The formation and characterization of copper(II) 1,4-benzenediolate and p-semiquinonate complexes

Strongly oxidizing p-quinones such as tetrachloro-1,4-benzoquinone and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone undergo stepwise oxidative addition reactions with copper(I) chloride and bromide in pyridine resulting in copper(II) p-semiquinone and dinuclear copper(II) 1,4-benzenediolate pyridine complexes.     

Cellulase activity and localization during induced abscission of Coleus blumei

Treatment with dimethipin (2,3-dihydro-5,6-dimethyl-1,4-dithiin 1,1,4,4 tetroxide) inhibited the increase in cellulase activity and decrease in breakstrength associated with the normal course of abscission in Coleus. Application of the surfactant UBI-1126 (Emery OAL 20 in isopropyl alcohol) increased cellulase activity and accelerated the process of abscission in Coleus expiants within 24 h of application. Cellulase activity was localized histochemically at the electron microscopic level in surfactant-treated tissue. The enzyme activity was localized primarily in the cell wall, middle lamella, and paramural bodies of abscission zone cells.     

Antileukemic activity and cellular effects of rhodium(III) crown thiaether complexes

The cytostatic properties of novel rhodium(III) thiacrown ether complexes [RhCl(LL)([9]aneS₃)]ⁿ⁺ with either aromatic κ² N ligands (n = 2) or anionic chelate ligands (n = 1) have been investigated for the human cancer cell lines HT-29 and MCF-7 and for immortalized HEK-293 cells. Taken together with literature IC₅₀ values for analogous complexes with polypyridyl ligands or 1,4-dithiane, the in vitro assays indicate that dicationic complexes with soft κ² N (imino) or κ² S (thiaether) ligands exhibit significantly higher antiproliferative effects than those with hard κ² N (amino) ligands. Dicationic complexes are more active than monocationic complexes with similar ligands. Pronounced apoptosis-inducing properties towards Jurkat cells were established for complexes with LL = bpm, dpq, and 1,4-dithiane. The order of activity (bpm > 1,4-dithiane > dpq > bpy) contrasts to that observed for adhesive cancer cells (bpm > bpy, 1,4-dithiane > dpq). Necrosis is insignificant in all cases. The percentage of Jurkat cells exhibiting apoptosis after 24 or 48 h incubation periods is directly correlated to the percentage of cells exhibiting high levels of reactive oxygen species. As established by online monitoring with a sensor chip system, treatment of MCF-7 cells with the bpm and 1,4-dithiane complexes leads to a significant and permanent concentration-dependent decrease in oxygen consumption and cellular adhesion.     

Twisted paddlewheel rhodium complexes: Contribution of central and axial chirality to ECD,VCD, and NMR spectra

Dirhodium complexes bearing N-substituted chiral amino acid ligands are investigated. These complexes have an unusual twisted paddlewheel structure, showing inherent chirality. We would like to demonstrate that parallel application of chiroptical spectroscopic methods (ECD and VCD) and NMR spectroscopy combined with quantum chemical calculations constitutes a powerful tool to determine the configuration of the complexes unequivocally. Two chiroptical methods are needed to determine the absolute configuration: ECD for the coordinated nitrogen atom and VCD for the rhodium core. A quick to use NMR method is also presented: Upon the coordination of small molecules in the axial position, the relative configuration of both the rhodium core and the nitrogen atom can be determined simultaneously by studying spatial proximities provided by 1D NOE spectra.     

Mixed ligand ruthenium(II) complexes of 5,6-dimethyl-1,10-phenanthroline: The role of ligand hydrophobicity on DNA binding of the complexes

