Phenanthroline Derivatives Research Articles

Synthesis of phenanthroline derivatives by Sonogashira reaction and the use of their ruthenium complexes as optical sensors

The phenanthroline derivatives, which have alkynyl groups, were synthesized by palladium-catalyzed, Sonogashira cross-coupling reaction to provide the following coupled products: 4,7-bis(4-phenylethynyl-phenyl)-[1,10]phenanthroline ( 6a) and 4,7-bis{4-(4-hydroxy-buty-1-ynyl)-phenyl)-[1,10]phenanthroline ( 6b) at 87 and 89% yield, respectively. Their ruthenium complexes, tris{4,7-bis(4-phenylethynyl-phenyl)-[1,10]phenanthroline} ruthenium(II) bis(hexafluorophosphate) ( 7a) and tris[4,7-bis{4-(4-hydroxy-buty-1-ynyl)-phenyl)-[1, 10]phenanthroline}ruthenium(II)bis(hexafluoro-phosphate) ( 7b), were synthesized under mild conditions. The former showed relative fluorescence intensity changes between fully oxygenated and fully deoxygenated atmospheres, while the latter showed a linear fluorescence intensity response between pH 6 and 13.

Tuning Photophysical and Electrochemical Properties of Cationic Iridium(III) Complex Salts with Imidazolyl Substituents by Proton and Anions

A series of cationic iridium(III) complex salts, 1−5, were synthesized containing different phenanthroline derivatives. Their photophysical and electrochemical properties were investigated. The influences of anions and proton on the photophysical and electrochemical properties were also studied in detail. Upon addition of CF3COOH, the emission wavelength was significantly red-shifted and the emission color changed from yellow to red. In addition, the addition of F-, CH3COO-, and H2PO4- can also cause significant variations in UV−vis absorption and emission spectra. Upon addition of F-, CH3COO-, and H2PO4-, the solution colors of 1−3 changed from yellow-green to brown and the emission of 1−3 was quenched completely, which can be observed by the naked eye.

Differential modulation of Alzheimer's disease amyloid β-peptide accumulation by diverse classes of metal ligands

Biometals have an important role in AD (Alzheimer's disease) and metal ligands have been investigated as potential therapeutic agents for treatment of AD. In recent studies the 8HQ (8-hydroxyquinoline) derivative CQ (clioquinol) has shown promising results in animal models and small clinical trials; however, the actual mode of action in vivo is still being investigated. We previously reported that CQ-metal complexes up-regulated MMP (matrix metalloprotease) activity in vitro by activating PI3K (phosphoinositide 3-kinase) and JNK (c-jun N-terminal kinase), and that the increased MMP activity resulted in enhanced degradation of secreted Abeta (amyloid beta) peptide. In the present study, we have further investigated the biochemical mechanisms by which metal ligands affect Abeta metabolism. To achieve this, we measured the effects of diverse metal ligands on cellular metal uptake and secreted Abeta levels in cell culture. We report that different classes of metal ligands including 8HQ and phenanthroline derivatives and the sulfur compound PDTC (pyrrolidine dithiocarbamate) elevated cellular metal levels (copper and zinc), and resulted in substantial loss of secreted Abeta. Generally, the ability to inhibit Abeta levels correlated with a higher lipid solubility of the ligands and their capacity to increase metal uptake. However, we also identified several ligands that potently inhibited Abeta levels while only inducing minimal change to cellular metal levels. Metal ligands that inhibited Abeta levels [e.g. CQ, 8HQ, NC (neocuproine), 1,10-phenanthroline and PDTC] induced metal-dependent activation of PI3K and JNK, resulting in JNK-mediated up-regulation of metalloprotease activity and subsequent loss of secreted Abeta. The findings in the present study show that diverse metal ligands with high lipid solubility can elevate cellular metal levels resulting in metalloprotease-dependent inhibition of Abeta. Given that a structurally diverse array of ligands was assessed, the results are consistent with the effects being due to metal transport rather than the chelating ligand interacting directly with a receptor.

