Iron(III) Complexes of a Pyridoxal Schiff Base for Enhanced Cellular Uptake with Selectivity and Remarkable Photocytotoxicity

Iron(III) complexes of pyridoxal (vitamin B6, VB6) or salicylaldehyde Schiff bases and modified dipicolylamines, namely, Fe(B)(L)](NO3) (15), where B is phenyl-N,N-bis((pyridin-2-yl)methyl)methanamine (phbpa in 1), (anthracen-9-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (anbpa in 2, 4) and (pyren-1-yl)-N,N-bis((pyridin-2-yl)methyl)methanamine (pybpa in 3, 5) (H2L1 is 3-hydroxy-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylp yridine (13) and H2L2 is 2-(2-hydroxyphenyl-imino)methyl]phenol), were prepared and their uptake in cancer cells and photocytotoxicity were studied. Complexes 4 and 5, having a non-pyridoxal Schiff base, were prepared to probe the role of the pyridoxal group in tumor targeting and cellular uptake. The PF6 salt (1a) of complex 1 is structurally characterized. The complexes have a distorted six-coordinate FeN4O2 core where the metal is in the +3 oxidation state with five unpaired electrons. The complexes display a ligand to metal charge transfer band near 520 and 420 nm from phenolate to the iron(III) center. The photophysical properties of the complexes are explained from the time dependent density functional theory calculations. The redox active complexes show a quasi-reversible Fe(III)/Fe(II) response near -0.3 V vs saturated calomel electrode. Complexes 2 and 3 exhibit remarkable photocytotoxicity in various cancer cells with IC50 values ranging from 0.4 to 5 mu M with 10-fold lower dark toxicity. The cell death proceeded by the apoptotic pathway due to generation of reactive oxygen species upon light exposure. The nonvitamin complexes 4 and 5 display 3-fold lower photocytotoxicity compared to their VB6 analogues, possibly due to preferential and faster uptake of the vitamin complexes in the cancer cells. Complexes 2 and 3 show significant uptake in the endoplasmic reticulum, while complexes 4 and 5 are distributed throughout the cells without any specific localization pattern.

NMR relaxation studies in doped poly-3-methylthiophene

NMR relaxation rates (1/T-1), magnetic susceptibility, and electrical conductivity studies in doped poly-3-methylthiophene are reported in this paper. The magnetic susceptibility data show the contributions from both Pauli and Curie spins, with the size of the Pauli term depending strongly on the doping level. Proton and fluorine NMR relaxation rates have been studied as a function of temperature (3-300 K) and field (for protons at 0.9, 9.0, 16.4, and 23.4 T, and for fluorine at 9.0 T). The temperature dependence of T-1 is classified into three regimes: (a) For T < (g mu(B) B/2k(B)), the relaxation mechanism follows a modified Korringa relation due to electron-electron interactions and disorder. H-1-T-1 is due to the electron-nuclear dipolar interaction in addition to the contact term. (b) For the intermediate temperature range (g mu(B) B/2k(B)) < T < T-BPP (the temperature where the contribution from the reorientation motion to the T-1 is insignificant) the relaxation mechanism is via spin diffusion to the paramagnetic centers. (c) In the high-temperature regime and at low Larmor frequency the relaxation follows the modified Bloembergen, Purcell, and Pound model. T-1 data analysis has been carried out in light of these models depending upon the temperature and frequency range of study. Fluorine relaxation data have been analyzed and attributed to the PF6 reorientation. The cross relaxation among the H-1 and F-19 nuclei has been observed in the entire temperature range suggesting the role of magnetic dipolar interaction modulated by the reorientation of the symmetric molecular subgroups. The data analysis shows that the enhancement in the Korringa ratio is greater in a less conducting sample. Intra-and interchain hopping of charge carriers is found to be a dominant relaxation mechanism at low temperature. Frequency dependence of T-1(-1) on temperature shows that at low temperature T < (g mu(B) B/2k(B))] the system shows three dimensions and changes to quasi one dimension at high temperature. Moreover, a good correlation between electrical conductivity, magnetic susceptibility, and NMR T-1 data has been observed.