A series of mixed ligand Ru(II) complexes of 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) as primary ligand and 1,10-phenanthroline (phen), 2,2′-bipyridine (bpy), pyridine (py) and NH₃ as co-ligands have been prepared and characterized by X-ray crystallography, elemental analysis and ¹H NMR and electronic absorption spectroscopy. The X-ray crystal structure of the complex [Ru(phen)₂(bpy)]Cl₂ reveals a distorted octahedral coordination geometry for the RuN₆ coordination sphere. The DNA binding constants obtained from the absorption spectral titrations decrease in the order, tris(5,6-dmp)Ru(II) > bis(5,6-dmp)Ru(II) > mono(5,6-dmp)Ru(II), which is consistent with the trend in apparent emission enhancement of the complexes on binding to DNA. These observations reveal that the DNA binding affinity of the complexes depend upon the number of 5,6-dmp ligands and hence the hydrophobic interaction of 5,6-dimethyl groups on the DNA surface, which is critical in determining the DNA binding affinity and the solvent accessibility of the exciplex. Among the bis(5,6-dmp)Ru(II) complexes, those with monodentate py (4) or NH₃ (5) co-ligands show DNA binding affinities slightly higher than the bpy and phen analogues. This reveals that they interact with DNA through the co-ligands while both the 5,6-dmp ligands interact with the exterior of the DNA surface. All these observations are supported by thermal denaturation and viscosity measurements. Two DNA binding modes - surface/electrostatic and strong hydrophobic/partial intercalative DNA interaction - are suggested for the mixed ligand complexes on the basis of time-resolved emission measurements. Interestingly, the 5,6-dmp ligands promote aggregation of the complexes on the DNA helix as a helical nanotemplate, as evidenced by induced CD signals in the UV region. The ionic strength variation experiments and competitive DNA binding studies on bis(5,6-dmp)Ru(II) complexes reveal that EthBr and the partially intercalated and kinetically inert [Ru(phen)₂(dppz)]²⁺ (dppz = dipyrido[3,2-a:2′,3′-c]phenazine) complexes revert the CD signals induced by exciton coupling of the DNA-bound complexes with the free complexes in solution.     

Vibrational and electronic circular dichroism monitoring of copper(II) coordination with a chiral ligand

Novel copper(II) coordination compounds with chiral macrocyclic imine ligands derived from R-/S-camphor were asymmetrically synthesized and characterized with the aid of chiroptical spectroscopies. Crystal structures of both enantiomers were determined by single crystal X-ray diffraction analysis. Circular dichroism (CD) spectra were analyzed using a simplified exciton model as well as quantum chemical computations. The absolute configuration of the copper(II) coordination compounds determined from CD was found consistent with the crystal data. The copper(II) complexes were further investigated by vibrational CD (VCD) measurement combined with density functional theory calculation. The complex formation was evidenced by spectral shifts of the characteristic bands in the CD and VCD spectra.     

Structures and electrochemistry of monomeric and dimeric CpCo(dithiolene) complexes with substituted benzene-1,2-dithiolate ligand

The molecular structures of [CpCo(tdt)] and [CpCo(Cl₃bdt)] were determined by X-ray diffraction studies. [CpCo(tdt)] was monomeric in the crystal, coordinatively unsaturated with 16-electrons and had a two-legged piano-stool geometry. [CpCo(Cl₃bdt)] was dimeric, coordinatively saturated with 18-electrons and became a three-legged piano-stool geometry. There were two crystallographically independent molecules in [CpCo(tdt)] and both molecules were associated with intermolecular Cp?Cp face-to-face interaction. Some intermolecular Co?S interactions were also observed between the crystallographically identical molecules of [CpCo(tdt)]. The cyclic voltammograms of [CpCo(tdt)] and [CpCo(Cl₂bdt)] exhibited single oxidation waves, but those of [CpCo(Cl₃bdt)] and [CpCo(Cl₄bdt)] showed two oxidation waves due to both the monomer and dimer in the solutions. Electrochemical oxidations of these monomers occurred dimerizations by EC reactions in the solutions, and the oxidized dimers could be rereduced to form the original monomers by EC reactions. Spectroelectrochemical data using OTTLE supported the reversible ECEC reactions. Abbreviations of dithiolene ligands are as follows: tdt = toluene-3,4-dithiolate, Cl₂bdt = 3,6-dichlorobenzene-1,2-dithiolate, Cl₃bdt = 3,4,6-trichlorobenzene-1,2-dithiolate, and Cl₄bdt = tetrachlorobenzene-1,2-dithiolate.     

The mitochondrial benzodiazepine receptor: Evidence for association with the voltage-dependent anion channel (VDAC)

Specific, high-affinity receptors for numerous drugs have recently been localized to mitochondrial membrane proteins. This review discusses the association of the mitochondrial receptor for benzodiazepines (mBzR) with the voltage-dependent anion channel (VDAC), indicating a possible auxiliary role for VDAC as a putative drug binding protein. The proposed subunit composition of the purified mBzR complex isolated from rat kidney mitochondria includes VDAC, which functions as a recognition site for benzodiazepines (e.g., flunitrazepam), the adenine nucleotide carrier (ADC), and an 18 kDa outer membrane protein identified by covalent labelling with the mBzR antagonists isoquinoline carboxamides (e.g., PK 14105).Abbreviations and chemical names: Ro5-4864: 7-chloro-1,3-dihydro-1-methyl-5-(p-chlorophenyl)-2H-1,4-benzodiazepin-2-one; Ro15-1788: ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-]-[1,4]benzodiazepine-3-carboxylate; AHN-086: (1-(2-isothiocyanatoethyl-7-chloro-1,3-dihydro-5-(4-chlorophenyl)-2H-1,4-benzodiazepin-2-one hydrochloride;) PK11195: 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-isoquinoline-3-carboxamide; PK14105: 1-(2-fluoro-5-nitrophenyl)-3-isoquinoline-carboxylic acid.     

