Photo-Oxidizing Ruthenium(II) Complexes with Enhanced Visible-Light Absorption and G-quadruplex DNA Binding Abilities

Photosensitizers that gather high photo-oxidizing power and strong visible-light absorption are of great interest in the development of new photo-chemotherapeutics. Indeed, such compounds constitute attractive candidates for the design of type I photosensitizers that are not dependent on the presence of oxygen. In this paper, we report on the synthesis and studies of new ruthenium(II) complexes that display strong visible-light absorption and can oxidize guanine residues under visible-light irradiation, as evidenced by nanosecond transient absorption spectroscopy. The reported compounds also tightly bind to G-quadruplex DNA structures from the human telomeric sequence (TTAGGG repeat). The kinetic and thermodynamic parameters of the interaction of these Ru(II) complexes with G-quadruplex and duplex DNA were studied thanks to luminescence titrations and bio-layer interferometry measurements, which revealed higher affinities towards the non-canonical G-quadruplex architecture. Docking experiments and non-covalent ionic analysis allowed us to gain information on the mode and the strength of the interaction of the compounds towards G-quadruplex and duplex DNA. The different studies emphasize the substantial influence of the position and the number of non-chelating nitrogen atoms on the interaction with both types of DNA secondary structures.     

含有席夫碱配体的钌配合物的合成、表征及抗肿瘤活性

设计并合成了3个含有席夫碱基团的配体（BLⁿ,n=1~3）及相应的双核联吡啶钌配合物[Ru （BLⁿ）（bpy）₂]₂（ClO₄）₄,其中bpy=2,2''-联吡啶,BLⁿ=（（PyCHN）-Ph-O-C₆H₄）₂R （PyCHN=N-2-吡啶亚甲基,R=none （Ru1）,—C （CH₃）₂（Ru2）,—SO₂（Ru3））。通过元素分析、核磁氢谱、红外光谱、质谱等方法对配体和配合物进行了表征。通过体外细胞毒性实验研究了Ru1~Ru3对宫颈癌细胞（Hela）、胃癌细胞（BGC823）、胃癌细胞（SGC-7901）三种肿瘤细胞和人正常胚肺成纤维细胞MRC-5的细胞毒性,实验结果表明Ru3的抗肿瘤活性最好,而Ru1~Ru3均对BGC823具有选择性。     

靶向抑制拓扑异构酶和端粒酶的钌配合物研究进展

金属配合物抗肿瘤研究,尤其是铂类药物,已取得了相对令人瞩目的成功,但同时也面临着包括耐药性和毒副作用等诸多问题。近年来钌配合物作为新的抗癌药物引起了人们的注意。在非铂系药物中,金钌配合物;拓扑异构酶;G-四链体;端粒酶属钌配合物是最有前途的抗癌药物之一,国际上普遍认为钌和钌的配合物属于低毒性,容易吸收并在体内很快排泄。本文将着重介绍钌配合物与DNA结合后进一步引发的细胞内核酶活性抑制研究,从新的角度来诠释钌配合物的抗肿瘤研究最新进展。     

靶向抑制拓扑异构酶和端粒酶的钌配合物研究进展

金属配合物抗肿瘤研究,尤其是铂类药物,已取得了相对令人瞩目的成功,但同时也面临着包括耐药性和毒副作用等诸多问题。近年来钌配合物作为新的抗癌药物引起了人们的注意。在非铂系药物中,金属钌配合物是最有前途的抗癌药物之一,国际上普遍认为钌和钌的配合物属于低毒性,容易吸收并在体内很快排泄。本文将着重介绍钌配合物与DNA结合后进一步引发的细胞内核酶活性抑制研究,从新的角度来诠释钌配合物的抗肿瘤研究最新进展。     

钌配合物稳定端粒DNA的作用及其诱导细胞凋亡分子机制的研究

端粒酶在肿瘤细胞中高表达,已经成为抗肿瘤药物的重要靶点,由于很多肿瘤细胞中富含G4-DNA,通过稳定G-四链体DNA的形成来抑制端粒酶的活性已成为抗癌药物的一个新策略. 本文设计了两种钌配合物,调查了这两种钌配合物稳定G4-DNA的能力,发现配合物2稳定端粒 G4-DNA的能力强于配合物1,配合物2能够诱导端粒 G4-DNA发生构型的转化,而配合物1不能诱导G4-DNA发生构型的转化,这项研究结果证明,钌配合物与G4-DNA的作用能力与配体的平面性有关. 在抗肿瘤活性方面,配合物2表现出更强的抗肿瘤活性,尤其是对HepG2细胞具有较强的抑制作用,推测其是以端粒酶为靶点发挥的抗肿瘤作用. 配合物2能够诱导肿瘤细胞凋亡,能诱导G1期细胞阻滞和DNA碎片的形成（细胞凋亡的特征）. 据此推测本论文设计的钌配合物是一个潜在的抗肿瘤药物.     

