Cell‐Selective,Apoptosis‐inducing Rhodium(III) Crown Thiaether Complexes

Half‐sandwich rhodium(III) polypyridyl (pp) complexes with the metal atom capped by the facial crown thiaether 1,4,7‐trithiacyclononane [9]aneS₃ represent a promising class of apoptosis‐inducing potent cytostatic agents. The necrotic damage caused by the complexes is negligible. In vitro cytotoxicity assays with the human cancer cell lines MCF‐7 and HT‐29 and immortalized HEK‐293 cells indicate that the dicationic κ²N(imino) complexes [([9]aneS₃)RhCl(pp)]²⁺ are much more active than monocationic complexes [([9]aneS₃)RhCl₂(L)]⁺ (L=imidazole, CH₃CN). Whereas the κ²N(amino) complex [([9]aneS₃)RhCl(piperazine)]²⁺ is inactive, replacing piperazine with the structurally analogous κ²S (thiaether) ligand 1,4‐dithiane restores cytotoxicity as evidenced by IC₅₀ values in the range 8.1‐11.6 μM . Spectroscopic (CD, UV/Vis, NOESY) and viscosity measurements indicate that the active dppz complex 8 (IC₅₀ values: 4.7–8.9 μM ) exhibits strong intercalative binding towards DNA whereas the even more potent bipyrimidine complex 9 (IC₅₀ values: 0.6–1.9 μM ) causes no alteration of the duplex B conformation. Weaker intercalative binding is observed for the dpq complex 7 . A comparative annexin V–propidium iodide binding assay with lymphoma (BJAB) cells and healthy leukocytes demonstrates that the cytotoxic activity of complex 8 and particularly complex 9 is highly selective towards the malignant cells.     

Structural and Dynamic Aspects of Palladium(II)‐Based Self‐Assembled Binuclear Coordination Complexes

Self‐assembled binuclear complexes of Pd₂L′₂L₂ and Pd₂L₄ type formulations have been achieved by combining the cis‐protected palladium(II) component i. e., [PdL′]²⁺ (where L′ stands for tmeda) and naked palladium(II) separately with a 3‐pyridyl appended non‐chelating bidentate ligand, L under suitable conditions. Supramolecular fusion of the Pd₂L₄ and PdL′₂ type complexes have been demonstrated that provided the corresponding Pd₂L′₂L₂ type complex. One pot synthesis of the binuclear Pd₂L′₂L₂ type complex is achieved by combining palladium(II), L′ and L at equimolar ratio, however, along with an unidentified trap. The crystal structure of a Pd₂L₄ type complex confirmed the binuclear architecture of the cage. Intermolecular H‐bonding and π‐π stacking interactions are analyzed from the crystal structure and the extended intermolecular interactions apparently generated a grid pattern.     

The ring‐opening polymerization of D,L‐lactide catalyzed by new complexes of Cu,Zn, Co,and Ni Schiff base derived from salicylidene and L‐aspartic acid

D ,L ‐lactide (LA) was first successfully ring‐opening polymerized in melt by Schiff base complexes K[ML]nH₂O [M = Cu(II), Zn(II), Co(II), Ni(II); n = 2, 2, 3, 3.5; H₃L = L‐aspartic acid‐salicylidene Schiff base], which were prepared by Schiff base ligand derived from salicylidene and L‐aspartic acid and corresponding acetates. The effects of various complexes, the molar ratio of K[ML]nH₂O/LA, the polymerization temperature, and time were studied in detail. The results show that all complexes studied have the ability to initiate the ring‐opening polymerization of D ,L ‐lactide in melt. More than 90% high polymerization conversion and narrow molecular weight distribution (MWD) can be obtained very easily. However, the Ni(II) complex shows better catalytic property than other complexes on the polymerization and the molecular weight (MW) of poly(D ,L ‐lactide) (PLA) produced. With a rise in temperature and a prolongation of time, the MW of PLA decreased remarkably. The MW of PLA prepared by all complexes is not very high, which might be related to the crystalline water of complexes. X‐ray study indicated that PLA produced by Ni(II) complex is an amorphous polymer. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 3312–3315, 2002     

First use of the maleamate(−1) ligand in coordination chemistry: Dinuclear copper(II) complexes with N-donors and their interesting ‘organic’ chemistry

