Synthesis,Characterization, and Cytotoxicity Studies of N-(4-Methoxybenzyl) Thiosemicarbazone Derivatives and Their Ruthenium(II)-p-cymene Complexes

The reaction of [Ru₂Cl₂(μ-Cl)₂(η⁶-p-cymene)₂] with two thiosemicarbazones obtained by the condensation of N-(4-methoxybenzyl) thiosemicarbazide and 1,4-hydroxy-3-methoxyphenyl)ethan-1-one (HL¹) or 2-fluoro-4-hydroxybenzaldehyde (HL²) was studied. The cationic complexes of formula [RuCl(η⁶-p-cymene)(HL)]⁺ were isolated as solid chloride and trifluoromethylsulfate (TfO) salts. A study of the solid state and NMR spectra suggests the presence in the material of two isomers that differ in the configuration in the iminic bond, C2=N3, of the coordinated thiosemicarbazone in the triflate salts and only the E isomer in the chloride. An X-ray study of single crystals of the complexes supports this hypothesis. The thiosemicarbazone ligand coordinates with the ruthenium center through the iminic and sulfur atoms to form a five-membered chelate ring. Furthermore, the isolation of single crystals containing the thiosemicarbazonate complex [Ru₂(μ-L²)₂(η⁶-p-cymene)₂]²⁺ suggests the easy labilization of the coordinated chloride in the complex. The redox behavior of the ligands and complexes was evaluated by cyclic voltammetry. It seems to be more difficult to oxidize the complex derived from HL¹ than HL². The ability of the complexes to inhibit cell growth against the NCI-H460, A549 and MDA-MB-231 lines was evaluated. The complexes did not show greater potency than cisplatin, although they did have greater efficacy, especially for the complex derived from HL¹.     

三氟甲磺酸铜催化新型苯并恶唑烷衍生物的合成

以三氟甲磺酸铜［Cu(OTf)₂］为催化剂,取代邻氨基苯酚(1a~1g)和取代联苯甲酰(2a~2g)为原料,合成了7个苯并恶唑烷衍生物（3a~3g,其中3b~3g为新化合物）,其结构经¹H NMR, ¹³C NMR, IR和HR-MS(ESI)表征。以3a的合成为例,研究了催化剂、溶剂、催化剂用量、物料比γ［n(1) : n(2)］和反应温度对3产率的影响。结果表明：在最佳反应条件［8 mmol%Cu(OTf)₂, 1,2-二氯乙烷为溶剂,1a~1g1.5 mmol, γ=3:1,于70 ℃反应10 h］下,3a~3g产率62%~91%。     

两种三齿多吡啶铜(Ⅱ)配合物的合成、表征及其与DNA的作用

本文合成了2个三齿多吡啶铜(Ⅱ)配合物[Cu(phpi)Cl₂]·H₂O和[Cu(tpy)Cl₂]·2H₂O(phpi=2-(苯并咪唑基-2)-1，10-邻菲咯啉，tpy=2，2:6′，2″-三联吡啶)，并通过元素分析、摩尔电导率、红外光谱、紫外光谱对其进行了表征。应用电子吸收光谱、荧光光谱和粘度法研究了配合物与DNA的相互作用。在抗坏血酸存在下，利用琼脂糖凝胶电泳方法研究了配合物对pBR322 DNA的切割作用并对其作用机理作了初步探讨。     

Copper(II), Nickel(II) and Cobalt(II) Complexes of Dibasic Tridentate Schiff Bases

Complexes of Cu(II), Ni(II) and Co(II) with the Schiff bases derived from o-aminobenzoic acid with salicylaldehyde and its 5-chloro and 5-bromo derivatives have been prepared. The 1:1 (metal-ligand) stoichiometry of these complexes is shown by elemental analysis, gravimetric estimations and conductometric titrations while the structures of the complexes are proved by i.r. spectra and thermogravimetric analysis. The magnetic susceptibility and electronic spectra of Cu(II) complexes indicate the nonplanar binuclear structures while that of Ni(II) and Co(II) show their paramagnetic octahedral geometry. The molar conductance values in nitrobenzene indicate the nonelectrolytic behaviour of the complexes. The results show that the complexes of the type (Cu·L)₂, Ni·L·3H₂O and Co·L·3H₂O are formed having solvent molecule in coordination with the metal ion. The monopyridine and monoammonia adducts of Cu(II) complexes were found to be monomeric.     

