Chemical Interconversion Research Articles

Ferric chloride assisted QuEChERS method for separate detection of bifenazate and bifenazate-diazene in citrus fruits and its field validation.

Bifenazate is widely recognized as an effective acaricide for citrus production in various regions. Detecting both the parent compound of bifenazate and its metabolite, bifenazate-diazene, simultaneously can be challenging owing to their tendency to undergo chemical interconversion. Current methods developed for detecting bifenazate or bifenazate-diazene residues often involve lengthy incubation periods and may not effectively separate the two compounds. In this study, we developed a convenient and fast method based on a modified QuEChERS method assisted by oxidants to concurrently detect bifenazate and bifenazate-diazene. Based on preliminary analysis, it appears that ferric chloride has the ability to react with a reducing substance present in citrus, which may prevent the reduction of bifenazate-diazene. The method was validated and applied in a field trial. This work reports a novel strategy to establish a balanced 'neutral' condition to create a potential method for efficient determination of bifenazate acaricide residues in fruit matrices.

Evidence of Enzymatic and Chemical Interconversions of Barley Malt 3-Sulfanylhexanol Conjugates during Mashing.

Recent studies have highlighted in malt the occurrence of the glutathionylated precursor of 3-sulfanylhexanol (G-3SHol) at concentrations reaching hundreds of μg/kg. Here, SIDA-LC-MS/MS was used to investigate the potential conversion of G-3SHol to its dipeptide and cysteinyl analogues during mashing. At 45 and 55 °C, malt γGT and carboxypeptidase activities quickly degrade G-3SHol (up to 90% loss), first to the cysteinylglycine conjugate and then to the cysteine conjugate (up to 205% increase). No γ-glutamylcysteine S-conjugate formation is observed. At 80 °C, despite enzyme inactivation, the G-3SHol level decreases steadily because of suspected imine formation with wort aldehydes at pH 5.5. More surprisingly, CysGly-3SHol is still generated at 80 °C. This indicates the presence in the wort of as yet unidentified precursors.

Chemical Zymogens: Specificity and Steroidal Control of Reactivation.

Activating and masking enzymatic activity on demand is of the highest importance in nature. It is achieved by chemical interconversion of enzymes and the corresponding zymogens through, for example, proteolytic processing or reversible phosphorylation, and affords on-demand activation of enzymes, controlled in space and/or time. In stark contrast, examples of chemical zymogens are very few, and in most cases these are based on disulfide chemistry, which is largely indiscriminate as to the nature of the activating thiol. In this work, we address an outstanding challenge of specificity of reactivation of chemical zymogens. We achieve this through engineering affinity between the chemical zymogen and the activator. Additional, higher-level control over zymogen reactivation is installed in a nature-mimicking approach using steroidal hormones. Taken together, the results of this study take a step towards establishing the specificity of reactivation of synthetic, chemical zymogens. We anticipate that the results of this study will contribute significantly to the development of chemical zymogens as tools for diverse use in chemical biology and biotechnology.

Glyclauxins A-E: Dimeric Oxaphenalenone Aminoglycosides from an Australian Wasp Nest-Derived Fungus Talaromyces sp. CMB-MW102.

Chemical analysis of cultures of a Queensland mud dauber wasp nest-derived fungus, Talaromyces sp. CMB-MW102, yielded the known dimeric oxaphenalenone duclauxin (1) along with a family of new 1-deoxy-d-glucosamine adducts, glyclauxins A-E (2-6). Despite 1D NMR spectra of 2-6 being compromised by broadening of selected resonances, structures inclusive of absolute configuration were assigned on the basis of detailed spectroscopic analysis and biogenetic considerations, as well as biomimetic semisynthesis and chemical interconversion. For example, exposure of duclauxin (1) to synthetic 1-deoxy-d-glucosamine yielded glyclauxin B (3), while on handling and storage, glyclauxins C (4) and D (5) (bearing a 7-OMe moiety) proved chemically labile and underwent quantitative transformation to glyclauxins B (3) and A (2), respectively. These latter observations on chemical reactivity and stability informed a proposed biogenetic relationship linking all known members of the extended duclauxin family. Notwithstanding their potential status as artifacts, the detection of glyclauxins B (3) and A (2) in a fresh CMB-MW102 culture extract confirmed their natural product status.

