Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS

The in vitro microsomal metabolism of JWH-015, a ligand that exhibits a high binding affinity at the peripheral cannabinoid receptor CB₂, has been studied. A total of 22 metabolites were identified and structurally characterized. The metabolites are products of: 1) monohydroxylation on the naphthalene ring (m/z 344, M20 and M21), indole ring (m/z 344, M17 and M18), or the N-alkyl group (m/z 344, M14); 2) arene oxidation leading to dihydrodiols (m/z 362, M12 and M15); 3) dihydroxylation on the naphthalene ring (m/z 360, M7) or indole ring (m/z 360, M13), resulting from a combination of monohydroxylations on both the naphthalene and indole rings (m/z 360, M16), or a combination of monohydroxylations on the naphthalene ring and on the N-propyl group (m/z 360, M9); 4) trihydroxylation (m/z 378, M1, M3, M4, M6, and M10); 5) N-dealkylation (m/z 286, M19); 6) N-dealkylation and monohydroxylation on the naphthalene ring (m/z 302, M11); 7) N-dealkylation and dihydrodiol formation from arene oxidation (m/z 320, M2 and M5); 8) dehydrogenation after monohydroxylation on the N-alkyl group (m/z 326, M22); 9) dehydrogenation and monohydroxylation on the indole ring (m/z 342, M8).     

Adsorption of nucleic acid bases on clays: an investigation using Langmuir and Freundlich isotherms and FT-IR spectroscopy

In the present paper, the adsorption of nucleic acid bases (A, adenine; C, cytosine; U, uracil; and T, thymine) on clays (bentonite, kaolinite, and montmorillonite) was studied at different pH (2.00 and 7.20). It should be pointed out there is no reported study of adsorption of nucleic acid bases on clays using seawater (with the major elements), and a wide range of pH. The main finding of this study was that the ratio of A and T adsorbed on clays ranged from 4.68 to 25.1, much higher than the ratio of their occurrence in organisms ranging from 0.95 to 1.05. The weaker adsorption of U and T on clays raises the question of the possibility of a genetic code based on purines only. The FT-IR spectra at pH 2.00 showed that the interaction of A, C, T, and U with the clays occurs through positively charged, protonated groups. Correspondence: Dr. Dimas A. M. Zaia, Departamento de Química-CCE, Universidade Estadual de Londrina, 86051-990 Londrina-PR, Brazil.     

Band‐Gap Manipulations of Monolayer Graphene by Phenyl Radical Adsorptions: A Density Functional Theory Study

Phenyl radical (Ph^.) adsorption on monolayer graphene sheets is used to investigate the band‐gap manipulation of graphene through density functional theory. Adsorption of a single Ph^. on graphene breaks the aromatic π‐bond and generates an unpaired electron, which is delocalized to the ortho or para position. Adsorption of a second radical at the ortho or para position saturates the radical by electron pairing and results in semiconducting graphene. Adsorption of a second radical at the ortho position (ortho–ortho pairing) is found to be more favorable than adsorption at the para position (ortho–para pairing), and the ortho–ortho pairing has stronger effects on band‐gap opening compared with ortho–para pairing. Adsorption of even numbers of Ph^. on graphene by ortho–ortho and ortho–para pairings, in general, increases the band gap. Our study shows promise of band‐gap manipulation in monolayer graphene by Ph^. adsorption, leading to potential wider applications of graphene.     

Study of Scaling Exponents of the Surface Evolved in 2 + 1 Dimension through Competitive Growth between Random Deposition and that with Surface Relaxation

