Effect of the metal ion and the medium on the electronic structure of anthranilic acid: a modelling study on the Li and the BeH derivatives

This computational organic chemistry study illustrates that the size of the metal ion is a critical point in determining the bonding mode of the anthranilate (2-aminobenzoate). The beryllium model structure is the first example in the chemical literature on the ability of this amino acid to bond as N–O chelate. The medium has variable effect on the energies and the dipole moments of the studied models, which was found originating essentially from the differences in the atomic charges of the metals. Analysis of the molecular charge distribution allowed stating a new theory on the effect of the medium on the two pairs of isomers.     

Effect of Microorganisms and Microbial Metabolites on Apatite Dissolution

The dissolution rate of apatite was determined in batch reactors in organic acid solutions and in microbial cultures. Inoculum for the cultures was from biotite plus apatite crystals from a granite weathering profile in South Eastern Australia. In both the biotic and the abiotic experiments, etching of the apatite surface leads to the formation of elongated spires parallel to the c axis. Apatite dissolution rates in the inorganic, acetate, and oxalate solutions increase as pH decreases from approximately 10 -11 mol/m -2 · s -1 at initial pH 5.5 to 10 -7 mol/m -2 · s -1 at initial pH 2. Under mildly acidic to near neutral pH conditions, both oxalate and acetate increased apatite dissolution by up to an order of magnitude compared to the inorganic conditions. Acetate catalyzed the reaction by forming complexes with Ca, either in solution or at the mineral surfaces. Oxalate forms complexes with Ca as well, and can also affect reaction rates and stoichiometry by forming Ca-oxalate precipitates, thus affecting solution saturation states. In all abiotic experiments, net phosphate release to solution approaches zero even when solutions are apparently undersaturated by several orders of magnitude with respect to the solubility of an ideal fluoroapatite mineral. In the microbial experiments, two enrichment cultures increased both apatite and biotite dissolution by producing organic acids, primarily pyruvate, fermentation products, and oxalate, and by lowering bulk solution pH to between 3 and 5. However, the microorganisms were also able to increase phosphate release from apatite (by two orders of magnitude) without lowering bulk solution pH by producing pyruvate and other compounds.     

Bioconversion of Phosphatidylserine by Phospholipase D from Streptomyces racemochromogenes in a Microaqueous Water-Immiscible Organic Solvent

Phospholipase D (PLD)-mediated transphosphatidylation of phosphatidylcholine (PC) in a biphasic system was limited by the hydrolysis reaction. A biphasic system can produce a large amount of water. To solve this problem, a microaqueous water-immiscible organic solvent was used for the first time in the bioconversion of phosphatidylserine (PS). The transphosphatidylation among 40 µmol PC, 800 µmol L-serine, and 0.17 U/mL PLD in 2.133 mL of butyl acetate with 6.25% water (V/V) was conducted at a trans-phosphatidylation rate of 88% (mol/mol), and no hydrolytic reaction was observed. Compared to commonly used biphasic systems, this system shows a similar transphosphatidylation rate, whereas the undesirable hydrolysis of phospholipids was completely suppressed.     

Studies on the Mode of Action of Polyoxins

(1) Chitin-UDP acetylglucosaminyltransferase (E.C. 2.4.1.16., chitin synthetase) in the cell-free system from phytopathogenic fungus Piricularia oryzae, and effects of various polyoxins and related compounds on the enzyme activity were studied. Polyoxins A~M, polyoxin A derivatives, polyoxin C derivatives, 5′-amino-5′-deoxyuridine, uridine and thymidine inhibited equally the incorporation of N-acetylglucosamine (GlcNAc) from UDP-N-acetylglucosamine (UDP-GlcNAc) into chitin.

(2) Competition between the above inhibitors and UDP-GlcNAc was observed by kinetic studies. The Km for UDP-GlcNAc was determined to be 3.3 × 10^?3 m and the Ki values for polyoxins A~M, except polyoxin C, were found to be in the range of 3.3 × 10^?5 m to 3.4 × 10^?6 m. For polyoxin C, 5′-amino-5′-deoxyuridine and uridine, the Ki values of 2.7 × 10^?3 m, 8.0 × 10^?3 m and 3.0 × 10^?3 m were given, respectively. The inhibitor constants for other related compounds were also calculated.

(3) The values of binding affinity, ?ΔG, for formation of substrate- or inhibitor-enzyme complexes were calculated from the Km or Ki values. In addition, partial binding affinities, ?Δg, for certain moieties or groups of polyoxins were estimated from the ?ΔG. For instance, the ?ΔG values for UDP-GlcNAc and polyoxin L were 5.7 kcal/mole and 9.2 kcal/mole, respectively. And the ?Δg values for the nucleoside moiety (part I), the carbamylpolyoxamic acid moiety (part II) and the carboxyl group at C5′ position of polyoxin L were 5.2, 3.5 and 0.7 kcal/mole, respectively.