Mononuclear five-coordinate cobalt(II) complexes with N-4-coordinate pyrazole based ligand and pseudohalogens: synthesis, structures, DNA and protein binding study

A series of mononuclear five-coordinate cobalt(II) complexes, Co(dbdmp)(X)]Y, where dbdmp=N,N-diethyl-N,N-bis((3,5-dimethyl-1H-pyrazol-1-yl)methyl)ethane-1, 2-diamine, X=N-3(-)/NCO-/NCS- and Y=PF6-/BF4-/ClO4-, have been synthesized and characterized by microanalyses and spectroscopic techniques. Crystal structures of Co(N-3)(dbdmp)]PF6 (1), Co(N-3)(dbdmp)]ClO4 (3), Co(NCO)(dbdmp)]PF6 (4), Co(NCO)(dbdmp)]ClO4 (6), and Co(NCS)(dbdmp)]ClO4 (9) have been solved by single-crystal X-ray diffraction studies and showed that all the complexes have distorted trigonal bipyramidal geometry; PF6- counter anion containing complexes Co(N-3)(dbdmp)]PF6 and Co(NCO)(dbdmp)]PF6 have chiral space groups. The binding ability of synthesized complexes with CT-DNA and bovine serum albumin (BSA) has been studied by spectroscopic methods and viscosity measurements. The experimental results of absorption titration of cobalt(II) complexes with CT-DNA indicate that the complexes have ability to form adducts and they can stabilize the DNA helix. The cobalt(II) complexes exhibit good binding propensity to BSA protein.

Visible light-induced cytotoxicity of a dinuclear iron(III) complex of curcumin with low-micromolar IC50 value in cancer cells

Photoactive metal complexes have emerged as potential candidates in the photodynamic therapy (PDT) of cancer. We present here the synthesis, characterization and visible light-triggered anticancer activity of two novel mixed-ligand oxo-bridged iron(III) complexes, viz., {Fe(L)(acac)}(2)(mu-O)](ClO4)(2) (1) and {Fe (L)(cur)}(2)(mu-O)](ClO4)(2) (2) where L is bis-(2-pyridylmethyl)-benzylamine, acac is acetylacetonate and cur is the monoanion of curcumin (bis(4-hydroxy-3-methoxyphenyl)-1,6-diene-3,5-dione). The crystal structure of complex 1 (as PF6 salt, 1a) shows distorted octahedral geometry of each iron(III) centre formed by the FeN3O3 core. The 1: 2 electrolytic complexes are stable in solution and retain their oxo-bridged identity in aqueous medium. Complex 2 has a strong absorption band in the visible region and shows promising photocytotoxicity in HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 3.1 +/- 0.4 lM and 4.9 +/- 0.5 lM while remains non-toxic in the dark (IC50 > 50 lM). The control complex 1 is inactive both in the light and dark. Complex 2 accumulates in cytoplasm of HeLa and MCF-7 cells as evidenced from fluorescence microscopy and triggers apoptotic cell death via light-assisted generation of reactive oxygen species (ROS). Taken together, complex 2 with its promising photocytotoxicity but negligible dark toxicity in cancer cells has significant photochemotherapeutic potential for applications in PDT. (C) 2015 Elsevier B.V. All rights reserved.