Rough surface develops through computer simulation by competition between growth mechanism random deposition (RD) with a probability of occurrence p and growth mechanism random deposition with surface relaxation (RDSR) with a probability of occurrence 1 − p, on L × L square plane for system size L to record the statistical average of time variation of surface roughness W(L, t) and average height H(t) for the model for specific values of L and p. Other than the pure RD model, the entire evolution may be divided into three regions separated by two specific cross-over times t_x and t_sat. The value of interface width at saturation W_sat depends on both L and p. The first growth exponent β₁ increases exponentially with an increase in p and does not depend on L. The values of the second growth exponent β₂, roughness exponent α, dynamic exponent z( = α/β₂ ), and α + z are 0.0234 ± 0.0008, 0.0506 ± 0.0065, 2.1577 ± 0.0073, and 2.2083 ± 0.0138 respectively and they show no dependence on L and p values. Value of the first cross-over time t_x increases exponentially with an increase in p and does not depend on L. Value of the second cross-over time t_sat increases with an increase in both p and L values. The average growth velocity is unity for the model and is independent of both L and p. For the model, the growth velocity is unity and the fractional porosity is zero. The scaling exponents show some deviation from the relevant universality classes and depend on competitive growth probability for this model. No finite-size effect is present in the model.     

Strontium magnesium phosphate,Sr2+xMg3−xP4O15 (x∼ 0.36), from laboratory X‐ray powder data

The previously unknown crystal structure of strontium magnesium phosphate, Sr_2+xMg_3−xP₄O₁₅ (x∼ 0.36), determined and refined from laboratory powder X‐ray diffraction data, represents a new structure type. The title compound was synthesized by high‐temperature solid‐state reaction and it crystallizes in the orthorhombic space group Cmcm. It was earlier thought to be stoichiometric Sr₂Mg₃P₄O₁₅, but our structural study indicates the nonstoichiometric composition. The asymmetric unit contains one Sr (site symmetry ..m on special position 8g), one M (= Mg 64%/Sr 36%; site symmetry 2/m.. on special position 4b), one Mg (site symmetry 2.. on special position 8e), two P (site symmetry m.. on special position 8f and site symmetry ..m on special position 8g), and six O sites [two on general positions 16h, two on 8g, one on 8f and one on special position 4c (site symmetry m2m)]. The nonstoichiometry is due to the mixing of magnesium and strontium ions on the M site. The structure consists of three‐dimensional networks of MgO₄ and PO₄ tetrahedra, and MO₆ octahedra with the other strontium ions occupying the larger cavities surrounded by ten O atoms. All the polyhedra are connected by corner‐sharing except the edge‐sharing MO₆ octahedra forming one‐dimensional arrangements along [001].     

13C chemical shifts of phenol derivatives. A correlation with electronic structure

The ¹³C chemical shifts of twenty chloro- and nitro-substituted phenols have been measured in d-chloroform. The influence of substituents on the screening at C-1, on the total charge at this position and on the dipole moments is reported and analysed. The results of this study suggest that variations of the chemical shifts at C-1 for meta-methyl-, meta-chloro-, meta-nitro-, ortho- and para-methyl-, ortho- and para-chlorosubstituents mainly reflect charge density changes. The influence of ortho-nitro groups on the screening of C-1 is more complex.     

Analysis of polymerization rates in radical polymerization with primary radical termination of some methacrylates

Polymerization rates in polymerizations with primary radical termination of ethyl methacrylate, β-phenylethyl methacrylate, β-methoxyethyl methacrylate, and phenyl methacrylate initiated by 2,2'-azobis-(2,4-dimethylvaleronitrile) at 60°C were analyzed by using a simple linear equation. The values obtained of k_ti/k_ik_p (where k_ti is the primary radical termination rate constant, k_i is the rate constant of addition on to monomer of primary radical, and k_p is the propagation rate constant) on these analyses are discussed on the theoretical base.     

Adsorption of CO2 and Coadsorption of H and CO2 on Potassium‐Promoted Cu(115)

The influence of potassium, in the submonolayer regime, on the adsorption and coadsorption of CO₂ and H on a stepped copper surface, Cu(115), has been studied by photoelectron spectroscopy, temperature‐programmed desorption, and work‐function measurements. Based on the fast recording of C 1s and O 1s core‐level spectra, the uptake of CO₂ on K/Cu(115) surfaces at 120 K has been followed in real time, and the different reaction products have been identified. The K 2p_3/2 peak exhibits a chemical shift of ?0.4 eV with CO₂ saturation, the C 1s peaks of the CO₃ and the CO species show shifts of ?0.8 and ?0.5 eV, respectively, and the C 1s peak of the physisorbed CO₂ exhibits no shift. The effects of gradually heating the CO₂/K/Cu(115) surface include the desorption of physisorbed CO₂ at 143 K; the desorption of CO at 193 K; the ordering of the CO₃ species, and subsequently the dissociation of the carbonate with desorption at 520–700 K. Formate, HCOO^?, was synthesized by the coadsorption of H and CO₂ on the K/Cu(115) surface at 125 K. Formate formed exclusively for potassium coverages of less than 0.4 monolayer, whereas both formate and carbonate were formed at higher coverages. The desorption of formate‐derived CO₂ took place in the temperature range 410–425 K and carbonate‐derived CO₂ desorbed at 645–660 K, depending on the potassium coverage.     