(4) From the results obtained, the mechanism of action and relation between chemical structure and competitive inhibition of chitin synthetase were discussed.

     

Effect of potassium diformate in combination with different amounts and sources of excessive dietary copper on production performance in weaning piglets

Three studies with each 96 weaning piglets were conducted to evaluate the combinatory effect of potassium diformate and high dietary doses of Cu on production performance. In Exp. 1, increasing dietary Cu (25, 75, 125, 175 ppm Cu) were tested at either no or 1.8% potassium diformate. In Exp. 2, rising dietary levels of potassium diformate (0%, 0.6%, 1.2% and 1.8%) were tested at either 25 or 175 ppm Cu. In Exp. 3, a basal dietary Cu content of 15 ppm was compared with dietary Cu levels of 95 or 175 ppm, each of them added as either Cu sulphate or Cu amino acid chelate or Cu formate. Rising dietary additions of potassium diformate and Cu improved weight gain, feed intake and feed conversion rate of piglets. The combination of potassium diformate and Cu failed to act additively at highest dose levels of the two supplements. Cu sulphate was efficient as growth stimulating additive in all 3 experiments, Cu formate failed to stimulate production performance, Cu chelate tended to depress production performance and to increase blood plasma Cu compared to equivalent amounts of Cu from Cu sulphate.     

Metagenomic insights into strategies of carbon conservation and unusual sulfur biogeochemistry in a hypersaline Antarctic lake

Organic Lake is a shallow, marine-derived hypersaline lake in the Vestfold Hills, Antarctica that has the highest reported concentration of dimethylsulfide (DMS) in a natural body of water. To determine the composition and functional potential of the microbial community and learn about the unusual sulfur chemistry in Organic Lake, shotgun metagenomics was performed on size-fractionated samples collected along a depth profile. Eucaryal phytoflagellates were the main photosynthetic organisms. Bacteria were dominated by the globally distributed heterotrophic taxa Marinobacter, Roseovarius and Psychroflexus. The dominance of heterotrophic degradation, coupled with low fixation potential, indicates possible net carbon loss. However, abundant marker genes for aerobic anoxygenic phototrophy, sulfur oxidation, rhodopsins and CO oxidation were also linked to the dominant heterotrophic bacteria, and indicate the use of photo- and lithoheterotrophy as mechanisms for conserving organic carbon. Similarly, a high genetic potential for the recycling of nitrogen compounds likely functions to retain fixed nitrogen in the lake. Dimethylsulfoniopropionate (DMSP) lyase genes were abundant, indicating that DMSP is a significant carbon and energy source. Unlike marine environments, DMSP demethylases were less abundant, indicating that DMSP cleavage is the likely source of high DMS concentration. DMSP cleavage, carbon mixotrophy (photoheterotrophy and lithoheterotrophy) and nitrogen remineralization by dominant Organic Lake bacteria are potentially important adaptations to nutrient constraints. In particular, carbon mixotrophy relieves the extent of carbon oxidation for energy production, allowing more carbon to be used for biosynthetic processes. The study sheds light on how the microbial community has adapted to this unique Antarctic lake environment.     

The sensitivity of water chemistry to climate in a forested,nitrogen-saturated catchment recovering from acidification

Fluxes of major ions and nutrients were measured in the N-saturated mountain forest catchment-lake system of Čertovo Lake (Czech Republic) from 1998 to 2014. The lake has been rapidly recovering from atmospheric acidification due to a 90% decrease in sulphate (SO₄²⁻) deposition since the late 1980s and nitrate (NO₃⁻) contribution to the pool of strong acid anion and leaching of dissolved organic carbon (DOC) have increased. Present concentrations of base cations, phosphorus (P), total organic N (TON), and ionic (Al_i) and organically bound (Al_o) aluminium in tributaries are thus predominantly governed by NO₃⁻ and DOC leaching. Despite a continuing recovery lasting 25 years, the Čertovo catchment is still a net source of protons (H⁺), producing 44 mmol m⁻² yr⁻¹ H⁺ on a catchment-area basis (corresponding to 35 μmol L⁻¹ on a concentration basis). Retention of the deposited inorganic N in the catchment averages 20%, and ammonium consumption (51 mmol m⁻² yr⁻¹) and net NO₃⁻ production (28 mol m⁻² yr⁻¹) are together the dominant terrestrial H⁺ generating processes. In contrast, the importance of SO₄²⁻ release from the soils on terrestrial H⁺ production is continuously decreasing, with an average of 47 mmol m⁻² yr⁻¹ during the study. The in-lake biogeochemical processes reduce the incoming acidity by ∼40%, neutralizing 23 μmol L⁻¹ H⁺ (i.e., 225 mmol m⁻² yr⁻¹ on a lake-area basis). Denitrification and photochemical and microbial decomposition of DOC are the most important in-lake H⁺ consuming processes (50 and 39%, respectively), while hydrolysis of Al_i (from tributaries and photochemically liberated from Al_o) is the dominant in-lake H⁺ generating process. Because the trends in water chemistry and H⁺ balance in the catchment-lake system are increasingly related to variability in NO₃⁻ and DOC leaching, they have become sensitive to climate-related factors (drought, elevated runoff) and forest damage that significantly modify the leaching of these anions. During the study period, increased exports of NO₃⁻ (accompanied by Al_i and base cations) from the Čertovo catchment occurred after a dry and hot summer, after forest damage, and during elevated winter runoff. Increasing DOC export due to decreasing acid deposition was further elevated during years with higher runoff (and especially during events with lateral flow), and was accompanied by P, TON, and Al_o leaching. The climate-related processes, which originally “only” confounded chemical trends in waters recovering from acidification, may soon become the dominant variables controlling water composition in N-saturated catchments.     

