Synthesis,reactions with DNA,and antitumor activity of platinum complexes with aminonitroxyl radicals

The work is a review of the data on the synthesis of mono- and biradical Pt^II complexes with mono- and diaminonitroxyl radicals, as well as of a binuclear complex with diaminonitroxyl radical. A “mild” method is considered for the synthesis of a number of Pt^IV nitroxyl complexes (9–11), whose lipophilicity varies within a wide range due to the trans-ligands, i.e., the linear aliphatic acid moieties. Correlations between the structures of the complexes, efficiency of their binding to DNA, and the effect of this binding on the DNA stability were established. Cytotoxic properties of the complexes against the HeLa, H1299, and MCF7 tumor cells, the effect of the complexes on the cell cycle, and the p53 protein expression were studied. The data on the antitumor activity of the complexes in the animal tumor model, P388 leukemia, are given. The rate of the development of resistance to complex 10a for P388 leukemia is 2.5 times lower than the corresponding value for cisplatin. It was found that a synergistic enhancement of antitumor activity is observed when low doses of cisplatin and complexes 9b or 10b are simultaneously administered. The specificities of biological activity of the platinum nitroxyl complexes are presumably due to the antioxidant properties of the nitroxyl pharmacophore and the ability of these complexes to cause the p53-independent tumor cell death.     

New versatile mechanism of enzymatic synthesis of adenosine triphosphate: theoretical foundation and experimental control

The energies of electron transfer between pyrophosphate metal complexes and hydrated metal complexes, which is the key reaction that models the radical ion mechanism of adenosine triphosphate (ATP) synthesis, were calculated. A threshold dependence of the energy on the number of water molecules n in the ion hydration sphere was established: for n < 4 the reaction is exothermic, while for n ≥ 4 it is endothermic. The switching of the energy regime accounts for the fact that ATP is synthesized only in molecular machines, enzymes, rather than in homogeneous aqueous solutions. It was predicted theoretically that the radical ion ATP synthesis may be catalyzed by not only magnesium ions as in living cells but also by calcium, zinc, barium, cadmium, and tin ions. This prediction was experimentally confirmed by the discovery of the magnetic isotope effect in the calcium- and zinc-catalyzed ATP synthesis by creatine kinase. The efficiency of ATP synthesis in the presence of ions with magnetic nuclei ⁴³Ca and ⁶⁷Zn is almost twice as high as that in the presence of the same ions with nonmagnetic nuclei ⁴⁰Ca and ⁶⁴Zn.     

Organotin(IV) complexes of carboxylic acid derivatives

A comprehensive review, >100 references, on organotin(IV) complexes of the carboxylic acid derivatives are presented with special reference to their methods of synthesis, spectroscopic and structural studies and their biological activities. The structures of these complexes are discussed on the basis of IR, multinuclear (¹H-, ¹³C- and ¹¹⁹Sn-) NMR.     

Mechanochemical synthesis of platinum(<Emphasis Type="SmallCaps">IV</Emphasis>) complexes with <Emphasis Type="Italic">N</Emphasis>-heterocyclic carbenes

A new method for the synthesis of complexes Pt^IV(NHC)X₄L (NHC is N-heterocyclic carbene of imidazole or benzimidazole series; X = Cl, Br; L is N-coordinated pyridine or NHC) based on mechanochemical oxidation of complexes Pt^II(NHC)X₂L with dichloroiodobenzene (PhICl₂) or pyridinium hydrobromide perbromide (PyHBr₃) was proposed. Mechanochemical activation led to reduction in the synthesis time and increase in the selectivity of halogenation and yields of the target Pt^IV complexes (74–98%) as compared to the reaction in solutions.     

Synthesis, characterization, antitumor activity of nickel(Ⅱ) and cobalt (Ⅱ) complexes of 2,2''''-diamino-4,4''''-bithiazole and their interaction with dGMP

New complexes,of bis(2,2'-diamino-4,4'-bithiazole)sulfate nickel(Ⅱ) and bis(2,2'-diami-no-4,4'-bithiazole)sulfate cobalt(Ⅱ),have been prepared.The complexes were characterized by infrared and UV-Vis spectroscopy,1H NMR,elemental analyses and molar conductivity.The effect of these complexes on the DNA synthesis of sarcoma 180 cells has been studied by the technique of isotopic liquid scintillation.The results indicated that complexes show ability to inhibit DNA synthesis of the tumor cells.In order to provide a molecular basis for understanding the biological effects,the probe,[trana-en2Os(η2-H2)](CF3SO3)2 (en,ethylenediamine) as a monitor was first used to explore interaction of the complexes with 2'-deoxyguanosine-5'-monophosphate (dGMP).     

