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Diesters of geminal diols (R-CH(O-CO-R′)2, RR′C(OCOR″)2, etc. with R = H, aryl or alkyl) are termed acylals according to IUPAC recommendations (Rule P-65.6.3.6 Acylals) if the acids involved are carboxylic acids. Similar condensation products can be obtained from various other acidic structures as well, but these related "non-classical acylals", as one might call them, differ in various aspects from classical acylals and will not be discussed in this article. Carboxylic acid diesters of geminal diols play a prominent role in organic chemistry, not only in their application as protective groups for aldehydes and ketones but also as precursors in the total synthesis of natural compounds and in a variety of organic reactions. What is more, acylals are useful as a key structural motif in clinically validated prodrug approaches. In this review, we summarise the syntheses and chemical properties of such classical acylals and show what potentially under-explored possibilities exist in the field of drug design, especially prodrugs, and classify this functional group in medicinal chemistry. [ABSTRACT FROM AUTHOR]

Diesters of geminal diols (R-CH(O-CO-R′)2, RR′C(OCOR″)2, etc. with R = H, aryl or alkyl) are termed acylals according to IUPAC recommendations (Rule P-65.6.3.6 Acylals) if the acids involved are carboxylic acids. Similar condensation products can be obtained from various other acidic structures as well, but these related “non-classical acylals”, as one might call them, differ in various aspects from classical acylals and will not be discussed in this article. Carboxylic acid diesters of geminal diols play a prominent role in organic chemistry, not only in their application as protective groups for aldehydes and ketones but also as precursors in the total synthesis of natural compounds and in a variety of organic reactions. What is more, acylals are useful as a key structural motif in clinically validated prodrug approaches. In this review, we summarise the syntheses and chemical properties of such classical acylals and show what potentially under-explored possibilities exist in the field of drug design, especially prodrugs, and classify this functional group in medicinal chemistry.

We present a mild, efficient, and one‐pot method for the silyl‐promoted transformation of cyclic anhydrides into homo‐ and hetero‐dicarboxylic acid diesters and amide esters. This versatile reaction operates under ambient conditions, on a gram scale, and accommodates a wide range of alcohols, amines, and cyclic anhydrides. The one‐pot process involves a two‐step sequence, starting with the nucleophilic opening of anhydride by an amine or alcohol, followed by esterification. TMSCl serves a dual role, acting as a sacrificial reagent to remove in situ water and as a Lewis acid to promote the anhydride opening. The reaction proceeds successfully in the absence and presence of a base, as confirmed by NMR and crossover experiments, which validated the formation of dicarboxylic acid monoester and alkyl silyl mixed diester respectively. Controlled experiments have shown that the one‐pot process yields higher efficiencies when compared to the same reaction conducted using a two‐step process. This is the first comprehensive study demonstrating a broad substrate scope for the conversion of cyclic anhydride into diesters and amide esters. The method finds application in the synthesis of various commercial plasticizers. [ABSTRACT FROM AUTHOR]

Carotenoids are the most abundant lipid-soluble phytochemicals and are used as dietary supplements to protect against diseases caused by oxidative stress. Astaxanthin, a xanthophyll carotenoid, is a very potent antioxidant with numerous beneficial effects on cellular functions and signaling pathways. In this study, using spleen cells from healthy Balb/c mice, we report the bio-functional effects of an astaxanthin-rich extract (EXT) prepared from the microalga Haematococcus pluvialis and its astaxanthin monoesters-rich fraction (ME) and astaxanthin diesters-rich fraction (DE) obtained by fractionation of EXT using countercurrent chromatography (CCC). After incubation under standard culture conditions (humidity, 37 °C, 5% CO2, atmospheric oxygen), the viability of untreated splenocytes, as determined by the trypan blue exclusion assay, the MTT assay, and the neutral red assay, decreases to approximately 75% after 24 h compared with naïve splenocytes. This effect correlated with the decrease in mitochondrial membrane potential and the transition of ~59% of cells to the early stage of apoptosis, as well as with the decreased ROS production, indicating that hyperoxia in cell-culture deteriorates cell functions. They are restored or stimulated by co-cultivation with EXT, ME, and DE up to 10 µg/mL in the order EXT > DE > ME, suggesting that esterification increases bioavailability to cells in vitro. ROS and H2O2 concentrations reflect mRNA transcriptional activity of Nrf2, superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 1, as well as SOD-mediated ROS conversion, whereas they inversely correlate with iNOS-mediated NO production. The highest-tested concentration of EXT, ME, and DE (40 µg/mL) is detrimental to cells, probably because of the overwhelming scavenging activity of astaxanthin and its esters for the reactive oxygen/nitrogen species required for cellular functions and signal transduction at low physiological concentrations. In this study, we demonstrate that differential activities of ME and DE contribute to the final antioxidant and cytoprotective effects of astaxanthin extract, which is beneficial in preventing a wide range of ROS-induced adverse effects, with DE being more effective. In addition, the selection of physioxia-like conditions for pharmacological research is highlighted. [ABSTRACT FROM AUTHOR]