萘基修饰二乙烯三胺配体的合成、铜离子键合及核酸酶活性

本文合成了两个具有平面萘环的二乙烯三胺配体：4-(α-萘甲基)-二乙烯三胺(L¹)和4-( β-萘甲基)-二乙烯三胺(L²)，用元素分析、NMR和ESI-MS等技术分别对它们进行了表征。通过电位滴定研究了这些配体的酸离解常数，它们与Cu(Ⅱ)离子结合的配位水分子的酸离解常数pK_a值，与未修饰的二乙烯三胺的铜配合物相比，配合物的配位水分子的酸离解常数pK_a值分别降低了1.09和0.59。这有利于配合物在接近生理pH值条件下对磷酸二酯键进行亲核活化。通过观察配体及其铜配合物对小牛胸腺DNA的粘度影响，证明配体和配合物可能以插入和部分插入两种方式与DNA作用。在无任何还原物质存在的条件下研究了两配体的铜配合物对质粒pBR322 DNA的断裂，结果表明两个配合物都能够有效切割超螺旋DNA为缺刻型DNA，且L¹的铜配合物具有更高的核酸酶活性。     

新型紫罗兰酮基双查尔酮缩氨基硫脲的合成及抗肿瘤活性

根据活性亚结构拼接原理,通过紫罗兰酮与(取代)苯甲醛反应合成了紫罗兰酮基双查尔酮,然后经与氨基硫脲缩合得到一系列未见报道的新型含紫罗兰酮、查尔酮及氨基硫脲3种优势结构单元的杂化体,它们的化学结构经傅里叶变换红外光谱(FT-IR)、核磁共振波谱(~1H NMR、~(13)C NMR)、元素分析及质谱(MS)等测试技术所证实。采用溴化噻唑蓝四氮唑(MTT)法初步测定其体外抗肿瘤活性(乳腺癌细胞(MCF-7),肝癌细胞(Hep G2),肺癌细胞(A549)),结果表明,对于不同类型的肿瘤细胞,化合物展现较好的增殖抑制活性。尤其是化合物3a与3b对MCF-7细胞展现较强的抗增殖活性,半数致死量(IC_(50))值分别为10.83和7.62μmol/L,化合物3e对A549细胞显示一定的增殖抑制活性效果(IC_(50)值为13.36μmol/L),化合物3f对Hep G2细胞表现了高效的抗增殖活性(IC_(50)值为8.55μmol/L)。目标物的抗增殖活性与紫罗兰酮结构及查尔酮环上不同电子效应的取代基有关。     

新型不对称三齿多吡啶配体及其混配钌(II)配合物的合成、表征及与DNA相互作用研究

合成了两个新型不对称三齿多吡啶配体 ,3 ( 1,10 菲咯啉基 2 ) 1,2 ,4 三唑 (PHT) ,3 ( 1,10 菲咯啉基 2 ) 5 甲基 1,2 ,4 三唑 (PHMT) ,及其混配配合物 [Ru(tpy) (PHT) ] 2 + (Ru1)和 [Ru(tpy) (PHMT) ] 2 + (Ru2 ) ,通过元素分析、FAB MS ,ES MS ,1HNMR ,IR ,UV vis ,发射光谱和电化学对它们进行了表征 .运用电子吸收光谱、竞争性结合实验和粘度测试等方法研究了配合物与DNA的作用机理 ,结果显示它们均是通过静电作用与DNA结合 ,且Ru2与DNA的作用比Ru1与DNA的作用更强 .     

