MEDT analysis of mechanism and selectivities in non-catalyzed and lewis acid-catalyzed diels-alder reactions between R-carvone and isoprene.

Within the context of Molecular Electronic Density Theory (MEDT), this study investigates the Diels-Alder reaction among isoprene (2) and R-carvone (1R) applying DFT simulations, with and without Lewis acid (LA) catalysis. The results show that carvone (1R) acts as an electrophile and isoprene (2) as a nucleophile in a polar process. LA catalysis increases the electrophilicity of carvone, thereby improving the reactivity and selectivity of the reaction by reducing the activation Gibbs free energy. Parr functions reveal that the C5=C6 double bond is more reactive than the C9=C10 double bond, indicating chemoselectivity. The examination of the Electron Localization Function (ELF) reveals high regio- and stereoselectivity, indicating an asynchronous mechanism for the LA-catalyzed DA reaction. Furthermore, it is suggested that cycloadduct 3 has great anti-HIV potential because it exhibits lower binding energies than azidothymidine (AZT) in the docking studies of cycloadducts 3 and 4 amongst a primary HIV-1protein (1A8O plus 5W4Q).

Insights into evolutionary interaction patterns of the 'Phosphorylation Activation Segment' in kinase.

We are interested in studying the phosphorylation of the kinase activation loop, distinguishing the passage from the unphosphorylated to the phosphorylated form without allostery. We performed an interaction study to trace the change of interactions between the activation segment and the kinase catalytic core, before and after phosphorylation. Results show that the structural changes are mainly due to the attraction between the phosphate group and guanidine groups of the arginine side chains of RD-pocket, which are constituted mainly of guanidine groups of the catalytic loop, the ß9, and the αC helix. This attraction causes propagation of structural variation of the activation segment, principally towards the N-terminal. The structural variations are not made on all the amino acids of the activation segment; they are conditioned by the existence of two beta sheets stabilizing the loop during phosphorylation. The first,ß6-ß9 sheet is usually present in most of the kinases; the second, ß10-ß11 is formed due to the interaction between the main chain amino acids of the activation loop and the αEF/αF loop.

Is the pericyclic transition structure of aza-Diels-Alder reaction aromatic?

The notion of aromaticity is an elusive concept, typically delineated as an electron delocalization pattern within a cyclic structure, and is characterized by unusual stability, reactivity, and other properties. Recently, the aromatic concept has been extended to inorganic molecules and saturated systems. In our work, the so-called pericyclic transition state structures (TSs) involved in aza-Diels-Alder reactions are investigated. Interestingly, geometries and energy barriers evidence that these reactions are highly energetic and are extremely asynchronous. Additionally the localized orbital locator, ELF and QTAIM topological analyses have proven that at least one pair of atoms is not bound at the TS configuration. Moreover, HOMA and PDI indexes show that these TSs where aromaticity is not important. Therefore, these results provoke us to rule out the aromatic character of these so-called pericyclic TSs structures.

C-C bond formation in the intramolecular Diels-Alder reaction of triene amides.

The mechanism nature of the intramolecular Diels-Alder reaction has been performed; and thus, the changes of C-C bond forming/breaking along IRC are characterized in this study. Conceptual DFT analyses of the most favorable adduct fused/exo shows that the flux electronic will take place from diene to dienophile moiety. Moreover, ELF topological analysis based on the electron density predicts that C-C bond is formed by the coupling of two pseudoradical centers generated at the most significant atoms of the molecules. However, C2 vs C3, also C1 and C4 interaction comes mainly from the global electron density transfer which takes place along the reaction. Two- stage one-step is the proposed mechanism of this reaction, the first stage aims for the formation of C2-C3 σ bond while the second stage aims for C1-C4 σ bond formation. Interestingly, the observed asynchronicity of this IMDA reaction due principally to the asymmetric reorganization of electron density at the most attractive centers.