- Superoxide dismutase activity of iron(II)TPEN complex and its derivatives
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Superoxide is involved in the pathogenesis of various diseases, such as inflammation, ischemia-reperfusion injury and carcinogenesis. Superoxide dismutases (SODs) catalyze the disproportionation reaction of superoxide to produce oxygen and hydrogen peroxide, and can protect living cells against the toxicity of free radicals derived from oxygen. Thus, SODs and their functional mimics have potential value as pharmaceuticals. We have previously reported that Fe(II)tetrakis-N,N,N',N'-(2-pyridylmethyl)ethylenediamine (Fe(II)TPEN) has an excellent SOD activity (IC50=0.5 μM) among many iron complexes examined (J. Biol. Chem., 264, 9243-9249 (1989)). Fe(II)TPEN can act like native SOD in living cells, and protect Escherichia coli cells from free radical toxicity caused by paraquat. In order to develop more effective SOD functional mimics, we synthesized Fe(II)TPEN derivatives with electron-donating or electron-withdrawing groups at the 4-position of all pyridines of TPEN, and measured the SOD activities and the redox potentials of these complexes. Fe(II) tetrakis-N,N,N',N'-(4-methoxy-2-pyridylmethyl)ethylenediamine (Fe(II)(4MeO)4TPEN) had the highest SOD activity (IC50=0.1 μM) among these iron-based SOD mimics. In addition, a good correlation was found between the redox potential and the SOD activity of 15 Fe(II) complexes, including iron-based SOD mimics reported in the previous paper (J. Organometal. Chem., in press). Iron-based SOD mimics may be clinically applicable, because these complexes are generally tissue-permeable and show low toxicity. Therefore our findings should be significant for the development of clinically useful SOD mimics.
- Tamura,Urano,Kikuchi,Higuchi,Hirobe,Nagano
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- Synthesis and Characterization of the Most Active Copper ATRP Catalyst Based on Tris[(4-dimethylaminopyridyl)methyl]amine
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The tris[(4-dimethylaminopyridyl)methyl]amine (TPMANMe2) as a ligand for copper-catalyzed atom transfer radical polymerization (ATRP) is reported. In solution, the [CuI(TPMANMe2)Br] complex shows fluxionality by variable-temperature NMR, indicating rapid ligand exchange. In the solid state, the [CuII(TPMANMe2)Br][Br] complex exhibits a slightly distorted trigonal bipyramidal geometry (τ = 0.89). The UV-vis spectrum of [CuII(TPMANMe2)Br]+ salts is similar to those of other pyridine-based ATRP catalysts. Electrochemical studies of [Cu(TPMANMe2)]2+ and [Cu(TPMANMe2)Br]+ showed highly negative redox potentials (E1/2 = -302 and -554 mV vs SCE, respectively), suggesting unprecedented ATRP catalytic activity. Cyclic voltammetry (CV) in the presence of methyl 2-bromopropionate (MBrP; acrylate mimic) was used to determine activation rate constant ka = 1.1 × 106 M-1 s-1, confirming the extremely high catalyst reactivity. In the presence of the more active ethyl α-bromoisobutyrate (EBiB; methacrylate mimic), total catalysis was observed and an activation rate constant ka = 7.2 × 106 M-1 s-1 was calculated with values of KATRP ≈ 1. ATRP of methyl acrylate showed a well-controlled polymerization using as little as 10 ppm of catalyst relative to monomer, while side reactions such as CuI-catalyzed radical termination (CRT) could be suppressed due to the low concentration of L/CuI at a steady state.