DNA Interaction,DNA Photocleavage,Photocytotoxicity In Vitro,and Molecular Docking of Naphthyl-Appended Ruthenium Complexes

With the development of metal-based drugs, Ru(II) compounds present potential applications of PDT (photodynamic therapy) and anticancer reagents. We herein synthesized two naphthyl-appended ruthenium complexes by the combination of the ligand with naphthyl and bipyridyl. The DNA affinities, photocleavage abilities, and photocytotoxicity were studied by various spectral methods, viscosity measurement, theoretical computation method, gel electrophoresis, and MTT method. Two complexes exhibited strong interaction with calf thymus DNA by intercalation. Production of singlet oxygen (¹O₂) led to obvious DNA photocleavage activities of two complexes under 365 nm light. Furthermore, two complexes displayed obvious photocytotoxicity and low dark cytotoxicity towards Hela, A549, and A375 cells.     

Synthesis, spectroscopy, electrochemistry and thermal study of vanadyl tridentate Schiff base complexes

The VO(IV) complexes of tridentate ONO Schiff ligands were synthesised and characterized by IR, UV–vis and elemental analysis. The electrochemical properties of the vanadyl complexes were investigated by cyclic voltammetry. A good correlation was observed between the oxidation potentials and the electron withdrawing character of the substituents on the Schiff base ligands, showing the following trend: MeO < H < Br < NO₂ and H < Cl. The thermogravimetry (TG) and differential thermoanalysis (DTA) of the VO(IV) complexes were carried out in the range of 20–700 °C. The VOL¹(OH₂) decomposed in two steps whereas the remaining six complexes decomposed in three steps. The thermal decomposition of these complexes is closely related to the nature of the Schiff base ligands and proceeds via first order kinetics.     

Synthesis,characterization, and DNA damaging of bivalent metal complexes incorporating tetradentate dinitrogen–dioxygen ligand as potential biocidal agents

A new symmetrical tetradentate Schiff base was prepared by the condensation of 5-nitro-o-vanillin and diaminoethane. Its complexes were synthesized and characterized by elemental analysis, magnetic moment, molar conductance, UV-Vis, IR, ¹H NMR, ESI-mass, and EPR spectra. The DNA-binding behavior of these complexes was investigated by absorption spectra, cyclic voltammetry, and viscosity measurements. The DNA-binding constants for Co(II), Ni(II), Cu(II), and Zn(II) complexes were 1.58?×?10⁴, 1.65?×?10⁴, 2.71?×?10⁴, and 1.83?×?10⁴ (mol?L^?1)^?1, respectively. The results suggest that the complexes intercalate between DNA base pairs. Further, all these complexes exhibit moderate to high ability to cleave pUC19 DNA. The ligand and its complexes have been screened for antimicrobial activities using the disc diffusion method against selected bacteria and fungi. Antibacterial activity was greater against Gram-positive than Gram-negative bacteria for Cu(II) complex and antifungal activity was greater against Aspergillus niger and Candida albicans for the Cu(II) complex.     

Synthesis and Structure of the Cerium Schiff‐Base Complexes [Ce(Salen′)2] and [(THF)2KCe(Salen′)2]

The synthesis of [Ce(Salen′)₂] ( 1 ) (H₂Salen′ = N,N′‐bis(3,5‐di‐tert‐butylsalicylidene)ethylenediamine) was performed using two different approaches. CeCl₃ reacts with two equivalents of K₂Salen′ in THF under the formation of [(THF)₂KCe(Salen′)₂] ( 2 ). Complex 2 could be converted to the Ce^IV complex 1 via oxidation with p‐benzoquinone and air, respectively. The reversible reduction process was realized using elemental potassium in boiling THF. Furthermore, the reaction of the Ce^IV starting material [(^tBuO)₄Ce(THF)₂] with the “free” ligand H₂Salen′ in boiling toluene lead in the formation of 1 as well.     

The use of Cu and Zn salicylaldimine complexes as catalyst precursors in ring opening polymerization of lactides: ligand effects on polymer characteristics

A range of monomeric tetra‐coordinate copper (II) and zinc (II) complexes based on N,O‐bidentate salicylaldimine Schiff base ligands has been synthesized and characterized using various spectroscopic techniques. These complexes were then evaluated as initiators in ring‐opening polymerization of lactides at both 70 °C and 110 °C. The effect of structural changes in the complexes on the ability of these compounds to initiate lactide polymerization as well as the impact on the chemical and physical characteristics of the polymers obtained indicate that the coordination geometry of the metal complex, M? O bond length and substituents on the Schiff base ligand all play a role in the catalyst activity. Electronic factors were dominant in the case of the copper complexes while steric factors prevailed in the case of Zn initiators. Both the Zn and Cu complexes exhibit characteristics of living ring opening polymerization. Copyright © 2010 John Wiley & Sons, Ltd.     