A Synthetic Strategy for Cofacial Porphyrin-Based Homo- and Heterobimetallic Complexes

We present a straightforward and generally applicable synthesis route for cofacially linked homo- and heterobimetallic porphyrin complexes. The protocol allows the synthesis of unsymmetrical aryl-based meso-meso as well as β-meso-linked porphyrins. Our method significantly increases the overall yield for the published compound known as o-phenylene-bisporphyrin (OBBP) by a factor of 6.8. Besides the synthesis of 16 novel homobimetallic complexes containing Mn^III, Fe^III, Ni^II, Cu^II, Zn^II, and Pd^II, we achieved the first single-crystal X-ray structure of an unsymmetrical cofacial benzene-linked porphyrin dimer containing both planar-chiral enantiomers of a Ni^II₂ complex. Additionally, this new methodology allows access to heterobimetallic complexes such as the Fe^III-Ni^II containing carbon monoxide dehydrogenase active site analogue. The isolated species were investigated by various techniques, including ion mobility spectrometry, DFT calculations, and UV/Vis spectroscopy. This allowed us to probe the influence of interplane distance on Soret band splitting.     

Donor-acceptor complexes of dipyrrolylmethenes with boron trifluoride as intermediates in the synthesis of Bodipy

The formation of donor-acceptor complexes of dipyrrolylmethene and structurally similar biladiene-a,c with boron trifluoride was studied by electronic absorption, IR, and ¹H NMR spectroscopies as well as by quantum chemical calculations. It was shown that the formation of donor-acceptor complexes is the first step of the synthesis of the corresponding boron fluoride chelate complexes (Bodipy). The hydrogen bond N—H...F—B additionaly stabilizes the donor-acceptor complexes. The stability constants, geometric parameters, and energy characteristics of the donoracceptor complexes were determined; the two-step mechanism of Bodipy synthesis was analyzed.     

Synthesis,DNA and Photocleavage Studies of Ru(II) Polypyridyl Complexes: [Ru(dppz)(pyz)4](ClO4)2 and [Ru(dppz)(dmpyz)4](ClO4)2 Complexes

In view of the growing interest for the synthesis of metal complexes and their interaction with DNA, we have synthesized and characterized two complexes containing ruthenium as metal center. The complexes are of the type [Ru(dppz)L₄](ClO₄)₂ where L are biologically important ligands such as pyrazole and dimethylpyrazole. The characterization of these complexes is done by ¹H NMR, ¹³C NMR, elemental analysis and mass spectroscopy. The interaction of these complexes with CT DNA was monitored and binding constants were determined using absorption and fluorescence spectroscopy. The mode of binding was found to be intercalative for both complexes and was determined using hydrodynamic viscosity studies. The complexes were further studied for photocleavage studies with supercoiled plasmid pBR322 DNA.     

Review: an overview of recent developments in coordination chemistry of polypyrazolylmethylamines. Complexes with N-scorpionate ligands created in situ from pyrazole derivatives and zerovalent metals

This paper reviews the coordination chemistry of polypyrazolylmethylamines as tripodal tetradentate (L^S = N,N,N-tris(3,5-dimethylpyrazol-1-ylmethyl)amine) and dipodal tridentate (L^D = N,N,-bis(3,5-dimethylpyrazol-1-ylmethyl)amine) ligands. References to the methods for the synthesis of both the ligands alone and their transition metal complexes are given with emphasis placed on the structural features of the latter. Special attention was paid to the one-pot synthesis, which is a new method for isolation of various metal complexes with N,N-bis- and N,N,N-trispyrazolylmethylamines and co-ligands, such as urotropine and 3,5-dimethylpyrazole. The complexes in question were created in situ from 1-hydroxymethyl-3,5-dimethylpyrazole (L⁰) and zerovalent metals.     

Synthesis of palladium complexes derived from imidazolidin‐2‐ylidene ligands and used for catalytic amination reactions

N‐Aryl amination and the Buchwald–Hartwig reaction are of great synthetic and industrial interest and scientists accept their usefulness and versatility for obtaining arylamines. In this study Ag–N‐heterocyclic carbene complexes were used as transmetallation reagents for the synthesis of Pd–N‐heterocyclic carbene complexes. The new Pd–N‐heterocyclic carbene complexes were characterized using elemental analysis and ¹H NMR, ¹³C NMR and infrared spectroscopies. The crystal structure of one, namely dichlorobis[1,3‐bis(2‐methylbenzyl)imidazolidin‐2‐yliden]palladium(II), is presented. The activity of the Pd(II) complexes in the coupling reaction of anilines or amines with bromobenzene was investigated. These complexes exhibited high catalytic activities in the direct synthesis of triarylamines and secondary amines in a single step. Copyright © 2016 John Wiley & Sons, Ltd.     

