Revisited Mechanism of Reaction between a Model Lysine Amino Acid Side Chain and 4-Hydroxynonenal in Different Solvent Environments

Škulj, Sanja; Vazdar, Katarina; Margetić, Davor; Vazdar, Mario (2019) Revisited Mechanism of Reaction between a Model Lysine Amino Acid Side Chain and 4-Hydroxynonenal in Different Solvent Environments. Journal of Organic Chemistry, 84 (2). pp. 526-535. ISSN 0022-3263

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Official URL: https://pubs.acs.org/doi/10.1021/acs.joc.8b02231

Abstract

We revisit the reaction mechanism of reaction between model lysine side chain and reactive aldehyde 4-hydroxynonenal in different solvents with increasing water content. We show by model organic reactions and qualitative spectrometric analysis that non-polar pyrrole adduct is dominantly formed in non-aqueous solvents dichloromethane and acetonitrile. On the other hand, in aqueous acetonitrile and neat water, other polar products are also isolated including Michael adducts, hemiacetal adducts and pyridinium salt adducts, at the same time decreasing the ratio of non-polar products vs polar products. The experiments are supported by detailed quantum chemical calculations of the reaction mechanism with different computational setups showing that the pyrrole adduct is the most thermodynamically stable product compared to Michael adducts and hemiacetal adducts and also indicating that water molecules released along the reaction pathway are catalyzing reaction steps involving proton transfer. Finally, we also identify the mechanism of the pyridinium salt adduct which is formed only in aqueous solutions.

Item Type:

Article

Additional Information:

This study was supported by the Croatian Science Foundation (Project UIP-2014-09-6090). The computational part of the research was performed using the resources of computer cluster Isabella based in SRCE-University of Zagreb University Computing Center. The authors also thank Dr. Ivanka Jeric and Dr. Lidija Brkljacic for the instrumental support.

Uncontrolled Keywords:

lysine ; 4-hydroxynonenal ; reaction mechanism ; quantum chemical calculations

Subjects:

NATURAL SCIENCES > Chemistry

Divisions:

Division of Organic Chemistry and Biochemistry

Projects: