Tyrosinase and catechol oxidase activity of copper(I) complexes supported by imidazole-based ligands: structure–reactivity correlations

Four new imidazole-based ligands, 4-((1H-imidazol-4-yl)methyl)-2-phenyl-4,5-dihydrooxyzole (L _OL 1), 4-((1H-imidazol-4-yl)methyl)-2-(tert-butyl)-4,5-dihydrooxyzole (L _OL 2), 4-((1H-imidazol-4-yl)methyl)-2-methyl-4,5-dihydrooxyzole (L _OL 3), and N-(2,2-dimethylpropylidene)-2-(1-trityl-1H-imidazol-4-yl-)ethyl amine (L _imz 1), have been synthesized. The corresponding copper(I) complexes [Cu(I)(L _OL 1)(CH₃CN)]PF₆ (CuL _OL 1), [Cu(I)(L _OL 2)(CH₃CN)]PF₆ (CuL _OL 2), [Cu(I)(L _OL 3)(CH₃CN)]PF₆ (CuL _OL 3), [Cu(I)(L _imz 1)(CH₃CN)₂]PF₆ (CuL _imz 1) as well as the Cu(I) complex derived from the known ligand bis(1-methylimidazol-2-yl)methane (BIMZ), [Cu(I)(BIMZ)(CH₃CN)]PF₆ (CuBIMZ), are screened as catalysts for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC-H₂) to 3,5-di-tert-butylquinone (3,5-DTBQ). The primary reaction product of these oxidations is 3,5-di-tert-butylsemiquinone (3,5-DTBSQ) which slowly converts to 3,5-DTBQ. Saturation kinetic studies reveal a trend of catalytic activity in the order CuL _OL 3 ≈ CuL _OL 1 > CuBIMZ > CuL _OL 2 > CuL _imz 1. Additionally, the catalytic activity of the copper(I) complexes towards the oxygenation of monophenols is investigated. As substrates 2,4-di-tert-butylphenol (2,4-DTBP-H), 3-tert-butylphenol (3-TBP-H), 4-methoxyphenol (4-MeOP-H), N-acetyl-l-tyrosine ethyl ester monohydrate (NATEE) and 8-hydroxyquinoline are employed. The oxygenation products are identified and characterized with the help of UV/Vis and NMR spectroscopy, mass spectrometry, and fluorescence measurements. Whereas the copper complexes with ligands containing combinations of imidazole and imine functions or two imidazole units (CuL _imz 1 and CuBIMZ) are found to exhibit catalytic tyrosinase activity, the systems with ligands containing oxazoline just mediate a stoichiometric conversion. Correlations between the structures of the complexes and their reactivities are discussed.     

Cadmium(II) and zinc(II) coordination polymers with mixed building blocks of benzenedicarboxyl and 2,5-bipyridyl-1,3,4-oxadiazole: Syntheses, crystal structures, and properties

Three Cd(II) and Zn(II) coordination polymers, including {[Cd(3-bpo)(mip)(H₂O)](H₂O)₂}_n (1), {[Cd(4-bpo)(hip)(H₂O)](H₂O)₄}_n (2), and {[Zn(4-bpo)(tp)](CH₃OH)}_n (3) were synthesized from the reactions of Cd^II or Zn^II nitrate with mixed organic ligands [3-bpo = 2,5-bis(3-pyridyl)-1,3,4-oxadiazole, H₂mip = 5-methylisophthalic acid, 4-bpo = 2,5-bis(4-pyridyl)-1,3,4-oxadiazole, H₂hip = 5-hydroxylisophthalic acid, H₂tp = terephthalic acid] under the similar layered diffusion condition. The resulting crystalline materials 1-3 were characterized by IR, microanalysis, powder X-ray diffraction (PXRD) techniques. Single-crystal X-ray diffraction indicates a 1-D tubular motif for 1, a 1-D dual-track array for 2, and a 2-D grid-like pattern for 3, constructed via different metal-ligand coordination contacts. Higher-dimensional supramolecular architectures are further assembled in 1-3 via H-bonding and aromatic stacking interactions. In addition, thermal stability and fluorescence of these polymeric complexes were also investigated and discussed.     