A systematic investigation of the reactions of 3d-metal ions with the maleamate(−1) ligand (HL⁻) in the presence of mono- , bi- or tridentate chelating N-donors has been initiated and the first results are described. Reaction schemes involving Cu(ClO₄)₂ · 6H₂O, HL⁻ and 1,10-phenanthroline or 2,6-bis(pyrazol-1-yl)pyridine (bppy) in MeCN gave complexes [Cu₂(HL)₃(phen)₂](ClO₄) (1) and [Cu₂(HL)₂(bppy)₂](ClO₄)₂ (3), respectively. The same reaction systems in MeOH afforded the new complexes [Cu₂L′₂(ClO₄)(phen)₂(MeOH)](ClO₄) (2b) and [Cu₂L′₂(bppy)₂](ClO₄)₂ (4) in which the maleamate(−1) ion has been transformed to the monomethyl maleate(−1) ligand L′⁻ via a novel, metal ion-assisted process. The reaction that leads to 2b takes place through the formation of the 1D coordination polymer [Cu(ClO₄)(phen)(MeOH)₂]_n(ClO₄)_n (2a), whose structure was assigned on the basis of its spectral similarity with the structurally characterized complex [Cu(ClO₄)(phen)(MeCN)₂]_n(ClO₄)_n (2c). Only the carboxylate oxygen atoms of HL⁻ and L′⁻ are coordinated to copper(II) in 1, 2b, 3 and 4.     

3,5‐Bis(benzylidene)‐4‐oxo‐1‐phosphonopiperidines and Related Diethyl Esters: Potent Cytotoxins with Multi‐Drug‐Resistance Reverting Properties

A series of 3,5‐bis(benzylidene)‐4‐piperidones 3 were converted into the corresponding 3,5‐bis(benzylidene)‐1‐phosphono‐4‐piperidones 5 via diethyl esters 4 . The analogues in series 4 and 5 displayed marked growth inhibitory properties toward human Molt 4/C8 and CEM T‐lymphocytes as well as murine leukemia L1210 cells. In general, the N‐phosphono compounds 5 , which are more hydrophilic than the analogues in series 3 and 4 , were the most potent cluster of cytotoxins, and, in particular, 3,5‐bis‐(2‐nitrobenzylidene)‐1‐phosphono‐4‐piperidone 5 g had an average IC₅₀ value of 34 nM toward the two T‐lymphocyte cell lines. Four of the compounds displayed potent cytotoxicity toward a panel of nearly 60 human tumor cell lines, and nanomolar IC₅₀ values were observed in a number of cases. The mode of action of 5 g includes the induction of apoptosis and inhibition of cellular respiration. Most of the members of series 4 as well as several analogues in series 5 are potent multi‐drug resistance (MDR) reverting compounds. Various correlations were noted between certain molecular features of series 4 and 5 and cytotoxic properties, affording some guidelines in expanding this study.     

Silica‐Supported Zirconium Complexes and their Polyoligosilsesquioxane Analogues in the Transesterification of Acrylates: Part 2. Activity,Recycling and Regeneration

The catalytic activity of both supported and soluble molecular zirconium complexes was studied in the transesterification reaction of ethyl acrylate by butanol. Two series of catalysts were employed: three well defined silica‐supported acetylacetonate and n‐butoxy zirconium(IV) complexes linked to the surface by one or three siloxane bonds, (SiO)Zr(acac)₃ ( 1 ) (SiO)₃Zr(acac) ( 2 ) and (SiO)₃Zr(O‐n‐Bu) ( 3 ), and their soluble polyoligosilsesquioxy analogues (c‐C₅H₉)₇Si₈O₁₂(CH₃)₂Zr(acac)₃ ( 1′ ), (c‐C₅H₉)₇Si₇O₁₂Zr(acac) ( 2′ ), and (c‐C₅H₉)₇Si₇O₁₂Zr(O‐n‐Bu) (3′ ). The reactivity of these complexes were compared to relevant molecular catalysts [zirconium tetraacetylacetonate, Zr(acac)₄ and zirconium tetra‐n‐butoxide, Zr(O‐n‐Bu)₄]. Strong activity relationships between the silica‐supported complexes and their polyoligosilsesquioxane analogues were established. Acetylacetonate complexes were found to be far superior to alkoxide complexes. The monopodal complexes 1 and 1′ were found to be the most active in their respective series. Studies on the recycling of the heterogeneous catalysts showed significant degradation of activity for the acetylacetonate complexes ( 1 and 2 ) but not for the less active tripodal alkoxide catalyst, 3 . Two factors are thought to contribute to the deactivation of catalyst: the lixivation of zirconium by cleavage of surface siloxide bonds and exchange reactions between acetylacetonate ligands and alcohols in the substrate/product solution. It was shown that the addition of acetylacetone to the low activity catalyst Zr(O‐n‐Bu)₄ produced a system that was as active as Zr(acac)₄. The applicability of ligand addition to heterogeneous systems was then studied. The addition of acetylacetone to the low activity solid catalyst 3 produced a highly active catalyst and the addition of a stoichiometric quantity of acetylacetone at each successive batch catalytic run greatly reduced catalyst deactivation for the highly active catalyst 1 .     

