- Reductive Transformations of a Pyrazolate-Based Bioinspired Diiron-Dinitrosyl Complex
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Flavo-diiron nitric oxide reductases (FNORs) are a subclass of nonheme diiron proteins in pathogenic bacteria that reductively transform NO to N2O, thereby abrogating the nitrosative stress exerted by macrophages as part of the immune response. Understanding the mechanism and intermediates in the NO detoxification process might be crucial for the development of a more efficient treatment against these bacteria. However, low molecular weight models are still rare, and only in a few cases have their reductive transformations been thoroughly investigated. Here, we report on the development of two complexes, based on a new dinucleating pyrazolate/triazacyclononane hybrid ligand L-, which serve as model systems for nonheme diiron active sites. Their ferrous nitrile precursors [L{Fe(R′CN)}2(μ-OOCR)](X)2 (1) can be readily converted into the corresponding nitrosyl adducts ([L{Fe(NO)}2(μ-OOCR)](X)2, 2). Spectroscopic characterization shows close resemblance to nitrosylated nonheme diiron sites in proteins as well as previous low molecular weight analogues. Crystallographic characterization reveals an anti orientation of the two {Fe(NO)}7 (Enemark-Feltham notation) units. The nitrosyl adducts 2 can be (electro)chemically reduced by one electron, as shown by cyclic voltammetry and UV/vis spectroscopy, but without the formation of N2O. Instead, various spectroscopic techniques including stopped-flow IR spectroscopy indicated the rapid formation, within few seconds, of two well-defined products upon reduction of 2a (R = Me, X = ClO4). As shown by IR and M?ssbauer spectroscopy as well as X-ray crystallographic characterization, the reduction products are a diiron tetranitrosyl complex ([L{Fe(NO)2}2](ClO4), 3a′) and a diacetato-bridged ferrous complex [LFe2(μ-OAc)2](ClO4) (3a″). Especially 3a′ parallels suggested products in the decay of nitrosylated methane monooxygenase hydroxylase (MMOH), for which N2O release is much less efficient than for FNORs.
- Kindermann, Nicole,Schober, Anne,Demeshko, Serhiy,Lehnert, Nicolai,Meyer, Franc
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- A proton-ionizable ester crown of 3,5-disubstituted 1H-pyrazole able to form stable dinuclear complexes with lipophilic phenethylamines
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A convenient synthesis of the proton-ionizable crown 3 is reported that uses dibutyltin oxide. In acetonitrile, the reaction of 3 (LH2) with phenethylamine and homoveratrylamine (molar ratio 1:2) affords solid dinuclear complexes [LH2]2RNH2 (4a,b), which spectroscopic (FAB-MS, IR, 1H and 13C NMR) data point toward a strong participation of the pyrazole nitrogens in the amine complexation. In DMSO-d6 solution, a 13C NMR study demonstrates the formation in situ of analogous neutral 4a-d[LH2]2RNH2 or charged 5a-d[L2-]2RNH3+ dinuclear complexes by reaction of 3 [LH2] or 3'[L2-]2Na+ with RNH2 (phenethylamine, homoveratrylamine, dopamine, and norepinephrine) or their RNH3+Cl- salts, respectively. Differences between the structure of complexes 4 and 5 have been evaluated by taking the homoveratrylamine derivatives 4b and 5b as models. An 1H and 13C NMR study (by raising the temperature) and measurements of intermolecular NOE effects (from NOESY and ROESY spectra) demonstrate that both complexes behave as prototropic isomers showing different conformations. By increasing the ionic strength, the 4b isomer structure becomes similar to that of 5b. The molecular modeling (GenMol software) of 4a-d and 5a-d shows that the assemblage in which both amine molecules are on the same side of the crown is the more stable. Lipophilic amines afford more stable complexes than hydrophilic ones and charged species are much more stable than the neutral ones.