Carotenoids are the most abundant lipid-soluble phytochemicals and are used as dietary supplements to protect against diseases caused by oxidative stress. Astaxanthin, a xanthophyll carotenoid, is a very potent antioxidant with numerous beneficial effects on cellular functions and signaling pathways. In this study, using spleen cells from healthy Balb/c mice, we report the bio-functional effects of an astaxanthin-rich extract (EXT) prepared from the microalga Haematococcus pluvialis and its astaxanthin monoesters-rich fraction (ME) and astaxanthin diesters-rich fraction (DE) obtained by fractionation of EXT using countercurrent chromatography (CCC). After incubation under standard culture conditions (humidity, 37 °C, 5% CO2, atmospheric oxygen), the viability of untreated splenocytes, as determined by the trypan blue exclusion assay, the MTT assay, and the neutral red assay, decreases to approximately 75% after 24 h compared with naïve splenocytes. This effect correlated with the decrease in mitochondrial membrane potential and the transition of ~59% of cells to the early stage of apoptosis, as well as with the decreased ROS production, indicating that hyperoxia in cell-culture deteriorates cell functions. They are restored or stimulated by co-cultivation with EXT, ME, and DE up to 10 µg/mL in the order EXT > DE > ME, suggesting that esterification increases bioavailability to cells in vitro. ROS and H2O2 concentrations reflect mRNA transcriptional activity of Nrf2, superoxide dismutase 1 (SOD1), catalase, and glutathione peroxidase 1, as well as SOD-mediated ROS conversion, whereas they inversely correlate with iNOS-mediated NO production. The highest-tested concentration of EXT, ME, and DE (40 µg/mL) is detrimental to cells, probably because of the overwhelming scavenging activity of astaxanthin and its esters for the reactive oxygen/nitrogen species required for cellular functions and signal transduction at low physiological concentrations. In this study, we demonstrate that differential activities of ME and DE contribute to the final antioxidant and cytoprotective effects of astaxanthin extract, which is beneficial in preventing a wide range of ROS-induced adverse effects, with DE being more effective. In addition, the selection of physioxia-like conditions for pharmacological research is highlighted.

The labile fraction of dissolved organic phosphorus (DOP) – predominantly consisting of phosphoric esters – is an important microbial P source in the subtropical oligotrophic ocean. However, unlike phosphate, knowledge for labile DOP is still limited due to the scarcity of broad and intensive observations. In this study, we examined the concentrations and size-fractionated hydrolysis rates of labile phosphoric monoesters and diesters along a >10,000 km longitudinal transect in the North Pacific (23°N; upper 200-m layer). Depth-integrated monoesters decreased westward with a maximum difference of fivefold. Vertical profiles of monoesters in the eastern and western basins showed decreasing and increasing trends with depth, respectively. The monoester-depleted shallow layer of the western basin was associated with phosphate depletion and monoesterase activity was predominant in the large size fraction (>0.8 μm), suggesting that monoesters are significant P sources particularly for large microbes. In contrast, diester concentrations were generally lower than monoester concentrations and showed no obvious horizontal or vertical variation in the study area. Despite the unclear distribution pattern of diesters, diesterase activity in the particulate fraction (>0.2 μm) increased in the phosphate-depleted shallow layer of the western basin, suggesting that the targeted diesters in the assay were also important microbial P sources. Diesterase activities in the dissolved fraction (

The labile fraction of dissolved organic phosphorus (DOP) – predominantly consisting of phosphoric esters – is an important microbial P source in the subtropical oligotrophic ocean. However, unlike phosphate, knowledge for labile DOP is still limited due to the scarcity of broad and intensive observations. In this study, we examined the concentrations and size-fractionated hydrolysis rates of labile phosphoric monoesters and diesters along a >10,000 km longitudinal transect in the North Pacific (23°N; upper 200-m layer). Depth-integrated monoesters decreased westward with a maximum difference of fivefold. Vertical profiles of monoesters in the eastern and western basins showed decreasing and increasing trends with depth, respectively. The monoester-depleted shallow layer of the western basin was associated with phosphate depletion and monoesterase activity was predominant in the large size fraction (>0.8 μm), suggesting that monoesters are significant P sources particularly for large microbes. In contrast, diester concentrations were generally lower than monoester concentrations and showed no obvious horizontal or vertical variation in the study area. Despite the unclear distribution pattern of diesters, diesterase activity in the particulate fraction (>0.2 μm) increased in the phosphate-depleted shallow layer of the western basin, suggesting that the targeted diesters in the assay were also important microbial P sources. Diesterase activities in the dissolved fraction (<0.2 μm) were not correlated with ambient phosphate concentrations; however, cell-free diesterase likely played a key role in P cycling, as dissolved diesterase activities were substantially higher than those in the particulate fraction. The horizontal and vertical variability of labile monoesters in the subtropical North Pacific were therefore predominantly regulated by P stress in particularly large microbes, whereas the distributions of labile diesters and diesterase activities were generally independent of microbial P stress, indicating a more complex regulation of diesters to that of monoesters. [ABSTRACT FROM AUTHOR]