- Ribelli, Thomas G.,Fantin, Marco,Daran, Jean-Claude,Augustine, Kyle F.,Poli, Rinaldo,Matyjaszewski, Krzysztof
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- THE PREPARATION OF 4- AND 6-CHLORO-2-CHLOROMETHYLPYRIDINE
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6-Chloro-2-chloromethylpyridine is prepared from 6-chloro-2-methylpyridine by a route in which the 2-Me substituent was successively converted to 2-acetoxymethyl, 2-hydroxymethyl and finaly to the required 2-chloromethyl substituent.Attempts to simultaneously monochlorinate the Me group and reduce the N-oxide function of 6-chloro-2-methylpyridine-N-oxide with methanesulphonyl chloride and p-toluenesulphonyl chloride gave only very small yields of 6-chloro-2-chloromethyl-pyridine. 4-Chloro-2-chloromethylpyridine is prepared from 2-methylpyridine-N-oxide by nitration, followed by substitution of the 4-nitro group by chloro using conc HCl; side chain chlorination of the 2-Me group using p-toluenesulphonyl chloride yields 4-chloro-2-chloromethylpyridine.Phosphoryl chloride reacts with 2-chloromethylpyridine-N-oxide hydrochloride to yield only 14.4percent of 4-chloro-2-chloromethylpyridine, together with 2-chloromethylpyridine (2.2percent), 2-dichloromethylpyridine (41.6percent) and 6-chloro-2-chloromethylpyridine (41.8percent).Attempts to N-oxidise 2-chloromethylpyridine with peracids led to either 2-hydroxymethylpyridine (peracetic, m-chloroperbenzoic and performic acid) or no reaction (perfluoroacetic acid); none of the peracids led to any detectable N-oxidation.
- Barnes, John H.,Hartley, Frank R.,Jones, Christopher E. L.
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- Multiple Sulfonation of Picolyl-Based Complexes Rendering Them Highly Water-Compatible
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Multidentate ligands chosen for the complexation of hard metals frequently exhibit negative charges, which consequently elicits Coulombic compensation of the metal-ion charge. However, ligands favored by soft metal ions are neutral, which prevents the chemist from obtaining electroneutral complexes, let alone ones with a negative total charge. Here, we report on an efficient synthetic method to decorate picolyl-displaying coordination compounds with multiple sulfonate units at their periphery. We further describe rare anionic versions of three standard complexes that have only been characterized as cationic so far. Our sulfonated complexes show extensive water solubility, which confers these species with great potential for broad application in the biomedical arena.
- Salaam, Jeremy,Pilet, Guillaume,Hasserodt, Jens
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- DINUCLEATING LIGAND OR DINUCLEAR METAL COMPLEX
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To provide a dinuclear metal complex that can be synthesized simply and easily and has a proper anticancer action.SOLUTION: The present disclosure provides a dinucleating ligand represented by the following formula (I) and a dinuclear metal complex thereof (where each X may be the same or different to represent H, Cl, OMe, or, Me, Y is H, a phenyl group, a substituted carbamoyl group or the like).SELECTED DRAWING: None
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Paragraph 0058; 0064-0065
(2021/03/19)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, IPF, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
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Paragraph 00416
(2015/07/07)
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- Design of coordination interaction of Zn(II) complex with oligo-aspartate peptide to afford a high-affinity tag-probe pair
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A complementary recognition pair consisting of a genetically encodable peptide tag and a small molecular probe isa powerful tool to specifically label and manipulate a protein ofinterest under biological conditions. In this study, we report the redesign of a tag-probe pair comprising an oligo-aspartate peptide tag (such as DDDD) and a binuclear zinc complex. Isothermal-titration calorimetry screening of binding between the series of peptides and zinc complexes revealed that the binding affinity was largely influenced by subtle changes of the ligand structure of the probe. However, the binding was tolerant to differences of the tag peptide sequence. Of those tested, a pair containing a peptide tag (DDAADD) and a binuclear zinc complex possessing 4-chloropyridines (3-2Zn(II)) showed the strongest binding affinity (Ka = 3.88 × 105 M-1), which was about 10-fold larger than the conventional pair of D4-peptide tag (DDDD) and 1-2Zn(II) containing nonsubstituted pyridines (Ka = 3.73 × 104 M-1). The strong binding of this new complementary recognition pair enabled the rapid covalent labeling of a tag-fused maltose binding protein with a fluorescent zinc complex, demonstrating its potential utility in protein analysis.