Relação entre a doença de Parkinson e o gene LRRK2: um estudo na população brasileira

A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais frequente depois da Doença de Alzheimer, afetando aproximadamente 1% da população com idade superior a 65 anos. Clinicamente, esta doença caracteriza-se pela presença de tremor em repouso, bradicinesia, rigidez muscular e instabilidade postural, os quais podem ser controlados com a administração do levodopa. As características patológicas da DP incluem a despigmentação da substância nigra devido à perda dos neurônios dopaminérgicos e a presença de inclusões proteicas denominadas corpos de Lewy nos neurônios sobreviventes. As vias moleculares envolvidas com esta patologia ainda são obscuras, porém a DP é uma doença complexa, resultante da interação entre fatores ambientais e causas genéticas. Mutações no gene leucine-rich repeat kinase 2 (LRRK2; OMIM 609007) constituem a forma mais comum de DP. Este gene codifica uma proteína, membro da família de proteínas ROCO, que possui, entre outros domínios, dois domínios funcionais GTPase (ROC) e quinase (MAPKKK). Neste estudo, os principais domínios do gene LRRK2 foram analisados em 204 pacientes brasileiros com DP por meio de sequenciamento dos produtos da PCR. Através da análise de 14 exons correspondentes aos domínios ROC, COR e MAPKKK foram identificadas 31 variantes. As alterações novas, p.C1770R e p.C2139S, possuem um potencial papel na etiologia da DP. Três alterações exônicas (p.R1398R, p.T1410M e p.Y2189C) e nove intrônicas (c.4317+16C>T, c.5317+59A>C, c.5509+20A>C, c.5509+52T>C, c.5509+122A>G, c.5657-46C>T, c.6382-36G>A, c.6382-37C>T e c.6576+44T>C) são potencialmente não patogênicas. Ao todo, dezessete variantes exônicas e intrônicas constituem polimorfismos já relatados na literatura (p.R1398H, p.K1423K, p.R1514Q, p.P1542S, c.4828-31T>C, p.G1624G, p.K1637K, p.M1646T, p.S1647T, c.5015+32A>G, c.5170+23T>A, c.5317+32C>T, p.G1819G, c.5948+48C>T, p.N2081D, p.E2108E e c.6381+30A>G). A frequência total de alterações potencialmente patogênicas ou patogênicas detectadas em nossa amostra foi de 3,4% (incluindo a mutação p.G2019S, anteriormente descrita em 2 artigos publicados por nosso grupo: Pimentel et al., 2008; Abdalla-Carvalho et al., 2010), sendo a frequência de mutações nos casos familiares (11,1%) cerca de seis vezes maior do que a encontrada nos casos isolados da DP (1,8%). Os resultados alcançados neste estudo revelam que mutações no gene LRRK2 desempenham um papel significativo como fator genético para o desenvolvimento da DP em pacientes brasileiros.

有机磷（膦）酸双溶剂体系及离子液基体系对稀土萃取的研究

本文系统研究了由酸性磷（膦）类萃取剂所构成的双溶剂萃取体系对稀土的协同萃取效应；考察了添加剂对磷（膦）类萃取体系的分离能力，反萃性能，界面性质及动力学机理的影响；运用绿色溶剂---室温离子液体替代挥发性有机溶剂为稀释剂，研究了磷（膦）类萃取剂在离子液体中萃取稀土的性能，具体的研究内容如下： 1． 考察了HDEHP， HHEOIPP， Cyanex272， Cyanex302，Cyanex301分别与HEHEHP构成混合萃取体系在盐酸介质中对RE3+的萃取和分离性能，推导了协萃反应方程式，计算了相邻稀土元素间的分离系数，讨论了各混合体系对部分稀土相互分离的可能性，并从萃取剂结构方面对不同萃取体系萃取能力的差别给出了解释。 2． 用层流恒界面池法研究了添加剂isooctanol对HEHEHP萃取体系萃取Yb3+的传质动力学的影响，综合搅拌速率判别法，界面判别法，温度判别法，得出了萃取过程为伴随有界面化学反应的扩散传质。考察了水相酸度、有机相浓度等因素对反应速率的影响，提出了萃取速率方程及动力学传质机理，计算了扩散层厚度及扩散速率常数，建立了传质模型。 3． 考察了甲庚醇浓度、温度、离子强度等因素对HEHEHP-isooctanol体系界面活性的影响，并定性探讨了极性添加剂isooctanol对HEHEHP-Yb3+-HCl体系萃取动力学的影响。 4． 选择室温离子液体[C8mim][PF6] 作为溶剂，系统研究了磷(膦)类萃取剂HEHEHP对稀土的萃取能力，计算了HEHEHP- IL体系的分离系数，推测了萃取体系的反应机理，并与相同萃取条件下庚烷体系中HEHEHP对稀土的萃取性能进行了比较。