Incorporation of manganese complexes into xylanase: new artificial metalloenzymes for enantioselective epoxidation

Here we report the best artificial metalloenzyme to date for the selective oxidation of aromatic alkenes; it was obtained by noncovalent insertion of Mn^III‐meso‐tetrakis(p‐carboxyphenyl)porphyrin [Mn(TpCPP), 1 ‐Mn] into a host protein, xylanase 10A from Streptomyces lividans (Xln10A). Two metallic complexes—N,N′‐ethylene bis(2‐hydroxybenzylimine)‐5,5′‐dicarboxylic acid Mn^III [(Mn‐salen), 2 ‐Mn] and 1 ‐Mn—were associated with Xln10A, and the two hybrid biocatalysts were characterised by UV–visible spectroscopy, circular dichroism and molecular modelling. Only the artificial metalloenzyme based on 1 ‐Mn and Xln10A was studied for its catalytic properties in the oxidation of various substituted styrene derivatives by KHSO₅: after optimisation, the 1 ‐Mn ‐ Xln10A artificial metalloenzyme was able to catalyse the oxidation of para‐methoxystyrene by KHSO₅ with a 16 % yield and the best enantioselectivity (80 % in favour of the R isomer) ever reported for an artificial metalloenzyme.     

Synthesis,Characterization, and Antimicrobial Activity of Silver(I) and Copper(II) Complexes of Phosphate Derivatives of Pyridine And Benzimidazole

Two silver(I) complexes—{[Ag(4‐pmOpe)]NO₃}_n and [Ag(2‐bimOpe)₂]NO₃—and three copper(II) complexes—[Cu₄Cl₆O(2‐bimOpe)₄], [CuCl₂(4‐pmOpe)₂], and [CuCl₂(2‐bis(pm)Ope]—were synthesized by reaction of silver(I) nitrate or copper(II) chloride with phosphate derivatives of pyridine and benzimidazole, namely diethyl (pyridin‐4‐ylmethyl)phosphate (4‐pmOpe), 1H‐benzimidazol‐2‐ylmethyl diethyl phosphate (2‐bimOpe), and ethyl bis(pyridin‐2‐ylmethyl)phosphate (2‐bis(pm)Ope). These compounds were characterized by ¹H, ¹³C, and ³¹P NMR as well as IR spectroscopy, elemental analysis, and ESIMS spectrometry. Additionally, molecular and crystal structures of {[Ag(4‐pmOpe)]NO₃}_n and [Cu₄Cl₆O(2‐bimOpe)₄] were determined by single‐crystal X‐ray diffraction analysis. The antimicrobial profiles of synthesized complexes and free ligands against test organisms from the ATCC and clinical sources were determined. Silver(I) complexes showed good antimicrobial activities against Candida albicans strains (MIC values of ～19 μM ). [Ag(2‐bimOpe)₂]NO₃ was particularly active against Pseudomonas aeruginosa and methicillin‐resistant Staphylococcus epidermidis, with MIC values of ～5 and ～10 μM , respectively. Neither copper(II) complexes nor the free ligands inhibited the growth of test organisms at concentrations below 500 μg mL^?1.     