Synthesis and Crystal Structure of a Mn(II) Complex with Thiosemicarbazone Derivative of Pyridine-3-carbaldehyde Showing Unusual Coordination Mode of Tridentate Thiosemicarbazone

1 INTRODUCTION Heterocyclic thiosemicarbazones as well as their metal complexes have been attracting considerable interest due to their biological activities, such as antiviral, antibacterial, antimalarial, antifungal, and antitumoral activities[1～5]. This prompted us to carry out structural studies of these complexes to provide a basis for understanding their behaviors in living systems. Although quite a number of investigations on the 2-heterocyclic thiosemicarbazones have ap- peared[6…     

Synthesis,Characterization, Crystal Structures,and Antibacterial Activity of Polynuclear Nickel(II) and Copper(II) Complexes with Similar Tridentate Schiff Bases

An end-on azido-bridged dinuclear nickel(II) complex [Ni₂(L¹)₂(μ_1,1-N₃)₂] · CH₃COOH (I) and an end-on azido-bridged polynuclear copper(II) complex [CuL²(μ_1,1-N₃)] _n , where L¹ is the deprotonated form of 2-[(2-ethylaminoethylimino)methyl]-4-fluorophenol and L2 is the deprotonated form of 2-[(2- dimethylaminoethylimino)methyl]-4-fluorophenol, were prepared and characterized by elemental analysis and FT-IR spectra. Crystal and molecular structures of the complexes were determined by single crystal X-ray diffraction method (CIF files CCDC nos. 942641 (I) and 942642 (II)). Single crystal X-ray structural studies indicate that the Schiff base ligands coordinate to the metal atoms through phenolate oxygen, imine nitrogen, and amine nitrogen. The Ni atoms in the nickel complex are in octahedral coordination, and the Cu atoms in the copper complex are in square pyramidal coordination. Crystals of the complexes are stabilized by hydrogen bonds. The Schiff bases and the complexes showed potent antibacterial activities.     

Binding Models of Copper(II) Thiosemicarbazone Complexes with Human Serum Albumin: A Speciation Study

Copper(II) complexes of thiosemicarbazones (TSCs) often exhibit anticancer properties, and their pharmacokinetic behavior can be affected by their interaction with blood transport proteins. Interaction of copper(II) complexes of an {N,N,S} donor α-N-pyridyl TSC (Triapine) and an {O,N,S} donor 2-hydroxybenzaldehyde TSC (STSC) with human serum albumin (HSA) was investigated by UV–visible and electron paramagnetic resonance spectroscopy at physiological pH. Asp-Ala-His-Lys and the monodentate N-methylimidazole were also applied as binding models. Conditional formation constants were determined for the ternary copper(II)-TSC complexes formed with HSA, DAHK, and N-methylimidazole based on the spectral changes of both charge transfer and d-d bands. The neutral N-methylimidazole displays a similar binding affinity to both TSC complexes. The partially negatively charged tetrapeptide binds stronger to the positively charged Triapine complex in comparison to the neutral STSC complex, while the opposite trend was observed for HSA, which demonstrates the limitations of the use of simple ligands to model the protein binding. The studied TSC complexes are able to bind to HSA in a fast process, and the conditional constants suggest that their binding strength is only weak-to-moderate.     

三齿多吡啶钴(II)配合物的合成、表征及其与DNA的相互作用研究

合成了两种三齿多吡啶钴(II)配合物 (A)和[Co(H₂Bzimpy)₂]Cl₂ (B), 用元素分析、IR对配合物的组成和结构进行了表征, 测定了配合物A的晶体结构. 用电子吸收光谱、荧光光谱、循环伏安法及凝胶电泳实验等方法研究了配合物与DNA的相互作用. 结果表明配合物A和B与小牛胸腺(CTDNA)的作用属部分插入和静电结合, 凝胶电泳实验表明配合物A在310 nm光辐射15 min, 可使超螺旋pBR322DNA断裂为开环缺口型和线型DNA.     

Copper(I) Complexes of Anionic Tridentate CNC Pincer Ligands

New monoanionic CNC pincer ligands, [N{SiMe₂CH₂(RIm)}₂]^– (R = tBu, iPr, Ph) featuring three different N-heterocyclic carbenes and a disilylamido moiety is reported. Treatment of the lithium salt of [N{SiMe₂CH₂(RIm)}₂]^– with Cu^IOTf afforded the corresponding copper complexes [N{SiMe₂CH₂(RIm)}₂]Cu in 41–56 % yield. X-ray crystal structures of [N{SiMe₂CH₂(RIm)}₂]Cu show that they are monomeric and feature three-coordinate, pseudo T-shaped copper(I) sites. The X-ray crystal structure of one of the precursor lithium complexes, [N{SiMe₂CH₂(tBuIm)}₂]Li is also presented.     