离子液体在铈（IV）钍及稀土（III）萃取分离中的应用研究

本文对1-辛基-3-甲基咪唑六氟磷酸盐离子液体（[C8mim]PF6）在包头稀土矿分离钍以及攀西矿分离铈工艺中的应用作了初步探索。论文首先研究了伯胺N1923溶于离子液体对硫酸体系钍的萃取分离行为，考察了酸度、盐析剂浓度、萃取剂浓度等对N1923/IL萃取钍的影响，并与庚烷体系的萃取规律作了对比。在此基础上对萃取机理进行了探讨，提出了不同于分子溶剂体系的萃取机理，认为N1923/IL在水相有硫酸钠作为盐析剂时对钍的萃取为“胶束增溶”萃取机理。此外，钍对稀土的分离考察结果认为，虽然N1923/IL对钍的萃取效率降低，但在一定条件下钍对稀土仍能保持较高的分离系数。由此本文对N1923/IL应用于钍的分离实践作了初步评估。 论文的另外一部分工作研究了纯[C8mim]PF6及其与2-乙基己基膦酸二（2-乙基己基）酯（DEHEHP）的混合体系对硝酸铈（IV）的萃取性能。研究发现纯[C8mim]PF6本身对硝酸铈（IV）有良好的萃取选择性，机理考察结果认为铈（IV）的萃取是由于Ce4+离子在富硝酸根溶液中形成络阴离子Ce(NO3)62-并与离子液体的阴离子PF6—发生交换的结果。一种新型含铈离子液体[C8mim]2Ce(NO3)6的合成进一步证实了这一机理。反萃考察发现被萃入离子液相的铈（IV）用水可完全反萃，且萃取和反萃过程中因离子交换机理导致的离子液体流失可以通过添加适量离子液体组分的方法予以抑制。此外，本文考察了DEHEHP溶于[C8mim]PF6对于含氟硝酸体系铈（IV）的萃取行为，发现在一定条件下DEHEHP对铈（IV）的萃取能获得与分子溶剂中等同的萃取机理。在此基础上，采用DEHEHP/IL从氟碳铈矿分解液中进行分离铈和氟的研究，获得纯度为99.9%以上的纳米CeF3产品。由此我们提出一个将离子液体应用于攀西氟碳铈矿铈钍稀土分离流程的模型，为离子液体在稀土清洁分离流程中实现溶剂绿色化的目标提供了一个范例。