Investigation of the photochemical properties of biopterin and its reduced forms

UV irradiation (270–390 nm, 20 min, I = 3.2 W m^?2) of deaerated biopterin solution containing electron donor (Na₂-EDTA) led to the formation of 7,8-dihydrobiopterin (H ₂ BPT), which, when excited, underwent reduction to form 5,6,7,8-tetrahydrobiopterin (H ₄ BPT). Protonated molecules of H₄BPT were resistant to oxidation by O₂ both in the “dark” incubated and UV-irradiated solutions at pH below 3.0. The rate of H₄BPT oxidation dramatically increased at pH above 3.0, and, then, up to pH 10.0, it did not change, showing no dependence on UV irradiation. At the initial stage (5 min) of H₄BPT oxidation in neutral solution, UV irradiation stimulated the accumulation of quinonoid 6,7-dihydrobiopterin (q-H ₂ BPT) in addition to H₂BPT. UV irradiation of H₂BPT induced its oxidation to biopterin and unidentified products.     

Distorted tetrahedral nickel-nitrosyl complexes: spectroscopic characterization and electronic structure

The linear nickel-nitrosyl complex [Ni(NO)(L3)] supported by a highly hindered tridentate nitrogen-based ligand, hydrotris(3-tertiary butyl-5-isopropyl-1-pyrazolyl)borate (denoted as L3), was prepared by the reaction of the potassium salt of the ligand with the nickel-nitrosyl precursor [Ni(NO)(Br)(PPh ₃ ) ₂ ]. The obtained nitrosyl complexes as well as the corresponding chlorido complexes [Ni(NO)(Cl)(PPh ₃ ) ₂ ] and [Ni(Cl)(L3)] were characterized by X-ray crystallography and different spectroscopic methods including IR/far-IR, UV–Vis, NMR, and multi-edge X-ray absorption spectroscopy at the Ni K-, Ni L-, Cl K-, and P K-edges. For comparative electronic structure analysis we also performed DFT calculations to further elucidate the electronic structure of [Ni(NO)(L3)]. These results provide the nickel oxidation state and the character of the Ni-NO bond. The complex [Ni(NO)(L3)] is best described as [Ni ^II (NO ^– )(L3)], and the spectroscopic results indicate that the phosphane complexes have a similar [Ni ^II (NO ^– )(X)(PPh ₃ ) ₂ ] ground state.     

Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents

In this study, the N,N,O metal chelator 2-pyridinecarboxaldehydeisonicotinoyl hydrazone (HPCIH, 1) and its derivatives 2-acetylpyridine-(HAPIH 2), 2-pyridineformamide-(HPAmIH, 3) and pyrazineformamide-(HPzAmIH, 4) were employed in the synthesis of four copper(II) complexes, [Cu(HPCIH)Cl₂]·0.4H₂O (5), [Cu(HAPIH)Cl₂]·1.25H₂O (6), [Cu(HPAmIH)Cl₂]·H₂O (7) and [Cu(HPzAmIH)Cl₂]·1.25H₂O (8). The compounds were assayed for their action toward Mycobacterium tuberculosis H37Rv ATCC 27294 strain and the human tumor cell lines OVCAR-8 (ovarian cancer), SF-295 (glioblastoma multiforme) and HCT-116 (colon adenocarcinoma). All copper(II) complexes were more effective in reducing growth of HCT-116 and SF-295 cells than the respective free hydrazones at 5 µg/mL, whereas only complex 7 was more cytotoxic toward OVCAR-8 lines than its ligand HPAmIH. 6 proved to be cytotoxic at submicromolar doses, whose IC₅₀ values (0.39–0.86 µM) are similar to those ones found for doxorubicin (0.23–0.43 µM). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 µM, respectively), as compared with isoniazid (MIC = 2.27 µM), which suggests the compounds are attractive candidates as antitubercular drugs.     

