Theoretical investigation of the alloxan–dialuric acid redox cycle

The redox cycle between alloxan, a mild oxidizing agent, and its reduction partner, dialuric acid, is investigated using density functional theory. It is found that the initial step is the one‐electron reduction of alloxan followed by protonation, yielding a stable neutral radical, AH^·. The radical can then accept another electron to form the dialuric acid anion. The formation of this anion is thermodynamically favored in both the gas phase and in solution. The radical may also undergo dimerization to alloxantin, followed by the transfer of a proton from one moiety to another, yielding alloxan and dialuric acid. This reduction is thermodynamically feasible in the gas phase, but not in aqueous solution. In the case of reduction of alloxan by glutathione at the physiological pH, computed redox potentials indicate that a two‐electron reduction is the favored course of reaction, yielding directly the dialuric acid anion, which then undergoes aerial oxidation to yield the superoxide radical. The redox cycling between alloxan and dialuric acid is responsible for the diabetogenic activity of alloxan, producing cytotoxic radicals on reoxidation of dialuric acid. © 2013 Wiley Periodicals, Inc.     

Regioselective Photocyclization Reactions of 3‐Allyloxy‐6‐chloro‐2‐(thiophen‐3‐yl)‐4H‐chromen‐4‐one: Solvent Effect

The photo‐irradiation of thienylchromenone resulted in the regioselective cyclization which is exclusively controlled by the nature of solvent used as reaction medium. Compared to nonpolar medium, polar solvent furnished a diverse array of novel angular tetracyclic photoproducts with gem‐dihydro functionality and exocyclic double bonds on the fused pyran ring, which is unprecedented to best of our knowledge.     

Polyketide Synthase-Mediated O-Methyloxime Formation in the Biosynthesis of the Oximidine Anticancer Agents

Bacterial trans-acyltransferase polyketide synthases (trans-AT PKSs) are modular megaenzymes that employ unusual catalytic domains to assemble diverse bioactive natural products. One such PKS is responsible for the biosynthesis of the oximidine anticancer agents, oxime-substituted benzolactone enamides that inhibit vacuolar H⁺-ATPases. Here, we describe the identification of the oximidine gene cluster in Pseudomonas baetica and the characterization of four novel oximidine variants, including a structurally simpler intermediate that retains potent anticancer activity. Using a combination of in vivo, in vitro and computational approaches, we experimentally elucidate the oximidine biosynthetic pathway and reveal an unprecedented mechanism for O-methyloxime formation. We show that this process involves a specialized monooxygenase and methyltransferase domain and provide insight into their activity, mechanism and specificity. Our findings expand the catalytic capabilities of trans-AT PKSs and identify potential strategies for the production of novel oximidine analogues.     

A journey through quality control

The Euroanalysis VII conference in Vienna included a two-day session: Quality Assurance in Analytical Chemistry. The contributions comprised 15 lectures devoted to: intra-laboratory quality measures, inter-laboratory control, formal aspects and accreditation and implementation. The paper presents an overview of the main items developed by the contributors.A survey on the session on Quality Assurance in Analytical Chemistry of Euroanalysis VIIThe authors thank the organizers of EUROANALYSIS VII and in particular Dr. B. Griepink and Dr. E. Maier of the Community Bureau of Reference (BCR) of the CEC for their support and considerable contributions.     

Evaluation of a novel composite based on functionalized multi-walled carbon nanotube and iron phthalocyanine for electroanalytical determination of isoniazid

A novel platform for electroanalysis of isoniazid based on graphene-functionalized multi-walled carbon nanotube as support for iron phthalocyanine (FePc/f-MWCNT) has been developed. The FePc/f-MWCNT composite has been dropped on glassy carbon forming FePc/f-MWCNT/GC electrode, which is sensible for isoniazid, decreasing substantially its oxidation potential to +200 mV vs Ag/AgCl. Electrochemical and electroanalytical properties of the FePc/f-MWCNT/GC-modified electrode were investigated by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electrochemical microscopy, and amperometry. The sensor presents better performance in 0.1 mol L^?1 phosphate buffer at pH 7.4. Under optimized conditions, a linear response range from 5 to 476 μmol L^?1 was obtained with a limit of detection and sensitivity of 0.56 μmol L^?1 and 0.023 μA L μmol^?1, respectively. The relative standard deviation for 10 determinations of 100 μmol L^?1 isoniazid was 2.5%. The sensor was successfully applied for isoniazid selective determination in simulated body fluids.     

