New piperazine derivatives helvamides B-C from the marine-derived fungus Penicillium velutinum ZK-14 uncovered by OSMAC (One Strain Many Compounds) strategy.

Four extracts of the marine-derived fungus Penicillium velutinum J.F.H. Beyma were obtained via metal ions stress conditions based on the OSMAC (One Strain Many Compounds) strategy. Using a combination of modern approaches such as LC/UV, LC/MS and bioactivity data analysis, as well as in silico calculations, influence metal stress factors to change metabolite profiles Penicillium velutinum were analyzed. From the ethyl acetate extract of the P. velutinum were isolated two new piperazine derivatives helvamides B (1) and C (2) together with known saroclazin A (3) (4S,5R,7S)-4,11-dihydroxy-guaia-1(2),9(10)-dien (4). Their structures were established based on spectroscopic methods. The absolute configuration of helvamide B (1) as 2R,5R was determined by a combination of the X-ray analysis and by time-dependent density functional theory (TD-DFT) calculations of electronic circular dichroism (ECD) spectra. The cytotoxic activity of the isolated compounds against human prostate cancer PC-3 and human embryonic kidney HEK-293 cells and growth inhibition activity against yeast-like fungi Candida albicans were assayed.

Phanogracilins A-C, New Bibenzochromenones of Crinoid Phanogenia gracilis (Hartlaub, 1890).

Three new bibenzochromenones named phanogracilins A-C (1-3) were isolated from the crinoid Phanogenia gracilis. The structure of 1 was established using X-ray crystallography as 5,5',6,6',8,8'-hexahydroxy-2,2'-dipropyl-4H,4'H-[7,9'-bibenzo[g]chromene]-4,4'-dione. This allowed us to assign reliably 2D NMR signals for compound 1 and subsequently for its isomer 2 that differed in the connecting position of two benzochromenone moieties (7,10' instead of 7,9'), and compound for 3 that differed in the length of the aliphatic chain of one of the fragments. Compound 4 was derived from 1 in alkaline conditions, and its structure was elucidated as 5,5',6',8,8'-pentahydroxy-2,2'-dipropyl-4H,4'H-[7,9'-bibenzo[g]chromene]-4,4',6,9-tetraone. Even though compounds 1-4 did not contain stereo centers, they possessed notable optical activity due to sterical hindrances, which limited the internal rotation of two benzochromenone fragments around C(7)-C(9'/10') bonds. Isolated bibenzochromenones 1-4 were tested for their antiradical, neuroprotective and antimicrobial activities. Compounds 1, 3 and 4 demonstrated significant antiradical properties towards ABTS radicals higher than the positive control trolox. Compounds 1 and 4 exhibited moderate neuroprotective activity, increasing the viability of rotenone-treated Neuro-2a cells at a concentration of 1 µM by 9.8% and 11.8%, respectively. Compounds 1 and 3 at concentrations from 25 to 100 µM dose-dependently inhibited the growth of Gram-positive bacteria S. aureus and yeast-like fungi C. albicans, and they also prevented the formation of their biofilms. Compounds 2 and 4 exhibited low antimicrobial activity.

Multigram-Scale Production of Hybrid Au-Si Nanomaterial by Laser Ablation in Liquid (LAL) for Temperature-Feedback Optical Nanosensing, Light-to-Heat Conversion, and Anticounterfeit Labeling.

Recent progress in hybrid optical nanomaterials composed of dissimilar constituents permitted an improvement in the performance and functionality of novel devices developed for optoelectronics, catalysis, medical diagnostics, and sensing. However, the rational combination of contrasting materials such as noble metals and semiconductors within individual hybrid nanostructures via a ready-to-use and lithography-free fabrication approach is still a challenge. Here, we report on a two-step synthesis of hybrid Au-Si microspheres generated by laser ablation of silicon in isopropanol followed by laser irradiation of the produced Si nanoparticles in the presence of HAuCl4. Thermal reduction of [AuCl4]- species to a metallic gold phase, along with its subsequent mixing with silicon under laser irradiation, creates a nanostructured material with a unique composition and morphology, as revealed by electron microscopy, tomography, and elemental analysis. A combination of basic plasmonic and nanophotonic materials such as gold and silicon within a single microsphere allows for efficient light-to-heat conversion, as well as single-particle SERS sensing with temperature-feedback modality and expanded functionality. Moreover, the characteristic Raman signal and hot-electron-induced nonlinear photoluminescence coexisting within the novel Au-Si hybrids, as well as the commonly criticized randomness of the nanomaterials prepared by laser ablation in liquid, were proved to be useful for the realization of anticounterfeiting labels based on a physically unclonable function approach.

