Solid-Phase Extraction at High pH as a Promising Tool for Targeted Isolation of Biologically Active Fractions of Humic Acids.

A search for novel sources of biologically active compounds is at the top of the agenda for biomedical technologies. Natural humic substances (HSs) contain a large variety of different chemotypes, such as condensed tannins, hydrolyzable tannins, terpenoids, lignins, etc. The goal of this work was to develop an efficient separation technique based on solid-phase extraction (SPE) for the isolation of narrow fractions of HS with higher biological activity compared to the initial material. We used lignite humic acid as the parent humic material, which showed moderate inhibition activity toward beta-lactamase TEM 1 and antioxidant activity. We applied two different SPE techniques: the first one was based on a gradient elution with water/methanol mixtures of the humic material sorbed at pH 2, and the second one implied separation by a difference in the pKa value by the use of sequential sorption of HS at pH from 8 to 3. SPE cartridges Bond Elute PPL (Agilent) were used in the fractionation experiments. The first and second techniques yielded 9 and 7 fractions, respectively. All fractions were characterized using high-resolution mass spectrometry and biological assays, including the determination of beta-lactamase (TEM 1) inhibition activity and antioxidant activity. The acidity-based separation technique demonstrated substantial advantages: it enabled the isolation of components, outcompeting the initial material at the first step of separation (sorption at pH 8). It showed moderate orthogonality in separation with regard to the polarity-based technique. Good perspectives are shown for developing a 2D separation scheme using a combination of polarity and acidity-based approaches to reduce structural heterogeneity of the narrow fractions of HS.

1,2-Bis(triazolyl)tetraphenyldigermanes: Synthesis, Structure and Properties.

Using the [3+2] cycloaddition reaction of [HC≡C-GePh2 -]2 (1) and a number of RCH2 N3 , this work described the synthesis of a series of novel heterocyclic digermanes, bitriazoles [1,4-C2 HN3 (CH2 R)GePh2 -]2 , 2-12 (R=Ph, p-Tol, p-C6 H4 NMe2 , p-C6 H4 OMe, p-C6 H4 Br, m-C6 H4 NO2 , 2-Naphth, CH2 -p-OC6 H4 CHO, CH2 -p-OC6 H4 COOMe, CH2 P(O)(OEt)2 , COOEt), difficult to produce by other methods. The structural peculiarities of these compounds were studied in detail by NMR spectroscopy and by XRD analysis (for 6, 9 and 10). The properties of 1-12 were studied by UV/vis and luminescence emission spectroscopy, electrochemistry and DFT calculations, indicating an effective conjugation in their molecules.

Structural Motifs in Aryl Organogermanium Ge-O Derivatives for Material Design.

The aim of this work was to understand the main structural features and ways of formation of Ge-O bonds in organogermanium compounds under the conditions of ArnGeHal4-n (Hal = halide) hydrolysis. The structural types of these compounds were considered, providing 11 blocks (A-K). The molecular structures of the novel compounds [(p-FC6H4)3Ge]2O (1), [(p-F3CC6H4)3Ge]2O (2), and cyclo-[(p-F3CC6H4)2GeO]4 (3) were studied through XRD (X-ray diffraction) analysis. The molecular structure of [(p-F3CC6H4)3GeO]4Ge (4), representing a novel structural type, was also investigated. The data presented in this study will be important in the design of materials with useful properties based on group 14 element derivatives with element-oxygen bonding.

Germanium Complexes with ONO Tridentate Ligands: O-H Bond Activation Control According to DFT Calculations.