- Campayo, Lucrecia,Bueno, Jose M.,Navarro, Pilar,Ochoa, Carmen,Jimenez-Barbero, Jesus,Pepe, Gerard,Samat, Andre
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- A novel one-dimensional nickel(II) alternating chain from discrete pyrazolate-based dinuclear complexes
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Hexadentate dinucleating ligands that are based on a bridging pyrazolate bearing chelating side arms [3,5-(R2NCH2)2C3N2H 2; R2N = Me2N(CH2)2NMe (HL1), Me2N(CH2)2NMe (HL2)] reacted with NiCl2·6H2O to yield complexes ClNi(μ-Cl)(μ-L1)NiCl 1 (Ni2L1Cl3) and ClNi(μ-Cl)(μ-L2)NiCl 2 (Ni2L2Cl3), respectively. Depending on the side-arm chain length and the solvent used for crystallisation these complexes either crystallised as dicrete bimetallic units (1) or were assembled via di-μ-chloro linkages to form a tetranuclear compound [ClNi(μ-Cl)-(μ-L2)Ni(μ-Cl) 2Ni(μ-Cl)(μ-L2)NiCl] 2a ([Ni2L2Cl3]2) or a novel bridge-alternating one-dimensional chain [Ni(μ-Cl)(μ-L1)Ni(μ-Cl)2]∞ 2b ([Ni2L2Cl3]∞) in the solid state. Variable-temperature magnetic susceptibility measurements revealed antiferromagnetic coupling within the basic μ-chloro-μ-pyrazolato bridged bimetallic framework in all cases and also suggested antiferromagnetic superexchange propagated by the di-μ-chloro linkage in 2b. The latter result is rationalised on the basis of the specific geometric findings for this di-μ-chloro linkage, in particular the unusually large Ni-Cl-Ni angle [101.37(4)°].
- Meyer, Franc,Ruschewitz, Uwe,Schober, Peter,Antelmann, Bjoern,Zsolnai, Laszlo
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- Versatility in the coordination behavior of a hexatopic compartmental Schiff-base ligand in the architecture of binuclear transition metal(II) complexes
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Condensation of 1H-pyrazole-3,5-dicarboxylic hydrazide with 1H-indole-2,3-dione (isatin) yield the compartmental ligand, which is capable of encapsulating two transition metal ions namely CoII, Ni II, CuII, and ZnII. The ligand is a binuclear hexadentate chelate with N4O2 donating sites. The pyrazole core provides the diazine fragment, which serves as an endogenous bridge between the two metal centers. In CoII and NiII complexes, the ligand is in the imidol form and the subsequent coordination through the imidol oxygen. In other complexes, the lactonic oxygen takes part in ligation. All the complexes are non-electrolytes and soluble in DMSO, DMF, and acetonitrile. Spectral and magnetic studies along with analytical data suggest octahedral geometry for the CoII and NiII complexes, whereas the CuII and ZnII complexes are assigned square pyramidal geometry. The CuII and NiII complexes show one electron redox behavior and the rest are electrochemically inactive.
- Budagumpi, Srinivasa,Kurdekar, Gurunath S.,Hegde, Ganesh S.,Bevinahalli, Nagaraj H.,Revankar, Vidyanand K.
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- Chiral bisoxazoline ligands designed to stabilize bimetallic complexes
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Chiral bisoxazoline ligands containing naphthyridine, pyridazine, pyrazole, and phenol bridging units were prepared and shown to form bimetallic complexes with various metal salts. X-ray crystal structures of bis-nickel naphthyridine-bridged, bis-zinc pyridazine-bridged, and bis-nickel as well as bis-palladium pyrazole-bridged complexes were obtained.
- Das, Deepankar,Mal, Rudrajit,Mittal, Nisha,Zhu, Zhengbo,Emge, Thomas J.,Seidel, Daniel
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- Hydrogen-bond-mediated self-assembly of 26-membered diaza tetraester crowns of 3,5-disubstituted 1 h -pyrazole. Dimerization study in the solid state and in CDCl3 solution
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By using an improved synthetic method reported earlier, the cyclic stannoxanes obtained from RN-diethanolamine (R = Me, Bu) and dibutyltin oxide have been reacted with 1H-pyrazole-3,5-dicarbonyl dichloride to afford 26-membered diaza tetraester crowns (1, R = Me; 3, R = Bu) and 39-membered triaza hexaester crowns (2, R = Me; 4, R = Bu). The new structures were identified from their analytical and spectroscopic (1H and 13C NMR, FAB-MS, and/or ESI-MS) data. Both diaza tetraester crowns (1 and 3), containing two 1H-pyrazole units, self-assemble into dimeric species through the formation of four hydrogen bonds involving the two NH pyrazole groups and the two tertiary amine groups of both crowns, as proved by X-ray crystallography and NMR analysis. Preliminary NMR, ESI-MS, MALDI-TOF-MS, and molecular modeling studies suggest that, in CDCl3 solution, 1 interacts with ethyleneurea (ETU), affording 1:1, 2:1, and 2:2 1-ETU complexes.
- Reviriego, Felipe,Navarro, Pilar,Aran, Vicente J.,Jimeno, Maria Luisa,Garcia-Espana, Enrique,Latorre, Julio,Yunta, Maria J. R.