Ag-Decorated Si Microspheres Produced by Laser Ablation in Liquid: All-in-One Temperature-Feedback SERS-Based Platform for Nanosensing.

Combination of dissimilar materials such as noble metals and common semiconductors within unified nanomaterials holds promise for optoelectronics, catalysis and optical sensing. Meanwhile, difficulty of obtaining such hybrid nanomaterials using common lithography-based techniques stimulates an active search for advanced, inexpensive, and straightforward fabrication methods. Here, we report one-pot one-step synthesis of Ag-decorated Si microspheres via nanosecond laser ablation of monocrystalline silicon in isopropanol containing AgNO3. Laser ablation of bulk silicon creates the suspension of the Si microspheres that host further preferential growth of Ag nanoclusters on their surface upon thermal-induced decomposition of AgNO3 species by subsequently incident laser pulses. The amount of the AgNO3 in the working solution controls the density, morphology, and arrangement of the Ag nanoclusters allowing them to achieve strong and uniform decoration of the Si microsphere surface. Such unique morphology makes Ag-decorated Si microspheres promising for molecular identification based on the surface-enhanced Raman scattering (SERS) effect. In particular, the designed single-particles sensing platform was shown to offer temperature-feedback modality as well as SERS signal enhancement up to 106, allowing reliable detection of the adsorbed molecules and tracing their plasmon-driven catalytic transformations. Considering the ability to control the decoration degree of Si microspheres by Ag nanoclusters via amount of the AgNO3, the developed one-pot easy-to-implement PLAL synthesis holds promise for gram-scale production of high-quality hybrid nanomaterial for various nanophotonics and sensing applications.

Meroantarctines A-C, Meroterpenoids with Rearranged Skeletons from the Alga-Derived Fungus Penicillium antarcticum KMM 4685 with Potent p-Glycoprotein Inhibitory Activity.

New meroterpenoids, meroantarctines A-C (1-3), with unique 6/5/6/6, 6/5/6/5/6, and 6/5/6/5 polycyclic systems were isolated from the alga-derived fungus Penicillium antarcticum KMM 4685. Their structures were elucidated by spectroscopic methods, X-ray diffraction, and quantum chemical calculations. A biogenetic pathway for 1-3 was proposed. Meroantarctines A-C (1-3) inhibited p-glycoprotein activity and could resensitize drug-resistant cancer cells to docetaxel.

Deep Subwavelength Laser-Induced Periodic Surface Structures on Silicon as a Novel Multifunctional Biosensing Platform.

Strong light localization inside the nanoscale gaps provides remarkable opportunities for creation of various medical and biosensing platforms stimulating an active search for inexpensive and easily scalable fabrication at a sub-100 nm resolution. In this paper, self-organized laser-induced periodic surface structures (LIPSSs) with the shortest ever reported periodicity of 70 ± 10 nm were directly imprinted on the crystalline Si wafer upon its direct femtosecond-laser ablation in isopropanol. Appearance of such a nanoscale morphology was explained by the formation of a periodic topography on the surface of photoexcited Si driven by interference phenomena as well as subsequent down-scaling of the imprinted grating period via Rayleigh-Taylor hydrodynamic instability. The produced deep subwavelength LIPSSs demonstrate strong anisotropic anti-reflection performance, ensuring efficient delivery of the incident far-field radiation to the electromagnetic "hot spots" localized in the Si nanogaps. This allows realization of various optical biosensing platforms operating via strong interactions of quantum emitters with nanoscale light fields. The demonstrated 80-fold enhancement of spontaneous emission from the attached nanolayer of organic dye molecules and in situ optical tracing of catalytic molecular transformations substantiate bare and metal-capped deep subwavelength Si LIPSSs as a promising inexpensive multifunctional biosensing platform.

Anthracene-containing complexes of boron difluoride. Dual luminescence, formation of excimers, and mechanochromism.