Synthesis and chiroptical properties of organometallic complexes of helicenic N‐heterocyclic carbenes

Novel [4, 6]helicenes ( 4a,b ) bearing a fused imidazolium unit have been prepared from [4, 6]helicene‐2,3‐di‐n‐propyl‐amines 3a,b . The in situ formation of N‐heterocyclic carbene (NHC) derivatives followed by their complexation to iridium(I) or rhodium(I) gave access to complexes 1a , 1′a , and 1b , containing mono‐coordinated helicene‐NHC, chloro and COD (COD = 1,5‐cyclooctadiene) ligands. Ir and Rh complexes 1a and 1′a were characterized by X‐ray crystallography. HPLC and NMR analyses showed that Ir(I) complex 1b existed as a mixture of two diastereomeric complexes corresponding to enantiomeric pairs M‐(?)/P‐(+)‐ 1b ¹ and M‐(?)/P‐(+)‐ 1b ² which differ by the position of COD through space. The chiroptical properties (electronic circular dichroism and optical rotation) of the four stereoisomers were measured. These complexes were also tested as catalysts in a transfer hydrogenation reaction.     

A Versatile Synthesis of Enantiomerically Pure D- and L-Pyranosyl Nucleoside Analogues

Abstract

2-[[O-(p-Methoxybenzyl)-oxy]methyl]-5,6-dihydro-1,4-dithiin 1 is a versatile three carbon homologation reagent which has been conveniently used in the synthesis of enantiomerically pure modified nucleosides.     

Solid state and solution NMR, X-ray and antimicrobial studies of 1:1 and 2:1 complexes of silver(I) cyanide with alkanediamine ligands

Several complexes of AgCN with alkanediamine ligands (where the ligands are ethylenediamine, propane-1,3-diamine, butane-1,4-diamine, N,N′-dimethyl-ethylenediamine, N,N′-di-iso-propyl-ethylenediamine, etc.) have been synthesized and structurally characterized. In these species, alkanediamine ligands act as chelating ligands. The X-ray structure of the complex cyano-(N,N′-di-iso-propyl-ethylenediamine)-silver(I) was determined. These complexes have been also characterized by IR, solution as well as solid-state NMR studies. There are two types of IR absorptions observed for mono and dinuclear complexes. For the mono nuclear complexes, a sharp CN band is observed between 2111 and 2131 cm⁻¹ range, whereas for binuclear complexes the bands are in the range 2136-2140 cm⁻¹. The effect of the size of the ligands as well as their substituents is discussed. The antimicrobial activity studies of AgCN and its complexes show that the former exhibits substantial antibacterial activities compared to its complexes.     

Chirality induction in cyclocopolymerization of bis(p-vinylbenzoate)s of carbohydrates with styrene: Chiroptical study of resulting polymer by exciton chirality method

Three bis(p-vinylbenzoate) monomers, 2,3-O-isopropylidene-1,4-bis-O-(p-vinylbenzoyl)-L-threitol (BIT), methyl 4,6-O-isopropylidene-2,3-bis-O-(p-vinylbenzoyl)-α,D -glucopyranoside (BIG), and 1,2:5,6-di-O-isopropylidene-3,4-bis-O(p-vinylbenzoyl)-D-mannitol (BIM), were prepared and cyclocopolymerized with styrene. The resulting copolymers were hydrolyzed with KOH to remove the chiral template, and treated with diazomethane to give poly[(methyl p-vinylbenzoate)-co-styrene] [poly(MVB-co-St)]. All the poly(MVB-co-St) had a specific rotation and their CD spectra exhibit a split Cotton effect. Poly(MVB-co-St) derived from poly(BIT-co-St) showed a positive Cotton effect at 255 nm and a negative one at 235 nm. According to the exciton chirality method, poly(MVB-co-St) possessed negative chirality, and the stereochemistry of the carbon atom attached to the 4-benzoyl group had the S configuration. The absolute configuration of poly(MVB-co-St) was determined as R for the BIG/St system and S for the BIM/St system. © 1995 Wiley-Liss, Inc.     

