ions. It was synthesized through postfunctionalization of acetamide‐based polyfluorene derivative. Upon the addition of Hg(II) ions, the thioacetamide groups of this polymer side chains were specifically reacted with Hg(II) ions, leading to this chemodosimeter with higher selectivity for Hg(II) over other metal ions tested under the same conditions. In addition, on the basis of the effect of fluorescent signal amplifications originated from electron transmission along the backbone, this designed conjugated polyfluorene with pendent reactive thioacetamide reached ultra high sensitivity for the detection of mercury ions. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012