A comparative study of the luminescence properties and crystal structure of boron difluoride 1-(anthracen-9-yl)butane-1,3-dionate (1) and their nitrogen-containing analogs with hydrogen and methyl substituents (2 and 3) has been performed. For boron difluoride beta-diketonate (1) and beta-ketoiminate with a hydrogen substituent (2), which does not create significant steric difficulties, the luminescence of crystals is determined by that of excimers and aggregates based on them. For the compounds 1-3, mechanofluorochromism has been observed, the spectral manifestation of which is different: at grinding the crystals of 1 and 2, a hypsochromic shift of the excitation and luminescence bands occurs, whereas in the case of crystals of 3, a bathochromic shift takes place. Dual luminescence has been detected for the solutions of 1. During the relaxation in the excited state of a molecule of 1 (S1 â†’ S'1), TICT is formed. It was possible to register the short-wavelength luminescence from the LE state in the dilute solutions of 1. TICT or LE luminescence can be excited, in the case of 1, by varying the wavelength of the exciting light.

Enhancing Lithium and Sodium Storage Properties of TiO2(B) Nanobelts by Doping with Nickel and Zinc.

Nickel- and zinc-doped TiO2(B) nanobelts were synthesized using a hydrothermal technique. It was found that the incorporation of 5 at.% Ni into bronze TiO2 expanded the unit cell by 4%. Furthermore, Ni dopant induced the 3d energy levels within TiO2(B) band structure and oxygen defects, narrowing the band gap from 3.28 eV (undoped) to 2.70 eV. Oppositely, Zn entered restrictedly into TiO2(B), but nonetheless, improves its electronic properties (Eg is narrowed to 3.21 eV). The conductivity of nickel- (2.24 × 10-8 S·cm-1) and zinc-containing (3.29 × 10-9 S·cm-1) TiO2(B) exceeds that of unmodified TiO2(B) (1.05 × 10-10 S·cm-1). When tested for electrochemical storage, nickel-doped mesoporous TiO2(B) nanobelts exhibited improved electrochemical performance. For lithium batteries, a reversible capacity of 173 mAh·g-1 was reached after 100 cycles at the current load of 50 mA·g-1, whereas, for unmodified and Zn-doped samples, around 140 and 151 mAh·g-1 was obtained. Moreover, Ni doping enhanced the rate capability of TiO2(B) nanobelts (104 mAh·g-1 at a current density of 1.8 A·g-1). In terms of sodium storage, nickel-doped TiO2(B) nanobelts exhibited improved cycling with a stabilized reversible capacity of 97 mAh·g-1 over 50 cycles at the current load of 35 mA·g-1.

New Deoxyisoaustamide Derivatives from the Coral-Derived Fungus Penicillium dimorphosporum KMM 4689.

Seven new deoxyisoaustamide derivatives (1-7) together with known compounds (8-10) were isolated from the coral-derived fungus Penicillium dimorphosporum KMM 4689. Their structures were established using spectroscopic methods, X-ray diffraction analysis and by comparison with related known compounds. The absolute configurations of some alkaloids were determined based on CD and NOESY data as well as biogenetic considerations. The cytotoxic and neuroprotective activities of some of the isolated compounds were examined and structure-activity relationships were pointed out. New deoxyisoaustamides 4-6 at concentration of 1 µM revealed a statistical increase of PQ(paraquat)-treated Neuro-2a cell viability by 30-39%.

Isolation and Structure Determination of Echinochrome A Oxidative Degradation Products.

Echinochrome A (Ech A, 1) is one of the main pigments of several sea urchin species and is registered in the Russian pharmacopeia as an active drug substance (Histochrome®), used in the fields of cardiology and ophthalmology. In this study, Ech A degradation products formed during oxidation by O2 in air-equilibrated aqueous solutions were identified, isolated, and structurally characterized. An HPLC method coupled with diode-array detection (DAD) and mass spectrometry (MS) was developed and validated to monitor the Ech A degradation process and identify the appearing compounds. Five primary oxidation products were detected and their structures were proposed on the basis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) as 7-ethyl-2,2,3,3,5,7,8-heptahydroxy-2,3-dihydro-1,4-naphthoquinone (2), 6-ethyl-5,7,8-trihydroxy-1,2,3,4-tetrahydronaphthalene-1,2,3,4-tetraone (3), 2,3-epoxy-7-ethyl-2,3-dihydro-2,3,5,6,8-pentahydroxy-1,4-naphthoquinone (4), 2,3,4,5,7-pentahydroxy-6-ethylinden-1-one (5), and 2,2,4,5,7-pentahydroxy-6-ethylindane-1,3-dione (6). Three novel oxidation products were isolated, and NMR and HR-ESI-MS methods were used to establish their structures as 4-ethyl-3,5,6-trihydroxy-2-oxalobenzoic acid (7), 4-ethyl-2-formyl-3,5,6-trihydroxybenzoic acid (8), and 4-ethyl-2,3,5-trihydroxybenzoic acid (9). The known compound 3-ethyl-2,5-dihydroxy-1,4-benzoquinone (10) was isolated along with products 7-9. Compound 7 turned out to be unstable; its anhydro derivative 11 was obtained in two crystal forms, the structure of which was elucidated using X-ray crystallography as 7-ethyl-5,6-dihydroxy-2,3-dioxo-2,3-dihydrobenzofuran-4-carboxylic acid and named echinolactone. The chemical mechanism of Ech A oxidative degradation is proposed. The in silico toxicity of Ech A and its degradation products 2 and 7-10 were predicted using the ProTox-II webserver. The predicted median lethal dose (LD50) value for product 2 was 221 mg/kg, and, for products 7-10, it appeared to be much lower (≥2000 mg/kg). For Ech A, the predicted toxicity and mutagenicity differed from our experimental data.