A novel zinc-chelating small molecule exhibits cancer cell growth inhibition in vitro and in vivo by induction of tumor suppressors early growth response 1 (Egr-1) and Krüppel-Like Factor 4 (KLF4)

14084 Background: Lead compound LT-253 was selected from a group of 2-indolyl imidazol [4,5-d] phenanthroline derivatives with anticancer activity. It shows potent and selective anti-proliferative activity against several human cancer types in vitro, and in vivo in xenograft mouse models of human colon carcinoma (HT-29) and non-small cell lung carcinoma (H460). Methods: The mechanism of cell growth inhibition of LT-253 was investigated in HT-29 colon cancer cells using the XTT cell proliferation assay, flow cytometry and apoptosis assays. In vitro and in vivo zinc chelation was determined by competition assays using fluorescent and chromophoric chelators. Gene expression studies were performed by human genome microarray analysis and confirmed by quantitative real- time PCR. The transcription factor activity profile of LT-253-treated cells was determined by a multiplex transcription factor array and electrophoretic mobility shift assays. The functional role of specific genes was evaluated by siRNA gene knock-down. Results: LT-253 functions as chelator of zinc in vitro, and of intracellular labile zinc in HT-29 cells. Moreover, LT-253-mediated HT-29 cell growth inhibition was reversed by zinc supplementation. Gene expression profiling confirmed sustained changes in zinc-sensitive genes such as metallothionine and several zinc transporters, but not copper-sensitive or iron-sensitive genes. LT-253 induces cancer cell growth inhibition primarily through G1/S phase cell cycle arrest. Gene expression and transcription factor activities of both Egr-1 and KLF4 are induced within 4 hr post LT-253 treatment. Moreover, increased expression of both Egr-1 and KLF4 is observed in LT-253-sensitive cancer cell lines of various origins. Importantly, Egr-1 and KLF4 gene knock-down by siRNA reversed the LT-253-mediated cell growth inhibition of HT-29 cells. Conclusion: Selective chelation of intracellular labile zinc pool by LT-253 triggers immediate induction of stress-responsive tumor suppressor Egr-1 and sustained induction of zinc-responsive tumor suppressor KLF4, leading to G1/S phase cell cycle arrest and inhibition of tumor growth. No significant financial relationships to disclose.

Highly Efficient Electron-transporting Phenanthroline Derivatives for Electroluminescent Devices

Abstract A series of phenanthroline derivatives containing quinoxaline moieties were synthesized, and their electron-transporting properties were investigated by using N,N′-di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (α-NPD) and tris(8-hydroxyquinolato)aluminum (Alq3) as the hole-transporting material and the emitting layer, respectively. Higher external quantum efficiency for the phenanthroline derivative than Alq3 in the electroluminescent devices at a luminance of 100 cd/m2 was obtained.

Effect of a New Phenanthroline Derivative on Testicular Tissue and Serum Testosterone Concentration and its Contraceptive Affects on Adult Balb/C Mouse Strain

In this research, the effect of 2, 6-diaminopyridinum as a new phenanthroline derivative was studied on the hypophysis-gonad axis, testicular tissue and sperm production in male Balb/C mice. Fifty adult male Balb/C mice were divided in five groups. First group was considered as untreated control. Saline was injected to second group and the remaining three groups received intraperitoneal injection of 15, 20 and 25 mg kg(-1) of 2, 6-diaminopyridinum every other day for 20 days. The LD50 was determined to be 35 mg kg(-1) body weight. The testicular tissues were studied morphologically and the serum concentration of FSH, LH and testosterone were measured. The results showed that 25 mg kg(-1) diaminopyridinum decreased the number of germ cells significantly and serum testosterone level with no change on FSH and LH levels. This study indicates that 25 mg kg(-1) of phenanthroline may directly affect testicular tissue causing a lower testosterone level and spermatogenesis in mice.

