Novel organically linked ZnII hydrogenselenite coordination polymers: synthesis, characterization, and efficient TiO2 photosensitization for enhanced photocatalytic hydrogen production.

This study focused on the solvothermal synthesis, characterization, and photocatalytic activities of two novel coordination polymers, namely [Zn(µ-HSeO3)2(bipy)]n (1) and [Zn(µ-HSeO3)2(phen)]n (2). These compounds represent the first organically linked ZnII hydrogenselenite coordination polymers. The synthesis of compounds 1 and 2 involved the addition of 2,2'-bipyridine and 1,10-phenanthroline, respectively, to SeO2 and ZnO in methanol as the solvent. The novel hydrogenselenite compounds were thoroughly characterized using spectroscopic and crystallographic methods. The photocatalytic solids (TiO2-1A and TiO2-2A) were prepared by immobilizing compounds 1-2 onto TiO2 through the sol-gel approach. These photocatalysts were then evaluated for hydrogen evolution via water splitting using a 300 W Hg/Xe lamp as the irradiation source. Among the newly synthesized photocatalytic materials, TiO2-1A demonstrated auspicious photocatalytic performance for hydrogen gas production. Its catalytic activity overcame the observed for the pure solid support TiO2 and Degussa P25 (commercial titania), making compound 1 a particularly attractive TiO2 photosensitizer. Additionally, TiO2-1A exhibited superior photocatalytic activity compared to TiO2-2A. The latter performed better than freshly prepared TiO2, approaching that of Degussa P25. These findings highlight the potential of compound 1 as an effective photosensitizer for TiO2-based photocatalysis, making it a promising candidate for applications in clean energy generation, specifically in hydrogen production by water splitting.

Synthesis of 4-(Phenylchalcogenyl)tetrazolo[1,5-a]quinolines by Bicyclization of 2-Azidobenzaldehydes with Phenylchalcogenylacetonitrile.

A general methodology to access valuable 4-(phenylchalcogenyl)tetrazolo[1,5-a]quinolines was developed by the reaction of 2-azidobenzaldehyde with phenylchalcogenylacetonitriles (sulfur and selenium) in the presence of potassium carbonate (20 mol%) as a catalyst. The reactions were conducted using a mixture of dimethylsulfoxide and water (7:3) as solvent at 80 °C for 4 h. This new methodology presents a good functional group tolerance to electron-deficient and electron-rich substituents, affording a total of twelve different 4-(phenylchalcogenyl)tetrazolo[1,5-a]quinolines selectively in moderate to excellent yields. The structure of the synthesized 4-(phenylselanyl)tetrazolo[1,5-a]quinoline was confirmed by X-ray analysis.

In vitro anti-Leishmania activity of new isomeric cobalt(II)complexes and in silico insights: Mitochondria impairment and apoptosis-like cell death of the parasite.

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 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.

Scavenging of reactive species probed by EPR and ex-vivo nanomolar reduction of lipid peroxidation of manganese complexes.

Antioxidant activity toward H2O2, anion radical superoxide, hydroxyl and DPPH (2,2-diphenyl-1-picrylhydrazyl) of two manganese complexes [Mn(III)(bpa)2]Cl.H2O (1) and [(Cl)Mn(µ-hbpclnol)(µ-bpclnol)Mn](ClO4).3H2O (2) (hbpa = (2-hydroxybenzyl-2-pyridylmethyl)amine and h2bpclnol = (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine) are presented. X-ray diffraction studies were performed for complex (1). Both complexes presented similar or better activities than reference complex [Mn(salen)Cl], when the interaction between them and ROS (H2O2, O2•- and •OH), was monitored, by EPR (Electron Paramagnetic Resonance), in PBS, DMSO and water. The antioxidant activity rank of complexes toward •OH, generated by Fenton reaction and monitored by EPR, is (2) > (1) > [Mn(salen)Cl], in water (0.1% of DMSO for each complex), with the values of the IC50 of 7.2 (±1.6), 15.5 (±1.8) and 29.1 (±2.01) µM respectively. EPR data presented herein suggest that complex (2) presents the better scavenging activity toward hydroxyl, being in good agreement with TBARS assay results, in which complex (2) presented the best inhibitory activity toward lipid peroxidation, employing Swiss mice liver homogenate tissue model. IC50 values obtained from the interaction between these complexes and hydroxyl, using TBARS method, were: 0.88 (± 0.029); 0.73 (± 0.01) and 42.7 (± 3.5) nM, respectively for (1), (2) and [Mn(salen)Cl]. Complexes (1) and (2) are regulating the lipid homeostasis, protecting the tissue from the lipid peroxidation, in nanomolar scale, motivating in vivo studies. Redox properties and radical scavenging activity of complexes toward DPPH are non-linear and solvent dependent. Furthermore, the monitoring of antioxidant activity probed by EPR could be a fair and appropriate study to guide more advanced investigations.