Design, synthesis and biomedical evaluation of mostotrin, a new water soluble tryptanthrin derivative.

Mostotrin (MT), a novel compound, at least five orders of magnitude more soluble in water than its mother substance, was designed and synthesised from tryptanthrin (TR). Its structure was established by nuclear magnetic resonance and mass spectrometry data and confirmed by X­ray analysis, revealing that MT is a pentacyclic product with an additional pseudo­cycle formed with the participation of one intramolecular hydrogen bond. Antimicrobial activity and cytotoxic action against tumour cells in vitro, as well as anti­tumour effects, acute toxicity and anti­inflammatory activities in vivo, were evaluated. Antimicrobial properties of MT against Mycobacterium spp and Bacillus cereus ATCC 10702 appeared to be the same as that of TR, but against the other strains used it was weaker. Furthermore, MT exhibited 5­10 times higher cytotoxic activities against tumour cell lines HCT­116, МСF­7 and K­562 than TR, but was less toxic than TR (LD50 of MT was 375 mg/kg, while LD50 for TR was 75 mg/kg). Additionally, compounds MT and TR were studied in DNA binding tests. The quenching of its fluorescence on addition to DNA solution established MT to be capable of binding to DNA. Its anti­tumour action in vivo on mice with the ascitic form of Ehrlich carcinoma was promising, particularly with joint application of MT and the antitumour drug doxorubicin. In this model, the survival and life span for the doxorubicin and 1 co­treatment group were significantly higher compared to doxorubicin treatment alone. The compound MT showed a lower immunosuppressive effect than TR at the early stages of inflammation induced in mice by LPS from E. Ñoli (MT hardly inhibited the release of IL­1, IL­2, or INF­Î³). These results demonstrated that MT is a perspective hit compound for drug development. In our opinion, further evaluation on the biological effects of MT and its synthetic analogues could lead to safer and more effective anti­tumour and anti­tuberculosis agents than TR itself. MT has also the prospect of application in combination with known anti­tumour drugs for the treatment of oncological diseases.

Long-pulse 4.4-4.6 µm laser oscillations of Fe2+ ions in a Zn1-xMnxSe (x = 0.3) crystal pumped by a 1940 nm Tm fiber laser through Cr2+ → Fe2+ energy transfer.

Millisecond-pulse laser operation of Fe2+ ions at 78 K is demonstrated in the Zn1-xMnxSe:Fe2+,Cr2+ (x=0.3) crystal under a Tm fiber 1940 nm laser pumping through a Cr2+→Fe2+ energy transfer process for the first time, to the best of our knowledge. The laser slope efficiency was 1% with respect to absorbed pumping energy at 1940 nm. The laser central wavelength shift from 4450 nm at 78 K up to 4510 nm at 110 K was observed. Tunability from 4350 up to 4670 nm at 78 K was achieved using an intracavity tuning element.

o-Hydroxydibenzoylmethanate of boron difluoride: A complex with multi-stimuli-responsive emission effects.

The structural, luminescence and chemosensor properties of boron difluoride o-hydroxydibenzoylmethanate (1) have been investigated. In the concentrated solution, PE (polyethylene) matrix, and crystals of 1, one observes the formation of J-aggregates. The crystal structure of 1 is in compliance with that of J-aggregates of the "brickwork type" consisting of dimers that comprise excimer traps. In time-resolved luminescence spectra of 1 in PE films and crystals, one observes luminescence bands corresponding to the luminescence of excimer J-aggregates. At application of external stimuli on the crystals of 1 (heating, grinding), one observes changes in the luminescence spectrum caused by redistribution of intensities of excimer and J-aggregate bands. 1 could act as an optic chemosensor for probing amines vapors with different response rates and different sensitivities controlled by their morphologies.