Photo-induced reduction of Cr<Superscript>6+</Superscript> by the hybrid systems “Cu<Superscript>II</Superscript> complex with Schiff base and TiO<Subscript>2</Subscript>”: dependence on irradiation wavelength

The synthesis of novel Cu^II complexes with a Schiff base obtained by condensation of salicylaldehyde and an l-aspartic acid ester are described. The physicochemical properties of the complexes were compared with those of related Cu^II complexes obtained earlier. All the complexes studied were characterized by elemental analysis as well as by IR, UV-Vis, and EPR spectroscopies. The activity of the complexes and their hybrid systems (HS) with TiO₂ in visible-light-driven photocatalysis in organic solvents was investigated. After irradiation with visible light, the complexes and corresponding HS reduce Cr⁶⁺ to Cr³⁺ more efficiently than bare TiO₂. To determine the molecular orbital compositions and energies and to explain the electronic spectra and redox properties of the systems studied, density functional calculations of the optimized structures of representative model complexes were performed.     

钒酰腙配合物的合成、结构及生物活性

以酰腙为配体钒的单核、双核配合物因其结构丰富、生物活性多样而引起广泛关注。目前该领域新配合物的合成、表征和生物活性的研究甚为活跃。本文回顾了近年来钒酰腙配合物的研究状况,主要从以下三个方面进行综述：(1)钒酰腙配合物的合成方法;(2)此类配合物的配位模式;(3)一些单、双核钒酰腙配合物抗变形虫,抗肿瘤,类胰岛素,抑制Na⁺, K⁺-ATP酶,与DNA作用的生物活性。文中着重阐述了钒酰腙化合物的结构和生物活性之间的关系。此外,还提出了钒酰腙配合物研究领域的不足之处并对其今后发展方向进行了展望。     

Synthesis,characterization, DNA binding,DNA cleavage,antioxidant and in vitro cytotoxicity studies of ruthenium(II) complexes containing hydrazone ligands

The synthesis, spectral characterization, and biological studies of ruthenium(II) hydrazone complexes [RuCl(CO)(PPh₃)₂L] (where L = hydrazone ligands) have been carried out. The hydrazones are monobasic bidentate ligands with O and N as the donors and are preferably found in the enol form in all the complexes. The molecular structure of the ligands HL¹, HL²_, and HL³ were determined by single-crystal X-ray diffraction. The DNA binding studies of the ligands and complexes were carried out by absorption spectroscopic and viscosity measurements. The results revealed that the ligands and complexes bind to DNA via intercalation. The DNA cleavage activity of the complexes, evaluated by gel electrophoresis assay, revealed that the complexes are good DNA cleaving agents. The antioxidant properties of the complexes were evaluated against DPPH, OH, and NO radicals, which showed that the complexes have strong radical-scavenging. Further, the in vitro cytotoxic effect of the complexes examined on HeLa and MCF-7 cancer cell lines showed that the complexes exhibited significant anticancer activity.     

Efficient Luminescence from Fluorene‐ and Spirobifluorene‐Based Lanthanide Complexes upon Near‐Visible Irradiation

We describe herein the synthesis and photophysical characterization of new lanthanide complexes that consist of a (9,9‐dimethylfluoren‐2‐yl)‐2‐oxoethyl or a (9,9′‐spirobifluoren‐2‐yl)‐2‐oxoethyl unit as the antenna, covalently linked to a 1,4,7,10‐tetraazacyclododecane‐1,4,7‐triacetic acid (DO3A) unit as the Ln³⁺ (Gd³⁺, Eu³⁺, Sm³⁺, Tb³⁺, Dy³⁺) coordination site. We were able to translate the spectroscopic properties of the innovative bipartite ligands into the formation of highly luminescent europium complexes that exhibit efficient emission (?_se>0.1) upon sensitization in the near‐visible region, that is, with an excitation wavelength above 350 nm. The luminescence of the Eu³⁺complexes is clearly detectable at concentrations as low as 10 pM . Furthermore, the structural organization of these bipartite ligands makes the complexes highly soluble in aqueous solutions and chemically stable over time.     

