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The emergence of multiple drug delivery systems can solve the disadvantages of single-drug therapy, such as high dose and easy generation of drug resistance. Here, we designed a sialic acid–targeted dextran-mercaptopurine prodrug linked by carbonyl vinyl sulfide for coordinate ZnO quantum dots to achieve multiple drug delivery (doxorubicin, 5-fluorouracil, 6-mercaptopurine), which can be released under the trigger of pH and glutathione. To enhance the antitumor effect, we used inorganic photosensitizer CdSe quantum dots to achieve photodynamic therapy, which can produce cytotoxic reactive oxygen species (hydroxyl radicals) under light conditions. Notably, we found that glutathione is consumed by the delivery of 6-mercaptopurine. It is able to efficiently amplify intracellular oxidative stress via increasing •OH generation. After chelating 99mTc4+ radioisotopes by diethylenetriamine pentaacetic acid, the drug delivery system could be tracked under in vivo single-photon emission computed tomography imaging. The results showed that the phenylboronic acid targeting substance can specifically recognize sialic acid, so that the drug system has a good accumulation in the tumor site, which can better increase the therapeutic effect. Compared to free doxorubicin, the drug system can reduce the IC50 value of cells 4.4-fold under light conditions and significantly inhibit tumor growth in vivo. These data indicate that the sialic acid–targeted nanomedicine system has achieved ideal antitumor effects and apparent photodynamic therapy effects and has broad application prospects.

Herein, we construct a charge - switchable polymer nano micelles poly (2-(hexamethyl eneimino) ethyl methacrylate) - b - poly (ethylene glycol) monomethyl ether methacrylate) - b - poly (diethyl en...

Supplemental material, Support_information for Sialic acid–targeted drug delivery and imaging system for pH- and glutathione-triggered multiple anticancer drug release and enhanced oxidative stress by Licong Peng, Xianwu Zeng, Qianqian Qi, Hailiang Zhang, Jinping Fu, Miao Zhou and Jianchao Yuan in Journal of Bioactive and Compatible Polymers

A series of α-diimine Ni(II) and Pd(II) complexes containing bulky steric groups, {[(4-R-2,6-Ph2C6H2N C)2Nap]MX2} (Nap: 1,8-naphthdiyl, MX2 = NiBr2, R = F (4a); R = Cl (4b); R = Me (4c); R = n-Bu (4d) and MX2 = PdCl2, R = F (5a); R = Cl, (5b); R = Me (5c); R = n-Bu (5d)), {[4-F-2,6-Ph2C6H2N C(Me)]2PdCl2}(5e), were synthesized and characterized. The crystal structures of ligands 3d, 3e and complexes 4a, 4b, 5a, 5b, 5e were determined by X-ray crystallography. These complexes, when activated with diethylaluminum chloride (DEAC), were used to catalyze polymerization of ethylene and methyl methacrylate (MMA) under mild conditions. The introduction of an electron-withdrawing group to the ligand framework improves the catalytic activity significantly. The Ni(II) catalysts 4a–d exhibited high catalytic activity in the polymerization of ethylene (up to106 g PE/(mol Ni h bar)) and produced highly branched polyethylenes at high temperature. Interestingly, complex 4a could produce syndiotactic-rich PMMAs at low temperature (0 °C, up to 77.2% of rr triads).

Novel passive–active dual tumor-targeting micelles for pH-triggered intracellular nitrogen mustard release were developed based on hydrophobic cores conjugated with anticancer drugs and shells functionalized with folic acid ligands for tumor cell targeting. The amphiphilic triblock copolymer, 4-( bis(2-chloroethyl)amino)benzaldehyde, N-(2-hydroxypropyl)methacrylamide, and folic acid copolymer (poly(mustard-acetal)- b-PHPMA- b-PFA), was synthesized via reversible addition fragmentation chain transfer polymerization. The amphiphilic copolymer was subsequently self-assembled into nanosized micelles of 83 nm with the nitrogen mustard drug safely encapsulated in the core. The cleavage of anticancer drug within the cores of micelles was effectively actuated under biologically relevant conditions, mildly acidic microenvironments (endosomal/lysosomal pH in the cytosol). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and fluorescence microscopy image analysis revealed that folate-conjugated nanosized micelles exhibited at least ~2.2-fold higher cellular uptake than folate unconjugated micelles against KB cells overexpressing folate receptors on the surface. Thus, poly(mustard-acetal)- b-PHPMA- b-PFA micelles could potentially be used as a promising system for triggering the release of nitrogen mustard drug.

