74621-40-2Relevant academic research and scientific papers
Reductive Transformations of a Pyrazolate-Based Bioinspired Diiron-Dinitrosyl Complex
Kindermann, Nicole,Schober, Anne,Demeshko, Serhiy,Lehnert, Nicolai,Meyer, Franc
, p. 11538 - 11550 (2016)
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.
A proton-ionizable ester crown of 3,5-disubstituted 1H-pyrazole able to form stable dinuclear complexes with lipophilic phenethylamines
Campayo, Lucrecia,Bueno, Jose M.,Navarro, Pilar,Ochoa, Carmen,Jimenez-Barbero, Jesus,Pepe, Gerard,Samat, Andre
, p. 2684 - 2693 (1997)
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.
A novel one-dimensional nickel(II) alternating chain from discrete pyrazolate-based dinuclear complexes
Meyer, Franc,Ruschewitz, Uwe,Schober, Peter,Antelmann, Bjoern,Zsolnai, Laszlo
, p. 1181 - 1186 (1998)
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)°].
Versatility in the coordination behavior of a hexatopic compartmental Schiff-base ligand in the architecture of binuclear transition metal(II) complexes
Budagumpi, Srinivasa,Kurdekar, Gurunath S.,Hegde, Ganesh S.,Bevinahalli, Nagaraj H.,Revankar, Vidyanand K.
, p. 1430 - 1439 (2010)
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.
Chiral bisoxazoline ligands designed to stabilize bimetallic complexes
Das, Deepankar,Mal, Rudrajit,Mittal, Nisha,Zhu, Zhengbo,Emge, Thomas J.,Seidel, Daniel
, p. 2002 - 2011 (2018)
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.
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
Reviriego, Felipe,Navarro, Pilar,Aran, Vicente J.,Jimeno, Maria Luisa,Garcia-Espana, Enrique,Latorre, Julio,Yunta, Maria J. R.
, p. 8223 - 8231 (2011)
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.
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
Budagumpi, Srinivasa,Kulkarni, Naveen V.,Kurdekar, Gurunath S.,Sathisha,Revankar, Vidyanand K.
, p. 455 - 462 (2010)
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.
A new diaza heteroaromatic crown of 3,5-disubstituted 1H-pyrazole which forms solid dinuclear complexes with lipophilic phenethylamines
Sanz, Ana M.,Navarro, Pilar,Gomez-Contreras, Fernando,Pardo, Mercedes,Pepe, Gerard,Samat, Andre
, p. 1174 - 1179 (1998)
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.
Synthesis and Biological Evaluation of Oral Prodrugs Based on the Structure of Gemcitabine
Zhao, Cuirong,Xue, Xiaoxia,Li, Gang,Sun, Cuicui,Sun, Changjun,Qu, Xianjun,Li, Wenbao
experimental part, p. 479 - 488 (2012/10/07)
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.
Synthesis, antimicrobial screening, and DNA-binding/cleavage of new pyrazole-based binuclear CoII, NiII, CuII, and ZnII complexes
Kulkarni, Naveen V.,Revankar, Vidyanand K.
experimental part, p. 725 - 741 (2011/12/16)
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.