Effect of surfactant adsorption time on the observation of Newton black film in foam film

Observation of Newton black film (NBF) in foam film is possible only with a certain probability W which depends on the concentration C of surfactant in the solution and on the time t_a during which adsorption of surfactant at the solution/air interface has taken place. In the paper, the W(C,t_a) dependence is derived and used to analyze the effect of t_a on the critical surfactant concentration C_c below which NBF in foam film practically cannot be observed. An expression for the C_c(t_a) function is obtained which reveals that C_c decreases substantially with increasing t_a. This expression is found to describe well experimental C_c(t_a) data for foam films obtained from aqueous solution of the therapeutic surfactant INFASURF.     

The Implications of (2S,4S)‐Hydroxyproline 4‐O‐Glycosylation for Prolyl Amide Isomerization

The conformations of peptides and proteins are often influenced by glycans O‐linked to serine (Ser) or threonine (Thr). (2S,4R)‐4‐Hydroxyproline (Hyp), together with L ‐proline (Pro), are interesting targets for O‐glycosylation because they have a unique influence on peptide and protein conformation. In previous work we found that glycosylation of Hyp does not affect the N‐terminal amide trans/cis ratios (K_trans/cis) or the rates of amide isomerization in model amides. The stereoisomer of Hyp—(2S,4S)‐4‐hydroxyproline (hyp)—is rarely found in nature, and has a different influence both on the conformation of the pyrrolidine ring and on K_trans/cis. Glycans attached to hyp would be expected to be projected from the opposite face of the prolyl side chain relative to Hyp; the impact this would have on K_trans/cis was unknown. Measurements of ³J coupling constants indicate that the glycan has little impact on the C^γ‐endo conformation produced by hyp. As a result, it was found that the D ‐galactose residue extending from a C^γ‐endo pucker affects both K_trans/cis and the rate of isomerization, which is not found to occur when it is projected from a C^γ‐exo pucker; this reflects the different environments delineated by the proline side chain. The enthalpic contributions to the stabilization of the trans amide isomer may be due to disruption of intramolecular interactions present in hyp; the change in enthalpy is balanced by a decrease in entropy incurred upon glycosylation. Because the different stereoisomers—Hyp and hyp—project the O‐linked carbohydrates in opposite spatial orientations, these glycosylated amino acids may be useful for understanding of how the projection of a glycan from the peptide or protein backbone exerts its influence.     

Antimicrobial and allelopathic metabolites produced by Penicillium brasilianum

Six known compounds, isoroquefortine C (1), griseofulvin (2), ergosterol peroxide (3), 3β-hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one (4), cerevisterol (5) and (22E,24R)-6β-methoxyergosta-7,22-diene-3β,5α-diol (6), were produced by the fungus Penicillium brasilianum, and their structures were elucidated by spectroscopic methods. This is the first report on isoroquefortine C as naturally occurring compound. Their bioactivities against five phytopathogenic fungi (Gibeberalla saubinetti, Fusarium solani, Botrytis cinerea, Colletotrichum gloeosporioides and Alternaria solani) and four pathogenic bacteria (Escherichia coli, Bacillus subtilis, Staphyloccocus aureus and Bacillus cereus), as well as allelopathic activities on Raphanus sativus were tested. Compound 1 exhibited a remarkable antifungal activity with minimum inhibitory concentration (MIC) of 12.5 μM against C. gloeosporioides, in comparison with positive control hymexazol (MIC 25 μM). Compound 2 displayed strong inhibitory effects on the growth of A. solani and S. aureus with MIC of 3.13 μM for each. Compounds 2 and 3 displayed a significant growth-inhibition activity on R. sativus.     