By studying the reactions of hydration of norbornene and 2-vinyl-2-methyl-gemdichlorocyclopropane and the reactions of styrene and norbornene with different alcohols and carbonic acids in presence of heterogenic catalyst, it was found that the selected zeolite H-Beta is active and selective catalyst for these reactions. Alcohols, ethers, esters and diesters of norbornene have exo-configuration. It has been established that reaction of norbornene with diols, catalyzing by zeolite Beta, leads to the formation of esters, which was not found before. [ABSTRACT FROM AUTHOR]

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury.

A straightforward and broad-scope procedure to obtain symmetrically substituted buta-1,3-diene-1,4-diyl diesters, based on the homocoupling of the corresponding (Z)-β-iodoenol esters, is presented. It involves the use of a catalytic system composed of [NiCl2 (PPh3)2 ] (10 mol%), NaI (10 mol%), and excess of Zn dust. The reactions proceed in THF at room temperature with exquisite preservation of the stereochemistry of the C=C bond of the starting iodoolefins, thus leading to the final dienes as the corresponding Z , Z -stereoisomers exclusively. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Lipids in tree shrew meibum were comprehensively characterized. • The lipid profile of tree shrew meibum shares many similarities with that of human meibum, making the tree shrew a viable model for study of dry eye. • The overall chain lengths of several lipid classes were increased in tree shrew meibum compared to human meibum. • Tree shrew meibum includes an additional subtype of (O -acyl)-ω-hydroxyl fatty acids. • Many phospholipids were detected, and further studies are warranted to determine their sources. Abstract Lipids secreted from the meibomian glands form the outermost layer of the tear film and reduce its evaporation. Abnormal changes in the quantities or compositions of lipids present in meibomian gland secretions (meibum) are known to lead to dry eye disease, although the underlying mechanism is not yet well understood. The tree shrew is the non-primate mammal most closely related to humans. To assess the utility of the tree shrew as a model for the study of dry eye disease, we analyzed the lipid profile of tree shrew meibum using an untargeted ESI-MS and MS/MSall shotgun approach. The resulting lipidome shared many similarities with human meibum, while displaying some interesting differences. For example, several classes of lipids, including wax esters, cholesteryl esters, diesters, and (O -acyl)-ω-hydroxy fatty acids, had relatively longer chain lengths in tree shrew meibum. These increases in length may promote more effective reduction of tear evaporation in the tree shrew, which likely underlies the much longer blinking interval of this mammal. Our results suggest that the tree shrew could be an effective model for the study of dry eye. [ABSTRACT FROM AUTHOR]

Glycolipids (trehalose-6,6'-dimycolates) found associated with the cell walls of mycobacteria as very complex mixtures. Cord factors are very strong signalling agents in the immune system. Synthetic analogues should be useful for diagnosis and treatment of TB, asthma, allergies and other immune system diseases. Trehalose dimycolate (TDM) is a molecule produced by Mycobacterium tuberculosis (Mb) and other mycobacteria. Trehalose monomycolate (TMM) is precursor of TDM, and is involved in providing mycolic acid to the cell wall arabinogalactan in order to form m-AGP complex. In this report, have been describe the synthesis ofregioselective monoacylation, by the protection of the α,α'-D-trehalose in the position of 4,6, 4',6' Di-O-benzylidene and 4',6'-O-benzylidene by changing the equivalents and then are coupled different fatty acids with protected trehalose to get tetraesters and diester. The final step was deprotection trehalose in order to get the final results, have got synthesis six tetraesters and three diester of α,α'-Dtrehalose. The synthesis of these compounds sets the stage for future biochemical studies to identify mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

The use of natural resources as a chemical feedstock for the synthesis of added-value products is gaining interest; as such we report an environmentally friendly method for the synthesis of para-menthane-3,8-diol from natural citronellal oil in 96% yield, under solvent free aqueous conditions. The acylation of para-menthane-3,8-diol with various acid anhydrides over polymer-supported scandium triflate (PS-Sc(OTf)3) catalyst was subsequently developed, where both hydroxy groups of para-menthane-3,8-diol could be simultaneous acylated under mild reaction conditions to form the corresponding diesters in good yields. The advantages of this method include a simple procedure from natural resources, using solvent-free reaction conditions.