Two new Ni(II) complexes containing methylphenyl groups, {bis[N,N′-(2,6-dimethyl-4-p-methylphenylphenyl)imino]acenaphthene}dibromonickel 4a and {bis[N,N′-(2-ethyl-4,6-di(p-methylphenyl)phenyl)imino]acenaphthene}dibromonickel 4b, were synthesized and characterized. The molecular structures of both complexes were determined by single-crystal X-ray diffraction. Both complexes have pseudo-tetrahedral geometry about the nickel center, showing pseudo C 2v and C 2 molecular symmetry, respectively. Complex 4c, {bis[N,N′-(2,4,6-trimethylphenyl)imino]acenaphthene}dibromonickel, was also synthesized for comparison. These complexes were tested as catalysts for the polymerization of ethylene and styrene under mild conditions using diethylaluminum chloride. The precatalyst 4b bearing one ortho-ethyl group and two bulky p-methylphenyl groups in the ortho- and para-aryl position of the ligand, displayed highly catalytic activity for the polymerization of ethylene [4.70 × 106 g PE/(mol Ni h bar)], and produced branched polyethylene (76 methyl, 8 ethyl, 5 propyl and 22 butyl or longer branches/1,000 C at 60 °C). Interestingly, complex 4b also displays high catalytic activity [5.46 × 105 g polystyrene/(mol Ni·h)] for styrene polymerization and produces nearly atactic polystyrene at 70 °C (stereo-triad distributions: rr, 39.9 %; mr, 30.4 %; mm, 29.8 %; stereo-diad distributions: r, 55.1 %; m, 44.9 %).

A series of new chiral and achiral nickel (II) complexes, {bis[N,N′-(2-methyl-6-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel rac-(RR/SS)-3a, {bis[N,N′-(4-isopropyl-2-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel rac-(RSRS)-3b, {bis[N,N′-(2-methyl-4,6-di(sec-phenethyl)phenyl)imino]-1,2-dimethylethane}dibromonickel rac-(RSRS)-3c, and {bis[N,N′-(2,6-diisopropyl-4-(p-methylphenyl)phenyl)imino]-1,2-dimethylethane}dibromonickel 3d, were synthesized and characterized. The molecular structures of the representative ligand rac-(RSRS)-2c, complex rac-(RR/SS)-3a, complex rac-( RSRS)-3b, and complex 3d were determined by X-ray crystallography. Complex 3e {bis[N,N′-(2,6-dimethylphenyl)imino]-1,2-dimethylethane}dibromonickel was also synthesized for comparison. These complexes, activated by diethylaluminum chloride (DEAC) were tested in the polymerization of ethylene and styrene under mild conditions. Complex rac-(RSRS)-3c bearing one ortho-methyl group and two chiral bulky sec-phenethyl groups in the ortho- and para-aryl position of the ligand, activated by diethylaluminum chloride (DEAC) shows highly catalytic activity for the polymerization of ethylene [5.56 × 106 g PE/(mol Ni h bar)] and produced branched polyethylene (75 methyl, 9 ethyl, 5 propyl and 19 butyl or longer branches/1000 C at 40 °C). Interestingly, complex rac-(RSRS)-3c also displays highly catalytic activity (3.62 × 105 g polystyrene/(mol Ni h)) for styrene polymerization, and could produce syndiotactic-rich polystyrene (stereo-triad distributions: rr, 66.2%; mr, 18.8%; mm, 15.0%; stereo-diad distributions: r, 75.6%; m, 24.4% at 70 °C). The achiral catalyst 3d gave nearly atactic polystyrene (stereo-triad distributions: rr, 37.0%; mr, 32.7%; mm, 30.3%; stereo-diad distributions: r, 53.4%; m, 46.6% at 70 °C).

