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

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

MIRJANA ECKERT-MAKSIĆ – Biography and Contributions

Biografija Mirjane Eckert MaksićBiography of Mirjana Eckert Maksi

Multireference Configuration Interaction Methods – An Application to the Valence Isomerism in Cyclobutadieno-p-benzoquinone and its Diprotonated Form

Multireference averaged quadratic coupled cluster (MR-AQCC) calculations for cyclobutadieno-p-benzoquinone indicate that valence bond isomers 1a and 1b can exist as distinct species. The energy barrier height for their interconversion are 4.6 and 4.5 kcal mol−1, respectively, what is by ca. 2 kcal mol−1 lower than in the parent cyclobutadiene, implying that they could perhaps exist only under extreme conditions, namely at very low temperatures. For double protonated cyclobutadieno-p-benzoquinone, the CASSCF calculations erroneously predict existence of two valence isomers, 2a and 2b, whereas the MR-AQCC calculations reveal that geometry of the double protonated species could be best described by structure 2b. This nicely illustrates the crucial role of dynamic correlation and the need for using a highly-correlated theoretical method including geometry optimization in studied molecules

Proton Affinities of Didehydroporphyrin and Subporphyrin in Ground and Excited States Obtained by Quantum Chemical Calculations

Quantum-chemical calculations were used to investigate molecular and electronic properties of porphyrin and subporphyrin. Their basicities were estimated in ground and excited states. It was found that multiple proton - nitrogen lone-pair coordination plays an important role in acid/base properties of the studied molecules. Lone pair-lone pair interactions in didehydroporphyrin and energetic stabilization of its protonated form lead to the increase of a proton affinity compared to porphyrin by 18 kcal mol(-1). A planarization of the protonated (dehydroporphyrin) structure leads to the complete reversal of the pi-electron ring currents indicating aromaticity of the protonated form. On the other hand, calculations indicate that subporphyrin is slightly (by 5 kcal mol(-1)) more basic than porphyrin, which was explained by non-planar geometry, imposed by smaller ring size

A Computational Insight into Reaction Between Different Amino Acids with Reactive Aldehydes 4-hydroxy-2-nonenal and 4-oxo-2-nonenal

In this work, we studied in detail the reaction mechanism of modification of arginine (Arg), cysteine (Cys) and histidine (His) model amino acids upon the reaction with biologically relevant reactive aldehydes 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) in acetonitrile and acetonitrile/water systems by using high level ab initio calculations. We identified and characterized all of the reaction steps along two possible pathways – Michael addition pathway and Schiff base pathway resulting in the formation of Michael adducts/hemiacetals and carbinolamine/Schiff base adducts, depending on the reactive aldehyde and the reaction pathway. Overall energetics suggests that Arg amino acid is more reactive than Cys and His amino acids in both reaction pathways. We established that the ONE is in general more reactive than HNE and also found out that addition of water in the reaction steps involving proton transfer strongly catalyzes the reaction by decreasing prohibitively high free energy barriers. This work is licensed under a Creative Commons Attribution 4.0 International License

Proton Affinities of Didehydroporphyrin and Subporphyrin in Ground and Excited States Obtained by Quantum Chemical Calculations

Quantum-chemical calculations were used to investigate molecular and electronic properties of porphyrin and subporphyrin. Their basicities were estimated in ground and excited states. It was found that multiple proton - nitrogen lone-pair coordination plays an important role in acid/base properties of the studied molecules. Lone pair-lone pair interactions in didehydroporphyrin and energetic stabilization of its protonated form lead to the increase of a proton affinity compared to porphyrin by 18 kcal mol−1. A planarization of the protonated (dehydroporphyrin) structure leads to the complete reversal of the π-electron ring currents indicating aromaticity of the protonated form. On the other hand, calculations indicate that subporphyrin is slightly (by 5 kcal mol−1) more basic than porphyrin, which was explained by non-planar geometry, imposed by smaller ring size

How Cardiolipin Peroxidation Alters the Properties of the Inner Mitochondrial Membrane?

Cardiolipins have multiple vital functions within biological cell membranes, most notably in the energy metabolism associated with the inner mitochondrial membrane. Considering their essential role, peroxidation of cardiolipins may plausibly have significant effects, as peroxidation is known to alter the functionality of lipid molecules. We used atomistic molecular dynamics simulations to study how peroxidation of cardiolipin affects the properties of the inner mitochondrial membrane. To this end, we explored what happens when varying fractions of fatty acid chains of cardiolipin are replaced by its four different oxidized products in systems modeling the inner mitochondrial membrane. We found that the oxidation of cardiolipin leads to a conformational change both in the backbone/head group and in chain regions of oxidized cardiolipin molecules. The oxidized groups were observed to shift closer to the membrane-water interface region, where they formed hydrogen bonds with several other groups. Additionally, the conformational change turned out to decrease bilayer thickness, and to increase the area per lipid chain, though these changes were minor. The acyl chain conformational order of unoxidized lipids exposed to interactions with oxidized cardiolipins was increased in carbons 3–5 and decreased in carbons 13–17 due to the structural reorganization of the cardiolipin molecules. Overall, the results bring up that the conformation of cardiolipin is altered upon oxidation, suggesting that its oxidation may interfere its interactions with mitochondrial proteins and thereby affect cardiolipin-dependent cellular processes such as electron and proton transport.Peer reviewe