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- Synthesis and spectroscopy of CoII, NiII, CuII and ZnII complexes derived from 3,5-disubstituted-1H-pyrazole derivative: A special emphasis on DNA binding and cleavage studies
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A series of novel CoII, NiII, CuII and ZnII complexes of 1H-pyrazole-3,5-dicarboxylic(2′-hydroxy-3′-hydrazinequinoxaline) has been prepared and characterized by the spectral and analytical techniques. CuII ion reacts with the ligand LH3 and forms the complex in one compartment of the ligand whereas, the other compartment remains free. In CoII, NiII and ZnII complexes both compartments of LH3 are involved in the coordination. DNA binding/cleavage studies were revealed the stronger binding capability of the present NiII complex, confirmed by the absorbance, viscometric and gel-electrophoresis studies. Similarly, remaining complexes do the same in the ligand field with lesser binding constants, subsequently, no complex was found to cleave the DNA. Finally, CuII complex shows growth inhibitory activity against biogram.
- Budagumpi, Srinivasa,Kulkarni, Naveen V.,Kurdekar, Gurunath S.,Sathisha,Revankar, Vidyanand K.
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- A new diaza heteroaromatic crown of 3,5-disubstituted 1H-pyrazole which forms solid dinuclear complexes with lipophilic phenethylamines
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The cyclic stannoxane obtained from N-methyldiethanolamine and dibutyltin oxide reacts with 1H-pyrazole-3,5-dicarbonyl dichloride to afford the new 26-membered diaza tetraester crown 3. In neutral medium, the above crown forms 1:2 solid dinuclear complexes with phenethylamine (3a) and homoveratrylamine (3b), which, after crystallization from acetonitrile, were isolated in high yield (90% and 85%, respectively). The 3, 3a, and 3b structures were identified from their analytical and spectroscopic (1H, 13C NMR, and MS (FAB)) data. The spectroscopic properties of 3a and 3b are demonstrating that, in each complexation centre, simultaneously to the strong participation of the four pyrazole nitrogens, an additional weaker interaction between the aliphatic nitrogen of the side chain and the amine is involved. Comparison of the total interaction energies calculated (GenMol software) for phenethylamine-derived complex (3a) and homoveratrylamine- derived one (3b) suggests that the o-dimethoxy substitution of the guest aromatic ring could be improving the stability of 3b in relation to 3a.
- Sanz, Ana M.,Navarro, Pilar,Gomez-Contreras, Fernando,Pardo, Mercedes,Pepe, Gerard,Samat, Andre
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- Synthesis and Biological Evaluation of Oral Prodrugs Based on the Structure of Gemcitabine
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A series of oral prodrugs based on the structure of gemcitabine (2′,2′-difluorodeoxycytidine) were synthesised by introducing an amide group at the N4-position of the cytidine ring. A total of 16 compounds were obtained, and their chemical and biological characteristics were evaluated. The half-maximal inhibitory concentrations (IC50s) for most of these compounds were higher than that of gemcitabine in vitro. Compounds 5d and 5m, the representative compounds, were examined in terms of their physiological stabilities and pharmacokinetics. Compound 5d showed good stability in PBS and simulated intestinal fluid, and an analysis of its pharmacokinetics in mice suggested that the introduction of an amide group to gemcitabine could greatly improve its bioavailability. Further evaluation of compound 5din vivo showed that this compound possesses higher activity than gemcitabine against the growth of HepG2 human hepatocellular carcinoma cells and HCT-116 colon adenocarcinoma cells with less toxicity to animals. These results suggest that compound 5d could be further developed as a potential oral anticancer agent for clinical applications in which gemcitabine is currently used. A series of oral prodrugs based on the structure of gemcitabine were synthesized. Physiological and metabolic stabilities, pharmacokinetics and antitumor activities were evaluated for representative compounds.
- Zhao, Cuirong,Xue, Xiaoxia,Li, Gang,Sun, Cuicui,Sun, Changjun,Qu, Xianjun,Li, Wenbao
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experimental part
p. 479 - 488
(2012/10/07)
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- Synthesis, antimicrobial screening, and DNA-binding/cleavage of new pyrazole-based binuclear CoII, NiII, CuII, and ZnII complexes
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Pyrazolato endogenous bridged binuclear CoII, NiII, CuII, and ZnII complexes were prepared and characterized by spectro-analytical methods. The hexadentate N4S2 donor was synthesized by condensation of 3,5-dichloroformyl-1H-pyrazole with thiosemicarbazide in dry ethanol. All the complexes were binuclear and octahedral in nature. The ligand and complexes are screened for antimicrobial and DNA-binding/cleavage activities. The binding/cleavage activities with Escherichia coli DNA are monitored with absorption, hydrodynamic, thermal denaturation, and electrophoresis studies. The ligand possesses significant activity against microbes which is further enhanced upon complexation. The DNA-binding study reveals classical intercalation. The NiII and CuII complexes exhibit higher binding ability.