Discretized hexagonal boron nitride quantum emitters and their chemical interconversion

Quantum emitters in two-dimensional hexagonal boron nitride (hBN) are of significant interest because of their unique photophysical properties, such as single-photon emission at room temperature, and promising applications in quantum computing and communications. The photoemission from hBN defects covers a wide range of emission energies but identifying and modulating the properties of specific emitters remain challenging due to uncontrolled formation of hBN defects. In this study, more than 2000 spectra are collected consisting of single, isolated zero-phonon lines (ZPLs) between 1.59 and 2.25 eV from diverse sample types. Most of ZPLs are organized into seven discretized emission energies. All emitters exhibit a range of lifetimes from 1 to 6 ns, and phonon sidebands offset by the dominant lattice phonon in hBN near 1370 cm−1. Two chemical processing schemes are developed based on water and boric acid etching that generate or preferentially interconvert specific emitters, respectively. The identification and chemical interconversion of these discretized emitters should significantly advance the understanding of solid-state chemistry and photophysics of hBN quantum emission.

Cytochalasins from coastal saline soil-derived fungus Aspergillus flavipes RD-13 and their cytotoxicities.

Chemical investigation of coastal saline soil-derived fungus Aspergillus flavipes RD-13 led to the isolation of two new seco-cytochalasins (1) and (2) along with nine known analogs. Their structures were elucidated by comprehensive spectral analysis, and the absolute configurations of these two new ones were determined through Rh2(OCOCF3)4-induced CD experiment and chemical interconversions. Moreover, the absolute configuration of a known compound named cytochalasins Z18 (3) was also determined for the first time. Structurally, compounds 1, 2 and 3 were the open ring derivatives of compounds 5, 8, and 4, respectively. All compounds were evaluated for their cytotoxic activities on A549, H1299 and H520 cells and 4 exhibited the strongest inhibitory activities towards the above cell lines with IC50 values of 0.15, 0.23 and 0.43 μg/mL, respectively. Preliminary structure-activity relationship analysis suggested the importance of macrocyclic ring in cytochalasins to confer cytotoxicity.

Targeted Isolation of Two New Anti-inflammatory and UV-A Protective Dipyrroloquinones from the Sponge-associated Fungus Aspergillus tamarii MCCF102.

In following up on observed in vitro anti-inflammatory activity of the organic extract of the marine sponge-derived fungus Aspergillus tamarii MCCF102, two new dipyrrolobenzoquinones, terreusinone B and C (1: and 2: ), were discovered along with the known analogue, terreusinone (3: ). The structures of 1: -3: were determined by spectroscopic and spectrometric analyses, along with chemical inter-conversion. In vitro testing on lipopolysaccharide (LPS) stimulated RAW 264.7 murine macrophage cells revealed that 1: -3: exhibit anti-inflammatory activity by inhibiting nitric oxide production in a dose-dependent manner (IC50 < 1 µM) without any cytotoxicity observed at the same concentrations. Due to this and the UV-A absorptive properties imparted by the highly conjugated structures of these molecules, the potential for using 1: -3: or related analogues as natural sunscreen components is suggested. Gene sequencing and informatics biosynthetic gene cluster comparisons were insufficient to confidently elucidate the biosynthetic origins of these compounds, possibly suggesting the occurrence of a gene cluster not detected in the initial sequencing or a non-canonical pathway that should be further investigated.

Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14.

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B–D (2–4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1–7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.

Polycyclic C-deoxyaminoglycoside-polyketides from an Australian Pasture Plant Derived Streptomyces sp.

The Australian plant pasture-derived Streptomyces sp. CMB-PB042 yielded the unprecedented polycyclic C-aminoglycoside-pyranonaphthoquinone polyketides glenthamine A (1) and glenthimine A (2), the latter being a rare example of a naturally occurring imine, along with the spiropolyketide glenthol A (3), its hydrolysis artifact glenthol B (4), and the highly rearranged C-aminoglycoside-pyranonaphthoquinone glenthamide A (5). Structures including absolute configurations of 1-5 were assigned by spectroscopic analysis, chemical interconversion, and biosynthetic considerations.

Cytotoxic Physalins from Aeroponically Grown Physalis acutifolia.

Aeroponically grown Physalis acutifolia afforded five new and six known withanolides including 10 physalins. The structures of the new withanolides, acutifolactone (1), 5β,6β-epoxyphysalin C (2), 5α-chloro-6β-hydroxyphysalin C (3), and an inseparable mixture of 5β,6β-epoxy-2,3-dihydrophysalin F-3β-O-sulfate (4) and 5β,6β-epoxy-2,3-dihydrophysalin C-3β-O-sulfate (5), were elucidated by analysis of their spectroscopic data and chemical interconversions. The known withanolides were identified as physalins B (6), D (7), F (8), H (9), I (10), and U (11) by comparison of their spectroscopic data with those reported. Evaluation of 1-11 and the derivatives, 13 and 13a, obtained from 4 and 5 against a panel of four human cancer cell lines [NCI-H460 (non-small-cell lung), SF-268 (CNS glioma), PC-3 (prostate adenocarcinoma), and MCF-7 (breast adenocarcinoma)] and normal human lung fibroblast (WI-38) cells revealed that physalins 2, 3, 8, and 9 exhibited selective cytotoxic activity to at least one of the cancer cell lines tested compared to the normal cells and that 7, 10, and 11 were inactive up to a concentration of 10.0 μM. These data provided some preliminary structure-activity relationships and suggested that the mechanism of cytotoxic activity of physalins may differ from other classes of withanolides.

