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

Abstract

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. Two reaction mechanisms will be analyzed using the REF’s decomposition in polarization and electron transfer effects. Results show that both mechanisms proceed as follows: (1) polarization effects initiate the reactions producing structural distortions; (2) electron transfer processes take over near the transition states, triggering specific chemical events such as bond forming and breaking which are responsible to push the reactions toward the products; (3) after passing the transition state, polarization shows up again and drives the relaxation process toward the product. Similar polarization effects were observed in both reactions, but they present an opposite behavior of the electronic transfer flux disclosing the fact that electron transfer phenomena govern the reaction mechanisms.

In Silico Investigation of the Mechanism of Disulfide Bond Dissociation by New Frustrated Lewis Pairs

“…Chemical potential (μ) can be written in terms of the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy. , Thus, the expression is μ ≅ true( E normalL normalU normalM normalO + E normalH normalO normalM normalO 2 true) where E LUMO ≈ −EA and E HOMO ≈ −IP, (EA = electron affinity, IP = ionization potential) as stated by Koopmans’ theorem . After getting μ in each step of the reaction, the reaction electronic flux (REF) can be calculated, which is introduced by Toro-Labbé et al − It can be represented as J false( ξ false) = − true( normald μ normald ξ true) where the positive J (ξ) profile corresponds to bond formation or the strengthening process, whereas the negative J (ξ) profile indicates the bond deformation or separation process. − …”

“…In this study, we conducted a detailed in silico investigation to elucidate the reaction mechanism of S–S bond cleavage in disulfides, specifically diisopropyl disulfide ( i Pr–S–S– i Pr), using a newly designed frustrated Lewis pair (FLP) consisting of P­( t Bu) 3 and B­(C 2 NBSHF 2 ) 3 . We aimed to gain insights into the detailed mechanism of this reaction by employing NBO (natural bond orbital) , analysis and reaction force − and reaction electronic flux − analysis.…”

Insights into the catalytic activity of boron-doped thiazoles in the Diels–Alder reaction

“…50 Later, it has been used to analyse several other reaction mechanisms. [54][55][56][57][58][59][60][61] It was stated that positive J(x)…”

“…50 Later, it has been used to analyse several other reaction mechanisms. 54–61 It was stated that positive J ( ξ ) represents bond-strengthening or bond-forming processes, whereas bond-weakening or bond-breaking processes are associated with a negative J ( ξ ) profile. The separation of J ( ξ ) in two terms, e.g.…”

Insight into acrolein activation by P/B intramolecular frustrated Lewis pairs

“…The detailed electronic activity along with IRC can be studied by generating the reaction electronic flux (REF). The reaction electronic flux (REF), 60–65 which is demonstrated by Toro‐Labe et al, can be expressed as …”