Synthesis, characterization, antioxidant potential, and cytotoxicity screening of new Cu(II) complexes with 4-(arylchalcogenyl)-1H-pyrazoles ligands.

Two new Cu(II) complexes based on 4-(arylchalcogenyl)-1H-pyrazoles monodentate bis(ligand) containing selenium or sulfur groups (2a and 2b) have been synthesized and characterized by IR spectroscopy, high-resolution mass spectrometry (HRMS), and by X-ray crystallography. In the effort to propose new applications for the biomedical area, we evaluated the antioxidant activity and cytotoxicity of the newly synthesized complexes. The antioxidant activity of the Cu(II) complexes (2a - 2b) were assessed through their ability to inhibit the formation of reactive species (RS) induced by sodium azide and to scavenge the synthetic radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS+). Both copper complexes containing selenium (2a) and sulfur (2b) presented in vitro antioxidant activity. The (1a - 1b and 2a - 2b) compounds did not show cytotoxicity in V79 cells at low concentrations. Furthermore, the antiproliferative activity of free ligands (1a - 1b) and their complexes (2a - 2b) were tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and HepG2 (hepatocarcinoma). Also, 2a was tested against U2OS (osteosarcoma). Our results demonstrated that 1a and 1b show little or no growth inhibition activities on human cell lines.The 2a compound exhibited good cytotoxic activity toward human tumor cell lines. However, 2a showed no selectivity, with a selectivity index of 1.12-1.40. Complex 2b was selective for the MCF-7 human tumor cell lines with IC50 of 59 ± 2 µM. This study demonstrates that the Cu(II) complexes 2a and 2b represent promising antitumoral compounds, and further studies are necessary to understand the molecular mechanisms of these effects.

Synthesis of Chalcogenylchromenes through Cyclization of Propargylic Aryl Ethers.

We describe here for the first time the synthesis of 2-(chalcogenyl)-3H-benzo[f]chromenes and the new 3-(phenylselanyl)-2H-chromenes by the radical or electrophilic cyclization of propargylic aryl ethers in the presence of diorganyl diselenides or ditellurides using Oxone as a green oxidant and acetonitrile as solvent in a sealed tube at 100 °C. In this study, thirty-one chalcogenylchromenes with a broad substrate scope were prepared in moderate to excellent yields (50-98%), including compounds derived from natural products.

Synthesis of Seleno-Dibenzocycloheptenones/Spiro[5.5]Trienones by Radical Cyclization of Biaryl Ynones.

We report herein an alternative method for the synthesis of seleno-dibenzocycloheptenones and seleno-spiro[5.5]trienones through the radical cyclization of biaryl ynones in the presence of diorganyl diselenides, using Oxone as a green oxidizing agent. The reactions were conducted using acetonitrile as the solvent in a sealed tube at 100 °C. The protocol is operationally simple and scalable, exhibits high regioselectivity, and allows the synthesis of 24 dibenzocycloheptenones/spiro[5.5]trienones in yields of up to 99%, 17 of which are unpublished compounds. Additionally, synthetic transformations of the prepared compounds, such as oxidation and reduction reactions, are demonstrated.

Selective synthesis of α-organylthio esters and α-organylthio ketones from ß-keto esters and sodium S-organyl sulfurothioates under basic conditions.

We described herein a selective method to prepare α-organylthio esters and α-organylthio ketones by the reaction of ß-keto esters with sodium S-benzyl sulfurothioate or sodium S-alkyl sulfurothioate (Bunte salts) under basic conditions in toluene as the solvent at 100 °C. When 4 equivalents of a base were used, a series of differently substituted α-thio esters were obtained with up to 90% yield. On the other hand, employing 2 equivalents of a base, α-thio ketones were achieved after 18 h under air. Furthermore, after a shorter reaction time, the isolation of keto-enol tautomers was possible, revealing them as significant intermediates for the mechanism elucidation.

Oxone-Promoted Synthesis of 4-(Chalcogenyl)isoquinoline-N-oxides from Alkynylbenzaldoximes and Diorganyl Dichalcogenides.

