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

International audienceThe 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

Homolysis of N-Alkoxyamines. A Computational Study

International audienceDuring 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. In order to provide a predictive tool, correlations between the calculated BDEs and the cleavage temperature (Tc ), and the dissociation rate constant (kd ), of the N-alkoxyamines are established. The homolytic cleavage of the N-OC bond is also investigated at the B3P86/6-311++G(d,p)//B3LYP/6-31G(d), level. Furthermore, a natural bond orbital analysis is carried out for some N-alkoxyamines with a O-C-ON(R1)R2fragment, and the strengthening of their C-ON(R1)R2 bond is interpreted in terms of stabilizing anomeric interactions

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

WOS:000465915600009The dissociation behavior of two stable nitroxides, namely 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO center dot) and N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide (SG1(center dot)), 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 MS3 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. While protonation of TEMPO center dot mainly occurred on the oxygen atom of the nitroxyl function, a series of protomers were found for SG1(center dot) with the adducted proton preferentially located onto the P=O group of this phosphorylated species. For both protonated nitroxides, major product ions measured in tandem mass spectrometry arose from reactions occurring at low energy costs via elimination of radical species. Formation of secondary fragments that were detected with low abundance when raising the activation level of both precursor ions could be rationalized with pathways proceeding via high energy transition states

Large phosphorus hyperfine coupling as a sensitive tool for studying molecular dynamics : ESR and Molecular Mechanics studies of ring interconversion in cis-2,5-diphosphoryl-2,5-dimethyl-pyrrolidinoxyl radical

ESR spectra of cis- and trans-â-diphosphorylated pyrrolidine-N-oxyl radicals, c-1 and t-1, were studied in liquid and frozen solution. The expected 1:2:1 triplet (aP (2)) of the 1:1:1 triplet (aN) was observed for t-1; however, for c-1, the inner lines of the 1:2:1 triplet showed a dramatic broadening characteristic of chemical exchange between two equivalent conformations. Owing to the large difference in the hyperfine splitting constants (hfsc) of the exchanging phosphorus (¢aP 21 G), the coalescence temperature was unusually high (193 K, in n-pentane), and the potential barrier for ring interconversion (10.5 kJ mol-1) was easily obtained from the temperature dependence of the exchange rate. This value was in very good agreement with the value obtained for an empirical pseudorotational potential (11 kJ mol-1) that was adjusted to fit the temperature dependence of the phosphorus hfsc. For c-1, molecular mechanics calculations gave similar characteristics for the pseudorotational potential and indicated the existence of two identical minima with distorted geometries lying between 3T4 and 3E or 4T3 and E3. For t-1, only the 3T4 conformer was found to be significantly populated. Frozen solution spectra showed that the phosphorus hfsc anisotropy is higher when the C-P bond is pseudoaxial; this result can be explained by a geometry-dependent delocalization of the unpaired electron into the phosphorus 3p orbitals

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.e., by chronological order: Myers–Saito cycloaromatization (M-S), intramolecular hydrogen atom transfer (HAT), and recombination of the resulting biradical. The enantiospecificity of the reaction results from a double transmission of the stereochemical information, from the original center to an axis and eventually from this axis to the final center. The first two steps lead to a transient diradical intermediate which retains the chirality via the conversion of the original static chirogenic element into a dynamic one, i.e., a center into an axis. The only available routes to the final closed-shell tetracyclic product imply rotations around two σ bonds (σ­(C–C) and σ­(C–N), bonds β and α respectively). The theoretical calculations confirmed that the formation of the enantiomerically pure product proceeds via the nonracemizing rotation around the σ­(C–C) pivot. They ruled out any rotation around the second σ­(C–N) pivot. The high level of configurational memory in this rearrangement relies on the steric impediment to the rotation around the C–N bond in the chiral native conformation of the diradical intermediate produced from tandem M-S/1,5-HAT