Synthesis of pentavalent imidovanadium complexes and their catalyses for the polymerization of ethylene and propylene

Imidovanadium complexes with cyclopentadienyl (Cp) ligands—(Cp)V(?NC₆H₄Me‐4)Cl₂ (1), (Cp)V(?N^tBu)Cl₂ (2), and (^tBuCp)V(?N^tBu)Cl₂ (3; ^tBuCp = tert‐butylcyclopentadienyl)—were synthesized through the reaction of imidovanadium trichloride with (trimethylsilyl)cyclopentadiene derivatives. The molecular structure of 3 was determined by X‐ray crystallography. The monocyclopentadienyl complex 1 exhibited moderate activity in combination with methylaluminoxane [MAO; 10.3 kg of polyethylene (mol of V)^?1 h^?1 atm^?1], whereas similar complexes with bulky ^tBu groups, 2 and 3, were less active. (2‐Methyl‐8‐quinolinolato)imidovanadium complexes, V(?NR)(O ?N)Cl₂ (R = C₆H₃ⁱPr₂‐2,6 (4) or n‐hexyl (5), O ?N = 2‐methyl‐8‐quinolinolato), were obtained from the reaction of imidovanadium trichloride with 2‐methyl‐8‐quinolinol. Upon activation with modified MAO, complex 4 showed moderate activities for the polymerization of ethylene at room temperature. The complex 5/MAO system also exhibited moderate activity at 0°C. The polyethylenes obtained by these complexes had considerably high melting points, which indicated the formation of linear polyethylene. Moreover, the 5/dried MAO system showed propylene polymerization activities and produced polymers with considerably high molecular weights and narrow molecular weight distributions. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 1008–1015, 2005     

Synthesis and characterization of sulfonated polyimides containing aliphatic linkages in the main chain

A series of six‐membered sulfonated polyimides with aliphatic linkages (SPIAs) was successfully synthesized using 1,4,5,8‐naphthalenetetracarboxylic dianhydride (NTDA), 4,4′‐diaminobiphenyl 2,2′‐disulfonic acid (BDSA) as the sulfonated diamine, and aliphatic diamines H₂N(CH₂)_nNH₂ where n = 6, 8, 10, 12. These SPIAs were evaluated for thermal stability, ion exchange capacity (IEC), water uptake, proton conductivity, and hydrolytic stability. Proton conductivity and hydrolytic stability of the SPIAs were compared with the fully aromatic polyimide (MDA‐SPI) prepared from 4,4′‐methylenedianiline (MDA), BDSA, and NTDA. All the SPIAs exhibited high thermal stability. As the chain length of the aliphatic diamine decreased, the IEC and water uptake of the SPIAs increased. The SPIAs showed higher proton conductivity than commercially available membranes such as Nafion 117 at high temperatures and higher proton conductivity than MDA‐SPI at all temperatures. All SPIAs exhibited a hydrolytic stability more than twice as high as that of MDA‐SPI. Copyright © 2006 Society of Chemical Industry     

Synthesis of N-Aryl- and N-alkyl-Substituted Imidazolium Silver Complexes: Cytotoxic Screening by Using Human Cell Lines Modelling Acute Myeloid Leukaemia

A series of N-aryl- and N-alkyl substituted imidazoles has been synthesised and complexed with Ag⁺ to obtain silver-NHC complexes of the form [Ag(NHC)₂]X. These silver-NHC complexes were tested in vitro against the human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). A substantial difference in cytotoxicity was revealed varying in the range 13–4 μM and 22–9 μM for HL-60 and MOLM-13, respectively. Furthermore, this study revealed that when an alkyl group is installed on the imidazole scaffold, its position substantially influences the cytotoxicity of the corresponding silver NHC complex.     

Salicylidene‐imine–zirconium(IV) complexes in combination with methylalumoxane as catalysts for the conversion of hexa‐1,5‐diene: adjusting of the catalytic activity