Synthesis, Characterization and Antibacterial Activity of Some Transition Metal cis-3,7-dimethyl-2,6-octadiensemicarbazone Complexes

The synthesis and characterization of some transition metal cis-3,7-dimethyl-2,6-octadiensemicarbazone (CDOSC) complexes are reported. The ligand CDOSC yields: [ML₂ Cl₂] and [ML₂ Cl₂] Cl type complexes, where M = Cr^III, Mn^II, Fe^III, Co^II, Ni^II, Cu^II, Zn^II, Cd^II and Hg^II, L = CDOSC. Structures of the complexes were determined using elemental analysis, molar conductivity, magnetic measurements, i.r. and electronic, as well as n.m.r spectra. CDOSC acts as a bidentate ligand in all the complexes. All the newly synthesized metal complexes, as well as the ligand, were screened for their antibacterial activity. All the complexes exhibit strong inhibitory action against Gram (+) bacteria Staphylococcus aureus and Gram (−) bacteria Escherichia coli. The antibacterial activities of the complexes are stronger than those of the ligand CDOSC itself.     

Gas-phase synthesis of lanthanide(III) benzoates Ln(Bz)<Subscript>3</Subscript> (Ln = La,Tb, Lu)

A new method for the synthesis and film deposition of nonvolatile aromatic lanthanide(III) carboxylates by ligand exchange reaction between the starting volatile components in the gas phase was proposed. The complexes Ln(Bz)₃ (Ln = La³⁺, Tb³⁺, Lu³⁺, HBz = benzoic acid) were synthesized by gas-phase ligand exchange reaction between the volatile Ln(Thd)₃ and HBz (HThd = 2,2,6,6-tetramethylheptane-3,5-dione). The composition of the complexes was confirmed by elemental, thermal, IR-spectroscopic, and photoluminescence analyses and, in the case of lanthanum and lutetium complexes, by ¹H NMR.     

Synthesis and magneto-spectral investigations of some six and nine coordinated complexes of lanthanides(III) derived from 4[N-(2′-hydroxy-1′-naphthalidene) amino]antipyrinethiosemicarbazone

The present work describes the synthesis and characterization of some six and nine coordinated complexes of trivalent lanthanide(III) with 4[N-(2′-hydroxy-1′-naphthalidene)amino]antipyrinethiosemicarbazone (HNAAPTS). All the complexes have the general composition LnX₃.n(HNAAPTS) (X = NO₃ ^?, n = 1; X = NCS^? or ClO₄ ^?, n = 2). The complexes were characterized through elemental analyses, molar mass, conductivity measurements, magnetic susceptibilities, and infrared and electronic spectra. Infrared spectra revealed that HNAAPTS acts as a neutral tridentate (N,N,S) donor. The coordination number in these complexes is either six or nine depending on the nature of the anionic ligand.     

Phosphonate complexes of 99mTc - Potential bone scintigraphy agents

The synthesis of several combined aminophosphonate ligands containing an N-carboxymethyl group is described. The complexes of these ligands were prepared both with ^99mTc and ⁹⁹Tc, and the dependence of their formation on pH and the stoichiometry of reagents was studied. All of the complexes were pharmacologically evaluated. The distribution of radioactivity and bone uptake were determined, and discussed in comparison with clinically used phosphonate complexes. This revised version was published online in August 2006 with corrections to the Cover Date.     

Novel tetradentate diamine dioxime ligands: synthesis,characterization and in vivo behavior of their 99mTc‐complexes

Two novel diamine dioxime ligands, 4,7‐diaza‐3,8‐diethyldecane‐2,9‐dione bis oxime (3) and 4,9‐diaza‐3,10‐diethyldodecane‐2,11‐dione bis oxime (5), were synthesized in order to develop new brain perfusion imaging agents, based on ^99mTc(V)‐complexes. The synthesis involved condensation of 2‐hydroxyimino‐3‐pentanone with appropriate diamine in protic solvent which afforded the bis imine adducts. Subsequent reduction of imine functional groups yielded a diastereoisomeric mixture of 3 and 5. UV–visible, IR, ¹H NMR, ¹³C NMR and elemental analysis were used to characterize the structures of the synthesized compounds. ^99mTc‐complexes of both diamine dioximes were prepared and radiolabeling conditions optimized to give the maximum yield. Physicochemical parameters of the labeled complexes as well as and their biodistribution in rats were investigated. Both compounds (3 and 5) formed ^99mTc‐complexes with a net charge of zero, determined by electrophoresis. The resultant lipophilic ^99mTc‐complexes of 3 and 5 were readily formed at pH ~9.0 within 10 min at room temperature with yields of 90% and 95%, respectively. The ^99mTc‐3 complex was found to be stable within 1 h, while ^99mTc‐5 was stable for a few hours. A significant brain uptake of ^99mTc‐3 (2.1% injected dose) and ^99mTc‐5 (1.8% injected dose) complexes, 2 min after injection, is in accordance with their lipophilicity. The present study suggests that both ligands are promising candidates as new ^99mTc‐based brain‐imaging agents. Copyright © 2012 John Wiley & Sons, Ltd.