Role of Hydrogen Bonding by Thiones in Protecting Biomolecules from Copper(I)-Mediated Oxidative Damage
Abstract
The sulfur-containing antioxidant molecule ergothioneine with an ability to protect metalloenzymes from reactive oxygen species (ROS) has attracted significant interest in both chemistry and biology. Herein, we demonstrated the importance of hydrogen bonding in S-oxygenation reactions between various thiones and H 2 O 2 and its significance in protecting the metal ion from H 2 O 2 -mediated oxidation. Among all imidazole- and benzimidazole-based thiones ( 1 – 10 ), Im Me S H ( 2 ) showed the highest reactivity toward H 2 O 2 —almost 10 and 75 times more reactive than N, N′ -disubstituted Im Me S Me ( 5 ) and Bz Me S Me ( 10 ), respectively. Moreover, metal-bound Im Me S H ( 2 ) of [TpmCu( 2 )] + ( 13 ) was found to be 51 and 1571 times more reactive toward H 2 O 2 than the metal-bound Im Me S Me ( 5 ) of [TpmCu( 5 )] + ( 16 ), and Bz Me S Me ( 10 ) of [TpmCu( 10 )] + ( 21 ), respectively. The electron-donating N–Me substituent and the free N–H group at the imidazole ring played a very crucial role in the high reactivity of Im Me S H toward H 2 O 2 . The initial adduct formation between Im Me S H and H 2 O 2 (Im Me S H ·H 2 O 2 ) was highly facilitated (−23.28 kcal mol –1 ) due to the presence of a free N–H group, which leads to its faster oxygenation than N, N′ -disubstituted Im Me S Me ( 5 ) or Bz Me S Me ( 10 ). As a result, Im Me S H ( 2 ) showed a promising effect in protecting the metal ion from H 2 O 2 -mediated oxidation. It protected biomolecules from Cu(I)-mediated oxidative damage of through coordination to the Cu(I) center of [TpmCu(CH 3 CN)] + ( 11 ), whereas metal-bound Im Me S Me or Bz Me S Me failed to protect biomolecules under identical reaction conditions.
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ERG has been shown to protect against a range of oxidative and toxic insults, including decreasing oxidative stress in rat liver and kidney, rescuing cells from β-amyloid-induced apoptotic death, protecting against palmitic acid-induced cell death, mercuric chloride-induced cellular dysfunction, and Cu-induced oxidative DNA damage.
“ERG has been shown to decrease oxidative stress in the liver and kidney of rats(469), rescued cells from β-amyloid-induced apoptotic death(231), protected against palmitic acid-induced cell death(470), mercuric chloride-induced cellular dysfunction(471), and prevented Cu-induced oxidative damage to DNA(472,473).”
From The biology of ergothioneine, an antioxidant nutraceutical (2020) · cites this paper as [472]
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- Authors
- Rai, R. K., Chalana, A., Karri, R., Das, R., Kumar, B., & Roy, G.
- Affiliations
- Shiv Nadar University (IN)
- Corresponding author
- Roy, Gouriprasanna
- Venue
- Inorganic Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2019-05-08
- Volume
- 58
- Issue
- 10
- Pages
- 6628-6638
- ISSN
- 0020-1669 (ISSN-L)
- 1520-510X
- OpenAlex
- W2943936318
- Cited by
- 19
- References
- 50
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 7
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Inorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Indo-French Centre for the Promotion of Advanced Research (5605-1)
- Shiv Nadar University
- Shiv Nadar Foundation
- Topics
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- ergothioneine, thiones, hydrogen bonding, copper(I) complexes, hydrogen peroxide, metal protection, N-H group, reactive oxygen species
- MeSH terms
- Antioxidants, Benzimidazoles, Copper, Hydrogen Bonding, Hydrogen Peroxide, Oxidation-Reduction, Oxygen, Thiones, Molecular Structure, Reactive Oxygen Species, Oxidative Stress
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