Carbonyl compounds are widely explored in medicinal inorganic chemistry and have drawn attention due to their signaling functions in homeostasis. Carbon-monoxide-releasing molecules (CORMs) were ...developed with the purpose of keeping the CO inactive until its release in the intracellular environment, considering its biological relevance. However, for therapeutic applications, the mechanisms of photorelease and which electronic and structural variations influence its rates must be fully understood. In this work, four ligands containing a pyridine, a secondary amine, and a phenolic group with different substituents were used to prepare new Mn(I) carbonyl compounds. Structural and physicochemical characterization of these complexes was carried out and confirmed the proposed structures. X-ray diffractometry structures obtained for the four organometallic compounds revealed that the substituents in the phenolic ring promote only negligible distortions in their geometry. Furthermore, UV-Vis and IR kinetics showed the direct dependence of the electron-withdrawing or donating ability of the substituent group, indicating an influence of the phenol ring on the CO release mechanism. These differences in properties were also supported by theoretical studies at the DFT, TD-DFT, and bonding situation analyses (EDA-NOCV). Two methods were used to determine the CO release constants (k
and k
), where Mn-HbpaBr (1) had the greatest k
by both methods (K
= 2.36 × 10
s
and k
= 2.37 × 10
s
). Carbon monoxide release was also evaluated using the myoglobin assay, indicating the release of 1.248 to 1.827 carbon monoxides upon light irradiation.
The catalytic properties of three copper complexes, Cu(en)2(ClO4)2 (1), Cu(amp)2(ClO4)2, (2) and Cu(bpy)2(ClO4)2 (3) (where en = ethylenediamine, amp = 2-aminomethylpyridine and bpy = ...2,2′-bipyridine), were explored upon the oxidation of benzyl alcohol (BnOH). Maximized conversions of the substrates to their respective products were obtained using a multivariate analysis approach, a powerful tool that allowed multiple variables to be optimized simultaneously, thus creating a more economical, fast and effective technique. Considering the studies in a fluid solution (homogeneous), all complexes strongly depended on the amount of the oxidizing agent (H2O2), followed by the catalyst load. In contrast, time seemed to be statistically less relevant for complexes 1 and 3 and not relevant for 2. All complexes showed high selectivity in their optimized conditions, and only benzaldehyde (BA) was obtained as a viable product. Quantitatively, the catalytic activity observed was 3 > 2 > 1, which is related to the π-acceptor character of the ligands employed in the study. Density functional theory (DFT) studies could corroborate this feature by correlating the geometric index for square pyramid Cu(II)-OOH species, which should be generated in the solution during the catalytic process. Complex 3 was successfully immobilized in silica-coated magnetic nanoparticles (Fe3O4@SiO2), and its oxidative activity was evaluated through heterogenous catalysis assays. Substrate conversion promoted by 3-Fe3O4@SiO2 generated only BA as a viable product, and the supported catalyst’s recyclability was proven. Reduced catalytic conversions in the presence of the radical scavenger (2,2,6,6-tetrametil-piperidi-1-nil)oxil (TEMPO) indicate that radical and non-radical mechanisms are involved.
The Front Cover shows the utilization of benzimidazole‐derivatized ligands and their mononuclear iron(III) complexes as a viable alternative for hydrolyzing organophosphate pesticides and also to ...evaluate the second coordination sphere effect of the benzimidazole moieties. Organophosphates are widely employed in safeguarding crops against pests and insects. However, due to their inherent toxicity, catalysts become imperative to facilitate their efficient degradation. The manuscript explores the investigation of the catalytic role played by benzimidazole groups, employing a comprehensive approach that encompasses experimental facets, as well as computational methods like DFT calculations. The findings skillfully strike a balance between the incorporation of aromatic‐nucleophilic groups within the second coordination sphere and the optimization of side chain length in order to augment phosphoesterase activity. More information can be found in the Research Article by F. R. Xavier, R. A. Peralta, and co‐workers.
Abstract Over the years, phosphate ester hydrolysis catalyzed by coordination compounds has attracted extensive research on developing new bioinspired compounds. However, the literature lacks ...sufficient examples displaying activity toward phosphate triesters specifically, limiting the understanding of efficient strategies for the hydrolysis of this compound hydrolysis. Herein, we report preparing and characterizing three mononuclear iron(III) complexes ( 1 , 2 , and 3 ) and their hydrolase‐like activity. Complexes 2 and 3 have benzimidazole (BIMZ) moieties and were strategically designed to separate the BIMZ moiety from the first coordination sphere, and complex 1 (without BIMZ) was used as a reference. Several techniques provided structural information, including spectrophotometry, spectrometry, electrochemistry, elemental analysis, and 57 Fe Mossbauer. Density functional theory (DFT) revealed distorted octahedral geometries due to the presence of the BIMZ groups. These groups also directly affected the protonation equilibria and catalytic activity. The phosphate triester diethyl‐2,4‐dinitrophenylphosphate (DEDNPP) hydrolysis was enhanced at least 27 times compared to the uncatalyzed reaction, with complexes 2 and 3 , thus showing higher catalytic rates ( k cat ). Moreover, a longer carbon chain led to a higher hydrolysis rate but less interaction with substrate. These findings provide background for further investigations and the development of efficient catalysts for agrochemical degradation.