2-(chromon-3-yl)imidazole derivatives as potential antimicrobial agents: synthesis,biological evaluation and molecular docking studies

A series of novel 2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (4a-h) were synthesized by one pot condensation of substituted 3-formylchromones (1a-h), benzil (2) and ammonium acetate (3) in refluxing acetic acid at 110 °C under N2 atmosphere. Allylation of compounds 4a-h with allyl bromide in the presence of fused K₂CO₃ furnished N-allyl-2-(chromon-3-yl)-4,5-diphenyl-1H-imidazoles (6a-h). The synthesized compounds were characterized spectroscopically and evaluated for in vitro antimicrobial activity against various pathogenic bacterial and fungal strains by disc diffusion method. Compounds bearing electron withdrawing substituents such as bromo (4f) showed significant inhibitory activity against S. cerevisiae (MIC 1.4 μg/ml) and 4g containing chloro substituent, displayed more inhibitory potential against C. albicans (MIC 1.5), as compared to the standard drugs. Compounds 6a and 4c exhibit remarkable inhibitory potential against B. subtilis with MIC 0.98 and 1.23, respectively. The time kill assay for active compound 6a was performed by viable cell count (VCC) method to elucidate the microbicidal nature of 2-(chromon-3-yl)imidazoles. A molecular docking study of most active compounds with target ‘lanosterol 14α-demethylase’ (CYP51) was performed to unravel the mode of antifungal action.     

Bioactive compounds of <Emphasis Type="Italic">Aspergillus terreus</Emphasis>—F7, an endophytic fungus from <Emphasis Type="Italic">Hyptis suaveolens</Emphasis> (L.) Poit

The compounds terrein (1), butyrolactone I (2), and butyrolactone V (3) were isolated from the ethyl acetate extract (EtOAc) of the endophytic fungus Aspergillus terreus—F7 obtained from Hyptis suaveolens (L.) Poit. The extract and the compounds presented schistosomicidal activity against Schistosoma mansoni; at 100 µg/mL for EtOAc extract, 1297.3 µM for compound 1, 235.6 µM for compound 2, and 454.1 µM for compound 3, they killed 100% of the parasites after 72 h of treatment. Compounds 1, 2, and 3 exerted moderate leishmanicidal activity against Leishmania amazonensis (IC₅₀ ranged from 23.7 to 78.6 µM). At 235.6 and 227.0 µM, compounds 2 and 3, respectively, scavenged 95.92 and 95.12% of the DPPH radical (2,2-diphenyl-1-picryl-hydrazyl), respectively. Regarding the cytotoxicity against the breast tumor cell lines MDA-MB-231 and MCF-7, compound 2 gave IC₅₀ of 34.4 and 17.4 µM, respectively, while compound 3 afforded IC₅₀ of 22.2 and 31.9 µM, respectively. At 117.6 µM, compound 2 inhibited the growth of and killed the pathogen Escherichia coli (ATCC 25922). Compounds 1, 2, and 3 displayed low toxicity against the normal line of human lung fibroblasts (GM07492A cells), with IC₅₀ of 15.3?×?10³, 3.4?×?10³, and 5.8?×?10³ µM, respectively. This is the first report on (i) the in vitro schistosomicidal and leishmanicidal activities of the EtOAc extract of A. terreus—F7 and compounds 1, 2, and 3; and (ii) the antitumor activity of compounds 2 and 3 against MDA-MB-231 and MCF-7 cells.     

Design and synthesis of an indol derivative as antibacterial agent against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

Several indole derivatives with antibacterial activity have been prepared using different protocols; however, some require special reagents and conditions. The aim of this study involved the synthesis of some indole derivatives using estrone and OTBS-estrone as chemical tools. The synthesis of the indole derivatives involves reactions such as follows: (1) synthesis of two indol derivatives (4 or 5) by reaction of estrone or OTBS-estrone with phenylhydrazine in medium acid; (2) reaction of 4 or 5 with 6-cloro-1-hexyne in medium basic to form two hexynyl-indol (7 or 8); (3) preparation of indol-propargylic alcohol derivatives (10 or 11) by reaction of benzaldehyde with 7 or 8 in medium basic; (4) synthesis of indol-aldehydes (12 or 13) via oxidation of 10 or 11 with DMSO; (5) synthesis of indeno-indol-carbaldehyde (15 or 16) via alkynylation/cyclization of 12 or 13 with hexyne in presence of copper(II); (6) preparation indeno-indol-carbaldehyde complex (19 or 20) via alkynylation/cyclization of 12 or 13 with 1-(hex-5-yn-1-yl)-2-phenyl-1H-imidazole. The antibacterial effect exerted by the indol-steroid derivatives against Streptococcus pneumoniae and Staphylococcus aureus bacteria was evaluated using dilution method and the minimum inhibitory concentration (MIC). The results showed that only the compound 19 inhibit the growth bacterial of S. aureus. In conclusion, these data indicate that antibacterial activity of 19 can be due mainly to functional groups involved in the chemical structure in comparison with the compounds studied.     