New Palladium(II) Complexes with a Tridentate PNO Ligand

The synthesis of neutral and cationic palladium complexes containing the tridentate monoanionic ligand [2-(2-Ph₂PC₆H₄-CH=N)C₆H₄O]^? is described. Deprotonation of the Schiff base formed by condensation of 2-(diphenylphosphino)benzaldehyde with 2-aminophenol in the presence of the appropriate palladium precursor ([Pd(AcO)₂] or [PdCl₂(PhCN)₂]) form the corresponding neutral complexes [Pd{2-(2-Ph₂PC₆H₄-CH=N)C₆H₄O}(AcO)] (1) or [Pd{2-(2-Ph₂PC₆H₄-CH=N)C₆H₄O}(Cl)] (2) in good yield. The first reacts smoothly with thiols and activated phenols to give complexes of general formula [Pd{2-(2-Ph₂PC₆H₄-CH=N)C₆H₄O}(X)] (X = OC₆F₅ (3), SEt (4), S^tBu (5), SC₆H₅ (6), SC₆H₄-4Me (7), SC₆H₄-4NO₂ (8)). When the chloro complex is treated with silver perchlorate and tertiary phosphines (L) the cationic derivatives [Pd{2-(2-Ph₂PC₆H₄-CH=N)C₆H₄O}(L)][ClO₄] (L = PPh₃ (9), PMePh₂ (10), PMe₂Ph (11), PEt₃ (12)) were obtained. The new complexes were characterized by partial elemental analyses and spectroscopic methods (IR, ¹H, ¹⁹F and ³¹P NMR).     

Synthesis,Characterization, and Magnetic Properties of Novel Cobalt(II) and Copper(II) Complexes with 5‐(Isonicotinamido)isophthalate Ligand

Two new complexes, {[Co(INAIP) · H₂O] · 2H₂O}_n ( 1 ), and {[Cu(INAIP)] · H₂O}_n ( 2 ) [H₂INAIP = 5‐(isonicotinamido)isophthalic acid] were synthesized under hydrothermal conditions, and characterized by single‐crystal X‐ray structure determination, thermogravimetric analysis, X‐ray powder diffraction, and magnetic studies. In complex 1 both Co^II atoms and INAIP^2– ligands act as four‐connected node, whereas in 2 both Cu^II atoms and INAIP^2– ligands act as three‐connected node.     

Synthesis and Structure of Copper(II) Phosphonodithioite Complexes

A series of new complexes of CuBr with phosphonodithioites were prepared and characterized by NMR and IR spectroscopy. As shown by single crystal X-ray diffraction, diethyl tert-butylphosphonodithioite forms with CuBr a tetrameric cubane-like complex with the monodentate coordination of the organophosphorus ligand via the P atom.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 6, 2005, pp. 903–907.Original Russian Text Copyright © 2005 by Kursheva, Kataeva, Perova, Batyeva, Sinyashin, Freilich.     

Synthesis and Characterization of Nickel(II) and Copper(II) Complexes with Non-symmetric Tetraaza[14]annulene Derivatives. X-ray Crystal Structure of Copper(II) Complex

The complexes 13,14-([X]benzo)-3-(p-[Y]benzoyl)-2,4,9,11-tetramethyl-1,5,8,12-tetraazacyclotetradeca-l,3,9,11-tetraenato(2-)nickel(II), wherein Y = CH₃, H, Cl, NO₂ or OCH₃, X = CH₃ or Cl, have been synthesized and characterized. IR spectra of the benzoylated complexes show intense bands in the regions 1641-1654 cm^?1 attributable to the stretching modes of C—O. Hammett plots of the l/γ _max of π→π ^? have positive slopes of 0.251 for A series (X = CH₃) and 0.233 for B series (X = Cl), respectively, which are quite similar to those based on the NMR resonances of methine protons. The cyclic voltammograms of the complexes show two one-electron irreversible oxidation processes in the potential range of +0.1 to +0.8 V and two, three or four reduction peaks between ?1.2 and ?2.8 V depending on the substituents. Hammett plots of first and second oxidation potentials are linear with the positive slopes (0.039 and 0.057 V for A series, 0.036 and 0.047V for B series). The structure of the copper(II) complex (orthorhombic, C222₁, a= 8.0994(11), b= 8.3187(10), c= 24.561(5)Å, α(=β=γ)= 90.0°, Z= 4, R ₁= 0.0474 and wR ₂= 0.1219) was characterized using single crystal X-ray diffraction method.     

