Károly Kubicskó, Ödön Farkas (2020.06.01 - 2020.11.30)

Eötvös Loránd University, Department of Organic Chemistry

Abstract: The metabolism of biogenic N,N-dimethyltryptamine (DMT) starts with its enzymatic oxidation to indole-3-N,N-dimethylethaniminium cation (imDMT+) by monoamine oxidase (MAO). Following this reaction, a non-enzymatic hydrolysis occurs, yielding indole-3-acetaldehyde (IAL) and dimethylamine (DMA). In our in silico study, using a hybrid DFT method at the M06-2X/aug-cc-pVDZ level, we examined the necessity of explicit water molecules to accurately model the hydrolysis. Our calculations revealed that despite an implicit continuum solvent model, one or two explicit solvent molecules should be added to obtain meaningful activation barriers. Thus, we demonstrate that the hydrolysis can occur in a human cell without enzymatic assistance, paving the way for deeper understanding of DMT metabolism.

Publication: Quantum chemical study of the hydrolysis of oxidized endogenous psychedelic N,N-dimethyltryptamine