A New Branched Phenanthroline Derivative Ligand: Synthesis, Solution Chemistry, and Crystal Structures of Copper(II) and Zinc(II) Complexes

The synthesis and characterization of the new ligand 2,9-bis[N,N-bis(2-aminoethyl)aminomethyl]-1,10-phenanthroline (L) are reported. L contains two diethylenetriamine units connected on the central nitrogen atom by a 1,10-phenanthroline group forming a symmetrical branched ligand. The basicity and binding properties of L toward Cu(II) and Zn(II) in aqueous solution were determined by means of potentiometric, UV-vis, fluorescence, and 1H and 13C NMR techniques. L behaves as pentaprotic base under the experimental conditions used; from HL+ to H4L4+ species it is the secondary amine functions that are protonated while in the H5L5+ species also the phenanthroline is involved in protonation. L does not show fluorescence properties in the range of pH (0-14) investigated. It forms both mono- and dinuclear stable species where the phenanthroline is directly involved with both nitrogens in the coordination of the first metal which is coordinated in a pentacoordination environment also by one dien unit. The other dien unit undergoes easy protonation in the mononuclear complex while it binds the second metal in the dinuclear species. For this reason, L, in providing two different binding areas for metal coordination, behaves as an unsymmetrical compartmental ligand; one area is formed by one dien unit and by the phenanthroline, and the other by the remaining dien unit. This produces unsymmetrical metal complexes both for the mono- and dinuclear species; however, the role of the binding areas is fast exchanging in aqueous solution, at least on the NMR time scale. Solution studies and the three crystal structures of the [Zn(H2L)]4+, [[Cu(H2L)](ClO4)]3+, and [[Cu2LCl2](ClO4)]+ species highlight the unsymmetrical compartmental behavior of L as well as the host properties of the complexes in adding exogenous ligands such as hydroxide, pherchlorate, and chloride anions.

Photoelectron spectroscopy investigations of pyrrolophenanthroline derivatives

Thin films of new pyrrolo[1,2-a][1,10]phenanthroline derivatives have been investigated by ultraviolet photoelectron spectroscopy, with a view of future applications in optoelectronic devices. The electronic band structure of investigated compounds (for electron energies ⩽25eV) is to a great extent determined by substituent (R = NO2, Cl) induced transformations of molecular orbitals.

Study of thermal conversion and patterning of a new soluble poly ( p-phenylenevinylene) (PPV) precursor

The investigation of conversion of new soluble poly( p-phenylenevinylene) (PPV) precursor and PPV patterns by irradiation with UV light of a film is reported. We obtained patterns by this method with well-defined edges and channel width up to 10 μm. Also, it was found that the PPV precursor polymer is a photoresist material. This allows the fabrication of PPV patterns, which can directly act as luminescent structures in organic light-emitting diodes (OLEDs). Using the atomic force microscopy (AFM) technique, investigations on the PPV thin films show that at 200 °C well-defined crystalline domains of PPV are detected, thus indicating the complete transformation of the precursor into the final polymer. The current–voltage characteristics of single and double PPV layer devices indicate that turn-on voltages around 9 and 8 V were recorded for double and single PPV layer devices, respectively. From the electroluminescence–voltage plot, an onset voltage at 10 V is detected for two PPV layers OLED. In addition, we investigate the optical, electrical and EL characteristics of pyrrolo[1,2-a][1,10]phenanthroline derivatives [Leontie L, Druta I, Danac R, Rusu GI. Synth Met 2005;155/1:138; Zugravescu I, Petrovanu M. 3+2 Dipolar cycloaddition. Bucharest: Roman Academic Publishing House; 1987 [in Romanian]; Druta I, Andrei M, Aburel P. Tetrahedron 1998;54:2107; Druta I, Dinica R, Bacu E, Humelnicu I. Tetrahedron 1998;54:10811; Dinica R, Druta I, Pettinari C. Synlett 2000;7:1013; Danac R, Rotaru A, Drochioiu G, Druta I. J Heterocyclic Chem 2003;40:283; Druta I, Danac R, Barbieru R, Tapu D, Andrei M. Sci Ann Al I Cuza Univ Iasi S Chem 2001;IX:149] as potential candidates for OLED applications. In this case, PPV was used as the hole-transport layer (HTL) and pyrrolo[1,2-a][1,10]phenanthroline derivatives, which were spin coated onto PPV, as the emissive layer. The structure of all PPV devices reported in this paper was fabricated using UV light for patterning.