The mechanisms for N-heterocyclic olefin-catalyzed formation of cyclic carbonate from CO<Subscript>2</Subscript> and propargylic alcohols

The mechanistic details of N-heterocyclic olefin-catalyzed formation of cyclic carbonate from CO₂ and propargylic alcohols were investigated by DFT calculations. Six mechanisms, four for the formation of five-membered cyclic carbonate (M-A, M-B, M-B’ and M-C), and two for six-membered cyclic carbonate (M-D and M-E), were fully investigated. The energy profiles in dichloromethane showed that M-B is the predominant reaction with the lowest barrier of 31.99 kcal mol^?1, while M-C and M-D may be kinetically competitive to M-B. The very high activation energy of 45.37 kcal mol^-1, 57.07 kcal mol^-1 and 59.61 kcal mol^?1 for M-A, M-B’ and M-E, respectively, suggest that they are of lesser importance in the overall mechanism.

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Graphical abstract Formations of five-membered ring product and six-membered ring product are kinetically competitive, but five-membered ring product is thermodynamically more preferable.

     

Isolation and Antibiotic Screening of Fungi from a Hydrothermal Vent Site and Characterization of Secondary Metabolites from a <Emphasis Type="Italic">Penicillium</Emphasis> Isolate

Five new compounds were isolated from Penicillium sp. Y-5-2 including an austin derivative 4, four isocoumarins 9, 11, 12, and 13, together with two known isocoumarins 8 and 10, and six known austin derivatives 1, 2, 3, 5, 6, and 7 and one phenol 14. Their structures and relative configurations were established by spectroscopic means. The absolute configurations of 4, 11, and 13 were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. The cyclization of the pentan-2-ol pendant at C-3 in compound 13 allowed the assignment of a new 2,3,4,4a,6,10b-hexahydro-1H-benzo[c]chromene isocoumarin skeleton. New compounds 9, 11, and 13 revealed inhibitory activities against E. coli at MIC values around 32 μg/mL. The known compound 14 showed potent antibiotic activity against Staphylococcus aureus and Bacillus subtilis with MIC values 8 and 2 μg/mL, respectively, with no cytotoxicity when tested in vitro. A rapid and efficient technique for selecting antibiotic fungal strain among eight marine-derived fungi was also described.     

An expeditious synthesis of blood-group antigens,ABO histo-blood group type II antigens and xenoantigen oligosaccharides with amino type spacer−arms

Blood group oligosaccharides are one of the most clinically important antigen families and they may also act as secondary ligands for bacterial toxins from Escherichia coli and Vibrio cholerae. Herein we report the synthesis of spacered (sp = CH₂CH₂CH₂NH₂) glycosides of A antigen {α-D-GalNAc-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-}, B antigen{α-D-Gal-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-}, LewisX{α-D-Gal-(l→4)-[α-L-Fuc-(l→3)]-β-D-GlcNAc-}, A type-II {α-D-GalNAc-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-(1→4)-β-D-GlcNAc-}, B type-II {α-D-Gal-(l→3)-[α-L-Fuc-(l→2)]-β-D-Gal-(1→4)-β-D-GlcNAc-}, H type-II{α-L-Fuc-(l→2)-β-D-Gal-(1→4)-β-D-GlcNAc-}, xenoantigen {α-D-Gal-(l→3)-β-D-Gal-(1→4)-[α-L-Fuc-(l→2)]-β-D-GlcNAc-} and Linear B Type II {α-D-Gal-(l→3)-β-D-Gal-(1→4)-β-D-GlcNAc-} useful for a range of biochemical investigations. This linker was chosen so as to facilitate the future conjugation of the antigens to proteins or other molecules. We also measured the affinities of some synthesized oligosaccharides against El Tor CTB strain from V. cholera.     