Polydentate ligands are used for thermodynamic stabilization of tetrylenes-low-valent derivatives of Group 14 elements (E = Si, Ge, Sn, Pb). This work shows by DFT calculations how the structure (the presence or absence of substituents) and type (alcoholic, Alk, or phenolic, Ar) of tridentate ligands 2,6-pyridinobis(1,2-ethanols) [AlkONOR]H2 and 2,6-pyridinobis(1,2-phenols) [ArONOR]H2 (R = H, Me) may affect the reactivity or stabilization of tetrylene, indicating the unprecedented behavior of Main Group elements. This enables the unique control of the type of the occurring reaction. We found that unhindered [ONOH]H2 ligands predominantly led to hypercoordinated bis-liganded {[ONOH]}2Ge complexes, where an E(+2) intermediate was inserted into the ArO-H bond with subsequent H2 evolution. In contrast, substituted [ONOMe]H2 ligands gave [ONOMe]Ge: germylenes, which may be regarded as kinetic stabilized products; their transformation into E(+4) species is also thermodynamically favorable. The latter reaction is more probable for phenolic [ArONO]H2 ligands than for alcoholic [AlkONO]H2. The thermodynamics and possible intermediates of the reactions were also investigated.

Aluminum Salen Complexes Modified with Unsaturated Alcohol: Synthesis, Characterization, and Their Activity towards Ring-Opening Polymerization of ε-Caprolactone and D,L-Lactide.

A highly efficient one-step approach to the macromonomer synthesis using modified aluminum complexes as catalysts of ring-opening polymerization (ROP) of ε-caprolactone and D,L-lactide was developed. The syntheses, structures, and catalytic activities of a wide range of aluminum salen complexes, 3a-c, functionalized with unsaturated alcohol (HO(CH2)4OCH=CH2) are reported. X-Ray diffraction studies revealed a tetragonal pyramidal structure for 3c. Among the complexes 3a-c, the highest activity in bulk ROP of ε-caprolactone and D,L-lactide was displayed by 3b, affording polyesters with controlled molecular weights at low monomer to initiator ratios (Mn up to 15,000 g mol-1), relatively high polydispersities (Ð~1.8) and high number-average functionalities (Fn up to 85%).

Formation of Azaphilone Pigments and Monasnicotinic Acid by the Fungus Aspergillus cavernicola.

Due to the ever-increasing demand for healthy and safe food, much attention has been gained by natural food colorants. This study showed the culture fluid extract of the fungus Aspergillus cavernicola VKM F-906 to contain red pigment and monasnicotinic acid (MNA) in predominant amounts. The structure of the pigment corresponded to cis-cavernamine (red pigment, RP). Two tautomers, NH and OH forms, in rapid equilibrium were present in a solution of RP. The critical factors for RP to form were the presence of NH4+ salt and pH 6.3-6.5. In vitro experiments showed that MNA was synthesized from RP as a result of chemical transformations without the participation of enzymes. In this case, the main influence on the reaction rate is exerted by the pH of the medium, which is associated with the keto-enol tautomerism of RP in solution. The culture broth extract and MNA exhibited antifungal activity against Fusarium fungi.

Oligoorganogermanes: Interplay between Aryl and Trimethylsilyl Substituents.

Derivatives of main group elements containing element-element bonds are characterized by unique properties due to σ-conjugation, which is an attractive subject for investigation. A novel series of digermanes, Ar3Ge-Ge(SiMe3)3, containing aryl (Ar = p-C6H4Me (1), p-C6H4F (2), C6F5 (3)) and trimethylsilyl substituents, was synthesized by the reaction of germyl potassium salt, [(Me3Si)3GeK*THF], with triarylchlorogermanes, Ar3GeCl. The optical and electronic properties of such substituted oligoorganogermanes were investigated spectroscopically by UV/vis absorption spectroscopy and theoretically by DFT calculations. The molecular structures of compounds 1 and 2 were studied by XRD analysis. Conjugation between all structural fragments (Ge-Ge, Ge-Si, Ge-Ar, where Ar is an electron-donating or withdrawing group) was found to affect the properties.

Optical Properties of Soil Dissolved Organic Matter Are Related to Acidic Functions of Its Components as Revealed by Fractionation, Selective Deuteromethylation, and Ultrahigh Resolution Mass Spectrometry.