Reaction of 6‐Aminoquinoline with Formaldehyde and Cyclic β‐Diketones. Synthesis of Benzo[b]‐ (V) and Indeno[2,1‐b][4,7]phenanthroline Derivatives (VIII).

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of Benzo[c][1,8]phenanthrolin‐6‐one Through Cyclization of N‐(Isoquinol‐5‐yl)‐2‐bromo‐benzamide Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Novel platinum(ii)-based anticancer complexes and molecular hosts as their drug delivery vehicles

Platinum(II)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure-activity relationship. The most cytotoxic are those that contain methylated-phenanthroline ligands and 1S,2S-diaminocyclohexane (S,S-dach) as the ancillary ligand. We have developed a new purification method using Sep-Pak C-18 reverse phase columns, which means these metal complexes can be made faster and cheaper compared to published methods. Platinum(II)-based complexes containing imidazole, pyrrole and beta-alanine subunits, that are capable of recognising specific DNA base-pair sequences have also been synthesised. These include linear or hairpin polyamide ligands that can recognise DNA sequences up to seven base-pairs in length and contain single platinum centres capable of forming monofunctional adducts with DNA. We have now synthesised and characterised, by (1)H and (195)Pt NMR, ESI-MS and elemental analysis, the first dinuclear platinum(II) DNA sequence selective agent. Finally, using (1)H NMR we have examined the encapsulation of our platinum(II)-based DNA intercalators by cucurbit[6]uril (CB[6]). Encapsulation by CB[6] was found to not significantly change the cytotoxicity of five platinum(II)-based DNA intercalators, indicating it may have utility as a molecular carrier for improved drug delivery.

Self-Assembled Monolayers Based on Phenanthroline−Gold(111) Bonding

The self-assembly of long-alkyl-chain substituted phenanthroline derivatives on highly oriented pyrolitic graphite (HOPG) and gold(111) is compared. Whereas the adsorption on HOPG is controlled by the affinity of alkyl chains for the substrate, which leads to flat-lying adsorbed molecules, alignments of upright-oriented molecules are formed on gold(111). This situation is explained by the bonding of chelating species with gold(111) surfaces and by the pi-stacking interaction between conjugated moieties. This intermediate situation between strong thiol-like chemical bonding and the weak n-alkane-like physical adsorption opens the route toward laterally organized functional molecular assemblies.

Synthesis of phenanthroline derivative by Suzuki coupling reaction and the use of its ruthenium complex as an optical pH sensor

A phenanthroline derivative, which has an aniline group, was synthesized by palladium catalyzed Suzuki cross coupling reactions. The aryl phosphine ligand, PPh3, showed higher activity than the alkyl phosphines, P(tBu)3 and PCy3, in the Suzuki couplings and provided the coupled product, 4-phenyl-7-(4′-amino-biphenyl-4-yl)-[1,10]phenanthroline (5), with 73% yield. Its ruthenium complex, bis(4,7-diphenyl-[1,10]phenanthroline){4-phenyl-7-(4′-amino-biphenyl-4-yl)-[1,10]phenanthroline} ruthenium(II) bis(hexafluorophosphate) (8), was synthesized under mild conditions. This complex showed a linear fluorescence intensity response between pH 3.5 and pH 8.5.