Aromaticity of graphene nanoflakes in a new way: fragment analysis by combination of the nucleus-independent chemical shifts and the anisotropy of current induced density

A graphene nanoflake (GNF) is a polycyclic aromatic hydrocarbon (PAH) with a huge two-dimensional π-conjugated carbon material in which a central benzene ring is surrounded by identical benzene-type rings through infinite alternant method. In this paper, we explore the structure-aromaticity relationship of the GNFs and the GNFs with hollow sites (GNFHs) by combining the nucleus-independent chemical shifts (NICS) with the anisotropy of the current induced density (ACID). Firstly, the benzene is a typical aromatic molecule (NICS = ?9.671 ppm), GNFs 1-6 is darned with benzene and the corresponding GNFHs 1′-6′. Secondly, the NICS values of GNFs 1-6 alternately vary: ?1.214 (1) > ?13.847 (2) < ?2.662 (3) > ?14.530 (4) < ?3.932 (5) > ?13.978 (6) ppm, the GNFs (2, 4, 6) with even fragments of annulene have larger aromaticity than that of GNFs (1, 3, 5) with odd fragments of annulene. Significantly, the NICS values of GNFs 1-6 can also be fragment analyzed by the NICS values and ACID of benzene and corresponding GNFHs 1′-6′. The NICS values for GNFs (2, 4, 6) can be roughly estimated by the NICS value of benzene minus the NICS value of the GNFHs (2′, 4′, 6′), respectively. The NICS values for GNFs (1, 3, 5) can be roughly estimated by the NICS value of the GNFHs (1′, 3′, 5′) minus the NICS value of benzene, respectively. We hope that the present work can provide a simple and reliable method for the rational design of the GNF with aromaticity, which may be used to understand the origin of the graphene nanoflake aromatic properties.     

Preparation,Structure, and Potent Antifouling Activity of Sclerotioramine Derivatives

A series of 30 sclerotioramine derivatives (2–31) of the natural compound, (+)-sclerotiorin (1), has been successfully semi-synthesized by a one-step reaction with high yields (up to 80%). The structures of these new derivatives were established by extensive spectroscopic methods and single-crystal X-ray diffraction analysis for 3, 6, and 10. (+)-Sclerotiorin (1) and its semisynthetic derivatives (2–31) were evaluated for their antifouling activity. Most of them except 6, 7, 8, 12, and 28 showed potent antifouling activity against the larval settlement of the barnacle Balanus amphitrite. More interestingly, most of the aromatic amino-derivatives (13–17, 19–21, 23, 25–27, and 29–31) showed strong antifouling activity; however, only two aliphatic amino-derivatives (5 and 10) had the activity.     

Theoretical study on <Emphasis Type="Italic">p</Emphasis>-type D-π-A sensitizers with modified π-spacers for dye-sensitized solar cells