A variety of substituted schiff base complexes of the composition (“salen”)ZrCl₂(thf) ( 1 – 21 ) were synthesized, with methylalumoxane (“MAO”) activated and used for a systematic study of their catalytic activity towards hexa‐1,5‐diene (“salen”: substituted salicylidene–ethylene‐iminato ligands). Main product of the catalytic cycle is methylenecyclopentane. Dimers are only formed in minor amounts. The catalytic activity and selectivity of the Ziegler–Natta systems strongly depend on the nature and the position of the peripheric substituents in the Schiff base ligands. Electron‐withdrawing substituents in para‐position to the phenolato oxygen (5‐position) decrease the catalytic activity. Improved activity and selectivity were obtained with electron‐donating substituents in 5‐position. Altering the ethylene bridge causes a lowering of the activity or inactivation. According to the x‐ray analysis the metal center in the related complex (L)ZrCl₂ ( 22 ) (L: N′,N′‐bis(ethylene)‐N′‐methyl‐N,N′′‐bis(benzoylacetonato‐imine) has a pentagonal‐bipyramidal environment. The pentadentate schiff base ligand lies in the plane, and both chloro groups occupy the axial positions. In contrast to the catalytically active salene complexes 22 can not rearrange to form a species in which the both chlorides are cis to each other. Consequently 22 is catalytically inactive.     

Silica‐Supported Zirconium Complexes and their Polyoligosilsesquioxane Analogues in the Transesterification of Acrylates: Part 1. Synthesis and Characterization

Various silica‐supported acetylacetonate and alkoxy zirconium(IV) complexes have been prepared and characterized by quantitative chemical measurements of the surface reaction products, quantitative surface microanalysis of the surface complexes, in situ infrared spectroscopy, CP‐MAS ¹³C NMR spectroscopy and EXAFS. The complex (SiO)Zr(acac)₃ (acac=acetylacetonate ligand) ( 1 ) can be obtained by reaction of zirconium tetraacetylacetonate [Zr(acac)₄] with a silica surface previously dehydroxylated at 500 °C. The complexes (SiO)₃Zr(acac) ( 2 ) and (SiO)₃Zr(O‐n‐Bu) (n‐Bu=butyl ligand) ( 3 ) can be synthesized by reaction of (SiO)₃Zr H with, respectively, acetylacetone and n‐butanol at room temperature. The spectroscopic data, including EXAFS spectroscopy, confirm that in compound 1 the zirconium is linked to the surface by only one Si O Zr bond whereas in the case of compounds 2 and 3 the zirconium is linked to 3 surface oxygen atoms which are sigma bonded. EXAFS data indicate also that the acetylacetonate ligands behave as chelating ligands leading to a hepta‐coordination around the zirconium atom in 1 and a penta‐coordination in 2 . In order to provide a molecular analogue of 1 , the synthesis of the following polyoligosilsesquioxane derivative (c‐C₅H₉)₇Si₈O₁₂(CH₃)₂Zr(acac)₃ ( 1′ ) was achieved. The compound 1′ is obtained by reacting (c‐C₅H₉)₇Si₈O₁₁(CH₃)₂(OH), 4 , with an equimolecular amount of Zr(acac)₄. In the same manner, syntheses of complexes (c‐C₅H₉)₇Si₇O₁₂Zr(acac) ( 2′ ) and of (c‐C₅H₉)₇Si₇O₁₂Zr(O‐n‐Bu) ( 3′ ) were achieved by reaction of the unmodified trisilanol, (c‐C₅H₉)₇Si₇O₉(OH)₃, with respectively Zr(acac)₄ and Zr(O‐n‐Bu)₄ at 60 °C in tetrahydrofuran. Compounds 1′ , 2′ and 3′ can be considered as good models of 1 , 2 and 3 since their spectroscopic properties are comparable with those of the surface complexes. The synthetic results obtained will permit us to study the catalytic properties of these surface complexes and of their molecular analogues with the ultimate goal of delineating clear structure‐activity relationships.     

Solid‐Liquid Extraction of Lanthanum(III), Europium(III), and Lutetium(III) by Acyl‐Hydroxypyrazoles Entrapped in Mesostructured Silica