Synthesis of New Phenanthroline‐Based Heteroditopic Ligands – Highly Efficient and Selective Fluorescence Sensors for Copper(II) Ions

AbstractThe heteroditopic phenanthroline derivatives 5,6‐bis(2‐pyridylcarboxamido)‐1,10‐phenanthroline (H2L1) and 5,6‐bis[(4‐methoxy‐2‐pyridyl)carboxamido]‐1,10‐phenanthroline (H2L2) have been prepared and characterized, together with their luminescent ruthenium(II) complexes [Ru(bpy)2(H2L1,2)](PF6)2 and [Ru(H2L1)3](PF6)2 and the corresponding iron(II) complex [Fe(H2L1)3](PF6)2. In these complexes, the metal ion is coordinated by the bidentate phen site of H2L. The luminescence of the ruthenium complexes (λex = 450 nm, λem ca. 620 nm) is completely quenched by Cu2+ ions in the micromolar concentration range and, to a lesser extent, by other metal ions. At pH 5, the response of the luminescent sensors is highly Cu2+‐selective. Heterodinuclear complexes [Ru(bpy)2(LM)](PF6)2, [Ru(LM)3](PF6)2, and [Fe(LM)3](PF6)2 have been isolated for M = Cu2+, Ni2+, Co2+, and Pd2+. It is suggested that M is coordinated to the tetradentate N4 site of L by two deprotonated amide N atoms and two pyridyl groups. This coordination type is confirmed by the EPR spectrum of the compound [RuII(bpy)2(L1CuII)](PF6)2.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Dynamic combinatorial library for fullerene receptors based on metal-assisted self-assembly

A dynamic combinatorial library was prepared by the metal-induced self-assembly of phenanthroline derivatives having a guest binding unit. The binding assay using ESI mass spectrometry found out the effective combination of guest binding units for fullerene binding.

Reaction of 6-aminoquinoline with formaldehyde and cyclic β-diketones. Synthesis of benzo[b]-and indeno[2,1-b][4,7]-phenanthroline derivatives

Three-component condensation of 6-aminoquinoline with formaldehyde and cyclic β-diketones (cyclohexane-1,3-dione and dimedone) gave new partially hydrogenated benzo[b][4,7]phenanthroline derivatives. An analogous reaction with indan-1,3-dione gave indeno[2,1-b][4,7]phenanthroline derivatives. The products were subjected to oxidative dehydrogenation.

Synthesis of benzo[c][1,8]phenanthrolin-6-one through cyclization ofN-(isoquinol-5-yl)-2-bromo-benzamide derivatives

In the course of our search for compounds with potential antitumor properties we have undertaken the synthesis of benzo[c][1,8]phenanthroline derivatives. Our project required the preparation of 8,9-dimethoxy benzo[c][1,8]phenanthrolin-6-ones. This was first attempted by the lithiumdiisopropylamide cyclization of N-(isoquinol-5-yl)-2-bromo-4,5-dimethoxybenzamide. The reaction led to 40% of the unexpected internal Diels-Alder adduct 3,4-dimethoxy-6H-pyrido[2,3-i]6,8a-ethenoindolo[cd]isoquinoline-2(1H)-one, which arose from a benzyne intermediate. In a second and more successful approach, the internal biaryl palladium diacetate-assisted coupling reaction of properly N-protected N-(isoquinol-5-yl)-2-bromo-4,5-dimethoxybenzamide was studied. The optimisation of the protecting group necessary for this procedure led to a 64% yield of the target compound starting from N,N-(isoquinol-5-yl)-bis-(2-bromo-4,5-dimethoxybenzamide).

Vanillin Esters of Aromatic Carboxylic Acids in the Synthesis of Benzo[a]acridine and Benzo[b][4,7]phenanthroline Derivatives.

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Synthesis of 5,6‐Dihydro[1,10]phenanthroline Derivatives and Their Properties as Hole‐Blocking Layer Materials for Phosphorescent Organic Light‐Emitting Diodes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.