仿生膜的电化学研究

仿生膜电化学是一门新兴的、也是当前很活跃的电化学和电分析化学的前沿领域。本文简要评述了生物膜领域的发展过程及研究现状，介绍了关于生物膜的一些基本性质和理论。概要总结了作为生物膜的研究模型一仿生膜在各个领域的研究情况及现状，展望了仿生膜在诸多领域应用的前景。采用电化学方法对支撑双层磷脂膜（s一BLM）和液／液界面等不同的模拟生物膜体系进行了研究，并结合AFM、XPS以及IR等谱学手段对蛋白质、核酸与生物膜之间的相互作用进行了初步探讨。主要结果如下：1．我们在玻碳电极表面成功地制备了嵌有DNA支撑双层磷脂膜，并用循环伏安法和阻抗谱图法证明了所形成的磷脂膜是双层。用循环伏安法、傅立叶红外和原子力显微镜表征了膜内DNA.此功能化膜表现出离子通道的行为，对其机理加以探讨，并且离子通道的形成通过电化学阻抗谱图证明。通道在激发物存在时形成打开，通道电流随激发物的增加而增强；反之，则通道关闭。此过程可反复多次。这种DNA修饰的电极可制成电化学传感器，利用离子通道原理，应用在基因检测和研究DNA与其它分子的反应等方面。2．我们提出了一种在云母上成膜的全新方法一直接将DMPC磷脂膜制备在新解理的云母片上。通过AFM和XP S证明了DMPC磷脂在云母上直接形成双层膜。用AFM观察了膜的形成与时间的关系，在成膜过程中，随着在KCI溶液中的浸泡时间的增长，逐渐由多层膜变成双层膜，整个成膜过程需20分钟，最后形成双层膜。探讨了成膜机理。此种成膜方法快速、简便、易行，且在空气中非常稳定。此种成膜方法为深入研究膜提供必要的前提和机会、为进一步研究生物材料提供了基础，有助于结构生物学的研究。 3．谷胺酸是基本的神经递质。用聚谷胺酸嵌入双层磷脂膜作为钙离子的接受器。研究了固定有功能基团的S一BLM的离子通道行为，探讨了离子通道形成的机理。在钙离子存在的情况下，离子通道打开，反之则离子通道处于关闭状态。此过程可反复多次。对钙离子的伏安响应快速，离子通道电流仅与钙离子的浓度有关，而与加入钙离子时间无关。 4．在玻碳电极表面上制备了由玻碳支持的磷脂膜，借助电化学阻抗分析技术，我们证明了在玻碳电极表面上的磷脂膜为双层磷脂膜。研究了六氟磷酸根阴离子(PF6-)与双层磷脂膜的相互作用及玻碳电极上的s一BLM的离子通道行为，s一BLM显示了较为敏感的通透性的变化，所产生的通道电流大小不仅与通道激发物浓度有关，而且也与时间有关。离子通道行为可用于测定PF6一。 5．我们用简单的方法制备了水一琼脂微电极，并且用此电极研究了简单离子和推动离子的转移过程。简单离子和推动离子在水一琼脂／1，2_二氯乙烷界面的转移过程的特点与其在水／1，2一二氯乙烷界面的转移过程的特点相似。进一步证明了，硅烷化对琼脂一水微电极几乎没有影响，此类琼脂一水微电极和固体微电极有着相似的特性，并且可作sECM的探头。6．用循环伏安法研究新型载体一端烯基液晶冠醚推动钠离子的转移，并且表明钠离子的转移是由扩散控制。探讨了影响钠离子转移的因素，诸如：端烯基液晶冠醚和钠离子浓度等。求算出端烯基液晶冠醚在1，2一二氯乙烷中的扩散系数是（2.61±0.12) * 10~(-6)CM~2s~(-1)，端烯基液晶冠醚和7.用循环伏安法对简单离子一四乙基钱阳离子（TEA~+）转移进行了研究。结果表明：TEA~+随微玻管内径减小（小于3μm），电流逐渐呈现拟稳态。随TEA~+浓度减小，i_p值也减小。峰电流与扫描速度的平方根成正比，并且符合Randles-Sevcik关系。同时讨论了微液／液界面TEA~+体系简单离子的转移机理。

An effective method for enhancing metal-ions' selectivity of ionic liquid-based extraction system: Adding water-soluble complexing agent

Selective extraction-separation of yttrium(Ill) from heavy lanthanides into 1-octyl-3-methylimidazolium hexafluorophosphate ([C(8)mim][PF6]) containing Cyanex 923 was achieved by adding a water-soluble complexing agent (EDTA) to aqueous phase. The simple and environmentally benign complexing method was proved to be an effective strategy for enhancing the selectivity of [C(n)mim] [PF6]/[Tf2N]-based extraction system without increasing the loss of [C(n)mim](+). (c) 2007 Elsevier B.V. All rights reserved.