A series of nickel(II) catalysts containing phenyl and chiral sec-phenethyl groups, {[(4-R1-2-R2C6H2NC)2Nap]NiBr2} (Nap: 1,8-naphthdiyl, R1 = Me, R2 = Ph (3a); R1 = Me, R2 = sec-phenethyl (3b); R1 = Cl, R2 = sec-phenethyl (3c); R1 = Me, R2 = Me (3d) were synthesized and characterized. All organic compounds were fully characterized by FT-IR and NMR spectroscopy and elemental analysis. The single crystal for X-ray crystallography was isolated from 3a in CH2Cl2/n-hexane under air; the crystal structure showed a binuclear complex 3a′, in which each nickel atom was six-coordinate. The two nickel atoms together with two bromine atoms form a planar four-membered ring, with a bromine and H2O axial ligands. These complexes, activated by diethylaluminum chloride and chiral nickel pre-catalysts rac-3c, exhibited good activities (up to 2.85 × 106 g PE (mol Ni h bar)−1) for ethylene polymerization, and produced polyethylene products with a high degree of branching (up to 117 branched per 1000 carbons) at high temperature. The type and amount of branches of the polyethylenes obtained were determined by 1H and 13C NMR spectroscopy. Copyright © 2014 John Wiley & Sons, Ltd.

A series of new chiral and achiral nickel(II) and palladium(II) complexes, {bis[N,N′-(2,6-diethyl-4-naphthylphenyl)imino]-1,2-dimethylethane}dibromonickel 3a, {bis[N,N′-(4-fluoro-2-methyl-6-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel rac-(RS)-3b, {bis[N,N′-(4-fluoro-6-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel rac-(RR/SS)-3c and {bis[N,N′-(4-fluoro-6-sec-phenethylphenyl)imino]-1,2-dimethylethane}dichloropalladium rac-(RR/SS)-3d were successfully synthesized and characterized. The molecular structures of representative ligand rac-(RS)-2b, nickel complex 3a, rac-(RR/SS)-3c and palladium complex rac-(RR/SS)-3d were determined by X-ray crystallography. The structures of complexes 3a and rac-(RR/SS)-3c have pseudo-tetrahedral geometry about the nickel center, showing C2 molecular symmetry. However, the structure of palladium complex rac-(RR/SS)-3d has pseudo-square planar geometry about the palladium center, showing C2 molecular symmetry. Complex 3e {bis[N,N′-(2,6-dimethylphenyl)imino]-1,2-dimethylethane}dibromonickel was also synthesized for comparison. Nickel complex rac-(RS)-3b bearing strong electron-withdrawing fluorine group in the para-aryl position and a chiral sec-phenethyl group in the ortho-aryl position of the ligand (one methyl group in the ortho-aryl position) displays the highest catalytic activity for ethylene and styrene polymerization, and produced highly branched polyethylene and syndiotactic-rich polystyrene. However, palladium complex rac-(RR/SS)-3d shows low catalytic activity for ethylene and styrene polymerization due to the poor leaving group, Cl, attached to palladium and the unfavorable molecular structure. Copyright © 2014 John Wiley & Sons, Ltd.

A series of new naphthyl-α-diimine nickel(II) complexes, {bis[N,N′-(1-naphthyl)imino]-1,2-dimethylethane}dibromonickel (2a), {bis[N,N′-(2-methyl-1-naphthyl)imino]-1,2-dimethylethane}dibromonickel (2b), {bis[N,N′-(2-sec-phenethyl-1-naphthyl)imino]-1,2-dimethylethane}dibromonickel (rac-(RR/SS)-2c), {bis[N,N′-(2-methyl-1-naphthyl)imino]acenaphthene}dibromonickel (2d), and {bis[N,N′-(2-naphthyl)imino]-1,2-dimethylethane}dibromonickel (2e), were synthesized and characterized. The crystal structures of ligands 1b, rac-(RR/SS)-1c, 1d, 1e and their representative complexes rac-(RR/SS)-2c and 2d were determined by X-ray crystallography. These complexes, activated by diethylaluminum chloride (DEAC), were tested in the polymerization of ethylene and methyl methacrylate under mild conditions. Complex rac-(RR/SS)-2c, bearing chiral bulky sec-phenethyl groups in the o-naphthyl position, activated by diethylaluminum chloride (DEAC) shows highly catalytic activity for the polymerization of ethylene (2.81 × 106 g PE/((mol...