Abstract

The solid‐liquid extraction of lanthanum(III), europium(III), and lutetium(III) by mesostructured silicas doped with 1‐phenyl‐3‐methyl‐4‐stearoyl‐5‐pyrazolone (HPMSP, bearing one chelating site) or with 1,12‐bis(1′‐phenyl‐3′‐methyl‐5′‐hydroxy‐4′‐pyrazolyl)‐dodecane‐1,12‐dione (HL‐10‐LH, bearing two chelating sites) has been studied and compared to the analogous solvent and micellar extractions in terms of the stoichiometry of the extracted complex and of the extraction efficiency. The solid‐liquid extraction order in the lanthanoid series is La<Eu<Lu; it is the usual liquid‐liquid extraction order obtained with acidic extractants. A theoretical model is used to determine the stoichiometries of the extracted complexes and the extraction yield is measured as a function of the pH, of the extractant/metal ratio (S/M) and of the volume ratio of the two phases (φ). For HPMSP, the extracted complexes involve three ligand molecules for one metal. For HL‐10‐LH, the complex stoichiometries are found to be either Ln(L‐10‐L)(L‐10‐LH) (Ln=La, Eu) or Lu₂(L‐10‐L)₃ for S/M=25, or Eu₂(L‐10‐L)₃ for S/M=5. For the first time, the synergistic solid‐liquid extraction is studied after a successful attempt at simultaneously immobilizing both extractants HL‐10‐LH and 2,4,6‐tri(2‐pyridyl)‐1,3,5‐triazine, “TPTZ”, into silica; the complex extracted in this case differs from the one obtained in solvent extraction.     

Metallkomplexe mit biologisch wichtigen Liganden. CXXIII. Darstellung von Isophthaloyl‐ und Terephthaloyl‐di‐[(β,γ,δ)‐amino‐α‐aminocarboxylat]‐verbrückten zweikernigen Ruthenium‐, Rhodium‐ und Iridium‐Halbsandwich‐Komplexen

The reaction of the Cu(II) bis N,O‐chelate‐complexes of L‐2,4‐diaminobutyric acid, L‐ornithine and L‐lysine {Cu[H₂N–CH(COO)(CH₂)_nNH₃]₂}²⁺(Cl^–)₂ (n = 2–4) with terephthaloyl dichloride or isophthaloyl dichloride gives the polymeric complexes {‐OC–C₆H₄–CO–NH–(CH₂)_n–CH(nh₂)(COO)Cu(OOC)(NH₂)CH–CH₂)_n–NH‐}_x 1 – 5 . From these the metal can be removed by precipitation of Cu(II) with H₂S. The liberated ω,ω′‐N,N′‐diterephthaloyl (or iso‐phthaloyl)‐diaminoacids 6 – 10 react with [Ru(cymene)Cl₂]₂, [Ru(C₆Me₆)Cl₂]₂, [Cp*RhCl₂]₂ or [Cp*IrCl₂]₂ to the ligand bridged bis‐amino acidate complexes [L_n(Cl)M–(OOC)(NH₂)CH–(CH₂)_nNH–CO]₂–C₆H₄ 11 – 14 .     

Introducing primary and tertiary amino groups into a neutral polymer: A simple way to fabricating highly efficient nonviral vectors for gene delivery

In this work, a brushed polycationic polymer with primary and tertiary amino groups was designed and synthesized for gene delivery. The backbone polymer was poly(N‐hydroxyethylacrylamide) (PHEAA) by the atom transfer radical polymerization (ATRP), and then 3,3′‐diaminodipropylamine (DPA) was grafted onto the PHEAA by the reaction between hydroxyl and the secondary amine. A brushed PHEAA‐DPA cationic polymer was achieved with primary and tertiary amino groups and the ratio was 2 : 1. The PHEAA₁₀₀‐DPA and PHEAA₂₀₀‐DPA could effectively condense plasmid DNA (pDNA) at the weight ratio of vector/DNA of 0.6 and 0.4, respectively. The cytotoxicity of PHEAA‐DPA/pDNA to COS‐7 cells and HepG‐2 cells within the weight ratio of vector/DNA of 16 : 1 was lower than that of PEI25k, and cell viability decreased with the increment of the weight ratio. Although the cytotoxicity of PHEAA₁₀₀‐DPA/pDNA was lower than PHEAA₂₀₀‐DPA/pDNA, the latter possessed higher transfection efficiency at the same weight ratio both in COS‐7 cells and HepG‐2 cells, compared with PEI25k, the transfection efficiency of PHEAA₂₀₀‐DPA/pDNA was better in COS‐7 cells and HepG‐2 cells with the weight ratio of 12 : 1 and 10 : 1, respectively. These results showed that the PHEAA‐DPA with less cytotoxicity and higher gene transfection efficiency has a broad perspective in gene therapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40468.     

