A new dinuclear Zn(II) compound, namely Zn2(mu-L)(mu-OAc)2]ClO4 (1), prepared with a new phenol-based ligand containing thioether substituents: 4-methyl-2,6-bis(((2-(methylthio)phenyl)(pyridin-2-ylmethyl)amino)methyl) phenol (HL) has been synthesized and characterized by different instrumental techniques such as UV-Vis, FTIR, 1H and 13C NMR, ESI-MS, single crystal X-ray diffraction studies. Single-crystal X-ray crystallography reveals that 1 exhibits a dinuclear zinc(II) structure with each ion hexacoordinated in a distorted octahedral geometry, with the same coordination sphere containing N2O3S-donor sites. Additionally, we demonstrated that the zinc complex is capable of degrading inactivated peptide bonds in bovine serum albumin (BSA) at micromolar concentrations. The BSA degradation is detected in a few hours and through a hydrolytic mechanism.

Metal complexes are well known for their DNA cleavage activity. Copper is a metal that stands out for this purpose because it is able to perform cleavage through oxidative mechanisms using the Haber–Weiss cycle. We report two unprecedented copper(II) complexes (2 and 3) with long-chain ligands and compare the results with those of a previously reported complex (1), which we use as a reference in our studies. They were all properly characterized using a set of physicochemical methods, including elemental analysis, electron paramagnetic resonance, spectroscopic and electrochemical analysis. Density functional theory (DFT) modeling revealed a pseudo-octahedral environment where the ligands are trans to each other. The interaction of 1, 2, and 3 with salmon sperm DNA was monitored spectrophotometrically, and the binding constants (Kb) were 4.24 × 104 L mol−1, 1.92 × 104 L mol−1, and 1.15 × 104 L mol−1, respectively. The interactions were supported by docking studies conducted with the CCDC GOLD® docking suite. Finally, all complexes exhibited DNA binding and cleavage properties, but 2 stood out as the most active one (2, kobs = 0.88 ± 0.09 h−1 > 1, kobs = 0.54 ± 0.06 h−1 > 3, kobs = 0.50 ± 0.03 h−1). These results support the idea that fine-tuning the length of the alkyl chain can enhance DNA-targeting activity and contribute to the development of efficient strategies for catalytic cleavage of nucleic acids.

In this study, the preparation and characterization of two new mixed-valence heterodinuclear complexes [FeIIINiII(BPPAMFF)(mu-OAc)2(H2O)]ClO4 (1) and [FeIIIZnII(BPPAMFF)(mu-OAc)2(H2O)]ClO4 (2) with the bioinspired ligand 2-[(N-benzyl-N-2-pyridylmethylamine)]-4-methyl-6-[N-(2-pyridylmethyl)aminomethyl)])-4methyl-6-formylphenol (H2BPPAMFF) are reported. These compounds were immobilized in 3-aminopropyl silica (APS) to afford composites APS-1 and APS-2 successfully. The aldehyde-containing ligand provided a reactive functional group, which could serve as a cross-linking group to bind the complexes to the directly aminomodified SiO2 surface. The complexes' chemical integrity on the APS inorganic platform were probed by spectroscopical techniques, such as FTIR, UV-Vis and EPR. Potentiometric and spectrophotometric titrations allowed the chemical species present in solution to be rationalized, and identified which of them were potentially active in the hydrolytic cleavage of phosphodiester 2,4-BDNPP. Kinetic studies showed that FeIIINiII species (1 and APS1) presented higher catalytic efficiency (E = kcat/KM) than FeIIIZnII species (2 and APS-2). Catalytic mechanisms were proposed based on a series of kinetic experiments, in which all the catalysts tested behaved as selective phosphodiesterases. In addition, it was also demonstrated that the hydrolase activity of the immobilized catalytic centers, APS-1 and APS-2, was better than the homogeneous processes, where second coordination sphere effects may be involved in directing and stabilizing the transition state.

In this study, a novel ligand: 2-((bis(2-(phenylthio)ethyl)amino)methyl)-6-((bis(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (HL) was prepared and subsequently used to synthesize the complexes [Zn(L)(OAc)]ClO4 (1) and [Fe2(L)(μ-OAc)(μ-O)](ClO4)2 (2). The metal complexes were comprehensively characterized using different techniques such as IR, Mass Spectrometry, UV-Vis, elemental analysis and X-ray analysis. The crystal structures show that compound 1 is a mononuclear pentacoordinate zinc(II) complex, while compound 2 is a dinuclear hexacoordinate iron(III) compound, with the metal centers connected by μ-oxo and μ-acetato bridges. In both cases, the phenol-based ligand features thioether substituents as pendant arms. We have evaluated the binding of the new complexes to DNA and also their capacity to cleave it. Both complexes have excellent antitumor activity against an astrocytic tumor derived from a primary human GBM1 cell line. SYNOPSIS: The paper reports synthesis and characterization of two new complexes [Zn(L)(OAc)]ClO4 (1) and [Fe2(L)(μ-OAc)(μ-O)](ClO4)2 (2). Complex 1 exhibits better activity than 2 at lower concentrations and with a faster rate of action, showing a preference for the minor groove. The cytotoxicity studies demonstrated a reduction in cell viability when exposed to the complexes, with GBM and C6 cells.