The goal of this study was to establish a relationship between the optical properties of soil dissolved organic matter (DOM) and acidic functions carried out by its individual constituents. We obtained 12 fractions of DOM samples using sequential solid phase extraction on nonionic sorbent at steadily lowered pH values: 7, 5, 3, 2, which correspond to low bounds of pKa values of phenols, aliphatic, and aromatic carboxylic acids, and ketoacids. The structural studies were conducted with the use of NMR and selective deuteromethylation of isolated fractions coupled to ultrahigh resolution mass spectrometry. First, a gradual shift of molecular compositions was observed from reduced components to aromatic oxidized compounds isolated at pH 7 and 2, respectively. Changes in molecular compositions were accompanied by a red shift of fluorescence spectra. Further application of deuteromethylation enabled us to distinguish DOM constituents with different amounts of carboxylic groups. Moreover, identification of structural isomers in a single DOM sample was achieved. Statistical analysis revealed that red shift of fluorescence is facilitated by the increase of a contribution of aromatic poly(carboxylic acid)s with high conjugation lengths. Additionally, analysis of the labeled fractionated permafrost thaw DOM directly showed carboxyl-rich alicyclic molecules, while the same components from lower-latitude DOM were assigned to lignin-like species.

Austalides V and W, new meroterpenoids from the fungus Aspergillus ustus and their antitumor activities.

Two new austalide meroterpenoids, named austalides V and W (1 and 2), were isolated from the fungus Aspergillus ustus VKM F-4692. Their structures were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. The main structural feature of both compounds is a tetrahydrofuranyl ring (G), a structural fragment, first found in austalides. Austalides V (1) and W (2) were able to inhibit the propagation of prostate and bladder cancer cells; this biologic activity is possibly related to the inhibition of a number of key pathways regulating cell growth and migration.

Hypercoordinated Oligosilanes Based on Aminotrisphenols.

The hypercoordinated silicon chlorides ClSi[(o-OC6H4)3N] (3) and ClSi[(OC6H2Me2CH2)3N] (5) were used for the synthesis of catenated derivatives (Me3Si)3SiSi[(o-OC6H4)3N] (9), (Me3Si)3SiSiMe2SiMe2Si(SiMe3)2Si[(o-OC6H4)3N] (11), and (Me3Si)3SiSi[(OC6H2Me2CH2)3N] (13) in reactions with (Me3Si)3SiK·THF (7) or (Me3Si)3SiK·[18-crown-6] (8). It was found that the nature of the (Me3Si)3SiK solvate determines the product of interaction, resulting in the formation of (Me3Si)3Si(CH2)4OSi[(OC6H2Me2CH2)3N] (12) or 13. Compounds obtained were characterized using multinuclear NMR and UV-vis spectroscopy and mass spectrometry. The molecular structures of 3, 9, and 11-13 were investigated by single-crystal X-ray analysis, featuring hypercoordinated Si atoms in a trigonal-bipyramidal coordination environment with O atoms in the equatorial plane. The structure of the side product [N(CH2C6H2Me2O)3Si]2O (6) was also studied, indicating highly tetrahedrally distorted trigonal-bipyramidal environment at the Si atoms, which was confirmed by crystal density functional theory calculations indicating the very weak Si ← N interaction. The Si···N interatomic distances span a broad range (2.23-2.78 Å). The dependence of structural and NMR parameters for hypercoordinated catenated compounds from the type of the ligand was established.

Oligothienyl catenated germanes and silanes: synthesis, structure, and properties.