Amaurones A-K: Polyketides from the Fish Gut-Derived Fungus Amauroascus sp. CMB-F713.

Using a molecular networking guided strategy, chemical analysis of the Australian mullet fish gastrointestinal tract-derived fungus Amauroascus sp. CMB-F713 yielded a family of polyketide pyrones, amaurones A-I (1-9), featuring an unprecedented carbon skeleton. Structures were assigned to 1-9 by detailed spectroscopic analysis (including X-ray analysis of 1), biosynthetic considerations, and chemical interconversions. For example, the orthoacetate 5 was unstable when stored dry at room temperature, transforming to the monoacetates 2 and 3, while mild heating (40 °C) prompted quantitative conversion of 3 to 2, via an intramolecular trans-acetylation. Likewise, during handling, the monoacetate 1 was prone to intramolecular trans-acetylation, leading to an equilibrium mixture with the isomeric monoacetate amaurone J (10), confirmed when partial hydrolysis of the diacetate 2 yielded the monoacetates 1 and 10 and the triol amaurone K (11).

Fungal Epithiodiketopiperazines Carrying α,β-Polysulfide Bridges from Penicillium steckii YE, and Their Chemical Interconversion.

Some fungal epithiodiketopiperazine alkaloids display α,β-polysulfide bridges alongside diverse structural variations. However, the logic of their chemical diversity has rarely been explored. Here, we report the identification of three new (2, 3, 8) and five known (1, 4-7) epithiodiketopiperazines of this subtype from a marine-derived Penicillium sp. The structure elucidation was supported by multiple spectroscopic analyses. Importantly, we observed multiple nonenzymatic interconversions of these analogues in aqueous solutions and organic solvents. Furthermore, the same biosynthetic origin of these compounds was supported by one mined gene cluster. The dominant analogue (1) demonstrated selective cytotoxicity to androgen-sensitive prostate cancer cells and HIF-depleted colorectal cells and mild antiaging activities, linking the bioactivity to oxidative stress. These results provide crucial insight into the formation of fungal epithiodiketopiperazines through chemical interconversions.

P1120QUANTIFICATION OF ACID-BASE TRANSPORT IN HEMODIALYZERS

Abstract Background and Aims Quantification of bicarbonate and dissolved carbon dioxide (CO2) transport in hemodialyzers can be described by the product of a dialysance (D) and their respective concentration differences between dialysate and plasma. It is typically assumed that D values are constant for a given hemodialyzer and flow conditions; however, this approach neglects the chemical interconversion of bicarbonate and dissolved CO2 within blood. We assessed the validity of this approach by developing a comprehensive mathematical model of acid-base transport in hemodialyzers. Method Mass balance relationships in a hemodialyzer were defined using a one-dimensional model with counter-current flows of blood and dialysate. The molecular biochemistry of bicarbonate, dissolved CO2, and non-bicarbonate buffer in both plasma and erythrocytes, together with carbaminohemoglobins within erythrocytes, was assumed to be in equilibrium as described by Rees and Andreassen (Crit Rev Biomed Eng 2005). The model equations were solved numerically, and optimal mass transfer-area coefficients for bicarbonate and dissolved CO2 were determined by comparing model predictions with the data from Sombolos et al (Artif Organs 2005). The latter data included measured concentrations of bicarbonate and dissolved CO2 in plasma and dialysate inlet and outlet flows at a blood flow rate of 300 mL/min, dialysate flow rate of 700 mL/min, and dialysate bicarbonate concentration of 32.5 mEq/L. Base excess of blood was assumed as -5 mEq/L. Model simulations then evaluated the effect of the plasma bicarbonate concentration at the blood inlet (assuming constant mass transfer-area coefficients and flow rates) on D for both bicarbonate (Dbic) and dissolved CO2 (DCO2). D values were calculated as the loss of the molecule from the dialysate divided by the difference in inlet concentrations of dialysate and plasma. Results Optimal mass transfer-area coefficients for bicarbonate and dissolved CO2 were 396 and 1360 mL/min, respectively. Simulation results at different plasma bicarbonate concentrations at the blood inlet ([Bicarbonate]) as expected during a typical hemodialysis treatment are tabulated: Conclusion Quantification of acid-base transport in hemodialyzers requires dialysance values for bicarbonate and dissolved CO2 that are not constant but instead are dependent on the plasma bicarbonate concentration at the blood inlet for a given hemodialyzer at fixed blood and dialysate flow rates.