Esters present several advantages when compared to traditional materials used for thermal energy storage, amongst which are better sustainability and greater chemical stability. However, at present, their thermal properties remain mostly unknown or not well documented. In this study, 12 diesters from four dicarboxylic acids (oxalic, succinic, suberic, sebacic) and three alcohols (methanol, 1-pentanol, 1-decanol) have been assessed as bio-based phase change materials for thermal energy storage. All diesters have been synthesized via Fischer esterification to high purities, and their chemical structures, as well as thermal properties, have been fully characterized. The diesters investigated show phase change transitions in a low−mid temperature range between −32 and 46 °C with maximum enthalpies of 172 J/g and show higher degrees of supercooling compared to fatty monoesters. Similarly to other esters classes, some trends correlating the chemical structures to the thermal properties were identified, which would allow for the development of property prediction tools.

Abstract: The pincer‐like double ester naphthalene‐2,3‐diyl‐bis(4‐fluorobenzoate) (2) is pentamorphic. Upon heating crystals of form I to below their melting point (441–443 K), they undergo a phase transition accompanied by a thermosalient effect, that is, rare and visually striking motility whereby the crystals jump or disintegrate. The phase transition and the thermosalient effect are reversible. Analysis of the crystal structure revealed that form I is a class II thermosalient solid. Crystals of form III also underwent a reversible phase transition in the temperature range of 160 to 170 K; however, they were not thermosalient. Comparison of the structures and the mechanical responses of the two polymorphs revealed that the thermosalient effect of form I was due to reversible closing and opening of the arms of the diester molecules in a tweezer‐like action. [ABSTRACT FROM AUTHOR]

In the present study, a new extraction method based on acid digestion and SPE clean-up (Oasis Wax) was developed for measuring four PFR metabolites (i.e. dibutyl phosphate (DBP), diphenyl phosphate (DPhP), bis(1,3-dichloro-2-propyl)phosphate (BDCPP) and bis(2-butoxy ethyl) phosphate (BBEP)) in hair and nails. The method optimization was done according to a combinatorial design (Taguchi) where several parameters were efficiently optimized. Precision was lower for hair than for nails (RSD % 18 and 28%). Recoveries were >74%. High DBP levels in procedural blanks were traced back to the use of SPE cartridges. Therefore a new SPE pre-treatment was tested, reducing significantly DBP levels (<1 ng). Levels of the PFR metabolites were measured in scalp hair, finger, and toe nails collected over two months in two volunteers (female and male). DPhP levels were extremely high (in μg/g range) in both finger and toe nails in the female. BDCPP and BBEP were the minor metabolites detected in nails (average levels of 28–64 ng/g and <2.2–4.1 ng/g, respectively). DPhP was the only metabolite detected in hair (0.23–0.25 ng/g). Results showed that there is a possible contribution from both an external (via deposition) and an internal exposure, however it was not possible to fully understand their extent. Since there were no records of lifestyle and due to the small sample size, the major exposure source could not be addressed here. Nevertheless, there is evidence that hair and nails (finger and toe) might be good indicators of human exposure to PFRs, especially to TPhP. [ABSTRACT FROM AUTHOR]

Purpose: Organic phosphorus (P) can play a role in in-stream productivity (e.g., periphyton or macrophyte growth), but little is known of the largest likely source of organic P-bed sediment. A survey was conducted of 76 bed sediment samples of rivers within the New Zealand National River Water Quality Network in an effort to determine the concentration and form of organic P species, and variation according to catchment and sediment characteristics or classifications used to characterise anthropogenic P inputs (e.g., as baseline [viz. reference] or impact sites) and therefore likely in-stream productivity. Materials and methods: Sediments were analysed for a range of physiochemical properties. NaOH-EDTA extracts were analysed by P nuclear magnetic resonance spectroscopy (P NMR), which isolated orthophosphate from other P species including orthophosphate monoesters, orthophosphate diesters and pyrophosphate. Results and discussion: More P was extracted from sediments at impact compared to baseline sites, while the proportion of organic P increased where microbial processing (as reflected by site elevation) decreased. Analysis by P NMR of sediments showed they contained fewer and less-enriched forms of organic P than profiles of typical lake sediments or soils (e.g., no phosphonates or polyphosphates). This was hypothesised to reflect either low P inputs via catchment runoff, or efficient utilisation due to strong P limitation. Conclusions: Some evidence was found of changes in the distribution and form of organic P species in relation to anthropogenic activity and sediment processes. However, organic P concentrations were small and only represented a single sampling. Hence, additional work needs to examine if these changes relate to changes in in-stream productivity over time. [ABSTRACT FROM AUTHOR]

