Challenges Posed to Bornyl Diphosphate Synthase: Diverging Reaction Mechanisms in Monoterpenes

摘要

Abstract: The simplest form of terpenoid chemistry is found for the monoterpenes, which give plantsnfragrance, flavor, and medicinal properties. Monoterpene synthases employ geranyl diphosphate as ansubstrate to generate an assortment of cyclic products. In the current study we present a detailed analysisnof the multiple gas-phase reaction pathways in the synthesis of bornyl cation from geranyl diphosphate.nAdditionally, the fate of the proposed bornyl cation intermediate in the bornyl diphosphate synthase reactionnis investigated by molecular dynamics simulations. We employ accurate density functional theory (DFT)nmethods after careful validation against high-level ab initio data for a set of model carbocations. The gas-nphase results for the monoterpene reactions indicate a diverging reaction mechanism with multiple productsnin the absence of enzymatic control. This complex potential energy surface includes several possiblenbifurcation points due to the presence of secondary cations. Additionally, the suggested bornyl cationnintermediate in the bornyl diphosphate synthase reaction is studied by molecular dynamics simulationsnemploying a hybrid quantum mechanics (DFT) molecular mechanics potential energy function. Thensimulations suggest that the bornyl cation is a transient species as in the gas phase and that electrostaticnsteering directs the formation of the final product, bornyl diphosphate.