Kinetics and mechanism of the anation of (αβ)-hydroxo(tetraethylenepentamine)cobalt(III) by thiosulfate, the base hydrolysis of the (sulfur-bonded) thiosulfato(tetraethylenepentamine)-cobalt(III) and photochemistry of oxygen and sulfur-bonded thiosulfato complexes

Summary The reaction of ()-(tetren)CoOH²⁺ with S₂O ₃ ^2- in the 7.25–8.28 pH range at 20–40 °C yielded S- (yellow) and O- (purple) bonded thiosulfato(tetren)cobalt(III) complexes, the former in larger quantities. The rate determining step is preceded by diffusion-controlled ion-pair [(tetren)CoOH²⁺,S₂O ₃ ^2- ] formation. Replacement of coordinated OH^- by S₂O ₃ ^2- is interpreted in terms of an internal conjugate base mechanism: (tetren)CoOH²⁺ (tetren-H)CoOH ₂ ²⁺ , the reactive amido conjugate base being generated by intramolecular proton transfer from the coordinated NH site.In acid medium the S-bonded (tetren)Co(S₂O₃)⁺ is highly stable to redox decomposition, in contrast to its pentaammine analogue. The complex however, undergoes base hydrolysis yielding the corresponding hydroxo complex. The rate and activation parameters for the base hydrolysis have been reported. Photolysis of O- and S-bonded isomers of [(tetren)CoS₂O₃]⁺ in acidic medium at 254 and 313 nm, respectively, yielded aquation products accompanied by some decomposition of S₂O ₃ ^2- .     

Coordination chemistry of f-block elements with imine acids. Part IV. Synthetic and chiroptical studies on lanthanide(III) complexes of imine acids derived from L-alanine,L-valine,L-tyrosine and L-glutamic acid

Summary N-(orthovanillidene)L-alanine (OVAlaH₂), N-(salicylidene)L-valine (SValH₂), N-(orthovanillidene)L-valine (OVValH₂), N-(orthovanillidene)L-tyrosine (OVTyrH₃) and N-(salicylidene)L-glutamic acid (SGluH₃) react with La^III, Pr^III, Nd^III and Sm^III to yield new chiral complexes. Their dominant conformers were determined from c.d. spectra supported by¹H n.m.r. data, except for the L-glutamic acid derived complexes which were insoluble.     

A Formal Total Synthesis of (+)-Methyl Trachyloban-18-oate and (+)-Methyl 16-Oxo-17-norkauran-18-oate: Regio- and Diastereoselective Preparation of Methyl (13S)-13-Hydroxyisoatisiren-18-oate from (−)-Abietic Acid

A novel preparation of methyl (13S)-13-hydroxyisoatisiren-18-oate ( 4 ), a key-intermediate in a synthesis of (+)-methyl trachyloban-18-oate ((+)- 1 ), from (?)-abietic acid, is described. Since (?)- 1 has been previously converted into (?)-methyl 16-oxo-17-norkauran-18-oate ((?)- 16 ), our preparation of 4 constitutes also a formal total synthesis, from (?)-abietic acid, of (+)- 16 . Key steps in this approach were the allene photoaddition to podocarp-8(14)-en-13-one ( 5 ) and the conversion of the endo-toluene-4-sulfonate 11 into the exo-benzoate 12b .     

Development and validation of a RP-HPLC method for Roflumilast and its degradation products

Roflumilast is a phosphodiesterase type 4 inhibitor that is administered orally as a long-term, in the clinical treatment of chronic obstructive pulmonary disease and asthma. Launched in 2010 for the European market, it currently does not have an official monograph. Here, a reproducible gradient RP-HPLC method was developed and validated for the separation and determination of Roflumilast in the presence of its six major degradation products. Separation was performed on a C₁₈ analytical column (250?×?4.6?mm, 5?µm) with a mobile phase-A of ACN and a phase-B of ammonium acetate buffer (5?mM, pH 4.2) containing triethylamine (0.5% v/v). The most effective RP-HPLC gradient program was determined to be 0/80, 35/10, 36/80, 40/80 (time in minutes/% mobile phase-B). The flow rate was 1.0?ml/min and the column temperature was 25°C. The success of separation of the degradation products with different chemical characteristics was obtained by extending the time of the gradient, changing the proportion of the mobile phases and increasing the velocity of the flow. Two detectors were evaluated for the identification of degradation products and Roflumilast: a diode-arrary detector and a charged aerosol detector. The inability of the charged aerosol detector to dectect one of the six degradation products indicated that the method developed with RP-HPLC and the diode-array detector was more suitable for Roflumilast analysis. The method was validated according to specificity, linearity, LOD, LOQ, accuracy, precision and robustness.