- Fuchida, Hirokazu,Tabata, Shigekazu,Shindo, Naoya,Takashima, Ippei,Leng, Qiao,Hatsuyama, Yuji,Hamachi, Itaru,Ojida, Akio
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supporting information
p. 784 - 791
(2015/06/25)
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- Fuel cells
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This invention provides a redox fuel cell comprising an anode and a cathode separated by an ion selective polymer electrolyte membrane; means for supplying a fuel to the anode region of the cell; means for supplying an oxidant to the cathode region of the cell; means for providing an electrical circuit between the anode and the cathode; a non-volatile catholyte solution flowing in fluid communication with the cathode, the catholyte solution comprising a redox mediator which is at least partially reduced at the cathode in operation of the cell, and at least partially regenerated by, optionally indirect, reaction with the oxidant after such reduction at the cathode, and a transition metal complex of a multidentate N-donor ligand as a redox catalyst catalyzing the regeneration of the mediator.
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- PYRIDINE DERIVATIVES SUBSTITUTED BY HETEROCYCLIC RING AND PHOSPHONOAMINO GROUP, AND ANTI-FUNGAL AGENT CONTAINING SAME
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Anti-fungal agent having excellent anti-fungal action physicochemical properties including safety and water solubility. Compound represented by formula (I), or salt thereof: wherein R1 represents hydrogen, halogen, amino, R11-NH- wherein R11 represents C1-6 alkyl, hydroxy C1-6 alkyl, C1-6 alkoxy C1-6 alkyl, or C1-6alkoxycarbonyl C1-6 alkyl, R12-(CO)-NH- wherein R12 represents C1-6 alkyl group or C1-6 alkoxy C1-6 alkyl, C1-6 alkyl, hydroxy C1-6 alkyl, cyano C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy C1-6 alkyl or a phosphonoamino group; R2 represents hydrogen, C1-6 alkyl, amino, or a di C1-6 alkylamino group or a phosphonoamino group; one of X and Y is nitrogen while the other is nitrogen or oxygen; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, oxygen, sulfur, -CH2O-, -OCH2-, -NH-, -CH2NH-, -NHCH2-, -CH2S-, or -SCH2-; R3 represents hydrogen or halogen or C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, a 5- or 6-member heteroaryl group or a 5- or 6-member nonaromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents hydrogen or halogen; provided that either R1 or R2 represents a phosphonoamino group.
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Page/Page column 99
(2009/04/24)
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- Use of Metal Complex Compounds as Oxidation Catalysts
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The present invention relates to the use, as oxidation catalysts, of metal complex compounds having tetradentate ligands of formula (2) wherein all substitutents have the meanings as defined in Claim 1. The present invention relates also to formulations comprising such metal complex compounds, to novel metal complex compounds and to novel ligands.
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- Heterocycles substituted pyridine derivatives and antifungal agent containing thereof
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An object of the present invention is to provide an antifungal agent which has excellent antifungal effects and is superior in terms of its physical properties, safety and metabolic stability. According to the present invention, there is disclosed a compound represented by the following formula (I), or a salt thereof: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group or a C1-6 alkoxy C1-6 alkyl group; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group or a di C1-6 alkylamino group; one of X and Y is a nitrogen atom while the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom, or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, —CH2O—, —OCH2—, —NH—, —CH2NH—, —NHCH2—, —CH2S—, or —SCH2—; R3 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-member heteroaryl group, or 5- or 6-member non-aromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents a hydrogen atom or a halogen atom.
