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The enzyme-catalyzed degradation of the biogenic amine serotonin is an essential regulatory mechanism of its level in the human organism. In particular, monoamine oxidase A (MAO A) is an important flavoenzyme involved in the metabolism of monoamine neurotransmitters. Despite extensive research efforts, neither the catalytic nor the inhibition mechanisms of MAO enzymes are currently fully understood. In this article, we present the quantum mechanics/molecular mechanics simulation of the rate-limiting step for the serotonin decomposition, which consists of hydride transfer from the serotonin methylene group to the N5 atom of the flavin moiety. Free-energy profiles of the reaction were computed by the empirical valence bond method. Apart from the enzymatic environment, the reference reaction in the gas phase was also simulated, facilitating the estimation of the catalytic effect of the enzyme. The calculated barrier for the enzyme-catalyzed reaction of 14.82 +/- 0.81 kcal mol(-1) is in good agreement with the experimental value of 16.0 kcal mol(-1), which provides strong evidence for the validity of the proposed hydride-transfer mechanism. Together with additional experimental and computational work, the results presented herein contribute to a deeper understanding of the catalytic mechanism of MAO A and flavoenzymes in general, and in the long run, they should pave the way toward applications in neuropsychiatry.

Despite the fact that the methanol synthesis process includes industrially some of the most important catalytic chemical reactions, it is still not clear how different gaseous species impact cataly...

While the function of enzymes has been well-known to researchers for decades, the driving force behind it is still a hotly debated topic. Herein, we report significant evidence for electrostatics being that driving force, using a simple, computationally inexpensive, multiscale model of monoamine oxidase A and phenylethylamine. We found that electrostatics provided by the enzyme substantially enhances the reaction by all the considered criteria (lowering the energy barrier, increasing charge transfer, decreasing the highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) gap, increasing the dipole moment). The catalytic effect can be rationalized by the stabilizing interaction between the dipole moment of the reacting moiety and the electric field exerted by the charged environment. Both the dipole moment and the electric field are perceivably larger in the transition state as compared to the state of reactants; hence the transition state is stabilized to a larger extent and bett...

Semi-interpenetrating polymer networks (semi-IPNs) were prepared by in situ simultaneous orthogonal polymerizations, where the linear poly(e-caprolactone) (PCL) was synthesized by ring-opening polymerization of e-caprolactone and the poly(styrene-co-divinylbenzene) (PS) network was formed by free-radical polymerization of styrene/divinylbenzene. Semi-IPNs were used as the precursors for the preparation of porous PS monoliths. To this end, the PCL domains were selectively removed by hydrolysis under basic conditions. By changing the amount of organocatalyst used for the ring-opening polymerization of e-caprolactone, the relative polymerization kinetics of both monomers was varied, which has a pronounced effect on the morphology of thus-obtained PS frameworks.