The synthesis of two new groups of oligothienyl catenated silanes and germanes, Me5M2Thn (1a-b), Me5M2ThnM2Me5 (2a-c) (terminal), and ThnM2Me4Thn (3a-d) (internal) (M = Si, Ge; n = 2, 3; Th = 2- or 2,5-thienyl), is reported. The study of their structural parameters as well as of their spectral (NMR), electrochemical (CV) and optical (UV/vis absorbance, luminescence) properties has been performed in detail; in addition, the unexpected compound [Th2Si2Me4Th]2 (3a') is also studied. Theoretical investigations have been performed for model compounds in order to establish structure-property relationships. The molecular structures of 2a (Me5Si2Th2Si2Me5), 2b (Me5Ge2Th2Ge2Me5), 3a (Th2Si2Me4Th2) and 3b (Th2Ge2Me4Th2) have been investigated by X-ray diffraction analysis. An effective conjugation with flattening of both Th planes in terminal 2a and 2b was observed. The main trends in the dependence of the optical and electrochemical properties on the structural parameters have been established. All of the compounds studied exhibit a strong emission within the 378-563 nm range, and the maximal quantum yield (up to 77%) is observed for the Si derivative 3a'. For the majority of the compounds, the quantum yields (20-30%) are significantly larger than for 2,2'-bi- and 2,2':5',5''-terthiophenes. Due to their good emission properties, these compounds could be used to develop new materials with specific spectral properties.

Synthesis of carboxylated styrene polymer for internal calibration of Fourier transform ion cyclotron resonance mass-spectrometry of humic substances.

We report synthesis and application of the novel carboxylated styrene for internal calibration of Fourier transform ion cyclotron resonance mass-spectra of humic substances. The calibrant was synthesized in five steps from acetylsalicylic acid (aspirin) followed by spontaneous polymerization of vinyl salicylic acid. Aromatic nature of the prepared polymer enabled its simultaneous analysis in the presence of the Suwannee River fulvic acid without using dual-spray approach. The major advantage of the calibrant proposed in this study is a lack of suppression of humic substances signals and maintenance of peak intensity distribution. The appropriate calibration resulted in an increased number of unambiguous identification in Suwannee River fulvic acid. Thanks to the higher mass accuracy, it was also possible to refine attribution of the CHOS species to hydrolysable tannins as opposed to the erroneous previous assignment to the condensed tannins.

Molecular Oligogermanes and Related Compounds: Structure, Optical and Semiconductor Properties.

The optical (UV/Vis absorbance, fluorescence in the solid state and in solution) and semiconducting properties of a number of di- and trigermanes as well as related silicon- and tin-containing germanes, 1-6 ((p-Tol)3 GeGeMe3 (1), Ph3 SnGe(SiMe3 )3 (2), (C6 F5 )3 GeGePh3 (3), (p-Tol)3 GeSiMe2 SiMe3 (4), (p-Tol)3 GeGeMe2 Ge(p-Tol)3 (5), (p-Tol)3 GeSiMe2 SiMe2 Ge(p-Tol)3 (6)) were investigated. Molecular structures of 5 and 6 were studied by X-ray diffraction analysis. All compounds displayed luminescence properties. In addition, a band gap (of about 3.3 eV) was measured for compounds 1-6 showing that those molecules display semiconductor properties.

Enumeration of carboxyl groups carried on individual components of humic systems using deuteromethylation and Fourier transform mass spectrometry.

Here, we report a novel approach to enumeration of carboxylic groups carried by individual molecules of humic substances using selective chemical modification and isotopic labeling (deuteromethylation) and high-resolution electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI FTICR MS). Esterification was conducted with a use of thionyl chloride-deuteromethanol reagent under mild conditions to avoid transesterification. The deuteromethylated products were subjected to solid phase extraction using PPL Bond Elute cartridges prior to FTICR MS analysis. An amount of carboxyl groups in the individual molecular component was estimated from the length of identified deuteromethylation series. The method allowed for discerning between compounds with close elemental compositions possessing different protolytic properties. We found that different carboxylic moieties occupy distinct regions in molecular space of humic substances (HS) projected onto Van Krevelen diagram. These locations do not depend on the source of the humic material and can be assigned to carboxyl-rich alicyclic molecules (5 to 6 COOH), hydrolyzable tannins (3-4 COOH), lignins (1 to 2 COOH), condensed tannins and lignans (0 to 1 COOH), and carbohydrates (0 COOH). At the same time, the alignment pattern of these carboxylated species along the structural evolution lines in Van Krevelen diagrams was characteristic to the specific transformation processes undergone by the humic materials in the different environments. The obtained data enable mapping of molecular ensemble of HS with regards to their specific acidic compartments and might be used for directed fractionation of HS. Graphical abstract Selective isotopic labeling followed by FTICR MS enables discerning between humic molecules with close elemental compositions carrying different numbers of carboxylic groups.