Properties and limits of some essential oils: chemical characterisation,antimicrobial activity,interaction with antibiotics and cytotoxicity

Because of the emergence of multi-drug resistance bacteria and fungi, alternatives to conventional antimicrobial therapy are needed. This study aims to evaluate in vitro the antimicrobial activity of: Mirtus communis, Coriandrum sativum, Pelargonium capitatum, Cuminum cyminum, Ocimum basilicum, Citrus aurantium amara, Cymbopogon. winterianus, Cymbopogon martini, Salvia sclarea, Melaleuca alternifolia and Mentha suaveolens essential oils on bacteria and fungi, in relation to their chemical composition. The potential interaction of M. alternifolia (TTO), C. sativum (CDO) and M. suaveolens (EOMS) essential oils when used in combination with gentamicin and fluconazole has been evaluated. The results obtained showed a synergic effect on some bacteria and fungi, with FICI values ≤5. The cytotoxicity of TTO, CDO and EOMS was investigated towards HeLa cells. Only EOMS did not result cytotoxic at the active concentrations on micro-organisms. Further studies are necessary to obtain optimal ratios and dosing regimens for higher therapeutic efficacy and to decrease toxicological profiles.     

Correlation between glass transition temperature and chain structure for randomly crosslinked high polymers

The empirical form for the dependence, T_g(n) ≅ T_g(∞)·(1 + α/n), of the glass transition temperature T_g on the average number n of repeat units between crosslinks, is generalized for randomly crosslinked high polymers. The new form, T_g(n) ≅ T_g(∞) · [1 + c/(n·N_rot)], is based on a correlation study of data for 77 samples of 10 different sets of resins. The fitting parameter α is resolved into composition-dependent N_rot and composition-independent c terms. N_rot summarizes the average number of rotational degrees of freedom per repeat unit, and is estimated in a straightforward manner from the structure and mol fraction of each repeat unit. The value of c is found from data analysis to be 5 ± 2. The results of this work are consistent with expectations based on the entropy theory of glasses, and provide improved understanding and predictive ability for the properties of crosslinked polymers. © 1996 John Wiley & Sons, Inc.     

Effect of a plant fortifier (Boundary) on pests and predators of greenhouse vegetable crops

Boundary, a plant fortifier composed of extracts of Sophora flavescens Aiton and brown algae, was tested for control of the leaf miner Tuta absoluta (Meyrick) on tomato (three trials) and of the red spider mite Tetranychus urticae Koch on eggplant (one trial) and for side effects on the whitefly predator Macrolophus pygmaeus (Kambur) (two trials) on tomato and on the thrips predators Orius laevigatus (Fieber) and Amblyseius swirskii Athias-Henriot (two trials) on pepper, all in cold greenhouses in South Italy. Control rates for T. absoluta were moderate (40–70%) in the autumn crop but very high and comparable to those for emamectin benzoate in the spring crops (96–100%). Boundary compared well with abamectin against T. urticae, with near complete control. M. pygmaeus was moderately injured in late autumn, but not in early autumn. At the tested application rate and predator population density Boundary was safe for O. laevigatus and A. swirskii.     

d-xylose transport by Candida succiphila and Kluyveromyces marxianus

The kinetics and regulation of d-xylose uptake were investigated in the efficient pentose fermentor Candida succiphila, and in Kluyveromyces marxianus, which assimilate but do not ferment pentose sugars. Active high-affinity (K _m ∼ 3.8 mM; V _max ∼ 15 nmol/[mg·min]) and putative facilitated diffusion low-affinity (K _m ∼ 140 mM; V _max ∼ 130 nmol/[mg·min]) transport activities were found in C. succiphila grown, respectively, on xylose or glucose. K. marxianus showed facilitated diffusion low-affinity (K _m ∼ 103 mM; V _max ∼ 190 nmol/[mg·min]) transport activity when grown on xylose under microaerobic conditions, and both a low-affinity and an active high-affinity (K _m ∼ 0.2 mM; V _max ∼ 10 nmol/[mg·min]) transport activity when grown on xylose under fully aerobic conditions.     