Problems,successes and challenges for the application of dispersion-corrected density-functional theory combined with dispersion-based implicit solvent models to large-scale hydrophobic self-assembly and polymorphism

The recent advent of dispersion-corrected density-functional theory (DFT) methods allows for quantitative modelling of molecular self-assembly processes, and we consider what is required to develop applications to the formation of large self-assembled monolayers (SAMs) on hydrophobic surfaces from organic solution. Focus is on application of the D3 dispersion correction of Grimme combined with the solvent dispersion model of Floris, Tomasi and Pascual–Ahuir to simulate observed scanning-tunnelling microscopy (STM) images of various polymorphs of tetraalkylporphyrin SAMs on highly oriented pyrolytic graphite surfaces. The most significant problem is identified as the need to treat SAM structures that are incommensurate with those of the substrate, providing a challenge to the use of traditional periodic-imaging boundary techniques. Using nearby commensurate lattices introduces non-systematic errors into calculated lattice constants and free energies of SAM formation that are larger than experimental uncertainties and polymorph differences. Developing non-periodic methods for polymorph interface simulation also remains a challenge. Despite these problems, existing methods can be used to interpret STM images and SAM atomic structures, distinguishing between multiple feasible polymorph types. They also provide critical insight into the factors controlling polymorphism. All this stems from a delicate balance that the intermolecular D3 and solvent Floris, Tomasi and Pascual–Ahuir corrections provide. Combined optimised treatments should yield fully quantitative approaches in the future.     

Formulation and antifungal performance of natamycin-loaded liposomal suspensions: the benefits of sterol-enrichment

The aim of this study is to develop and evaluate food-grade liposomal delivery systems for the antifungal compound natamycin. Liposomes made of various soybean lecithins are prepared by solvent injection, leading to small unilamellar vesicles (<130?nm) with controlled polydispersity, able to encapsulate natamycin without significant modification of their size characteristics. Presence of charged phospholipids and reduced content of phosphatidylcholine in the lecithin mixture are found to be beneficial for natamycin encapsulation, indicating electrostatic interactions of the preservative with the polar head of the phospholipids. The chemical instability of natamycin upon storage in these formulations is however significant and proves that uncontrolled leakage out of the liposomes occurs. Efficient prevention of natamycin degradation is obtained by incorporation of sterols (cholesterol, ergosterol) in the lipid mixture and is linked to higher entrapment levels and reduced permeability of the phospholipid membrane provided by the ordering effect of sterols. Comparable action of ergosterol is observed at concentrations 2.5-fold lower than cholesterol and attributed to a preferential interaction of natamycin–ergosterol as well as a higher control of membrane permeability. Fine-tuning of sterol concentration allows preparation of liposomal suspensions presenting modulated in vitro release kinetics rates and enhanced antifungal activity against the model yeast Saccharomyces cerevisiae.     

Synthesis,anticancer activity,and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system

Described herein are our limited structure–activity relationship (SAR) studies on a 5:7-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focused on judicial attachment of substituents at N-1 and N⁶-positions of the heterocyclic ring. Our results suggest that there is some subtle correlation between the substituents attached at the N-1 position and those attached at the N⁶-position of the heterocycle. It is likely that there is a common hydrophobic binding pocket on the target protein that is occupied by the substituents attached at the N-1 and N⁶-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N⁶ and no attachment at N-1, or a combined C-10 at N⁶ and a CH₂Ph at N-1. Any alkyl chain shorter or longer than C-10 at N⁶ with a CH₂Ph attached at N-1, would result in decrease of biological activity.