Collision-induced dissociation of stable nitroxides: A combined tandem mass spectrometry and computational study of TEMPO and SG1

The dissociation behavior of two stable nitroxides, namely 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide (SG1), subjected as protonated molecules to collisional activation was investigated using a combination of different mass spectrometry experiments and theoretical calculations. Elemental composition of reaction products was derived from accurate mass data measured in high resolution tandem mass spectrometry experiments, primary fragments were distinguished from secondary ions based on both breakdown curves and MS data, and H/D exchange experiments were performed to support proposed structures. Postulated fragmentation pathways were then studied in terms of energetic, using the standard B3LYP/6-31G(d) method.

Synthesis and properties of a series of β-cyclodextrin/nitrone spin traps for improved superoxide detection.

Three new DEPMPO-based spin traps have been designed and synthesized for improved superoxide detection, each carrying a cyclodextrin (CD) moiety but with a different alkyl chain on the phosphorus atom or with a long spacer arm. EPR spectroscopy allowed us to estimate the half-life of the superoxide spin adducts which is close to the value previously reported for CD-DEPMPO (t ≈ 50-55 min under the conditions investigated). The spectra are typical of superoxide adducts (almost no features of the HO˙ adduct that usually forms with time for other nitrone spin traps such as DMPO) and we show that at 250 μM, the new spin trap enables the reliable detection of superoxide by 1 scan at the position opposite to the corresponding spin trap without the CD moiety.

New Amino-Acid-Based β-Phosphorylated Nitroxides for Probing Acidic pH in Biological Systems by EPR Spectroscopy.

There is increasing interest in measuring pH in biological samples by using nitroxides with pH-dependent electron paramagnetic resonance (EPR) spectra. Aiming to improve the spectral sensitivity (Δa ) of these probes (i.e.

Spin exchange monitoring of the strong positive homotropic allosteric binding of a tetraradical by a synthetic receptor in water.

The flexible tetranitroxide 4T has been prepared and was shown to exhibit a nine line EPR spectrum in water, characteristic of significant through space spin exchange (J(ij)) between four electron spins interacting with four nitrogen nuclei (J(ij) ≫ a(N)). Addition of CB[8] to 4T decreases dramatically all the Jij couplings, and the nine line spectrum is replaced by the characteristic three line spectrum of a mononitroxide. The supramolecular association between 4T and CB[8] involves a highly cooperative asymmetric complexation by two CB[8] (K1 = 4027 M(-1); K2 = 202,800 M(-1); α = 201) leading to a rigid complex with remote nitroxide moieties.

Origin of the enantioselectivity in organocatalytic Michael additions of β-ketoamides to α,β-unsaturated carbonyls: a combined experimental, spectroscopic and theoretical study.

The organocatalytic enantioselective conjugate addition of secondary β-ketoamides to α,β-unsaturated carbonyl compounds is reported. Use of bifunctional Takemoto's thiourea catalyst allows enantiocontrol of the reaction leading either to simple Michael adducts or spirocyclic aminals in up to 99 % ee. The origin of the enantioselectivity has been rationalised based on combined DFT calculations and kinetic analysis.

Theoretical study to explain how chirality is stored and evolves throughout the radical cascade rearrangement of enyne-allenes.

This article reports a theoretical study to explain how the intrinsic property of chirality is retained throughout the radical cascade rearrangement of an enantiopure chiral enyne-allene (bearing one stereogenic center) selected as a model for this family of reactions. Calculations at the MRPT2/6-31G(d)//CASSCF(10,10)/6-31G(d) level of theory were used to determine the entire reaction pathway which includes singlet state diradicals and closed-shell species. The cascade process involves three elementary steps, i.

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.

A cooperative participation of the amido group in the organocatalytic construction of all-carbon quaternary stereocenters by Michael addition with β-ketoamides.

The secondary amido group of α-substituted β-ketoamides plays a crucial role in the control of the reactivity and spatial arrangement (selectivity) in the organocatalyzed Michael addition to unsaturated carbonyls. This results in an unprecedented activation mode of substrates through H-bonding interactions allowing the construction of enantiomerically enriched functionalized all-carbon quaternary centers and spiroaminals of high synthetic potential.

Expeditious synthesis and biological evaluation of new C-6 1,2,3-triazole adenosine derivatives A1 receptor antagonists or agonists.

The synthesis of new C-6 1,2,3-triazole adenosine derivatives via microwave assisted 1,3-dipolar cycloaddition as key step is described. The binding on membranes of cells that over express A(1) adenosine receptors (A(1)AR) was also evaluated. Among them, four compounds increased cAMP production, in a dose-dependent manner acting as antagonists of the A(1)AR, while two compounds act as agonists.

Design, synthesis and biological evaluation of a bivalent micro opiate and adenosine A1 receptor antagonist.

The cross talk between different membrane receptors is the source of increasing research. We designed and synthesized a new hetero-bivalent ligand that has antagonist properties on both A(1) adenosine and mu opiate receptors with a K(i) of 0.8+/-0.

Breaking of ketene bonds during HCl addition to trimethylsilylketene.

IR spectroscopy is coupled with the matrix isolation technique to study the reaction of trimethylsilylketene with HCl. From 50 K trimethylsilylketene reacts with hydrogen chloride, leading to the cleavage of the Si-C bond and the formation of trimethylsilyl chloride and acetyl chloride, through intermediate trimethylsilylacetyl chloride which was identified. A reaction profile for this result is proposed based on a theoretical study carried out at the DFT level.

Homolysis of N-alkoxyamines: a computational study.

During nitroxide-mediated polymerization (NMP) in the presence of a nitroxide R2(R1)NO*, the reversible formation of N-alkoxyamines [P-ON(R1)R2] reduces significantly the concentration of polymer radicals (P*) and their involvement in termination reactions. The control of the livingness and polydispersity of the resulting polymer depends strongly on the magnitude of the bond dissociation energy (BDE) of the C-ON(R1)R2 bond. In this study, theoretical BDEs of a large series of model N-alkoxyamines are calculated with the PM3 method.