We report a protocol for the synthesis of 3-organyl-4-(organylchalcogenyl)isoquinoline-2-oxides via electrophilic cyclization between alkynylbenzaldoximes and diorganyl dichalcogenides promoted by Oxone. A total of 21 3-organyl-4-(organylchalcogenyl)isoquinoline-2-oxides were selectively obtained in yields of up 93% under an ultrasound irradiation condition in short reaction times (10-70 min). Additionally, the synthetic usefulness of the 3-phenyl-4-(phenylselanyl)isoquinoline-2-oxide was demonstrated in the annulation reaction with 1-(2-bromophenyl)-3-phenylprop-2-yn-1-one and in the deoxygenation reaction with phenylboronic acid.

Synthesis, molecular structure and antioxidant activity of bis [L(µ2-chloro)copper(II)] supported by phenoxy/naphthoxy-imine ligands.

A new series of Cu(II) complexes [bis[{(µ2-chloro)-2-MeO-Ph-CH2-(N=CH)-2,4-tert-butyl-2-OC6H2)}Cu(II)] (Cu1); bis[{(µ2-chloro)-2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(OC6H2)}Cu(II)] (Cu2); bis[{(µ2-chloro)-2-MeO-Ph-CH2-(N=CH)-2-(OC10H6)} Cu(II)] (Cu3); bis[{(µ2-chloro)-2-MeS-Ph-CH2-(N=CH)-2-(OC10H6)}Cu(II)] complex (Cu4); bis[{2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(OC6H2)}Cu(II)] (Cu5)] have been synthesized and characterized by elemental analysis, IR, UV-Visible and by X-ray crystallography for Cu1, Cu4 and Cu5. In the solid state, Cu1 features of a chloro-bridged dimer complex with κ2 coordination of the monoanionic phenoxy-imine ligand onto the copper center. On the other hand, the molecular structure of Cu4 reveals the naphthoxy-imine ligand with pendant S-group coordinated to the copper atom in tridentate meridional fashion. Treatment of [Cu(OAc)2·H2O] with two equiv. of [2-MeS-Ph-CH2-(N=CH)-2,4-tert-butyl-2-(HOC6H2)] led to a monomeric complex Cu5, with the ONS-donor Schiff base acting as a bidentate ligand. The redox behavior was explored by cyclic voltammetry. The reduction/oxidation potential of Cu(II) complexes depends on the structure and conformation of the central atom in the coordination compounds. Antioxidant activities of the complexes, Cu1 - Cu5, were determined by in vitro assays such as 1,1-diphenyl-2-picryl-hydrazyl free radicals (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) radicals (ABTS+). The dinuclear compounds Cu1-Cu4, from the concentration of 5 µM, presented a good activity in scavenging DPPH radical. In addition, most of the Cu(II) complexes showed ABTS.+ radical-scavenging activity. The monomeric complex Cu5 at all concentrations tested showed antioxidant inability. The cytotoxicity of the Cu1 and Cu3 was determined in V79 cell line by reduction of 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay.

Therapeutic potential of selanyl amide derivatives in the in vitro anticholinesterase activity and in in vivo antiamnesic action.

The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N-(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide (1) and N-(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide (2) inhibited the in vitro AChE activity in mice. Another objective was to assess the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 (10 mg/kg, intragastrically) attenuated the latency to find the escape box and the number of holes visited in the Barnes maze task, without altering the locomotor and exploratory activities in an open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of mice. In conclusion, the present study evidenced the in vitro anticholinesterase effect of two new selanyl amide derivatives in the cerebral structures of mice. Moreover, compound 1, a selanyl amide derivative containing a furan ring, demonstrated antiamnesic action due to its antioxidant and anticholinesterase activities in cerebral structures.

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles.

A one-pot iodine-catalyzed multicomponent reaction has been developed for the selective preparation of 5-amino-4-(arylselanyl)-1H-pyrazoles from a diverse array of benzoylacetonitriles, arylhydrazines and diaryl diselenides. The reactions were conducted in MeCN as solvent at reflux temperature under air. The methodology presents a large functional group tolerance to electron-deficient, electron-rich, and bulky substituents and gave the expected products in good to excellent yields. The synthesized 1,3-diphenyl-4-(phenylselanyl)-1H-pyrazol-5-amine was submitted to an oxidative dehydrogenative coupling to produce a diazo compound confirmed by X-ray analysis.