The electrosynthesis of substituted isoquinolines via silver-mediated intramolecular cyclization of 2-ethynylbenzaldehydes with ammonium acetate is presented. The reaction employs Ag-(+)|C(-) electrodes in a DMF/isopropanol mixture at 60 °C using LiClO4 as the supporting electrolyte, affording isoquinoline derivatives in yields up to 76%. Control experiments and DFT calculations were conducted to support a plausible reaction mechanism.

The use of photoCORMs to release carbon monoxide in a specific biological target has been widely studied because their therapeutic properties. This work presents the synthesis and photochemical and mechanistic insight of the CO photorelease of three water-soluble Re(I) photoCORMs: [Re(aaz)(CO)3]Cl (1), [Re(Me2aaz) (CO)3]Cl (2), and [Re(tacn)(CO)3]Cl (3) (aaz = 6-amino-6-methylperhydro-1,4-diazepine; Me2aaz = 6-amino-1,4,6-trimethyl-1,4-diazacycloheptane; and tacn = 1,4,7-triazacyclononane). All compounds presented photo-triggered carbon monoxide release when exposed to UV light (lambda 254 = 254 +/- 10 nm), affording bis and mono-carbonyl intermediates identified via spectroscopic, electrochemical, and mass techniques. The quantum yields and rates of CO release were determined where its release mechanism probably involves a three-step mechanistic pathway. Despite recent studies, the mechanism of CO release associated with Re(I) photoCORMs and spin-orbit coupling has not been explored in-depth, and it could be a critical factor in developing new and more efficient photoCORMs.

Effective degradation of non-natural phosphate triesters (PTs) widely used in pesticides and warfare agents is of paramount relevance for human and environmental safety, particularly under acidic conditions where they are highly stable. Here, we present a detailed reactivity and mechanistic study pioneering discrete {Zr6O8} clusters, which are commonly employed as building blocks for Zr-MOFs and as non-classical soluble coordination compounds for the degradation of PTs using the pesticide ethyl paraoxon as a model. Combined computational studies, mechanistic experiments, and EXAFS analysis show that the reactivity of these clusters arises from their ZrIV-ZrIV bimetallic sites, which hydrolyze ethyl paraoxon under acidic conditions through an intramolecular pathway. Remarkably, the energetics of the reaction is dependent on the protonation state of the active sites, and a weakly acidic medium favors the reaction. Moreover, catalyst stability allowed for its recovery and reuse. Such a mechanism is in close analogy to enzymatic reactions and different from that previously reported for Zr-MOFs. These findings outline the potential of MIV-MIV active sites for PT degradation under challenging aqueous acidic conditions and contribute to the development of bioinspired catalysts and materials.

This paper describes the synthesis, structural analysis, as well as the magnetic and spectroscopic characterizations of three new dicopper(II) complexes with dinucleating phenol-based ligands containing different thioether donor substituents: aromatic (1), aliphatic (2) or thiophene (3). Temperature-dependent magnetometry reveals the presence of antiferromagnetic coupling for 1 and 3 (J = -2.27 cm(-1) and -5.01 cm(-1), respectively, H = -2JS(1)S(2)) and ferromagnetic coupling for 2 (J = 5.72 cm(-1)). Broken symmetry DFT calculations attribute this behavior to a major contribution from the d(z2) orbitals for 1 and 3, and from the d(x2-y2) orbitals for 2, along with the p orbitals of the oxygens. The bioinspired catalytic activities of these complexes related to catechol oxidase were studied using 3,5-di-tert-butylcatechol as substrate. The order of catalytic rates for the substrate oxidation follows the trend 1 > 2 > 3 with k(cat) of (90.79 +/- 2.90) x 10(-3) for 1, (64.21 +/- 0.99) x 10(-3) for 2 and (14.20 +/- 0.32) x 10(-3) s(-1) for 3. The complexes also cleave DNA through an oxidative mechanism with minor-groove preference, as indicated by experimental and molecular docking assays. Antimicrobial potential of these highly active complexes has shown that 3 inhibits both Staphylococcus aureus bacterium and Epidermophyton floccosum fungus. Notably, the complexes were found to be nontoxic to normal cells but exhibited cytotoxicity against epidermoid carcinoma cells, surpassing the activity of the metallodrug cisplatin. This research shows the multifaceted properties of these complexes, making them promising candidates for various applications in catalysis, nucleic acids research, and antimicrobial activities.