A series of {bis[N,N’N′-(2-ethyl-6-methylphenyl)imino]-1,2-dimethylethane}dibromonickels have been synthesized and characterized. The crystal structures of representative chiral ligand, bis[N,N’N′-(2-ethyl-6-methyl-4-s-phenethylphenyl)imino]-1,2-dimethylethane (S,R)–2a and its chiral complex, {bis[N,N’N′-(2-ethyl-6-methyl-4- sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel (S,R)–3a, have been confirmed by X-ray crystallographic analysis. The asymmetric unit of chiral (S,R)–2a contains one half-molecule which exhibits a crystallographically imposed center of symmetry. The single C-–C bond in 1,4-diazabutadiene fragment is trans-configured and situated on an inversion center. However, the trans-configured ligand can be transformed into cis-configured ligand in order to facilitate the formation of chiral complex (S,R)–3a. Complex (S,R)–3a has pseudo-tetrahedral geometry about the nickel center. Complex (S,R)–3a bearing one ethyl and one methyl in the ortho-aryl position and an electron-donating sec-phenethyl groups in the para-aryl position, activated by diethylaluminum chloride (DEAC), shows highly catalytic activity for the polymerization of ethylene [3.22 × 106 106 g g PE/(mol Ni. h. bar)]. Interestingly, complex 3b bearing one ethyl and one methyl groups in the ortho-aryl position and a strong electron-withdrawing Cl substituent group in the para-aryl position produced the more dendritic polyethylenes (branching degree: 92, 114 and 139 branches/1000 C at 20, 40 and 60 60 (°C, respectively) under low ethylene pressure. The dendritic polyethylene particle size can be controlled in the 1–20 nm range, and could be expected to become the nano-targeted drug carrier after modified with water-soluble oligo(ethylene glycol) (OEG).

A series of new α-diimine nickel(II) catalysts bearing bulky chiral sec-phenethyl groups have been synthesized and characterized. The molecular structure of representative chiral ligand, bis[N,N′-(4-methyl-2,6-di-sec-phenethylphenyl)imino]-1,2-dimethylethane rac-1c and chiral complexes, {bis[N,N′-(4-methyl-2-sec-phenethylphenyl)imino]-2,3-butadiene}dibromidonickel rac-2a and bis{bis[N,N′-(4-methyl-2-sec-phenethylphenyl)imino]-2,3-butadiene}dibromidonickel rac-2b, were confirmed by X-ray crystallographic analysis. Complex rac-2c bearing two chiral sec-phenethyl groups in the ortho-aryl position and a methyl group in the para-aryl position, activated by diethylaluminum chloride (DEAC), showed highly catalytic activity for the polymerization of ethylene [4.12 × 106 g PE (mol Ni.h.bar)−1], and produced highly branched polyethylenes under low ethylene pressure (branching degree: 104, 118 and 126 branches/1000 C at 20, 40 and 60°C, respectively). Chiral 20-electron bis-α-diimine Ni(II) complex rac-2b also exhibited high activity toward ethylene polymerization [1.71 × 106 g PE (mol Ni · h · bar)−1]. The type and amount of branches of the polyethylenes obtained were determined by 1H and 13C NMR. Copyright © 2013 John Wiley & Sons, Ltd.