双水杨醛缩环己二胺类西佛碱及其配合物的合成、性质研究

合成了两种双水杨醛缩环已二胺类西佛碱N，N’-(二羟苯次甲基)环已二胺(1)和N，N’-二(3，5-二叔丁基-2-羟苯次甲基)环已二胺(2)，以及它们的金属锌配合物(3)和(4)，通过核磁共振、元素分析和红外光谱确定了四种物质的结构，研究了它们的紫外吸收光谱、荧光光谱，测定了(3)和(4)的荧光量子效率．(4)中四个叔丁基的存在使其荧光量子效率提高．此类双西佛碱金属配合物可以应用于有机电致发光材料中．     

A NEW CYCLOBUTANE SUBSTITUTED SCHIFF BASE LIGAND,SYNTHESIS OF ITS Cd(II), Co(II), Cu(II), Ni(II) AND Zn(II) COMPLEXES AND INVESTIGATION OF THEIR STRUCTURE

Abstract

A new, thiazole derivative ligand, 4-(1-phenyl-1-methylcyclobutane-3-yl)-2-(2-hydroxy-5-bromo benzylidenehydrazino) thiazole (LH), has been synthesized by the reaction of 2-hydroxy-5-bromobenzaldehyde, thiosemicarbazide and subsequently 1-phenyl-1-methyl-3-(2-chloro-1-oxoethyl) cyclobutane. Mononuclear complexes with a metal-ligand ratio of 1 : 2 have been prepared with Cd(II), Co(II), Cu(II), Ni(II) and Zn(II). The authenticity of the ligand and its complexes was established by elemental analyses, IR, ¹³C and ¹H NMR spectra, magnetic susceptibility measurements and thermogravimetric analyses (TGA) and differential scanning calorimetry (DSC).     

DNA-binding,oxidative DNA cleavage,and coordination mode of later 3d transition metal complexes of a Schiff base derived from isatin as antimicrobial agents

A Schiff base, obtained by the condensation of isatin monohydrazone with 2,3,5-trichlorobenzaldehyde, and its Co(II), Ni(II), Cu(II), and Zn(II) complexes have been synthesized and characterized. The interaction of these complexes with DNA is investigated using viscosity, absorption titration, and electrochemical techniques. The results indicate that the complexes bind to Calf thymus DNA through intercalation. Oxidative cleavage activities of the complexes are studied using supercoiled pBR322 DNA by gel electrophoresis. Antimicrobial study reveals that copper and zinc complexes are better antimicrobial agents than the Schiff base and its other complexes.     

Organotin(IV) complexes of dibasic tridentate Schiff bases containing ONO donor atoms

Organotin(IV) Schiff base complexes of the type (L)SnR₂ [where R?CH₃, C₆H₅ or CH₂CH₂CO₂ CH₃], (LH)Sn(C₆H₅)₃ and (L)SnCl(CH₂CH₂CO₂ CH₃) [where LH₂?2-N-salicylideneimino-2-methyl-1-propanol, derived from the condensation of salicylaldehyde and 2-amino-2-methyl-1-propanol] have been prepared and characterized on the basis of their elemental analyses, IR, ¹H, ¹³C and ¹¹⁹Sn NMR studies. In these mononuclear complexes the Schiff base acts either as a dianionic tridentate or as a monobasic bidentate moiety by coordinating through an alkoxy group, an azomethine nitrogen and a phenoxide ion to tin. Sulphur dioxide inserts in the tin–methyl/–phenyl bond in the above Schiff base complexes to give tin–O–sulphinates of formulae (L)RSn(SO₂R) and (LH)(C₆H₅)₂Sn(SO₂C₆H₅).     

Schiff碱二价金属离子配合物的合成及抗菌性

氨基酸、肽、蛋白质、酶等生物大分子中半光氨酸残基上的硫原子与一些过渡金属离子形成的配合物具有特殊的生物活性,因此配体和配合物的研究一直受到人们的重视[1,2]。我们设计并合成出的乙酰基硫代甲酰取代苯胺缩氨基脲Schiff碱具有与这些生物大分子相同的配位原子,可以作为研     

新型双核席夫碱配合物的合成及谱学性质

Eight novel binuclear tetradentate Schiff base complexes (M=Cu(Ⅱ),Ni(Ⅱ),Zn(Ⅱ)) are synthesized. The structure of complexes is two discrete Schiff base unit bridged. The complexes were condensed from series sub-stituent Ketones (5-chloro-2-hydroxybenzophenone, 5-methyl-2-hydroxy-benzophenone, 5-Bromo-2-hydroxybenzop- henone) and dialdehydes (5,5′-methylene-disalicylaldehyde) with the amino group of 1,2-diaminobenzene, and by Metal ion as template. The compounds were characterized by elemental analyses, FT-infrared spectra, Raman, ¹H NMR, UV-vis electronic spectra, EPR spectra. The FT-infrared spectra and Raman spectra of complexes were compared and discussed. The UV-vis election spectra, ¹H NMR and EPR spectra of complexes have also been attributed and minutely analyzed.