How does dopamine convert into norepinephrine? Insights on the key step of the reaction.

Context: Dopamine -monooxygenase (D M) is an essential enzyme in the organism that regioselectively converts dopamine into R-norepinephrine, the key step of the reaction, studied in this paper, is a hydrogen atom transfer (HAT) from dopamine to a superoxo complex on D M, forming a hydroperoxo intermediate and dopamine radical. It was found that the formation of a hydrogen bond between dopamine and the D M catalyst strengthens the substrate-enzyme interaction and facilitates the HAT which takes place selectively to give the desired enantiomeric form of the product. Six reactions leading to the hydroperoxo intermediate were analyzed in detail using theoretical and computational tools in order to identify the most probable reaction mechanism.

Complexes between 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH) and cucurbit[]uril hosts modulate the yield and fate of photolytically-generated AAPH radicals.

Using theoretical and experimental tools we investigated the recognition of AAPH (2,2'-azobis(2-methylpropionamidine) dihydrochloride), a well-known water-soluble azo-compound employed as a source of peroxyl radicals, by cucurbit[6]uril (CB[6]), and cucurbit[8]uril (CB[8]). Density functional theory calculations and isothermal titration calorimetry experiments demonstrated that AAPH was not included in the cavity of CB[6], however, an exclusion complex was generated. Inclusion of AAPH in the CB[8] cavity was favored, forming stable inclusion complexes at 1 : 1 and 2 : 1 stoichiometries; AAPH@CB[8] and 2AAPH@CB[8], respectively.

Computational study of the supramolecular complexation of azocompounds with cucurbit[7]uril: effects on the production and release of free radicals.

Context: An inclusion complex between 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH), a widely employed azocompound, and cucurbit[7]util (CB[7]), has shown an increased yield of radicals derived from the homolytic cleavage of the azo bond. Aimed to get insights about the formation of complexes and their effect on the yield of radicals production, complexes of CB[7] with seven azocompounds were studied by computational methods. Molecular electrostatic surfaces and structural analysis showed that the inclusion of symmetrical azocompounds inside of CB[7] depends mainly on the charge density and position of the functional groups at the main chain of the azoderivative.

How Does Electronic Activity Drive Chemical Reactions? Insights from the Reaction Electronic Flux for the Conversion of Dopamine into Norepinephrine.

Hydrogen atom transfer (HAT) is a crucial step in the physiological conversion of dopamine into norepinephrine catalyzed by dopamine β-monooxygenase. The way the reaction takes place is unclear, and a rational explanation on how the electronic activity drives the HAT seems to be necessary. In this work, we answer this question using the reaction electronic flux (REF), a DFT-based descriptor of electronic activity.