Three new α-diimine Ni(II) complexes {bis[N,N′-(4-fluoro-2,6-diphenylphenyl)imino]acenaphthene}dibromonickel 4a, {bis[N,N′-(4-chloro-2,6-diphenylphenyl)imino]acenaphthene}dibromonickel 4b, and {bis[N,N′-(4-methyl-2,6-diphenylphenyl)imino]acenaphthene}dibromonickel 4c, were synthesized and characterized. The crystal structure of the complex 4a was determined by X-ray crystallography. Complex 4a has pseudo-tetrahedral geometry about the nickel center, showing C2v molecular symmetry. These complexes, activated by diethylaluminum chloride (DEAC) were tested in the polymerization of ethylene under mild conditions. Complex 4a bearing 2,6-diphenyl and strong electron-withdrawing 4-fluorine groups, activated by diethylaluminum chloride (DEAC) shows highly catalytic activity for the polymerization of ethylene [4.95 × 106 g PE/(mol Ni h bar)] and produced dendritic polyethylene (153.3 branches/1000 C). The dendritic polyethylene particle size obtained by 4a/DEAC can be controlled in the 1–20 nm under 0.2 bar ethylene pressure, and could be expected to become a nano-targeted drug carrier after modified with water-soluble oligo(ethylene glycol) (OEG).

Human hepatocellular carcinoma (HCC) is one of the major causes of death worldwide. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific sulfapyridine HPMA (HPMA: N-(2-hydroxypropyl methacrylamide)) copolymer (sulfapyridine: SPD) conjugates, nonspecific HPMA copolymer conjugates, and DTPA are described in this study. The poly(HPMA)-SPD-DTPA (DTPA: diethylenetriaminepentaacetic acid), poly(HPMA)-DTPA, and DTPA conjugates were radiolabeled with the radionuclide (99m)Tc and tested for uptake by cultured H22 cells. The cellular accumulation of poly(HPMA)-SPD-DTPA-(99m)Tc complex was found to be time-dependent. The poly(HPMA)-SPD-DTPA-(99m)Tc tracer exhibited rapid uptake kinetics in cell culture with a t(1/2) of ~5 min. The uptake of poly(HPMA)-SPD-DTPA-(99m)Tc was significantly higher than that of poly(HPMA)-DTPA-(99m)Tc, indicating that the uptake of the poly(HPMA)-SPD-DTPA-(99m)T was active binding. The uptake of poly(HPMA)-DTPA-(99m)Tc was significantly higher than that of DTPA-(99m)Tc, suggesting that the uptake of the poly(HPMA)-DTPA-(99m)T was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p0.001) tumor localization for poly(HPMA)-SPD-DTPA-(99m)Tc (4.98 ± 0.48%ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-(99m)Tc (2.69 ± 0.15% ID/g) and DTPA-(99m)Tc (0.83 ± 0.03%ID/g). Moreover, higher T/B for poly(HPMA)-SPD-DTPA-(99m)Tc indicated reduced extravazation of the targeted polymeric conjugates in normal tissues. Specific molecular targeting and nonspecific vascular permeability are both significant in the relative tumor localization of poly(HPMA)-SPD-DTPA-(99m)Tc. Extravascular leak in nonspecific organs appears to be a major factor in reducing the T/B for the sulfapyridine molecules. Thus, the poly(HPMA)-SPD-DTPA is expected to be used as the potential macromolecular targeting carrier for hepatoma carcinoma in mice.

Two new α-diimine containing Ni(II) complexes, {bis[N,N′-(2,6-dimethyl-4-naphthylphenyl)imino]-1,2-dimethylethane}dibromonickel 3a and {bis[N,N′-(2-methyl-4-naphthylphenyl)imino]-1,2-dimethylethane}dibromonickel 3b were synthesized and characterized. The crystal structures of representative ligand 2a and its complex 3a were determined by X-ray crystallography. Complex 3a bearing 2,6-dimethyl and 4-naphthyl groups, activated by diethylaluminum chloride (DEAC), shows high catalytic activity for the polymerization of ethylene [4.43 × 106 g PE/(mol Ni h bar)]. Interestingly, complexes 3a and 3b bearing the naphthyl substituent in the para-aryl position produced dendritic polyethylenes (branching degree, 3a: 112, 118, and 147; 3b: 113, 127, and 151 branches/1,000 C at 20, 40, and 60 °C, respectively). The dendritic polyethylene particle size obtained by 3a and 3b/DEAC can be controlled in the 1–20 nm range under low ethylene pressure (diameter, 3a: 18.31, 14.44, and 11.09; 3b: 12.29, 8.98 and 6.27 nm at 20, 40, and 60 °C, respectively) and could be expected to produce a nano-targeted drug carrier after modification with water-soluble oligo(ethylene glycol).

Recent studies have identified that sulfadiazine derivatives can be concentrated in the hepatocellular carcinoma tissue. Herein, we report the synthesis, characterization, and evaluation of a novel sulfamethazine N-(2-hydroxypropyl)methacrylamide copolymer conjugates for tumor targeting. N-(3-Aminopropyl)methacrylamide-diethylenetriaminepentaacetic acid monomer 1, methacryloyl-sulfamethazine monomer 2, poly( N-(2-hydroxypropyl)methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid conjugate 4, and poly( N-(2-hydroxypropyl)methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid-99mTc were successfully synthesized and characterized. Poly( N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid conjugate 3, diethylenetriaminepentaacetic acid-99mTc, and poly( N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid-99mTc were also synthesized and characterized for comparison (99mTc: metastable technetium-99). A 24-h necropsy data in the hepatocellular carcinoma tumor model showed significantly higher ( p < 0.001) tumor localization for poly( N-(2-hydroxypropyl)methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid-99mTc (4.82%ID/g ± 0.46%ID/g (percentage injected dose per gram tissue)) compared with poly( N-(2-hydroxypropyl)methacrylamide)-diethylenetriaminepentaacetic acid-99mTc (2.69%ID/g ± 0.15%ID/g) and diethylenetriaminepentaacetic acid-99mTc (0.83%ID/g ± 0.03%ID/g). Moreover, higher tumor/organ ratios for poly( N-(2-hydroxypropyl)methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid-99mTc indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly( N-(2-hydroxypropyl)methacrylamide)-sulfamethazine-diethylenetriaminepentaacetic acid can potentially be used as a macromolecular targeting carrier for hepatocellular carcinoma in mice.

To develop a theranostic agent for diagnostic imaging and treatment of hepatocellular carcinoma (HCC), poly(HPMA)-APMA-DTPA-99mTc (HPMA: N-(2-hydroxypropyl methacrylamide; APMA: N-(3-aminopropyl)methacrylamide; DTPA: diethylenetriaminepentaacetic acid) and DTPA-99mTc were synthesized and characterized, and their HCC targeting was tested by in vitro cellular uptake and in vivo tumor imaging in this study. Radioactivity of HCC cells incubated with poly(HPMA)-APMA-DTPA-99mTc was significant higher (16.40%) than that of the cells incubated with DTPA-99mTc (2.98%). Scintigraphic images of HCC in mice obtained at 8 h after injection of poly(HPMA)-APMA-DTPA-99mTc showed increased radioactivity compared with that in mice injected with DTPA-99mTc. The results of postmortem tissue radioactivity assay demonstrated higher radioactivity of HCC tumor tissues (2.69 ± 0.15% ID/g) from the tumor-bearing mice injected with poly(HPMA)-APMA-DTPA-99mTc compared with that of HCC tumor tissues in the tumor-bearing mice injected with DTPA-99mTc (0.83 ± 0.03 %ID/g), (P

Three new 20-electron bis-α-diimine nickel (II) complexes containing chloro-substituted ligands, bis{bis[N,N′-(3-chloro-2-methylphenyl)imino]-1,2-dimethylethane}dibromonickel 2a, bis{bis[N,N′-(3-chloro-2,6-dimethylphenyl)imino]-1,2-dimethylethane}dibromonickel 2b and bis{bis[N,N′-(4-chloro-2,6-dimethyl-phenyl)imino]-1,2-dimethylethane}dibromonickel 2c, were synthesized and characterized. The molecular structure of complex 2a was determined by X-ray crystallography. In the solid state, complex 2a has a pseudo-octahedral geometry about the nickel center, containing two α-diimine ligands in the pseudo-equatorial plane and two trans bromide ligands occupying the axial positions. These complexes, activated by diethylaluminum chloride (DEAC) were tested in the polymerization of ethylene under mild conditions. NMR analysis shows that highly branched polyethylenes are obtained using these bis-α-diimine nickel(II) complexes containing electron-withdrawing Cl groups in the aryl groups (e.g. 84 branches/1000 C, at 20 °C). The catalytic activity, polymer molecular weight and polymer degree of branching were significantly affected by the number of methyl substituents in the ortho-aryl position and the chlorine substituent position in the aryl rings of the coordinated α-diimine ligands.