Study of structural parameters on the adsorption selectivity of a molecularly imprinted polymer

This work was focused on the influence of match degree of structure parameters i.e. molecular size, volume and polarity (denoted as R_d, V_d and P_d) between imprinted cavities in Qu-MIP and Xn on the adsorption selectivity. The results presented that the influence of R_d on the adsorption selectivity was the largest and the most regular, while the influence of P_d was the smallest and the most irregular. Besides, the influence degree of V_d was decreased in general with the increase of R_d. However, as R_d was in the threshold of [0.99, 1.02], V_d would rise to the major influence factor. Furthermore, utilizing data obtained from experiment, the influence authority of R_d, V_d and P_d on the adsorption selectivity was calculated theoretically through multiple linear regression and principal component analysis of IBM SPSS Statistics 20, and results showed the authority order was R_d, V_d and P_d at any circumstance despite the value was different, which was in accordance with the result we directly inducted from the experiment.     

Excess properties of the mixture bis(2-dichloroethyl)ether (chlorex) + 2,2,4-trimethylpentane (isooctane)

The excess properties of the mixture bis(2-dichloroethyl)ether (chlorex) + 2,2,4-trimethylpentane (isooctane), i.e. excess volumev ^E, excess enthalpyh ^E, excessGibbs energyg ^E and excess heat capacityc _p ^E are reported. The excess volume is small, negative on the chlorex side and positive on the isooctane side. The excess enthalpy at 293.15 K is 1 913 J mol^–1 for equimolar composition, the excessGibbs energy amounts to 1 367 J mol^–1 under the same conditions. The system undergoes phase separation below 290.47 K. Due to the nearness of the critical point,c _p ^E exhibits a strong maximum at the critical composition (x _isooctane=0.508), though the basic part ofc _p ^E is negative. Discussion focusses on the effects of polarity of chlorex as mixing partner, on near-critical properties, and on mixing rules of avan der Waals-type equation of state.Dedicated to Prof. Dr.K. Komarek on the occasion of his 60th birthday.     

Orbital electronegativity and analytical representation of atom valence state energy

An analytical representation of atom valence state energy (E(n_j), j = 1,…?4; E(n_j) is a nonlinear function of orbital occupancy numbers n_j) is proposed and explicitly derived for H? Ar; the values of electronegativity calculated based on E(n_j) agree within truncation error with those of Hinze and Jaffe. However, in our representation, orbital electronegativity χ and hardness parameters η of a given orbital always include nonlinear contributions from other orbitals, hence accounting for their influence on χ and η. An atomic charge calculation procedure based on E(n_j) is also described and shown to perform well.     

Photochemical reaction mechanism of cyclobutanone: CASSCF study

The photochemical reaction channels of cyclobutanone have been studied at the CASSCF level with a 6‐31G* basis set. Starting from the n‐π* excited‐state (S₁) cyclobutanone, the three reactions can take place: decarbonylation (produce CO and cyclopropane or propylene), cycloelimination (produce ketene and ethylene), and ring expansion (produce oxacarbene). Our computation indicates that decarbonylation products CO and triplet trimethylene are formed on the triplet n‐π* excited state (T₁) in a stepwise way via a biradical intermediate after intersystem crossing (ISC) to T₁ from S₁. And, then, the triplet trimethylene undergoes a second ISC to the ground state (S₀) to produce the singlet trimethylene from which cyclopropane can be produced rapidly only overcoming a 1 to 2‐kcal/mol barrier while propylene can be formed as a secondary product. The cycloelimination products ketene and ethylene are formed on the S₀ in a concerted mechanism after internal conversion (IC) to S₀ from S₁ via a biradical conical intersection. The reaction channels corresponding to ring expansion on the S₀, T₁, and S₁ states have also been discussed, and the likeliest reaction path is that oxacarbene is formed on the ground state following S₁/S₀ internal conversion. The surface topology of cyclobutanone on the S₁ surface is characterized by a transition state separating the minimum from the S₁/S₀ conical intersection, which is consistent with the previous computations and can explain the wavelength dependence of the fluorescence emission yield. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004