A simple and environmentally benign procedure for electrochemical oxidative mono‐ and bis‐selenylation of the resveratrol C(sp2)−H bond was developed. Driven by galvanostatic electrolysis in an ...undivided cell, it provided efficient transformation under oxidant‐, base‐, and transition metal‐free conditions, in an open system at room temperature. With satisfactory functional group compatibility, it required a substoichiometric amount of NaI, which acted as an electrolyte and mediator.
The work describes an electrochemical oxidative C(sp2)−H selenylation of resveratrol. Driven by galvanostatic electrolysis in an undivided cell, it provided efficient transformation in an open system at room temperature. Using this benign, atom‐economic protocol, the desired selenylated products were obtained regioselectively, in good to excellent yields by using half molar equiv. of the diselenides.
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•2-Substituted benzimidazoles was synthesized employing Ce(NO3)3·6H2O as promoter.•The procedure afforded the products from good to excellent yields.•The reactions are performed ...employing atmospheric air as an efficient oxidant.•The method is simple, selective, and general.
A series of 2-substituted benzimidazoles was synthesized under aerobic conditions, by simply heating 1,2-diaminobenzene and aldehydes in DMF at 80°C, employing Ce(NO3)3·6H2O as promoter and atmospheric air as an efficient oxidant. The procedure afforded the products from good to excellent yields. Furthermore, this new economic and eco-friendly protocol avoids the use of toxic metal catalysts, as well as additional bases and oxidants.
Inspired by copper-containing enzymes such as galactose oxidase and catechol oxidase, in which distinct coordination environments and nuclearities lead to specific catalytic activities, we summarize ...here the catalytic properties of dinuclear and mononuclear copper species towards benzyl alcohol oxidation using a multivariate statistical approach. The new dinuclear Cu2(μ-L1)(μ-pz)2+ (1) is compared against the mononuclear CuL2Cl (2), where (L1)− and (L2)− are the respective deprotonated forms of 2,6-bis((bis(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol, and 3-((bis(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy-5-methylbenzaldehyde and (pz)− is a pyrazolato bridge. Copper(II) perchlorate (CP) is used as control. The catalytic oxidation of benzyl alcohol is pursued, aiming to assess the role of the ligand environment and nuclearity. The multivariate statistical approach allows for the search of optimal catalytic conditions, considering variables such as catalyst load, hydrogen peroxide load, and time. Species 1, 2 and CP promoted selective production of benzaldehyde at different yields, with only negligible amounts of benzoic acid. Under normalized conditions, 2 showed superior catalytic activity. This species is 3.5-fold more active than the monometallic control CP, and points out to the need for an efficient ligand framework. Species 2 is 6-fold more active than the dinuclear 1, and indicates the favored nuclearity for the conversion of alcohols into aldehydes.
The catalytic properties of the dinuclear and mononuclear bioinspired copper species towards benzyl alcohol oxidation using a multivariate statistical approach were described. The role of the ligand environment and nuclearity were assessed. Under normalized conditions, the mononuclear compound showed superior catalytic activity. Display omitted
•A new bioinspired copper complex was prepared.•Multivariate analysis was applied to the catalytic oxidation of benzyl alcohol.•The catalytic role of complexes' nuclearity and ligand framework was probed.•The mononuclear copper complex is the best catalyst.
Coordination compounds that mimic Purple Acid Phosphatases (PAPs) have drawn attention in the bioinorganic field due to their capacity to cleave phosphodiester bonds. However, their catalytic ...activity upon phosphate triesters is still unexplored. Thus, we report the synthesis and characterization of two binuclear complexes, MnIIMnIII(L1)(OAc)2BF4 (1) and MnIIFeIII(L1)(OAc)2BF4 (2) (H2L1 = 2-N,N-bis-(2- pyridilmethyl)aminomethyl-4-methyl-6-N-(2-hydroxy-3-formyl-5-methylbenzyl)-N-(2-pyridylmethyl)aminomethylphenol), their hydrolytic activity and antioxidant potential. The complexes were fully characterized, including the X-Ray diffraction (XRD) of 1. Density functional theory (DFT) calculations were performed to better understand their electronic and structural properties and phosphate conjugates. The catalytic activity was analyzed for two model substrates, a diester (BDNPP) and a triester phosphate (DEDNPP). The results suggest enhancement of the hydrolysis reaction by 170 to 1500 times, depending on the substrate and complex. It was possible to accompany the catalytic reaction of DEDNPP hydrolysis by phosphorus nuclear magnetic resonance (31P NMR), showing that both 1 and 2 are efficient catalysts. Moreover, we also addressed that 1 and 2 present a relevant antioxidant potential, protecting the yeast Saccharomyces cerevisiae, used as eukaryotic model of study, against the exposure of cells to acute oxidative stress.