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Page/Page column 98-99
(2010/11/27)
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- Resonance Raman investigation of equatorial ligand donor effects on the CU2O22+ core in end-on and side-on μ-peroxo-dicopper(II) and bis-μ-oxo-dicopper(III) complexes
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The effect of endogenous donor strength on CU2O2 bonds was studied by electronically perturbing [{(R-TMPA)CuII}2(O2)]2+ and [{(R-MePY2)Cu}2(O2)]2+ (R = H, MeO, Me2N), which form the end-on μ-1,2 bound peroxide and an equilibrium mixture of side-on peroxo- dicopper(II) and bis-μ-oxo-dicopper(III) isomers, respectively. For [{(R-TMPA)CUII}2(O2)]2+, vo-o shifts from 827 to 822 to 812 cm-1 and VCu-O(sym) shifts from 561 to 557 to 551 cm-1, respectively, as R- varies from H to MeO to Me2N. Thus, increasing the N-donor strength to the copper decreases peroxide π*σ donation to the copper, weakening the Cu-O and O-O bonds. A decrease in vCu-O of the bis-μ-oxo- dicopper(III) complex was also observed with increasing N-donor strength for the R-MePY2 ligand system. However, no change was observed for vO-O of the side-on peroxo. This is attributed to a reduced charge donation from the peroxide π*σ orbital with increased N-donor strength, which increases the negative charge on the peroxide and adversely affects the back-bonding from the Cu to the peroxide σ*orbital. However, an increase in the bis-μ-oxo-dicopper(III) isomer relative to side-on peroxo-dicopper(II) species is observed for R-MePY2 with R = H 2N. This effect is attributed to the thermodynamic stabilization of the bis-μ-oxo-dicopper(III) isomer relative to the side-on peroxo-dicopper(II) isomer by strong donor ligands. Thus, the side-on peroxo-dicopper(II)/bis-μ-oxo-dicopper(III) equilibrium can be controlled by electronic as well as steric effects.
- Henson, Mark J.,Vance, Michael A.,Zhang, Christiana Xin,Hong-Chang, Liang,Karlin, Kenneth D.,Solomon, Edward I.
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p. 5186 - 5192
(2007/10/03)
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- INHIBITORS OF FARNESYL-PROTEIN TRANSFERASE
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invention and methods for inhibiting farnesyl-protein transferase and the farnesylation of the oncogene protein Ras
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- Structure-activity relationship of 2-[[(2-Pyridyl)methyl]thio]-1H- benzimidazoles as anti Helicobacter pylori agents in vitro and evaluation of their in vivo efficacy
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A relationship between the structure of 21 2-[[(2-pyridyl)methyl]thio]- 1H-benzimidazoles (6) and their anti Helicobacter pylori activity expressed as minimum bactericidal concentration (MBC) values is described. Observed MBCs ranged from 256 to 1 μg/mL. The structure - activity relationship (SAR) showed that larger and more lipophilic compounds, especially compounds with such substituents in the 4-position of the pyridyl moiety, generally had lower MBC values. Four new compounds 'that were predicted to be potent by the established SAR model were synthesized and tested. One such compound, i.e., 2-[[(4-[(cyclopropylmethyl)oxy]3-methyl-2-pyridyl)methyl]thio]-1H- benzimidazole (18), was tested for in vivo efficacy in a mouse Helicobacter felis model (125 μmol/kg bid given orally for 4 days, n = 4). Unfortunately, antibacterial activity could not be clearly demonstrated in this model. Instead a potent acid secretion inhibition was observed. This finding was attributed to the methylthio compound being oxidized to the corresponding methyl sulfinyl derivative, i.e., a proton pump inhibitor, in vivo. Although the antibacterial activity had the potential of decreasing H. felis cell counts in vivo the proton pump inhibitory effect became dominant and actually promoted H. felis cell growth. Hence, we conclude that the antibacterial utility of the 2-[[(2-pyridyl)methyl]thio]1H-benzimidazoles (6) as a compound class is compromised by their propensity to become proton pump inhibitors upon metabolic oxidation in vivo.
- Kühler, Thomas C.,Swanson, Marianne,Shcherbuchin, Vladimir,Larsson, H?kan,Mellg?rd, Bj?rn,Sj?str?m, Jan-Eric
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p. 1777 - 1788
(2007/10/03)
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