Aluminum complexes based on pyridine substituted alcohols: synthesis, structure, and catalytic application in ROP.

A series of substituted pyridine dialcohols (2,6-bis(hydroxyalkyl)pyridines), 1-4, was used for the synthesis of various types of aluminum complexes. Aluminum methyl derivatives, 2-4a, were obtained by the reaction of AlMe3 with the corresponding ligand or transmetallation reactions of germylenes. Aluminum chloride complexes, 3-4b, were obtained by substitution of the Me group under the action of chlorinating agents. Methoxy-, 2-4c, or benzyloxy-, 2d, aluminum complexes were synthesized in transalkoxylation reaction of Me2Al(OX) (X = Me, Bn) by the corresponding ligand. All complexes obtained were thoroughly investigated by multinuclear NMR and X-ray analysis. It has been established that the structure of the ligand (number of carbon atoms) determines the nature of the complexes formed. Compounds were used as initiators of ring-opening polymerization of l-lactide and ε-caprolactone and showed moderate activity with controlled or immortal character.

Synthesis of model humic substances: a mechanistic study using controllable H/D exchange and Fourier transform ion cyclotron resonance mass spectrometry.

The products of the oxidative coupling of phenols are frequently used as synthetic analogues to natural humic substances (HS) for biomedical research. However, their molecular compositions and exact structures remain largely unknown. The objective of this study was to develop a novel approach for the molecular-level analysis of phenolic polymerisates that is capable of inventorying molecular constituents and resolving their distinct structural formulas. For this purpose, we have synthesized the model HS using the oxidative coupling of a specifically designed phenylpropanoic monomer, 3-(4-hydroxy-3-methoxyphenyl)-3-oxopropionic acid, to hydroquinone. We have characterized the synthesized model HS using high resolution Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), (1)H NMR spectroscopy, and controllable hydrogen/deuterium (H/D) exchange. We succeeded in the molecular inventory of the model HS. The assigned molecular formulas occupied the substantial space of CHO compositions in the Van Krevelen diagram with a maximum density found in the regions of tannins and lignins, resembling those of natural HS. To identify the exact structural formulas of the individual constituents in the model HS, we have applied selective H/D exchange of non-labile backbone protons by a choice of basic or acidic catalytic conditions followed by FTICR MS. The determined formulas allowed us to verify the proposed pathways of hydroxylation and carboxylation in the course of the phenolic coupling and to identify the acetylation of aromatic rings as an important side reaction. We conclude that the proposed analytical approach may be used to identify the molecular carriers of biological activity within the phenolic polymerisates and eventually within natural HS.

Crystal structure of (tert-butyl-dimethyl-sil-yl)tri-phenyl-germane, Ph3Ge-SiMe2(t-Bu).

In the title compound, Ph3Ge-SiMe2(t-Bu) or C24H30GeSi, the Si and Ge atoms both possess a tetra-hedral coordination environment with C-E-C (E = Si, Ge) angles in the range 104.47 (5)-114.67 (5)°. The mol-ecule adopts an eclipsed conformation, with three torsion angles less than 29.5°. In the crystal, neighbouring mol-ecules are combined to dimers by six T-shaped C-H⋯π inter-actions, forming sixfold phenyl embraces (6PE).