Based on a prototype sensitizer W2, we designed triarylamine-based p-type sensitizers W2-1 to W2-7 that contain modified π-spacers (π'), a π-spacer and two anchors. For W2-1 to W2-4, instead of 2,1,3-benzothiadiazole in W2, thieno[3,4-b]-1,4-dioxin, thiophene, thieno[3,4-c][1,2,5]thiadizole, thiazolo[5,4-d]thiazole are π' and thiophene as π-spacer. For W2-5 to W2-8, π' and π are same, with 2,1,3-benzothiadiazole, thieno[3,4-b]-1,4-dioxin, thieno[3,4-c][1,2,5]thiadiazo, thiazolo[5,4-d]thiazole, respectively, as the π'-spacers. Structure optimization, electronic level and absorption characters were calculated with density functional theory (DFT) and time-dependent DFT (TDDFT) at the CAM-B3LYP/6-311G (d,p). The solvent effect was involved using a polarized continuum model in chloroform. The results showed that the highest occupied molecular orbital and the lowest unoccupied molecular orbital guarantee sufficient hole injection (lower than –0.2 eV), and dye regeneration (lower than –0.2 eV). W2-4 has higher light-harvesting efficiency (LHE) (0.994) and larger overlap with the visible light from 400 nm to 600 nm. Finally, the results suggest that the driving force of hole injection, dye regeneration and charge recombination (ΔG_inj, ΔG_reg and ΔG_CR) of W2-4 are the best, with more negative ΔG_inj (–4.33), ΔG_reg (–1.74) and more positive ΔG_CR (1.92). Replacing 2,1,3-benzothiadiazole with thiazolo[5,4-d]thiazole as π'-spacers is a effective way to improve the performance of the dyes. An introduction of thiazolo[5,4-d]thiazole group can improve the absorption ability and hinder charge recombination.

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Graphical abstract Absorption spectra of p-type D-π-A sensitizers with modified π-spacers

     

Bonding,aromaticity, and planar tetracoordinated carbon in Si<Subscript>2</Subscript>CH<Subscript>2</Subscript> and Ge<Subscript>2</Subscript>CH<Subscript>2</Subscript>

Natural bond orbital (NBO) analyses and dissected nucleus-independent chemical shifts (NICS _{π z z} ) were computed to evaluate the bonding (bond type, electron occupation, hybridization) and aromatic character of the three lowest-lying Si₂CH₂ (1-Si, 2-Si, 3-Si) and Ge₂CH₂ (1-Ge, 2-Ge, 3-Ge) isomers. While their carbon C₃H₂ analogs favor classical alkene, allene, and alkyne type bonding, these Si and Ge derivatives are more polarizable and can favor “highly electron delocalized”? and “non-classical”? structures. The lowest energy Si ₂CH₂ and Ge ₂CH₂ isomers, 1-Si and 1-Ge, exhibit two sets of 3–center 2–electron (3c-2e) bonding; a π-3c-2e bond involving the heavy atoms (C–Si–Si and C–Ge–Ge), and a σ-3c-2e bond (Si–H–Si, Ge–H–Ge). Both 3-Si and 3-Ge exhibit π and σ-3c-2e bonding involving a planar tetracoordinated carbon (ptC) center. Despite their highly electron delocalized nature, all of the Si₂CH₂ and Ge₂CH₂ isomers considered display only modest two π electron aromatic character (NICS(0) _{π z z} =--6.2 to –8.9 ppm, computed at the heavy atom ring center) compared to the cyclic-C ₃H₂ (–13.3 ppm).

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Graphical Abstract The three lowest Si2CH2 and Ge2CH2 isomers.

     

Computational studies of metal carbonyl complexes of 3[4-ethyl(phenly)imino][indoline-2-one] and 3[4-butyl(phenly)imino][indoline-2-one]

Use and application of Schiff bases are extended to many different fields of technology. (ISE)M(CO)₅ complex [M?=?Cr (1), Mo (2), W (3), and where ISE is 3[4-ethyl(phenly)imino][indoline-2-one]; and (ISB)M(CO)₅ [M?=?Cr (4), Mo (5), W (6)], where ISB is 3[4-butly(phenly)imino][indoline-2-one] were investigated by computational methods. Computations were carried out using density functional theory (DFT) with B3LYP and CAM-B3LYP functionals, in conjunction with LanL2DZ basis set for metals and cc-PVTZ basis set for other atoms. Time-dependent density functional theory (TDDFT) was used at the same level to obtain the electronic transitions. Molecular orbital energies, UV-Vis spectra, and total electron densities of investigated molecules were shown in the gas phase and in THF. Metal complexes showed higher absorption coefficients compared to ISE and ISB in the visible region. Additionally, they displayed absorption peaks at longer wavelengths and full MLCT character in solution, and W complexes required less energy compared to the complexes of other investigated metal ions. Among the investigated systems, (ISE)W(CO)₅ and (ISB)W(CO)₅ complexes with lowest HOMO-LUMO gaps are found to be the best candidates for photosensitive material production.