Solution phosphorus (P) nuclear magnetic resonance (NMR) spectroscopy following extraction with sodium hydroxide–ethylenediaminetetraacetic acid (NaOH–EDTA) is the most powerful and widely used technique for characterising soil organic P. However, poor spectral sensitivity (related to the signal to noise ratio) can limit its applicability for soils of low organic P content, especially in subsurface layers. Sensitivity can potentially be improved by employing a much narrower (1:4) soil to solution ratio than usual (1:10 or 1:20), which increases the density of P in the NMR tube. Pasture soils were collected at two depths (0–4 cm and 4–10 cm) from across the high rainfall zone of eastern Australia, and were extracted with NaOH–EDTA at a 1:4 and 1:10 extraction ratio. The extracts were analysed for molybdate-reactive P (i.e. an estimate of inorganic P), and total extractable concentrations of aluminium (Al), iron (Fe), magnesium (Mg), manganese (Mn) and P using inductively coupled plasma optical emission spectroscopy (ICP-OES). Total concentrations of P in soil were determined by laboratory X-ray fluorescence. Extraction efficiency of total soil P was on average only slightly lower for the 1:4 extracts (41%) than for the 1:10 extracts (47%). Extraction efficiencies for paramagnetic (Fe, Mn) and non-paramagnetic (Al, Mg) metals were also similar at the two extraction ratios. Solution 31 P NMR spectra of 1:4 extracts were considerably better in terms of spectral sensitivity than those of the 1:10 extracts, particularly for soils of low organic P content. This study demonstrates that in soils of low organic P content, NaOH–EDTA extraction using a 1:4 soil to solution ratio is a viable alternative to the more commonly used 1:10 soil to solution ratio. [ABSTRACT FROM AUTHOR]

Scalable lipase-catalytic method for the kinetic resolution of long-chain 1,2-alkanediol enantiomers via stereoselective cleavage of esters was developed. The influence of lipase, reaction medium, nucleophile, temperature and the structure of the acyl group on the reaction velocity, the stereopreference and the stereoselectivity of the deacylation was studied. In addition, the rate of the spontaneous intramolecular migration of different acyl groups was determined for the intermediate 2-monoesters. The acyl group migration may diminish the apparent stereoselectivity of the two-step process if fast migrating acyl groups are used. It was found that the migration rate of different acyl groups differs by up to two orders of magnitude, being faster for acetyl and isobutyryl and much slower for butyryl and benzoyl groups. The best results were obtained by the sequential methanolysis of bis -butyryl-1,2-alkanediols in an acetonitrile/methanol mixture catalyzed by Candida antarctica lipase B (CALB) at 20 °C, affording ( S )-1,2-alkanediols. Stereo- and chemoselective crystallization of the deacylated ( S )-1,2-alkanediols from the reaction mixture complements the enzymatic process improving the stereochemical purity to up to ee > 99.8%. ( R )-1,2-Alkanediol 2-monoesters were separated from the mother liquor and enriched stereochemically by repeated incubation with CALB, then separated, hydrolyzed with alkali and crystallized to afford ( R )-alkanediols of ee > 99.8%. [ABSTRACT FROM AUTHOR]

A systematic study for esterification procedures to the synthesis of BINOL diesters is described. Reaction conditions with trifluoracetic acid anhydride (TFAA) and 85% H3PO4 were selected as the best procedure to prepare enantiomerically pure (S)-l.1'-bi-2-naphthol (BINOL) diesters VIII to XI with almost quantitative yields and very short reaction times. [ABSTRACT FROM AUTHOR]

Two series of diesters with bend-rod shapes were synthesized and their thermal properties characterized by POM and DSC. The central group conformational mobility and polarity as well as the length of the mesogenic groups were varied in order to correlate these parameters with mesophase stability. Results indicate that series II diesters are enantiotropic and that their mesophase sensitivity to central group structural changes is limited.

Abstract: Diester prodrugs of apomorphine, diacetyl apomorphine (DAA), and diisobutyryl apomorphine (DIA) were synthesized, and their partition coefficients, capacity factor (log K′), enzymatic hydrolysis, and in vitro permeation across nude mouse skin were characterized. The lipophilicity of the diesters was between that of apomorphine HCl and the apomorphine base. The prodrugs were chemically stable, but enzymatically unstable in esterase medium, skin homogenate, and human plasma. DAA showed a faster hydrolysis in plasma compared to DIA. Total fluxes (nmol/cm2/h) of the parent drug and prodrug were significantly greater after topical treatment with the diesters in aqueous solutions (water, 30% polyethylene glycol in water, and 30% glycerol in water) compared to treatment with HCl and base forms of apomorphine. DIA flux from deionized water was 51nmol/cm2/h, which exceeded the flux of apomorphine HCl by 10-fold. The extent of parent drug regeneration after topical application ranged 51–88% and 34–61% for DAA and DIA, respectively, depending on the vehicles selected. Permeation measurements using intact and stratum corneum-stripped skins demonstrated that the viable epidermis/dermis was an important barrier to prodrug permeation. Nano-sized lipid emulsions were also used as carriers for apomorphine and its prodrugs. Diester prodrugs exhibited superior skin permeation compared to the parent drug when formulated into the emulsions. DAA and DIA fluxes from lipid emulsions were 11- and 3-fold higher than that of apomorphine HCl. The results in the present work suggest the feasibility of diester prodrugs for the transdermal delivery of apomorphine. [Copyright &y& Elsevier]

