Biodegradation of Herbicides by a Plant Nonheme Iron Dioxygenase: Mechanism and Selectivity of Substrate Analogues.

Aryloxyalkanoate dioxygenases are unique herbicide biodegrading nonheme iron enzymes found in plants and hence, from environmental and agricultural point of view they are important and valuable. However, they often are substrate specific and little is known on the details of the mechanism and the substrate scope. To this end, we created enzyme models and calculate the mechanism for 2,4-dichlorophenoxyacetic acid biodegradation and 2-methyl substituted analogues by density functional theory. The work shows that the substrate binding is tight and positions the aliphatic group close to the metal center to enable a chemoselective reaction mechanism to form the C2 -hydroxy products, whereas the aromatic hydroxylation barriers are well higher in energy. Subsequently, we investigated the metabolism of R- and S-methyl substituted inhibitors and show that these do not react as efficiently as 2,4-dichlorophenoxyacetic acid substrate due to stereochemical clashes in the active site and particularly for the R-isomer give high rebound barriers.

Revealing the Mechanism and Origin of Reactivity of Au(I)-Catalyzed Functionalized Indenone Formation of Cyclic and Acyclic Acetals of Alkynylaldehydes.

A density functional theory study is presented here to offer mechanistic insights and explications of experimentally intriguing observations in the Au(I)-catalyzed cyclization of cyclic and acyclic acetals of alkynylaldehydes that leads to indenone formation. The reactivity of catalytic cycles with and without methoxy migration is clearly defined when the alkyne terminus is phenylated. The reaction mechanism of indenone formation proceeds first with the coordination of Au(I) to alkyne to initiate the reaction with 1,5-H shift as a rate-determining step (RDS), and the fastest 1,5-H shift is achieved when one phenyl ring carries an electron-donating group and the other one is substituted with an electron-withdrawing group. Following the 1,5-H shift, the reaction undergoes feasible steps that are cyclization and 1,2-H shift before elimination to persist the iterative cycle, but the reactivity of both steps is highly affected by the existence of the phenyl group on the alkyne terminus. The unreactivity of the alkyne terminus not bearing a phenyl ring is because the cyclization is thermodynamically disfavorable, subsequently deactivating the 1,2-H shift kinetically and thermodynamically. The absence of a tether in the acetal unit considerably outpaces any 1,5-H shift and instead activates 1,5-methoxy migration, giving methoxy-migrated indenone, with the 1,2-OMe shift being an RDS.