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 57Fe 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 (kcat). 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. This research addresses the scarcity of examples in phosphate triester hydrolysis by introducing three mononuclear iron(III) complexes. Notably, complexes 2 and 3, featuring benzimidazole moieties, demonstrated strategic variations in aliphatic chain lengths, influencing catalytic activity. Structural analyses, including spectrophotometry and DFT modelling, revealed their high-spin nature and distorted octahedral geometries. Catalytic experiments showed a significant (27 times) enhancement in hydrolysis rates for diethyl-2,4-dinitrophenylphosphate, highlighting the potential of these complexes as efficient catalysts for agrochemical degradation. image

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 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)Cl2]0.4,2H2O (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 mu mol L- 1 (72 h), and for complex (2) were 2.09, 4.20 and 2.80 mu mol 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 mi-croscopy 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.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

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 (kCO,old and kCO,new), where Mn-HbpaBr (1) had the greatest kCO by both methods (Kco,old = 2.36 × 10−3 s−1 and kCO,new = 2.37 × 10−3 s−1). Carbon monoxide release was also evaluated using the myoglobin assay, indicating the release of 1.248 to 1.827 carbon monoxides upon light irradiation.

An electrochemical synthesis of flavanones via oxa-Michael addition using silver electrode as a sacrifice is reported. This electrosynthetic system showed good yields, broad substrate scope, and good functional group tolerance. Additionally, the method proved to be applicable on a gram-scale. Several studies were carried out to elucidate the reaction mechanism, such as control reactions, cyclic voltammetry, and theoretical studies, allowing the proposal of a plausible pathway for this transformation.

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

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.

Potential estrogenic effects and changes in fertility are some of the health problems associated with bisphenol A (BPA) derivatives used to produce some polymers, including dental materials that contain Bis-GMA. Those issues drove this study proposing the synthesis of methacrylate resveratrol and phenolphthalein monomers that, combined with diluent monomers, generate copolymers. Their key characteristics were determined and analyzed on the chemical structure-property perspective considering monomer planarity and flexibility based on molecular dynamic simulations. METHODS:Methacrylate resveratrol ((E)-5-(4-(methacryloyloxy)styryl)-1,3-phenylenebis(2-methylacrylate)), EMPM) and methacrylate phenolphthalein ((3-oxo-1,3-dihydroisobenzofuran-1,1-diyl)bis(4,1-phenylene)bis(2-methylacrylate)), DIFPM) were synthesized through the reaction of precursors with methacryloyl chloride. After monomers purification and spectroscopic characterization (FTIR and NMR), the following copolymers were produced: DIFPM/TEGDMA and Bis-GMA/TEGDMA, EMPM/HEMA and Bis-GMA/HEMA. Microhardness, degree of conversion, water sorption and contact angle data were statistically analyzed through one-way ANOVA and Tukey's test (p ≤ 0.05). RESULTS:The DIFPM molecular structure's reduced flexibility proved to be an important factor to inhibit TEGDMA cyclization. In turn, the EMPM molecule's high planarity modified the spatial organization of the HEMA copolymer, altering the water diffusion and, therefore, the water sorption when compared to Bis-GMA copolymers. CONCLUSION:The scientific findings contribute to better understand the effect of monomer chemical structures, molecular geometry, and planarity on some physicochemical properties of copolymers. Knowledge that can contribute to the design of new monomers to replace Bis-GMA.

The unprecedented mononucleated ligand (6,6-di(1H-indol-3-yl)-N,N-bis(pyridin-2-ylmethyl)hexan-1-amine (LC5) with an N3-donor set and its complexes [Zn(LC5)Cl2] • 2CH3OH (1) and [Zn(LC5)2](ClO4)2 (2), were successfully prepared. All compounds were fully characterized by a suite of physicochemical methods. Fluid 1H and 13C NMR spectroscopy, as well as DFT and TD-DFT calculations, were carried out to propose a viable structural arrangement for both complexes. The interaction between these compounds and DNA was monitored in the UV region where binding constants (Kb) were estimated (2 > 1 > LC5). These data were corroborated by DNA cleavage assays using groove binders, circular dichroism, and docking studies. Both complexes confirmed their biocide activity against selected microorganisms: Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria, the filamentous fungi A. fumigatus and S. cerevisiae. Finally, the cytotoxic activities of 1 and 2 were tested against the erythroleukemia K562 cell line. For all biological studies, it was probed that the presence of the indole moieties and the zinc atoms in the chemical composition of the complexes studied could increase the magnitude of the activity following the order: 2 > 1 > LC5, where a linear relationship between the biological activity upon K562 cells (IC50) and DNA binding studies (Kb) was found.

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)2]BF4 (1) and [MnIIFeIII(L1)(OAc)2]BF4 (2) (H2L1 = 2-[N,N-bis-(2- pyridilmethyl)aminomethyl]-4-methyl-6-[N-(2-hydroxy-3-formyl-5-methylbenzyl)-N-(2-pyridylmethyl)aminomethyl]phenol), 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.