Abstract: l-Amino acyl (1–4) esters of carbohydrates (5–15) were synthesized through Candida rugosa lipase catalysis in non-polar solvent with yields in the range of 7–79%. In a reaction, involving unprotected and unactivated l-amino acids and carbohydrates, both monoesters (1-O-, 2-O-, 3-O-, 4-O-, 5-O-, 6-O- and 6′-O-) and diesters (1,6-di-O-, 2,5-di-O-, 2,6-di-O-, 3,6-di-O-, 4,6-di-O- and 6,6′-di-O-) were found to be formed in different proportions depending on the l-amino acids and carbohydrates employed. Among 80 individual esters synthesized by this procedure, 67 are being reported for the first time. [Copyright &y& Elsevier]

Abstract: Synthesis of l-alanyl esters of carbohydrates like aldohexoses (d-glucose, d-galactose and d-mannose), ketohexose (d-fructose), pentoses (d-arabinose and d-ribose) and disaccharides (lactose, maltose and sucrose) were carried out using Rhizomucor miehei lipase (RML) in organic solvents with conversion yields in the range 8–56%. Enzymatic esterification between l-alanine and d-glucose using RML and porcine pancreas lipase (PPL) was investigated in terms of incubation period, enzyme concentration, substrate concentration, buffer salts (pH and concentration) and enzyme reusability. RML has shown a maximum conversion yield of 28% (1.12–0.88mmol monoesters and 0.24mmol diesters) at 1mmol d-glucose and 4mmol l-alanine in presence of 30% RML (w/w, d-glucose) and 0.1mM (0.1ml) pH 4.0 acetate buffer in 72h. PPL showed a maximum yield of 18% (0.36–0.28mmol monoesters and 0.08mmol diesters) at 1mmol d-glucose and 2mmol l-alanine in presence of 40% lipase (w/w, d-glucose) and 0.1mM (0.1ml) pH 5.0 acetate buffer in 72h. In presence of buffer salts, RML showed 22% higher ester yield than in its absence under the same experimental conditions. However, buffer salts did not enhance esterification with PPL. Two-dimensional HSQCT NMR confirmed formation of 1-O-, 2-O-, 3-O-, 4-O-, 5-O-, 6-O- and 6′-O-monoesters and 1,6-di-O-, 2,5-di-O-, 2,6-di-O-, 3,5-di-O-, 3,6-di-O-, 4,6-di-O and 6,6′-di-O-diesters to varying extents depending on the carbohydrate employed. [Copyright &y& Elsevier]

Abstract: The distribution and form of P in soil is central to the sustainability of agricultural practice. This study used sequential fractionation and 31P nuclear magnetic resonance spectroscopy (31P NMR) of NaOH–EDTA extracts to examine the influence of pastoral, native (undisturbed) and forest land use on soil P forms in 5 contrasting soils ranging from a Regosol to a Rendzina in Otago, New Zealand. Climatic factors likely to influence soil P distribution were negated by careful site selection. Together with a decrease in soil organic C (31%), total P decreased in forested soils (mean=674 mg kg−1) compared to native soils (mean=784 mg kg−1). In contrast, the ratio of inorganic to organic P increased (10%) probably due to mineralization of organic P in forest soils, while for pasture soils, accumulation of P in inorganic forms due to P inputs via fertilisers and animal dung was to blame. Investigation of the organic P forms in NaOH–EDTA extracts of each land use by 31P NMR indicated that diesters were greatest in the native soil (4–12% of total P in spectra), and declined as a proportion of total P in pasture soils and more so in forest soils. This was reflected in a decline of the diester to monoester ratio. However, the ratio was generally greater in forest than pasture soils and attributed to the labile nature of diesters, mineralization of monoesters in forest soils, and an increase in monoesters in pasture soils from inositol phosphates in plant debris. This effect was pronounced in the Regosol due to sandy texture and the preferential accumulation of plant debris in coarse particle size fractions. Due to the depletion of soil P reserves, forest soils in the area should be followed by pasture and well managed fertiliser additions before replanting. [Copyright &y& Elsevier]

Phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy has become popular for the characterization of P species in environmental samples. However, these are commonly made alkaline (pH&ThickSpace;>&ThickSpace;13) to facilitate sample comparison and ease peak identification, but this may cause hydrolysis of some compounds. This study examined the chemical shift of known P compounds and supplemented this with published data to determine the viability of examining samples at their native pH, thereby minimizing sample disturbance. A 31 P NMR pH titration of known P compounds resulted in chemical shifts ranging from about -22 to 8 ppm in the pH range 5–13. Categorization and calculation of chemical shifts for over 100 naturally occurring compounds indicated that good distinction between orthophosphate diesters, orthophosphate monoesters, nucleotides, phosphonates, and phosphagens was best at ≥pH 7, but unlikely below this pH. Analysis of several water extracts of soil and dung, overland flow samples, and lake water indicated a wide variety of well-defined peaks that were assigned to orthophosphate, orthophosphate monoesters, orthophosphate diesters, pyrophosphate, polyphosphate, or phosphonates. Changing the sample pH to >13 caused many species (such as phosphonates, orthophosphate diesters, and polyphosphates) to decrease either by hydrolysis or precipitation. Hence, it is recommended that samples be analysed at their native pH but, if poorly resolved, should have their pH raised to ≥7. [ABSTRACT FROM AUTHOR]

Knowledge of organic phosphorus (P) species quantity and distribution in sediments and soils is needed to determine the potential for aquatic and terrestrial organism growth. This can be achieved with 31 P nuclear magnetic resonance spectroscopy (NMR), but resolving peaks within spectra can be problematic because of broadening via paramagnetics, which can cause peaks to overlap. We compared 31 P NMR spectra of NaOH-EDTA extracts of three sediments and three soils to those that had first been pre-treated with Ca-EDTA-dithionite to remove Fe and Mn, paramagnetics that cause broadening of peaks, but leave organic P alone. Broadening of peaks in Ca-EDTA-dithionite pre-treated samples decreased by 46% and revealed peaks that were hidden compared to untreated samples. The spectrum of one pre-treated soil was similar if not better than the same soil that had received pre-treatment with Chelex resin (also to remove paramagnetics). Therefore, pre-treatment with Ca-EDTA-dithionite is recommended as a simple and cost-effective method for improving organic P idenTIFication and determination in subsequent NaOH-EDTA extracts of sediments and soils rich in Fe and Mn. [ABSTRACT FROM AUTHOR]

The complete spectroscopic data and other physical constants of two naturally occuring, diastereomeric, optically active γ-lactones derived from inexpensive 2-hydroxycitric acids, namely garcinia acid [(2S,3S)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid] and hibiscus acid [(2S,3R)-tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid] and related derivatives have been described for the first time. [Copyright &y& Elsevier]

Prevention of acute kidney injury caused by drugs is still a clinical problem to be solved urgently. Astaxanthin (AST) and docosahexaenoic acid (DHA) are important marine-derived active ingredients, and they are reported to exhibit renal protective activity. It is noteworthy that the existing forms of AST in nature are mainly fatty acid-acylated AST monoesters and diesters, as well as unesterified AST, in which DHA is an esterified fatty acid. However, no reports focus on the different bioactivities of unesterified AST, monoesters and diesters, as well as the recombination of DHA and unesterified AST on nephrotoxicity. In the present study, vancomycin-treated mice were used to evaluate the effects of DHA-acylated AST monoesters, DHA-acylated AST diesters, unesterified AST, and the recombination of AST and DHA in alleviating nephrotoxicity by determining serum biochemical index, histopathological changes, and the enzyme activity related to oxidative stress. Results found that the intervention of DHA-acylated AST diesters significantly ameliorated kidney dysfunction by decreasing the levels of urea nitrogen and creatinine, alleviating pathological damage and oxidative stress compared to AST monoester, unesterified AST, and the recombination of AST and DHA. Further studies revealed that dietary DHA-acylated AST esters could inhibit the activation of the caspase cascade and MAPKs signaling pathway, and reduce the levels of pro-inflammatory cytokines. These findings indicated that the administration of DHA-acylated AST esters could alleviate vancomycin-induced nephrotoxicity, which represented a potentially novel candidate or therapeutic adjuvant for alleviating acute kidney injury. [ABSTRACT FROM AUTHOR]

Diesters such as succinylcholine chloride (SCC) and dioctylsulfosuccinate (DOSS) can be converted to hydroxamic acids which are found to react with Fe3+ in methanol to form a purple chelate complex having an useful absorption band at 520 nm with a molar absorptivity of about 171 L/mole*cm, and a detection limit of 1.5 × 10−4 M. To adapt this method for flow injection, a methanol-water solvent and acidification of the sample were required to reduce the large blank peak. The reproducibility of the flow injection method was a factor of two better than standard spectrophotometry but the detection limit of the former method was two times higher. This colorimetric method can permit analysis of pharmaceutical products containing either SCC or DOSS. Phosphatidylcholine (lecithin) can also be determined using this method. [ABSTRACT FROM AUTHOR]