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Graphical Abstract UV-Vis absorption spectra of ISE and (ISE)W(CO)₅

     

Nematicidal metabolites from <Emphasis Type="Italic">Gliocladium roseum</Emphasis> YMF1.00133

A strain of the fungus Gliocladium roseum YMF1.00133 was found to secrete nematicidal metabolites against nematodes Panagrellus redivivus, Caenothabditis elegans and Bursaphelenchus xylophilus in experiments searching for nematicidal fungi. Through bioassay-guided fractionations, a unique trioxopiperazine alkaloid, gliocladin C (compound 1), and an alkylane resorcinol, 5-n-heneicosylresorcinol (compound 2) were obtained from the methanol extract of the fungus and determined by single-crystal X-ray analysis and spectroscopic data. In vitro immersion experiments showed that the ED₅₀ values of compounds 1 and 2 after 24 h incubation were 15 and 30 μg/mL against C. elegans, 50 and 80 μg/mL against P. redivivus, and 200 and 180 μg/mL against B. xylophilus, respectively. The X-ray diffraction data of compound 1 and the nematicidal activity of compounds 1 and 2 were reported for the first time.     

Design and synthesis of a new steroid-macrocyclic derivative with biological activity

The aims of this study were to evaluate the positive inotropic effect of a new macrocyclic derivative (compound 11) and characterize the molecular mechanism involved in its biological activity. The first step was achieved by synthesis of a macrocyclic derivative involving a series of reactions for the preparation of several steroid derivatives such as (a) steroid-pyrimidinone (3 and 4), (b) steroid-amino (5), (c) steroid-imino (6), (d) ester-steroid (7 and 8), and (e) amido-steroid (9 and 10). Finally, 11 was prepared by removing the tert-butyldimethylsilane fragment of 10. The biological activity of compounds on perfusion pressure and vascular resistance was evaluated on isolated rat heart using the Langendorff model. The inotropic activity of 11 was evaluated in presence of prazosin, metoprolol, indomethacin, nifedipine, and flutamide to characterize its molecular mechanism. Theoretical experiments were carried out with a Docking model, to assess potential interactions of androgen receptor with 11. The results showed that only this macrocyclic derivative exerts changes on perfusion pressure and vascular resistance translated as the positive inotropic effect, and this effect was blocked with flutamide; these data indicate that the positive inotropic activity induced by this macrocyclic derivative was via androgen receptor activation. The theoretical results indicated that the interaction of the macrocyclic derivative with the androgen receptor involves several amino acid residues such as Leu₇₀₄, Asn₇₀₅, Met₇₈₀, Cys₇₈₄, Met₇₄₉, Leu₇₆₂, Phe₇₆₄, Ser₇₇₈, and Met₇₈₇. In conclusion, all these data suggest that the positive inotropic activity of the macrocyclic derivative may depend on its chemical structure.     

DFT study of isomers of the ruthenium dihydride complex RuH<Subscript>2</Subscript>(CO)<Subscript>2</Subscript>(AsMe<Subscript>2</Subscript>Ph)<Subscript>2</Subscript>

A density functional theory (DFT) study of cct-As, ccc, and cct-CO isomers of the ruthenium dihydride complex RuH₂(CO)₂(AsMe₂Ph)₂ is reported (see Scheme for the labeling isomer 34 structures of RuH₂(CO)₂(AsMe₂Ph)₂). Complex geometries and relative energies of different isomers have been calculated with both B3LYP and M06-2X functionals. The results show that the B3LYP calculated Boltzmann populations of cct-As, ccc, and cct-CO isomers are 65.5, 34.2, and 0.3%, respectively. These are in better agreement with the experimental data than those calculated at the M06-2X level. However, the calculations of ¹H NMR chemical shifts were found to be better described with M06-2X than with B3LYP or with HF level of theories. In addition, a transition state between the two most stable isomers was determined through DFT/(B3LYP or M06-2X) calculations.

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Graphical Abstract Scheme: Labeling structure of RuH₂(CO)₂(AsMe₂Ph)₂