MnIIMnIII and FeIIIMnII complexes, their characterization, DFT studies and kinetics assays using a phosphate esters as substrates are reported. The results suggest enhancement of the hydrolysis reaction by 170 to 1500 times, depending on the system. We also addressed the relevant antioxidant potential, protecting cells against oxidative stress. Display omitted
•Dinuclear complexes showed activity in the degradation of phosphate triester and diester.•The degradation reaction of phosphate esters were followed by 31P NMR.•FeIIIMnII and MnIIIMnII complexes protected cells against oxidative stress.
The synthesis, physico-chemical characterization and in vitro antiproliferative activity against the promastigote form of Leishmania amazonensis of two new cobalt(II) coordination compounds (i.e. ...Co(HL1)Cl20.4,2H2O (1) and Co(HL2)(Cl)(CH3OH)(ClO4).2H2O (2)) are reported, where HL1 = 4-{3-bis(pyridin-2-ylmethyl)amino-2-hydroxypropoxy}-2H-chromen-2-one and HL2 = 7-{3-bis(pyridin-2-ylmethyl)amino-2-hydroxypropoxy}-2H-chromen-2-one. X-ray diffraction studies were performed for complex (2) and the structure of complex (1) was built through Density Functional Theory (DFT) calculations. Complex (1) presented no cytotoxicity to LLC-MK2, but complex (2) was toxic. IC50 against promastigotes of L. amazonensis for complex (1) were 4.90 (24 h), 3.50 (48 h) and 3. 80 μmol L−1 (72 h), and for complex (2) were 2.09, 4.20 and 2.80 μmol L−1, respectively. Due to the high toxicity presented by complex (2) against LLC-MK2 host cells, mechanistic studies, to shed light on the probable mode of leishmanicidal activity, were carried out only for the non-cytotoxic complex. Complex (1) was able to elevate mitochondrial membrane potential of the parasites after treatment. Transmission electron microscopy revealed typical apoptotic condensation of chromatin, altered kinetoplast and mitochondria structures, suggesting that apoptosis-like cell death of the protozoa is probably mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway). Molecular docking studies with complex (1) upon protein tyrosine phosphatase (LmPRL-1) suggests a plausible positive complex anchoring mainly by hydrophobic and hydrogen bond forces close to the enzyme's catalytic site. These promising results for complex 1 will prompt future investigations against amastigote form of L. amazonensis.
The anti-Leishmania activity of new Co(II) complex containing coumarin group involves mitochondrial dysfunction of parasite, suggesting apoptosis-like cell death. Display omitted
•Two new isomeric cobalt(II) complexes, containing coumarin groups are described.•X-ray diffraction studies were performed for complex (2).•Complex (1) exhibited in vitro anti-Leishmania activity (promastigote form).•TEM shows mitochondria impairment and apoptosis-like cell death of the parasite.
Purple acid phosphatases (PAPs) are a group of metallohydrolases that contain a dinuclear FeIIIMII center (MII = Fe, Mn, Zn) in the active site and are able to catalyze the hydrolysis of a variety of ...phosphoric acid esters. The dinuclear complex (H2O)FeIII(μ-OH)ZnII(L-H)(ClO4)2 (2) with the ligand 2-N-bis(2-pyridylmethyl)aminomethyl-4-methyl-6-N′-(2-pyridylmethyl)(2-hydroxybenzyl) aminomethylphenol (H2 L-H) has recently been prepared and is found to closely mimic the coordination environment of the FeIIIZnII active site found in red kidney bean PAP (Neves et al. J. Am. Chem. Soc. 2007, 129, 7486). The biomimetic shows significant catalytic activity in hydrolytic reactions. By using a variety of structural, spectroscopic, and computational techniques the electronic structure of the FeIII center of this biomimetic complex was determined. In the solid state the electronic ground state reflects the rhombically distorted FeIIIN2O4 octahedron with a dominant tetragonal compression aligned along the μ-OH−Fe−Ophenolate direction. To probe the role of the Fe−Ophenolate bond, the phenolate moiety was modified to contain electron-donating or -withdrawing groups (−CH3, −H, −Br, −NO2) in the 5-position. The effects of the substituents on the electronic properties of the biomimetic complexes were studied with a range of experimental and computational techniques. This study establishes benchmarks against accurate crystallographic structural information using spectroscopic techniques that are not restricted to single crystals. Kinetic studies on the hydrolysis reaction revealed that the phosphodiesterase activity increases in the order −NO2 ←Br ←H ←CH3 when 2,4-bis(dinitrophenyl)phosphate (2,4-bdnpp) was used as substrate, and a linear free energy relationship is found when log(k cat/k 0) is plotted against the Hammett parameter σ. However, nuclease activity measurements in the cleavage of double stranded DNA showed that the complexes containing the electron-withdrawing −NO2 and electron-donating −CH3 groups are the most active while the cytotoxic activity of the biomimetics on leukemia and lung tumoral cells is highest for complexes with electron-donating groups.
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