Research on the preparation and characterization of chitosan grafted polyvinylpyrrolidone gel membrane with iodine

The chitosan grafted polyvinylpyrrolidone gel membrane with iodine (CS‐PVP‐I₂‐G‐M) was prepared by chitosan–polyvinylpyrrolidone–iodine complex liquid (CS‐PVP‐I₂‐L) mixed with gelatin. The intermediate product CS‐PVP‐I₂‐L was prepared by CS grafted PVP in the protection of N₂ with dimethyl 2,2′‐azobis (2‐methylpropionate) (AIBME) as initiator, then a certain amounts of iodine in ethanol solution was added. The properties of CS‐PVP‐I₂‐G‐M were characterized by IR, UV–Vis, SEM, XRD, DSC, and so forth. The iodine release results coherent with the release kinetic model—Fick diffusion laws, has a burst effect first, and then spread, and the emission of iodine was maintained within a certain range and kept at a stable level permanently, showed a sustained‐release effect of iodine. The inhibition zone diameters of CS‐PVP‐I₂‐G‐M against Staphylococcus aureus and Escherichia coli were both greater than 16 mm, it demonstrated significant antibacterial activity. Double effects sustained‐release effect of iodine and the significant antibacterial activity made CS‐PVP‐I₂‐G‐M highly potential for applications as a novel natural biomedical sterilization materials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41797.     

Cytotoxic action of carboxyborane heterocyclic amine adducts

The heterocyclic carboxyborane amines were found to be potent cytotoxic agents in the murine L1210 lymphoid leukemia and human HeLa suspended carcinoma cells. These agents were observed to inhibit HeLa DNA topoisomerase II activity ~ 200 muM and L1210 topoisomerase II activity >/= 100 muM. These agents did not cause DNA protein linked breaks themselves, but upon incubation for 14-24 hr did enhance the ability of VP-16 to cause cleavable complexes. The heterocyclic amineboranes inhibited DNA synthesis and caused DNA strand scission. They were additive with VP-16 in affording these results as well as inhibiting colony growth of L1210 cells after co-incubation for 1 hr. The agents inhibited in vitro PKC phosphorylation of both L1210 lymphoid leukemia and human topoisomerase II enzyme.     

Synthesis and in vitro Anticancer Activity of Octahedral Platinum(IV) Complexes with Cyclohexyl‐Functionalized Ethylenediamine‐N,N′‐Diacetate‐Type Ligands

The present study describes the synthesis and anticancer activity of novel octahedral Pt^IV complexes with cyclohexyl functionalized ethylenediamine‐N,N′‐diacetate‐type ligands. Molecular mechanics calculations and density functional theory analysis revealed that s‐cis is the preferred geometry of these Pt^IV complexes with tetradentate‐coordinated (S,S)‐ethylenediamine‐N,N′‐di‐2‐(3‐cyclohexyl)propanoate. The viability of cancer cell lines (U251 human glioma, C6 rat glioma, L929 mouse fibrosarcoma, and B16 human melanoma) was assessed by measuring mitochondrial dehydrogenase activity and lactate dehydrogenase release. Cell‐cycle distribution, oxidative stress, caspase activation, and induction of autophagy were analyzed by flow cytometry using appropriate fluorescent reporter dyes. The cytotoxic activity of novel Pt^IV complexes against various cancer cell lines (IC₅₀ range: 1.9–8.7 μM ) was higher than that of cisplatin (IC₅₀ range: 10.9–67.0 μM ) and proceeded through completely different mechanisms. Cisplatin induced caspase‐dependent apoptosis associated with the cytoprotective autophagic response. In contrast, the new Pt^IV complexes caused rapid, caspase‐independent, oxidative stress‐mediated non‐apoptotic cell death characterized by massive cytoplasmic vacuolization, cell membrane damage, and the absence of protective autophagy.     

Polypyridyl CoII-Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents

Four new Co^II complexes, [Co(bpy)₂(acac)]Cl ( 1 ), [Co(phen)₂(acac)]Cl ( 2 ), [Co(bpy)₂(cur)]Cl ( 3 ), [Co(phen)₂(cur)]Cl ( 4 ), where bpy=2,2’-bipyridine ( 1 and 3 ), phen=1,10-phenanthroline ( 2 and 4 ), acac = acetylacetonate ( 1 and 2 ), cur=curcumin monoanion ( 3 and 4 ) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN₄O₂ core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λ_em≈565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes ( 1 and 2 ) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the Co^II-based anticancer and antibacterial drug development.