A Br-substituted α-diimine ligand, bis[N,N′-(4-bromo-2,6-dimethylphenyl)imino]-2,3-butadiene L1, and its corresponding Ni(II) complex, {bis[N,N′-(4-bromo-2,6-dimethylphenyl)imino]-2,3-butadiene} dibromonicke [NiBr 2 (L1)], have been synthesized and characterized. The crystal structure of the free ligand (L1) was determined by X-ray crystallography. Two α-diimine-Ni(II) catalysts, {bis[N,N′-(2,4,6-dimethylphenyl)imino]-2,3-butanedione} dibromonickel [NiBr 2 (L2)] and {bis[N,N′-(2,6-dimethylphenyl)imino]-2,3-butanedione} dibromonickel [NiBr 2 (L3)], were also synthesized and characterized for comparison. The complex [NiBr 2 (L1)], when activated by diethylaluminum chloride, produces the most active catalytic system for the polymerization of ethylene among the three complexes. NMR analysis shows that the degree of branching of polyethylene increases in the presence of electron-withdrawing groups under the same reaction conditions.

Porphyrins typically show preferential uptake and retention by tumor tissues via receptor-mediated endocytosis of low-density lipoproteins. To investigate the relative importance of active and passive targeting strategies, the synthesis, characterization, in vitro uptake, and in vivo biodistribution of specific targeting porphyrin HPMA [HPMA: N-(2-hydroxypropyl)methacrylamide] copolymer tracer poly(HPMA)-porphyrin-DTPA-(99m)Tc (DTPA: diethylenetriaminepentaacetic acid), nonspecific targeting HPMA copolymer tracer poly(HPMA)-DTPA-(99m)Tc, and nontargeting tracer DTPA-(99m)Tc are described in this study. The results showed that the cellular accumulation of poly(HPMA)-porphyrin-DTPA-(99m)Tc complex was found to be time-dependent. The uptake of poly(HPMA)-porphyrin-DTPA-(99m)Tc was significantly higher than that of poly(HPMA)-DTPA-(99m)Tc, indicating that uptake of the poly(HPMA)-porphyrin-DTPA-(99m)Tc was active binding. The uptake of poly(HPMA)-DTPA-(99m)Tc was significantly higher than that of DTPA-(99m)Tc, suggesting that uptake of the poly(HPMA)-DTPA-(99m)Tc was passive binding. Twenty-four hour necropsy data in the hepatocellular carcinoma tumor model showed significantly higher (p0.001) tumor localization for poly(HPMA)-porphyrin-DTPA-(99m)Tc (5.18 ± 0.50% ID/g [percentage injected dose per gram tissue]) compared with poly(HPMA)-DTPA-(99m)Tc (2.69 ± 0.15% ID/g) and DTPA-(99m)Tc (0.83 ± 0.03% ID/g). Moreover, higher T/B for poly(HPMA)-porphyrin-DTPA-(99m)Tc indicated reduced extravasation of the targeted polymeric conjugates in normal tissues. Thus, the poly(HPMA)-porphyrin-DTPA-(99m)Tc is a potential macromolecular tumor targeting molecular agent.

In the title compound, C36H36N2, a product of the condensation reaction of 2,3-dimethyl-6-phenylvinylbenzenamine and 2,3-butanedione, the complete molecule is generated by the application of an inversion centre. The central C—C bond in the 1,4-diazabutadiene fragment istrans-configured and situated about the inversion center. The dihedral angle between the ring attached to N and the 1,4-diazabutadiene plane is 78.24 (36)°, while the 1,4-diazabutadiene plane makes an angle of 30.71 (26)° with the phenyl ring.

Poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers were synthesized and characterized for tumor localization in vivo as a theranostic scaffold for cancer imaging and anticancer drug delivery targeting tumor angiogenesis. Tumor localization of the poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers was visualized in mice bearing human prostate cancer xenografts by positron emission tomography (PET) using a microPET scanner. PET quantitative analysis demonstrated that tumor 64Cu radioactivity (2.75 ± 0.34 %ID/g) in tumor-bearing mice 3 hours following intravenous injection of the poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers was significantly higher than the tumor 64Cu radioactivity (1.29 ± 0.26 %ID/g) in tumor-bearing mice injected with the nontargeted poly(HPMA)-DOTA-64Cu copolymers (p = .004). The poly(HPMA)-c(RGDyK)-DOTA-64Cu copolymers hold potential as a theranostic scaffold for cancer imaging and radiochemotherapy of prostate cancer targeting tumor angiogenesis by noninvasive tracking with PET.

Two alpha-diimine monometallic Ni catalysts, catalyst 1 and catalyst 2, were studied in the copolymerization reaction of ethylene (E) with methyl methacrylate (MMA). The reaction products of these reactions were characterized using not only the usual techniques such as NMR, GPC and DSC but also the Langmuir balance and AFM. 1H and 13C NMR spectra revealed that both copolymers and mixtures of E and MMA (in a range of 20–70 mol% of MMA) could be obtained with these catalysts. A better insight of the products was possible with 1H DOSY NMR. Since p(E-MMA) copolymers comprising hydrophobic PE blocks and surface active PMMA blocks are amphiphilic, the Langmuir monolayer technique provided further information on the two-dimensional phase behavior of copolymer monolayers at the air-water interface. Additionally, AFM topographic images of the Langmuir-Blodgett (LB) monolayers deposited on mica substrates clearly showed that the morphology of the copolymer LB monolayer is quite different from the corresponding mixture of PE and PMMA homopolymers. These techniques together with molecular modeling calculations allowed us to conclude that with catalyst 2 it was possible to obtain a true block copolymer by a mechanism involving a cationic ester-enolate metal complex as the active species.

The asymmetric unit of the title compound, C20H24N2, contains one half -molecule which exhibits a crystallographically imposed center of symmetry. The benzene rings are inclined to the 1,4-diazabutadiene mean plane by 78.3 (2)°.

To develop new radiopharmaceuticals for interventional radionuclide therapy of locally recurrent prostate cancer, poly[N-(3-aminopropyl)methacrylamide] [poly(APMA)] polymers were synthesized by free radical precipitation polymerization in acetone-dimethylsulfoxide using N,N'-azobis(isobutyronitrile) as the initiator. The polymers were characterized with nuclear magnetic resonance, size exclusion chromatography, and dynamic light scattering (M(n) = 2.40 x 10(4), M(w)/M(n) = 1.87). Subsequently, poly[APMA] was coupled with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride as an activator, followed by conjugation with (64)Cu radionuclide. Prolonged retention of poly[APMA]-DOTA-(64)Cu conjugates within the tumor tissues was demonstrated by micro-positron emission tomography at 24 hours following intra-tumoral injection of the conjugates to human prostate xenografts in mice. The data suggest that the poly[APMA]-DOTA-(64)Cu conjugates might be useful for interventional radionuclide therapy of locally recurrent prostate cancer in humans.

The complex molecule in the title compound, [NiBr2(C36H40N2)], has mirror symmetry. The NiIIatom and two Br atoms are located on the mirror plane. The NiIIatom is four-coordinated by the two Br atoms and two N atoms from anN,N′-bis(2,6-diethyl-4-phenylphenyl)butane-2,3-diimine ligand in a distorted tetrahedral geometry. The dihedral angle formed between the two adjacent benzene rings is 47.1 (1)°.

In the title compound, C18H18Cl2N2, the complete molecule is generated by the application of C2 symmetry. The C=N bond has an E configuration. The dihedral angle between the benzene ring and the 1,4-diazabutadiene plane is 66.81 (9)°.