Effect of the Carboxylate Salt on the C?ON Bond Homolysis of SG1‐Based Alkoxyamines

Alkoxyamines and persistent nitroxides are important regulators of the nitroxide mediated radical polymerization (NMP). Since the polymerization time decreases with increasing values of the homolysis rate constant (k_d) for the C? ON bond between the polymer chain and the nitroxide moiety, the factors influencing k_d are of considerable interest. Environmentally friendly polymerization methods, such as NMP in emulsion medium, have now been developed. The success of the polymerization depends not only on the strength of the C? ON bond but also on the solubility of the initiator/controller alkoxyamines, which control the nucleation. Various salts of SG1‐based alkoxyamines (S^+?OOCCMeH‐SG1) labelled 1 a–f , where S⁺=Li⁺ ( a ), Na⁺ ( b ), K⁺ ( c ), nBu₃HN⁺ ( d ), NH₄⁺ ( e ), and nBu₄N⁺ ( f ) are prepared, all of which are soluble in most organic solvents (e.g. pentane, dichlomethane, benzene, ethanol, etc.) as well as in water. Their k_d values, which are measured in tert‐butylbenzene, reveal unexpected behaviors depending on the diastereoisomers. For the RR/SS diatereoisomers (i.e. slowly homolyzing isomers), k_d was not found to be sensitive to any of the salts, whereas for the RS/SR diastereoisomers (i.e. quickly homolyzing isomers), k_d is observed to decrease to a greater or lesser extent depending on the type of salt. The conformations of the diastereoisomers of several salts are determined by means of DFT calculations, and the orbital interactions are studied by natural bond orbital (NBO) analysis.     

Automatic filtration and filter flush for robust online solid-phase extraction liquid chromatography

Online solid-phase extraction-liquid chromatography (SPE-LC) with microbore or capillary columns was significantly improved regarding robustness, as an easily installed automatic filtration and filter flushing (AFFL) procedure was added to avoid system clogging. Specifically, an injected sample is passed through a union containing a stainless steel filter prior to SPE trapping. The filter stops any particulate matter from reaching the SPE. When the SPE is subsequently connected to the LC column by column switching, a separate pump backflushes the filter-union, removing the particulate matter off the filter after each injection. This feature greatly reduced backpressure buildup over the entire system.     

Simultaneous quantitative profiling of N-acyl-l-homoserine lactone and 2-alkyl-4(1H)-quinolone families of quorum-sensing signaling molecules using LC-MS/MS

An LC-MS/MS method, using positive mode electrospray ionization, for the simultaneous, quantitative and targeted profiling of the N-acyl-L-homoserine lactone (AHL) and 2-alkyl 4-(1H)-quinolone (AQ) families of bacterial quorum-sensing signaling molecules (QSSMs) is presented. This LC-MS/MS technique was applied to determine the relative molar ratios of AHLs and AQs produced by Pseudomonas aeruginosa and the consequences of mutating individual or multiple QSSM synthase genes (lasI, rhlI, pqsA) on AHL and AQ profiles and concentrations. The AHL profile of P. aeruginosa was dominated by N-butanoyl-L-homoserine lactone (C4-HSL) with lesser concentrations of N-hexanoyl-L-homoserine lactone (C6-HSL) and 3-oxo-substituted longer chain AHLs including N-(3-oxodecanoyl)-L-homoserine lactone (3-oxo-C10-HSL) and N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL). The AQ profile of P. aeruginosa comprised the C7 and C9 long alkyl chain AQs including 2-heptyl-4-hydroxyquinoline (HHQ), 2-nonyl-4-hydroxyquinoline, the "pseudomonas quinolone signal" (2-heptyl-3-hydroxy-4-quinolone) and the N-oxides, 2-heptyl-4-hydroxyquinoline N-oxide and 2-nonyl-4-hydroxyquinoline N-oxide. Application of the method showed significant effects of growth medium type on the ratio and the nature of the QSSMs synthesized and the dramatic effect of single, double and triple mutations in the P. aeruginosa QS synthase genes. The LC-MS/MS methodology is applicable in organisms where either or both AHL and AQ QSSMs are produced and can provide comprehensive profiles and concentrations from a single sample.     

Magnetic exchange coupling in bis-nitroxides: a theoretical analysis of the solvent effects

Magnetic properties of nitroxide radicals can be greatly affected by solvent effects. In this study, the change of the magnetic exchange interaction J, coupling the two unpaired electrons of a model solvated antiferromagnetic bis-iminyl-nitroxide molecule (2IN), is rationalized thanks to different geometric and electronic criteria provided by density functional theory calculations. It is shown that for a given geometry, simple tools can be used to analyze with good accuracy the dependence of J with the solvent polarity. Estimates of two important magnetic parameters are given: the magnetic orbitals exchange and the in-site energy gap between ionic and neutral configurations. 2IN can be engaged in different hydrogen-bonds with first shell water molecules, modifying both the 2IN geometry and the electrostatic potential felt by the molecule. In all, the additivity of electrostatic and hydrogen-bond solvent effects is found to be responsible for J variations as large as 50%.     

Mechanistic investigation of enediyne-connected amino ester rearrangement. Theoretical rationale for the exclusive preference for 1,6- or 1,5-hydrogen atom transfer depending on the substrate. A potential route to chiral naphthoazepines

Memory of chirality (MOC) and deuterium-labeling studies were used to demonstrate that the cascade rearrangement of enediyne-connected amino esters 1a and 1b evolved through exclusive 1,5- or 1,6-hydrogen atom transfer, subsequent to 1,3-proton shift and Saito-Myers cyclization, depending on the structure of the starting material. These results were independently confirmed by DFT theoretical calculations performed on model monoradicals. These calculations clearly demonstrate that in the alanine series, 1,5-hydrogen shift is kinetically favored over 1,6-hydrogen shift because of its greater exergonicity. In the valine series, the bulk of the substituent at the nitrogen atom has a major influence on the fate of the reaction. N-Tosylation increases the barrier to 1,5-hydrogen shift to the benefit of 1,6-hydrogen shift. The ready availability of 1,6-hydrogen atom transfer was explored as a potential route for the enantioselective synthesis of naphthoazepines.     

Aminomethylation of Michael acceptors: complementary radical and polar approaches mediated by dialkylzincs

Phtalimidomethyl iodide and substituted maleimidomethyl iodide were used as radical precursors in dialkylzinc-mediated radical addition to diethyl fumarate. The reactions led stereoselectively to functionalized pyrrolizidines. The radical mechanism was supported by spin-trapping experiments and rationalized by theoretical calculations. Radical additions, on the one hand, and carbozincation followed by transmetalation with copper(I), on the other, were shown to be complementary methods to achieve the formal aminomethylation of activated unsaturated compounds.     

Synthesis and structure of 5,5-diethoxycarbonyl-1-pyrroline N-oxide (DECPO). Application to superoxide radical trapping

DECPO, a new analogue of EMPO was synthesized through a two-step synthetic pathway. Its structure and its application to trap superoxide were investigated. The ESR detection of the DECPO-OOH spin adduct is easy even at low concentration of superoxide. In comparison with DEPMPO, the trapping of superoxide with DECPO is faster and the detection of DECPO-OOH can be performed using a very low nitrone concentration (0.5 mM).     

Efficient synthesis of substituted dihydrotetraazapentacenes

We describe a versatile and very efficient synthesis of previously unknown substituted 5,14-dihydro-5,7,12,14-tetraazapentacenes (DHTAPs). A structural study by NMR spectroscopy showed that the conjugated pi-system of the pentacyclic skeleton rearranges depending on the electronic effect of the substituent(s).