Synthesis and Structure of Copper(II) Complexes with Methyl [(Pyrazolo-1-carbothioyl)-amino]propionate Derivatives

Methyl 3-[(3,5-dimethylpyrazole-1-carbothioyl)-amino]propionate (L¹) and the optically active derivative of natural monoterpene (+)-3-carene, (3bS,4aR)-3-[(3,4,4-trimethyl-3b,4,4a,5-tetrahydro-cyclopropa[3,4]cyclopenta[1,2-c]pyrazole-1-carbothioyl)-amino]propionate (L²), are synthesized. The paramagnetic CuL¹Cl₂ (I) and [Cu₂L² ₂Cl₄] (II) complexes are obtained. According to the X-ray diffraction data, in mononuclear complex I, the L¹ molecule performs a bidentate-cyclic function due to the coordination of the S atom of the C=S group and the N atom of the pyrazole cycle. The CuCl₂NS coordination polyhedron is a distorted tetrahedron. Two molecules of complex I form an associate due to weak Cu···S interactions. Compound II is binuclear due to the bridging function of two Cl^- ions, and analogous functions of the L¹ and L² ligands. The coordination polyhedron in complex II is CuCl₃NS. The _eff values for compounds I and II are equal to 1.81 and 1.79 _B, respectively, and are constant in the interval from 78 to 300 K, indicating that noticeable exchange interactions between unpaired electrons of the Cu²⁺ ions are absent. The EPR spectra of the complexes in the solid phase are examined.     

Copper(II) Complexes with Ethyl [(Pyrazolo-1-carbothioyl)-amino]acetate Derivatives: Synthesis and Structure

Optically active derivative of the natural monoterpene (+)-3-carene, namely, ethyl (3bS,4aR)-[(3,4,4-trimethyl-3b,4,4a,5-tetrahydrocyclopropa[3,4]cyclopenta[1,2-c]pyrazole-1-carbothioyl)-amino]acetate (HL¹) and ethyl [(3,5-dimethyl-pyrazole-1-carbothioyl)-amino]acetate (HL²) were synthesized. Paramagnetic complexes [CuL¹Cl] _n (I) and [Cu₂L² ₂Cl₂] (II) were prepared. According to X-ray diffraction data, complex Iwith anion of (+)-3-carene derivative has chain structure, whereas complex IIwith anion of HL², which has no carbocyclic fragments, is a pseudodimer. Organic anions act as tetradentate bridging, cyclic ligands forming five-membered CuN₃C and CuNOC₂metal cycles. Coordination polyhedron of Cu(ClN₂O + S) in complexes Iand IIis a square pyramid. The values of _efffor complexes Iand II(1.88 and 1.84 _B, respectively) are constant in the temperature interval 78–300 K, which means that the unpaired electrons of Cu(II) ions do not exhibit any noticeable exchange interactions.     

新型三齿多吡啶钴(II)、钌(II)配合物的合成、表征及其与DNA的作用研究

合成了两种新型三齿多吡啶钴(II)和钌(II)的混配配合物[Co(TolylTPy)(H₂Bzimpy)]Cl₂ [TolylTPy＝4'-对甲基苯 基-2,2':6',2'-三联吡啶, H₂Bzimpy＝2,6-二(苯并咪唑-2)吡啶] (A)和Ru(TolylTPy)(Bzimpy) (B). 用元素分析, IR, ¹H NMR等对它们进行了表征, 测定了配合物B的晶体结构, 用电子吸收光谱、荧光光谱等研究了配合物与小牛胸腺DNA(CTDNA)的相互作用及其对pBR322 DNA的断裂作用. 结果表明, 配合物A和B与CTDNA的作用属静电结合, 凝胶电泳实验说明配合物A在310 nm光辐射15 min, 可使超螺旋pBR322 DNA断裂为开环缺口型和线型DNA.