ARTHROBACTER AS BIOFACTORY OF THERAPEUTIC ENZYMES

Therapeutic enzymes are proteins which can be used to treat rare and deadly diseases. They represent a small but profitable market. Therapeutic enzymes are superior to non-enzymatic drugs owing to their high specificity toward the target and also their ability to multiple substrate conversion. They are essential for speeding up all the metabolic processes and many a life-supporting chemical inter-conversions. Actinomycetes including Arthrobacter form an enormous reservoir of secondary metabolites and enzymes. The characterization of L-asparaginase, β-glucosidase, urate oxidase, methionine γ-lyase, acetyl cholinesterase, and arginase activities from actinomycetes Arthrobacter clearly demonstrate the potential of Arthrobacter as potent producer of therapeutic enzymes. These metabolic enzymes can be used either separately or in combination with other therapies for the treatment of several diseases such as leukemia, gout, asthma, and neurological disorders. The objective of this review is to compile the information on the application of therapeutic enzymes produced by Arthrobacter and their future prospects as drugs.

Observable Signatures of Wind-driven Chemistry with a Fully Consistent Three-dimensional Radiative Hydrodynamics Model of HD 209458b

Abstract We present a study of the effect of wind-driven advection on the chemical composition of hot-Jupiter atmospheres using a fully consistent 3D hydrodynamics, chemistry, and radiative transfer code, the Met Office Unified Model (UM). Chemical modeling of exoplanet atmospheres has primarily been restricted to 1D models that cannot account for 3D dynamical processes. In this work, we couple a chemical relaxation scheme to the UM to account for the chemical interconversion of methane and carbon monoxide. This is done consistently with the radiative transfer meaning that departures from chemical equilibrium are included in the heating rates (and emission) and hence complete the feedback between the dynamics, thermal structure, and chemical composition. In this Letter, we simulate the well studied atmosphere of HD 209458b. We find that the combined effect of horizontal and vertical advection leads to an increase in the methane abundance by several orders of magnitude, which is directly opposite to the trend found in previous works. Our results demonstrate the need to include 3D effects when considering the chemistry of hot-Jupiter atmospheres. We calculate transmission and emission spectra, as well as the emission phase curve, from our simulations. We conclude that gas-phase nonequilibrium chemistry is unlikely to explain the model–observation discrepancy in the 4.5 μm Spitzer/IRAC channel. However, we highlight other spectral regions, observable with the James Webb Space Telescope, where signatures of wind-driven chemistry are more prominant.

Influence of gaseous and particulate species on neutralization processes of polar aerosol and snow - A case study from Ny-Ålesund.

The inter-conversion of nitrogen and sulfur species between the gas and particulate phases and their interaction with alkaline species influences the acidity of the aerosols and surface snow. To better understand these processes, a short field campaign was undertaken in Ny-Ålesund, Svalbard, during 13th April 2012 to 24th April 2012. Air measurements were carried out through a particulate sampler equipped with denuders and filter packs for simultaneous collection of trace gases (HNO3, NO2, SO2 and reactive nitrogen compounds) and aerosols, with daily collection of snow samples. Ionic composition of the samples was analyzed using ion chromatography technique. The results suggested that nitrate-rich aerosols are formed when PAN (peroxy acetyl nitrate) disassociates to form NO2 and HNO3 which further hydrolyzes to form pNO3- (particulate nitrate). This resulted in a high contribution of pNO3- (62%) to the total nitrogen budget over the study area. The acidity of the aerosols and snow evaluated through cation/anion ratio (C/A) indicated alkaline conditions with C/A>2. The bicarbonates/carbonates of Mg2+ played an important role in neutralization processes of surface snow while the role of NH3 was dominant in aerosol neutralization processes. Such neutralization processes can increase the aerosol hygroscopicity causing warming. Chloride depletion in the snow was significant as compared to the aerosols, indicating two important processes, scavenging of coarse sea salt by the snow and gaseous adsorption of SO2 on the snow surface. However, a more systematic and long term study is required for a better understanding of the neutralization processes and chemical inter-conversions.

Cytochalasins from an Australian Marine Sediment-Derived Phomopsis sp. (CMB-M0042F): Acid-Mediated Intramolecular Cycloadditions Enhance Chemical Diversity.