The solid-liquid extraction of yttrium from rare earths by solvent (ionic liquid) impreganated resin coupled with complexing method

A kind of solvent (ionic liquid) impreganated resin (IL-SIR) was developed herein for ameliorating imidazolium-type IL-based liquid-liquid extraction of metal ions. In this study, [C(8)mim][PF6] containing Cyanex923 was immobilized on XAD-7 resin for solid-liquid extraction of rare earth (RE). The solid-liquid extraction contributed to ameliorating mass transfer efficiency, i.e. shortening equilibrium time from 40 min to 20 min, increasing extraction efficiency from 29% to 80%. In additional, the novel IL-SIR could separate Y(III) from Sc(III), Ho(III), Er(III), Yb(III) effectively by adding water-soluble complexing agent.

Ionic liquid-based "all-in-one" synthesis and photoluminescence properties of lanthanide fluorides

A facile route to the synthesis of LnF(3) nanocrystals has been accomplished in three ionic liquids (ILs) (OmimPF(6), OmimBF(4), and BmimPF(6)). The partial hydrolysis of PF6- and BF4- was utilized to introduce a new fluoride source. Uniform LnF(3) (Ln = La, Ce, Pr, Nd, Sm, Eu, Er), Tb3+-doped CeF3, and Eu3+-doped LaF3 nanocrystals could be obtained in a large scale, and the products were up to 0.15 g per 10 mL solvents. In the "all-in-one" systems, the ILs acted as solvents, reaction agents, and templates.

Direct Electrochemistry and Electrocatalysis of Hemoglobin in Lipid Film Incorporated with Room-Temperature Ionic Liquid

A facile phospholipid/room-temperature ionic liquid (RTIL) composite material based on dimyristoylphosphatidylcholine (DMPC) and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim]PF6) was exploited as a new matrix for immobilizing protein. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were adopted to characterize this composite film. Hemoglobin (Hb) was chosen as a model protein to investigate the composite system. UV-vis absorbance spectra showed that Hb still maintained its heme crevice integrity in this composite film.

Reversed micellar solubilization extraction and separation of thorium(IV) from rare earth(III) by primary amine N1923 in ionic liquid

The extraction behavior of thorium(IV) sulfate by primary amine N1923 in imidazolium-based ionic liquid (IL) namely 1-octyl-3-methylimidazolium hexafluorophosphate ([C(8)mim]PF6) was systematically studied in this paper. Results showed that the extraction behavior was quite different from that using conventional solvent as diluent. A reversed micellar solubilization extraction mechanism was proposed for the extraction of thorium(IV) by N1923/[C(8)mim]PF6 via slope analysis method and polarized optical microscopy (POM)/transmission electron microscopy (TEM) observation. The salt-out agent, Na2SO4, was demonstrated to prompt this extraction mechanism.

Ionic liquid-based "all-in-one" synthesis and photoluminescence properties of lanthanide fluorides

A facile route to the synthesis of LnF(3) nanocrystals has been accomplished in three ionic liquids (ILs) (OmimPF(6), OmimBF(4), and BmimPF(6)). The partial hydrolysis of PF6- and BF4- was utilized to introduce a new fluoride source. Uniform LnF(3) (Ln = La, Ce, Pr, Nd, Sm, Eu, Er), Tb3+-doped CeF3, and Eu3+-doped LaF3 nanocrystals could be obtained in a large scale, and the products were up to 0.15 g per 10 mL solvents. In the "all-in-one" systems, the ILs acted as solvents, reaction agents, and templates.

Synthesis of Tributylphosphate Capped Luminescent Rare Earth Phosphate Nanocrystals in an Ionic Liquid Microemulsion

Uniform rare earth phosphate (REPO4, RE = La-Tb) nanocrystals were successfully synthesized in a properly designed TBP/[Omim]Cl/H2O (tributylphosphate/1-octyl-3-methyl-imidazolium chloride/water) microemulsion system. The phosphoryl groups anchored the TBP molecules oil the surfaces of the nanocrystals, and this made the nanocrystals easily dispersed in some imidazolium-based ILs. LaPO4:Eu3+ and CePO4:Tb3+ nanocrystals capped with TBP showed bright red and green emission under UV excitation, with enhanced emission intensity and lifetimes compared with the uncapped ones.