Phosphorus (P) can leach from topsoil in inorganic and organic forms. While some evidence has shown inorganic P (orthophosphate) can leach to depth in some soils, less is known of dissolved organic P (DOP). This is not helped by a paucity DOP data for groundwater. We hypothesized that DOP species would leach in greater amounts to depth and at a faster rate through aquifer gravels than orthophosphate. We applied superphosphate with or without dung to a low P-sorption soil under pasture and irrigation. Between 0.7 (control) and 2.4 (dung +superphosphate) kg P ha−1 was leached through 30 cm with a mean ratio of DRP to DOP of 1.5. At 50 cm, 0.7 and 1.3 kg P ha−1 was leached with the DRP to DOP ratio decreasing to 1.1 due to greater DOP leaching (or DRP sorption). There was little difference in DRP losses measured at 50 and 150 cm depth. All DOP compounds except the monoester – inositol hexakisphosphate were leached at a faster rate than orthophosphate through aquifer gravels. These data suggest that where low P-sorption soils overlay similarly low P-sorption aquifers, DOP may reach groundwater at a faster rate than orthophosphate. Furthermore, as many DOP species are bioavailable to periphyton, our data suggest that DOP should be included in the assessment of the risk of P contamination of groundwater where connection to baseflow could be a long-term stimulant of periphyton growth. Unlabelled Image • Very few data are available on the leaching of dissolved organic phosphorus (DOP) from soil. • Losses of DOP increased relative to dissolved reactive P (DRP) with depth. • The load of P leached past 50 and 150 cm were similar. • Most DOP species were leached at a faster rate than orthophosphate through aquifer gravels. • DOP should be included as part of groundwater monitoring programmes. [ABSTRACT FROM AUTHOR]

• Subcellular distribution determines translocation capacity of OPEs in wheat. • In vivo hydrolysis of OPEs in wheat mainly occurs in the cell wall. • The contribution of root uptake to DnBP concentration in wheat cannot be ignored. • The aquaporins and anion channels are involved in the root uptake of OPEs. To reveal the metabolic characteristic of organophosphate esters (OPEs) in plants, uptake efficiency, subcellular distribution and hydrolysis of OPEs and their hydrolysis metabolites in wheat (Triticum aestivum L.) were investigated by hydroponic experiments. Tris(2-chloroethyl) phosphate (TCEP) and bis(2-chloroethyl) phosphate (BCEP) were prone to transporting to shoots by transpiration stream, with the translocation factors of 6.2 and 21 for TCEP and BCEP, respectively, as greater than 40% of TCEP and BECP were distributed in the cell sap due to their hydrophilicity. Hydrophobic OPEs (i.e. tri- n -butyl phosphate [TnBP] and triphenyl phosphate [TPhP]), and their hydrolysis metabolites (di- n -butyl phosphate [DnBP] and diphenyl phosphate [DPhP]) were stored in roots, resulting in low translocation capacity in wheat. As organophosphate diesters with relatively high proportions in cell walls (70–84% of DnBP and 41–43% of DPhP) are difficult to being transmembrane transported due to electrical repulsion of the cytomembrane, it is supposed that cell walls could be a main location for in vivo hydrolysis of OPEs. For DnBP, absorption by roots after in vitro hydrolysis of TnBP in hydroponic media was also an important source in wheat. Inhibition experiments showed that it is usually a non-energy-consuming process for root uptake of OPEs and their hydrolysis metabolites. The uptake of OPEs (i.e. TCEP, TnBP, and TPhP) and DPhP were facilitated diffusion mediated by aquaporins or anion channels, while uptake of BCEP and DnBP were simple diffusion processes. This study illustrated the distribution characteristics and translocation capacity of OPEs and their diester metabolites at the subcellular level. [ABSTRACT FROM AUTHOR]

The precorneal tear film keeps the eye surface moist and helps to maintain normal eye function. The outermost lipid layer of the tear film, which attenuates tear film evaporation, contains meibum secreted from the meibomian gland. Most meibum lipids are neutral, including wax esters (WEs), cholesteryl esters (CEs), and diesters (DEs), along with some polar lipids including free fatty acids (FFAs), O-acyl-ω-hydroxy fatty acids (OAHFAs), and trace phospholipids. Detection of neutral lipids by mass spectrometry (MS) is challenging due to interference from impurities, particularly when working with minute-volume meibum samples. Here, we describe procedures for sample preparation and MS analysis of these elusive meibum lipids that can be used to examine dry eye disease mechanisms. Because the method described here minimizes impurity peaks for lipids generally, neutral and otherwise, it may be applied to high-sensitivity analysis of other biological samples.