Novel N-quinonyl amino acids and their transformation to 3-substituted p-isoxazinones

Summary. Quinonyl amino acids are building blocks in the preparation of peptides which target the quinonic drug to cancer damaged area. Novel N-(3-chloro-1,4-dihydro-1,4-dioxonaphthalen-2-yl)-α-amino acids 1a–f were prepared by direct substitution of 2,3-dichloro-1,4-naphthoquinone. The quinonic moiety was reduced by NaBH₄ to yield the corresponding hydroquinones 2a–f, which in acidic conditions underwent internal cyclization to yield the 3,4-dihydro-2H-naphth[1,2-b]-1,4-oxazine-2-ones (six-membered azlactones) 3a–f. Received February 2, 2000 Accepted March 29, 2000     

DNA binding and cleavage activity of [Ru(NH3)4(diimine)]Cl2 complexes

The interaction of a series of mixed ligand complexes of the type [Ru(NH₃)₄(diimine)]Cl₂, where diimine=2,2^′-bipyridine (bipy), 1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp), 4,7-dimethyl-1,10-phenanthroline (4,7-dmp), 2,9-dimethyl-1,10-phenanthroline (2,9-dmp), 3,4,7,8-tetra-methyl-1,10-phenanthroline (Me₄phen), with calf thymus DNA has been studied using absorption, emission and circular dichroic spectral measurements and viscometry and electrochemical techniques. On interaction with DNA the complexes show hypochromism and red-shift in their MLCT band suggesting that the complexes bind to DNA. The magnitude of the binding constant (K_b) obtained from absorption spectral titration varies depending upon the nature of the diimine ligand: Me₄phen > 5,6-dmp > 4,7-dmp > phen suggesting the use of diimine ‘face’ of the octahedral complexes in binding to DNA. The interaction of phen complex possibly involves phen ring partially inserted into the DNA base pairs. In contrast, the methyl-substituted phen complexes would involve hydrophobic interaction of the phen ring in the grooves of DNA, which is supported by hydrogen bonding interactions of the ammonia ligands with the intrastrand nucleobases. Also the shape and size of the phen ligand as modified by the methyl substituents determine the DNA binding site sizes (0.12-0.45 base pairs). The relative emission intensities (I/I₀) of the DNA-bound complexes parallel the variation in K_b values. Almost all the metal complexes exhibit induced CD bands on binding to B DNA, with the 4,7-dmp and Me₄phen complexes inducing certain structural modifications on the biopolymer. DNA melting curves obtained in the presence of metal complexes reveal a monophasic melting of the DNA strands, the Me₄phen complex exhibiting a slightly enhanced tendency to stabilize the double-stranded DNA. There were slight to appreciable changes in the relative viscosities of DNA, which are consistent with enhanced hydrophobic interaction of the methyl-substituted phen rings. Upon interaction with CT DNA, the Me₄phen, 4,7-dmp and 5,6-dmp complexes, in contrast to bipy, phen and 2,9-dmp complexes, show a decrease in anodic peak current in their cyclic voltammograms suggesting that they exhibit enhanced DNA binding. DNA cleavage experiments show that all the complexes induce cleavage of pBR322 plasmid DNA, the Me₄phen and 5,6-dmp complexes being remarkably more efficient than other complexes.     

Design,synthesis and evaluation of novel 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenyl-3,4-substituted phenyl methanone analogues

In present investigation, a series of substituted phenyl-5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenylmethanone analogues were synthesized and were tested for their potential for treating AD disease. All the newly synthesized compounds were showing moderate to high AChE inhibitory activities, with compound 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-2-indenyl-3,4,5-trimethoxyphenylmethanone (5f) produced significant activities with 2.7 ± 0.01 μmol/L.     

Comparison of Soybean Tissue Extracted with Different Solvents

The enantioselective hydrolysis of (R,S)-3-acetoxymethyl-7,8-difluoro-2,3-dihydro-4H-[1,4]benzoxazine (I) with enzymes was investigated. Optically active I and its hydrolyzate, 7,8-difluoro-2,3-dihydro-3-hydroxymethyl-4H-[1,4]benzoxazine (II), are the intermediates for preparing optically active ofloxacins, whose racemate is known to be an excellent antibacterial agent. Lipoprotein lipase from Pseudomonas fluorescens (LPL Amano 3) was found to predominantly hydrolyze (S)-I, giving (R)-I in 54% e.e. and (R)-II in 44% e.e. On the other hand, lipase from Candida cylindracea was found to predominantly hydrolyze (R)-I, giving (S)-I in 24% e.e. and (S)-II in 20% e.e. Since, the optical purities of I and II thus obtained were not particularly high, these optically active I and II were converted into 3-acetoxymethyl-7,8-difluoro-2,3-dihydro-4-(3,5-dinitrobenzoyl)-4H-[1,4]benzoxazine (IV). After recrystallizing IV from ethyl acetate-hexane, (S)- and (R)-II were obtained with high enantiomeric excess by removing the crystallized racemic IV and subsequently hydrolyzing the resulting optically active IV with alkali. The reduction of II afforded 7,8-difluoro-2,3-dihydro-3-methyl-4H-[1,4]benzoxazine (III), for which the optical purity was estimated to be >96%e.e. by HPLC analysis. (R)- and (S)-ofloxacin were prepared from (R)- and (S)-III with retention of their configuration.     