Crystal structure of 4,8-di-tert-butyl-6,6-di-chloro-13-ethyl-2,10-dimethyl-13,14-di-hydro-12H-dibenzo[d,i][1,3,7,2]dioxaza-silecine toluene 0.25-solvate.

The coordination polyhedron at the silicon atom in the title compound, C26H37Cl2NO2Si·0.25C7H8, is typical for penta-coordinated silicon derivatives and represents a slightly distorted trigonal bipyramid with an N atom and a Cl atom in the apical positions and the two O atoms and the other Cl atom occupying the equatorial sites. There are two independent mol-ecules in the asymmetric unit. The N-Si-Cl fragment in each is close to linear [178.24 (5) and 178.71 (5)°], in good agreement with 4e-3c theory, as is the elongation of the apical bond lengths [Si-Cl = 2.1663 (7) and 2.1797 (7) Å] in comparison with the equatorial bonds [Si-Cl = 2.0784 (7) and 2.0748 (7) Å]. Orthogonal least-squares fitting of the two independent mol-ecules resulted in r.m.s. deviation of 0.017 Å. The conformations of the two mol-ecules are almost the same, with corresponding torsion angles differing by less than 5.5°. The toluene solvent mol-ecule is disordered about an inversion centre.

Crystal structure of 2,6-bis-(2-hy-droxy-5-methyl-phen-yl)-4-phenyl-pyridinium bromide di-chloro-methane hemisolvate hemihydrate.

The asymmetric unit in the structure of the title compound, C25H22NO2 (+)·Br (-)·0.5CH2Cl2·0.5H2O, comprises two pseudosymmetry-related cations, two bromide anions, a di-chloro-methane molecule and a water mol-ecule of solvation. The two independent cations are conformationally similar with the comparative dihedral angles between the central pyridine ring and the three benzene substituent rings being 3.0 (2), 36.4 (1) and 24.2 (1)°, and 3.7 (2), 36.5 (1) and 24.8 (1)°, respectively. In the crystal, the cations, anions and water mol-ecules are linked through O-H⋯O and O-H⋯Br hydrogen bonds, forming an insular unit. Within the cations there are also intra-molecular N-H⋯O hydrogen bonds. Adjacent centrosymmetrically related aggregates are linked by π-π stacking inter-actions between the pyridine ring and a benzene ring in both cations [ring-centroid separations = 3.525 (3) and 3.668 (3) Å], forming chains extending across the ac diagonal. Voids between these chains are filled by dichloromethane molecules.

Crystal structure of a mixed-valence µ-oxide Sn12 cluster.

The mixed-valence µ-oxide Sn12 cluster, deca-carbonyl-tetra-µ4-oxido-hexa-µ3-oxido-tetra-kis-[µ-2,2'-(pyridine-2,6-di-yl)bis(1,1-di-phenyl-ethano-lato)]deca-tin(II)ditin(IV)dimolyb-denum(O)(2 Mo-Sn) toluene hepta-solvate, [Mo2Sn12(C33H27NO2)4O10(CO)10]·7C7H8, has a crystallographically imposed inversion centre. The asymmetric unit also contains three and a half toluene solvent mol-ecules, one of which is disordered about a centre of symmetry. The complex mol-ecule comprises six distinct Sn atom species with four different coordination numbers, namely 3, 4, 5, and 6. The Sn(II) atoms forming the central Sn10O10 core adopt distorted trigonal-pyramidal, square-pyramidal and octa-hedral coordination geometries provided by the µ-oxide atoms and by the O- and N-donor atoms of two pyridinedi-ethano-late ligands. The terminal Sn(IV) atoms have distorted trigonal-bipyramidal coordination geometries, with a µ4-oxide atom and the N atom of a pyridinedi-ethano-late ligand occupying the axial positions, and the Mo atom of a Mo(CO)5 group and the alk-oxy O atoms of a ligand forming the equatorial plane. In the crystal, weak intra- and inter-molecular C-H⋯O hydrogen bonds are observed.