- Kulkarni, Naveen V.,Revankar, Vidyanand K.
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experimental part
p. 725 - 741
(2011/12/16)
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- Pyrazole bridged binuclear transition metal complexes: Synthesis, characterization, antimicrobial activity and DNA binding/cleavage studies
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A new ligand system having pyrazolato endogenous bridging component and N4S2 donating sites is synthesized by the condensation of 3,5-dichloroformyl-1H-pyrazole with phenylthiosemicarbazide. Both ligand and its binuclear CoII/s
- Kulkarni, Naveen V.,Kamath, Anupama,Budagumpi, Srinivasa,Revankar, Vidyanand K.
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experimental part
p. 580 - 588
(2012/02/03)
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- Ethylene oligomerizations by diazene bridged Ni(II) catalysts derived from pyrazole-scaffold-based binucleating ligands with alkyl and aryl pendant arms
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The coordination and organometallic chemistry of a series of diazene (N2)-bridged Ni(II) catalysts derived from pyrazole-scaffold-based ligands bearing alkyl and aryl pendent arms was investigated. Binucleating ligands were obtained as products of the condensation reaction between 3,5-dichloroformyl-1H-pyrazole and aliphatic/aromatic primary/secondary amines under anhydrous conditions. The Ni(II) catalysts were activated with ethyl aluminum sesquichloride (EASC) to oligomerize the ethylene mainly into C4, C6, C8, and C10 fractions with activities up to 1.2 and 0.5 × 106 g (mol-Ni)-1 bar-1 h-1 at 30 and 50 °C, respectively. All catalysts were found to be electrochemically active in the working potential range of -2 to +2 V. A change in the potential of Ni(II) was provoked by the N4 donor bridging ligands, increasing the ethylene oligomerization activity.
- Budagumpi, Srinivasa,Johnson, Renjith P.,Suh, Hongsuk,Ha, Chang-Sik,Kim, Il
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experimental part
p. 1219 - 1227
(2012/06/29)
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- Diazatetraester 1H-pyrazole crowns as fluorescent chemosensors for AMPH, METH, MDMA (Ecstasy), and dopamine
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(Chemical Equation Presented) The synthesis and steady-state fluorescence studies on the interaction with AMPH, METH, MDMA, and DA of two diazatetraester pyrazole crowns containing appended N-(9H-fluoren-9-yl) and N-(naphth-2- ylmethyl) functions, in a water/ethanol 70:30 mixture at physiological pH, are described.
- Reviriego, Felipe,Navarro, Pilar,Garcia-Espana, Enrique,Albelda, M. Teresa,Frias, Juan C.,Domenech, Antonio,Yunta, Maria J. R.,Costa, Ruben,Orti, Enrique
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supporting information; experimental part
p. 5099 - 5102
(2009/06/06)
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- Synthesis and characterisation of new polynuclear copper(I) pyrazolate complexes and their catalytic activity in the cyclopropanation of olefins
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The reaction of [Cu(CH3CN)4](BF4) with racemic pyrazole-3,5-dicarboxylic acid di-sec-butyl ester (3,5-dicarbo-sec-butoxypyrazole, Hdcsbpz) or with pyrazole-3,5-di-ter-butyl (3,5-di-ter-butylpyrazole, Hdtbpz) quantitatively yields the new [Cu(dcsbpz)]4 and [Cu(dtbpz)]4 complexes, respectively. Crystals of [Cu(dcsbpz)]4 are triclinic, P1?, a =10.9748(7), b =11.8399(8), c =26.5575(17) ?, α =100.605(2), β =90.783(2), γ =105.362(2)°; [Cu(dtbpz)]4·CH2Cl2 is monoclinic, P21/n, a =10.902(3), b =19.200(3), c =25.772(4) ?, β =93.86(2)°. Both species contain cyclic tetrameric molecules, with the heterocyclic ligands binding in the common N,N′-exo-bidentate mode; however, the shape and geometry of the inner Cu4 moiety is remarkably different, as highlighted, for example, by the absolute values of the 1,2 and 1,3 (non-bonding) Cu?Cu interactions. These polynuclear copper(I) pyrazolate complexes catalyse the conversion of alkenes into the corresponding cyclopropane derivatives with interesting diastereomeric excesses. Aiming at the evaluation of their catalytic activities, a systematic study of the cyclopropanation reactions in the presence of ethyl diazoacetate has been performed.