Chemical analysis of an Australian coastal marine sediment-derived fungus, Phomopsis sp. (CMB-M0042F), yielded the known cytochalasins J (1) and H (2), together with five new analogues, cytochalasins J1-J3 (3-5) and H1 and H2 (6 and 7). Structures of 1-7 were assigned on the basis of detailed spectroscopic analysis, chemical interconversion, and biosynthetic and mechanistic considerations. Of note, 1 and 2 proved to be highly sensitive to acid-mediated transformation, with 1 affording 3-5 and 2 affording 6 and 7. Whereas 1, 2, 4, and 5 were detected as natural products in crude culture extracts, 3, 6, and 7 were designated as acid-mediated handling artifacts. We propose novel stereo- and regiospecific intramolecular cycloadditions, under tight functional group control, that facilitate selective conversion of 1 and 2 to the rare 5/6/6/7/5- and 5/6/5/8-fused heterocycles 5 and 7, respectively. Knowledge of acid sensitivity within the cytochalasin family provides a valuable cautionary lesson that has the potential to inform our analysis of past and future investigations into this structure class and inspire novel biomimetic transformations leading to new chemical diversity.

Effects on Rotational Dynamics of Azo and Hydrazodicarboxamide-Based Rotaxanes.

The synthesis of novel hydrogen-bonded [2]rotaxanes having two pyridine rings in the macrocycle and azo- and hydrazodicarboxamide-based templates decorated with four cyclohexyl groups is described. The different affinity of the binding sites for the benzylic amide macrocycle and the formation of programmed non-covalent interactions between the interlocked components have an important effect on the dynamic behavior of these compounds. Having this in mind, the chemical interconversion between the azo and hydrazo forms of the [2]rotaxane was investigated to provide a chemically-driven interlocked system enable to switch its circumrotation rate as a function of the oxidation level of the binding site. Different structural modifications were carried out to further functionalize the nitrogen of the pyridine rings, including oxidation, alkylation or protonation reactions, affording interlocked azo-derivatives whose rotation dynamics were also analyzed.

Determination of the Quantitative Composition of Mixtures of Substances and Chemical Reaction Products by Multidimensional Spectroscopy

We consider general questions arising in formulation of the problem of determining the quantitative composition of mixtures of substances and chemical reaction products as a function of time, using multidimensional spectroscopy data. We have analyzed the basic variants of the problem of quantitative standardless spectral analysis that are of practical importance, and propose algorithms for their solution. We show that the solution of the problem over the entire time interval is robust with respect to possible uncertainties in specifying the initial spectral data. The result obtained is quite satisfactory even when quantum beats are not only present but can even be observed. This allows us, based on the spectral data, to obtain a complete picture of the course of the chemical reaction and to determine the probability of chemical interconversions. The proposed algorithm allows us to construct time-dependent multidimensional surfaces of histograms showing the distribution of the concentrations found. The performance of the algorithms has been studied using computer experiments.

Intramolecular Processes and Their Applications in Prodrugs Approaches- Experimental and Computational Studies

This review supplies the reader with a detailed overview on the utilization of intramolecular processes for a design and synthesis of prodrugs. It is well known that a respected number of drugs suffer from low bioavailability, toxicity, unpleasant taste and presystemic first-pass metabolism which result in drug inactivation. The classical prodrug approach in which the linkage attaching the parent drug to its non-toxic linker and cleaved by in vivo enzyme’s catalyzed reactions has proven its success in solving toxicity and bioavailability related issues. On the other hand, prodrugs based on chemical interconversion in which the prodrug releases the corresponding active parent drug via inter or intramolecular chemical process in the absence of an enzyme is considered as a better alternative approach since the prodrug cleavage is not dependent in the efficiency or quantity of the enzyme catalyzes the interconversion of the prodrug. Examples of successful prodrugs using the chemical approach via intramolecular processes such as cyclization reactions are illustrated as well. In addition, another part of this review is devoted to cover reported studies on enzyme models and their utilization for the design and synthesis of a variety of novel prodrugs. In this approach, computational calculations using DFT and MM methods were exploited and correlations between experimentally determined and computed values of the rate-limiting step in the studied intramolecular processes were utilized in the prodrugs design. Selected examples of the designed prodrugs include aza-nucleosides for the treatment of myelodysplastic syndromes, the anti-Parkinson’s agent dopamine, the anti-viral acyclovir, the anti-malarial atovaquone, and statins for lowering cholesterol levels in the blood, the antihypertensive atenolol, the antibacterial cefuroxime, the anti-bleeding tranexamic acid, the decongestant phenylephrine, and the pain killer paracetamol.