Triazole groups as biomimetic amide groups in peptides can trigger racemization

Hättasch, Toni; Schmuck, Carsten; Niemeyer, Jochen

doi:10.24820/ark.5550190.p011.484

Cited by 1 publication

(1 citation statement)

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“…Even though regioselective reactions that can produce high concentrations of a single enantiomer [6] have been studied to increase the conversion of optically active compounds in drug design processes [7], pure enantiomeric products can be racemized in a different environment because factors such as pH, temperature, catalysts, enzymes, and substrate structure have been shown to allow different racemization rates [8]. Hence, even if a regioselective process allowed an enantiomeric pure product, it could be racemized after being ingested.…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Racemization Mechanism of Aliphatic and Aromatic Amino Acids by In Silico Tools

Andino,

Mora,

Paz

et al. 2023

IJMS

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The racemization of biomolecules in the active site can reduce the biological activity of drugs, and the mechanism involved in this process is still not fully comprehended. The present study investigates the impact of aromaticity on racemization using advanced theoretical techniques based on density functional theory. Calculations were performed at the ωb97xd/6-311++g(d,p) level of theory. A compelling explanation for the observed aromatic stabilization via resonance is put forward, involving a carbanion intermediate. The analysis, employing Hammett’s parameters, convincingly supports the presence of a negative charge within the transition state of aromatic compounds. Moreover, the combined utilization of natural bond orbital (NBO) analysis and intrinsic reaction coordinate (IRC) calculations confirms the pronounced stabilization of electron distribution within the carbanion intermediate. To enhance our understanding of the racemization process, a thorough examination of the evolution of NBO charges and Wiberg bond indices (WBIs) at all points along the IRC profile is performed. This approach offers valuable insights into the synchronicity parameters governing the racemization reactions.

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Section: Introductionmentioning

confidence: 99%