- Maspero, Angelo,Brenna, Stefano,Galli, Simona,Penoni, Andrea
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p. 123 - 129
(2007/10/03)
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- Novel dinucleating ligand systems containing two adjacent coordination compartments of the potential triamidoamine-type - Nickel(II) and cobalt(II) coordination chemistry
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The preparation of novel dinucleating pyrazolate ligands H5L3 - H5L8 carrying chelating side arms with appending secondary amine functions is reported. Following different synthetic routes, either CH2
- Buchler, Silke,Meyer, Franc,Jacobi, Albrecht,Kircher, Peter,Zsolnai, Laszlo
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p. 1295 - 1306
(2007/10/03)
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- Unsymmetrically substituted pyrazolates: Nickel(II) complexes of a novel dinucleating ligand providing both N- and S-rich co-ordination spheres
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An unsymmetric pyrazolate ligand with different chelating side arms in the 3 and 5 positions of the heterocycle {3-[(EtSCH2CH2)2NCH2]-5-[(Et 2NCH2CH2)2NCH2]C 3N2H2 (HL1)} and its symmetrical analogue {3,5-[(EtSCH2CH2)2NCH2] 2C3N2H2(HL2)} have been prepared. Upon reaction with NiCl2·6OH2O they afforded dinuclear complexes [Ni2L1Cl3] 2 and [Ni2L2Cl3] 1 that contain both a bridging pyrazolate and a bridging chlorine atom. While all nickel(II) ions within the N2S2 compartments of the primary ligands are six-co-ordinate, one of the amino side arms of L1 in the former complex is non-co-ordinating, leaving the respective nickel centre in a square-pyramidal environment. This dangling arm is co-ordinated to the metal ion upon treatment of 2 with NaBPh4 due to substitution of the terminal chlorine atom to form [Ni2L1Cl2][BPh4] 3. All new complexes were characterised by means of X-ray crystallography; 2 and 3 represent rare examples of dinuclear complexes exhibiting various kinds of asymmetry. The electrochemical and magnetic properties of the complexes are reported.
- Konrad, Matthias,Meyer, Franc,Heinze, Katja,Zsolnai, Laszlo
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p. 199 - 205
(2007/10/03)
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- Formation of mono- and di-nuclear complexes of Zn2+ from a 26 membered tetraester crown of 3,5-disubstituted pyrazole able to act as neutral and dianionic ligand
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A selective synthesis of bis(3,5-diketo-1H-pyrazole)-[26]crown- 12 (1, L1) has been performed. Its deprotonation pKa values, and those of the acyclic analogues (3-5) have been measured. The disodium dipyrazolate salt of 1 (2, [L2]2- 2Na+) has been isolated, and mono- and di- nuclear complexes of Zn2+ obtained from 1 ([L1Zn]2+) and 2 ([L2Zn2]2+) have been studied by 13C NMR spectroscopy in DMSO-d6 solution.
- Acerete, Carmen,Bueno, Jose M.,Campayo, Lucrecia,Navarro, Pilar,Isabel Rodriguez-Franco,Samat, Andre
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p. 4765 - 4774
(2007/10/02)
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- Synthesis and Characterization of Masked Aminopyrazolecarboxylic Acid Synthons
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The synthesis of the masked aminopyrazolecarboxylic acid synthons (11a,b and 12a,b) from pyrazole-3,5-dicarboxylic acid (6) and the determination of their structures by X-ray crystallography are detailed.The compounds are useful for the synthesis of polypyrazolecarboxamides analogous to the DNA minor groove binding antibiotics distamycin A and netropsin.
- Lee, Ho H.,Cain, Bruce F.,Denny, William A.,Buckleton, John S.,Clark, George R.
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p. 428 - 431
(2007/10/02)
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- SYNTHESIS OF NEW MACROCYCLIC POLYETHER DI- OR TETRAESTER LIGANDS CONTAINING PYRAZOLE UNITS
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A new series of macrocyclic polyether - diester compounds containing one or two pyrazole rings (NH or N-methyl substituted) have been prepared by treating 3,5-pyrazolyldicarbonyl chlorides with tetraethylene glycol in the presence of triethylamine.Their complexation abilities towards the shift reagent Eu(Fod)3 have been studied by 1H NMR in CDCl3 solution.
- Elguero, J.,Navarro, P.,Franco, M. I. Rodriguez
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p. 425 - 428
(2007/10/02)
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