Spectroelectrochemical studies of some ruthenium(II) complexes with polypyridyl bridging ligands

Ruthenium(II) bis(2,2″-pyridyl) complexes with bridging ligands: 6,7-dichloro-2,3-di(2-pyridyl)quinoxaline; 2,3-di(2-pyridyl)-quinoxaline; 5-methyl-2,3-di(2-pyridyl) quinoxaline; 6,7-dibenzo-2,3-di(2-pyridyl)quinoxaline have been prepared. The electrochemical and spectroscopic properties of these complexes are reported. The resonance Raman spectroelectrochemical results indicate the presence of oxidation state sensitive marker bands in the resonance Raman spectra of the oxidized complexes. The spectroscopic data for the reduced complexes is similar for all four species. The resonance Raman data for the reduced species are dominated by 2,2″-bipyridyl vibrations.     

Urinary 8-epi-PGF2alpha and its endogenous beta-oxidation products (2,3-dinor and 2,3-dinor-5,6-dihydro) as biomarkers of total body oxidative stress

Although measurements of plasma F2-isoprostanes are established markers of oxidative stress, their quantification only reflects acute non-enzymatic lipid peroxidation. In this study, a new approach is described for the rapid isolation and measurement of urinary 8-epi-PGF2alpha and its endogenous beta-oxidation metabolites (2,3-dinor-8-epi-PGF2alpha and 2,3-dinor-5,6-dihydro-PGF2alpha) for use as index of total body oxidative stress. Isoprostanes were partitioned with ethyl acetate and subsequently purified by chromatography on an aminopropyl (NH2) and silica (Si) cartridge. Final analysis of F2-isoprostanes as trimethylsilyl-ester/pentafluorobenzyl ester derivatives was carried out by stable isotope dilution mass spectrometry. Overall recovery of F2-isoprostanes was 80+/-4%. Inter- and intra-assay coefficients of variation were 5% and 7%, respectively. In a group of healthy humans, the mean excretion rates expressed as nmol/mmol creatinine for 2,3-dinor-8-epi-PGF2alpha, 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha, and 8-epi-PGF2alpha were 5.43+/-1.93, 2.16+/-0.71, and 0.36+/-0.16, respectively. Correlations were obtained between 8-epi-PGF2alpha and 2,3-dinor-8-epi-PGF2alpha or 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.998 and r=0.937, respectively). A strong relationship was also seen between 2,3-dinor-8-epi-PGF2 and 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.949). The new technique allows for high sample throughput and avoids the need for HPLC and/or other expensive equipment required for the initial sample preparation. Simultaneous analysis of urinary 8-epi-PGF2alpha and its metabolites should provide unique tool in clinical trials exploring the role of oxidant injury in human disease.     

Metal complexs of poly (α-amino acids): Cu(II) chelates of acetoacetylated poly(L-lysine), poly(L-ornithine), and poly(L-diaminobutyric acid)

The cupric complexes of poly(N^ε-acetoacetyl-L -lysine), [Lys(Acac)]_n′ poly(N^δ-acetoacetyl-L -ornithine), [Orn(Acac)]_n′ and poly(N^γ-acetoacetyl-L -diaminobutyric acid), [A₂bu-(Acac)]_n, as well as of the model compound n-hexyl acetoacetamide, have been investigated by means of absorption, potentiometric, equilibrium dialysis, and CD measurements. While in the complex of the model compound, one chelating group is bound to one cupric ion, in the polymeric complexes two β-ketoamide groups are bound to Cu(II) under the same experimental conditions. The binding constant of cupric ions to the three polymers and the formation constant of the Cu(II)-nhexylacetoacetamide complex have been evluated. Investigation on the chiroptical properties of the three polymeric complexes shows that the peptide backbone does not undergo conformational transitions, remaining α-helical when up to 20% of the side chains are bound to Cu(II). The optical activity of the β-ketoamide chromophores is substantially affected by complex formation and is discussed in terms of asymmetric induction from the chiral backbone.