Guitarrins A-E and Aluminumguitarrin A: 5-Azaindoles from the Northwestern Pacific Marine Sponge Guitarra fimbriata.

Guitarrins A-E (1-5), the first natural 5-azaindoles, and aluminumguitarrin A (1a), the first aluminum-containing compound from marine invertebrates, were isolated from the sponge Guitarra fimbriata. The structures of these compounds were established using detailed analysis of 1D and 2D NMR data, mass spectra, and X-ray analysis of 1 and 1a. Compound 3 was proved to be a natural inhibitor of alkaline phosphatase.

Prenylated indole alkaloids from co-culture of marine-derived fungi Aspergillus sulphureus and Isaria felina.

Five new prenylated indole alkaloids, 17-hydroxynotoamide D (1), 17-O-ethylnotoamide M (2), 10-O-acetylsclerotiamide (3), 10-O-ethylsclerotiamide (4), and 10-O-ethylnotoamide R (5) were isolated from a co-culture of marine-derived fungi Aspergillus sulphureus KMM 4640 and Isaria felina KMM 4639. The structures of 1-5 were determined by detailed analysis of spectroscopic data and by comparison with related known compounds. The absolute configurations of 1-5 were determined by time-dependent density functional theory (TD-DFT) calculations of ECD spectra. Compound 2 is able to inhibit the colony formation of human prostate cancer cells 22Rv1 at non-cytotoxic concentration of 10 µM.

Pallidopenillines: Polyketides from the Alga-Derived Fungus Penicillium thomii Maire KMM 4675.

Eleven new polyketides, pallidopenillines 1-11, were isolated from the alga-derived fungus Penicillium thomii. The structures of these compounds were established based on spectroscopic methods. The absolute configuration of pallidopenilline A (1) as 4R, 5S, 8S, 9R, 10R, 13R was established using a combination of the modified Mosher's method, X-ray analysis, and NOESY data. The absolute configurations of 2-5 were determined by time-dependent density functional theory calculations of the ECD spectra and ECD and NOESY data. It was shown that 1-acetylpallidopenilline A (2) and pallidopenilline G (10) inhibit the growth of colonies of 22Rv1 cells by 40% at 2 and 1 µM, respectively.

Synthesis of four different antimony(III) O,O'-dialkyldithiophosphates: characterization by 31P CP/MAS NMR, single-crystal X-ray diffraction, and adsorption at a stibnite surface (Sb2S3).

Four different dialkyldithiophosphate (DTP) ions, (RO)(2)PSS(-) (R=C(3)H(7), iso-C(3)H(7), iso-C(4)H(9), and cyclo-C(6)H(11)), have been adsorbed on the surface of synthetically prepared stibnite, Sb(2)S(3), and studied by means of (31)P CP/MAS NMR. Corresponding individual [Sb{S(2)P(OR)(2)}(3)] complexes have also been synthesized and used for comparison with the surface-adsorbed DTP species. The results show that a low concentration of collector at the surface leads to a chemisorbed monolayer of DTP on the mineral surface. At high concentration of DTP, a surface precipitate of Sb(DTP)(3) is formed. (31)P CP/MAS NMR and chemical shift anisotropy data indicate that the SPS bite angle of the chemisorbed DTP groups on the surface is larger than in the corresponding precipitated complexes and the coordination of the ligands differs. Using single-crystal X-ray diffraction technique, the molecular structure of a solvated form of crystalline O,O'-di-cyclo-hexyldithiophosphate antimony(III) complex has been resolved. In this novel molecular structure, the central antimony atom S,S'-anisobidentately coordinates three structurally non-equivalent DTP groups, and therefore, the geometry of the [SbS(6)] chromophore can be approximated by a distorted octahedron. Besides that, useful correlations between (31)P CSA parameters and structural data on this complex were also established.

Spongian diterpenoids from the sponge Spongia (Heterofibria) sp.

Five new (1, 2, 4-6) and one known (3) diterpenoid were isolated from the keratose sponge Spongia (Heterofibria) sp. Structures of these compounds and their absolute configurations were proposed on the basis of X-ray analysis of 1, its CD spectrum, and NMR and MS spectroscopic studies of 1-6. One of the new diterpenoids was shown to be 2(R),3(S),4(S)-3,18-methylene-2-acetoxyspongia-13(16),14-diene (6), possessing a novel carbon skeleton system.