Triplet-Energy Quenching Functions of Antioxidant Molecules
UV-like DNA damage is created in the dark by chemiexcitation, in which UV-activated enzymes generate reactive oxygen and nitrogen species that create a dioxetane on melanin. Thermal cleavage creates an electronically excited triplet-state carbonyl whose high energy transfers to DNA. Screening natura...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/11/2/357 |
| _version_ | 1797483203271852032 |
|---|---|
| author | Carlos Angelé-Martínez Leticia Christina Pires Goncalves Sanjay Premi Felipe A. Augusto Meg A. Palmatier Saroj K. Amar Douglas E. Brash |
| author_facet | Carlos Angelé-Martínez Leticia Christina Pires Goncalves Sanjay Premi Felipe A. Augusto Meg A. Palmatier Saroj K. Amar Douglas E. Brash |
| author_sort | Carlos Angelé-Martínez |
| collection | DOAJ |
| description | UV-like DNA damage is created in the dark by chemiexcitation, in which UV-activated enzymes generate reactive oxygen and nitrogen species that create a dioxetane on melanin. Thermal cleavage creates an electronically excited triplet-state carbonyl whose high energy transfers to DNA. Screening natural compounds for the ability to quench this energy identified polyenes, polyphenols, mycosporine-like amino acids, and related compounds better known as antioxidants. To eliminate false positives such as ROS and RNS scavengers, we then used the generator of triplet-state acetone, tetramethyl-1,2-dioxetane (TMD), to excite the triplet-energy reporter 9,10-dibromoanthracene-2-sulfonate (DBAS). Quenching measured as reduction in DBAS luminescence revealed three clusters of 50% inhibitory concentration, ~50 μM, 200–500 μM, and >600 μM, with the former including sorbate, ferulic acid, and resveratrol. Representative triplet-state quenchers prevented chemiexcitation-induced “dark” cyclobutane pyrimidine dimers (dCPD) in DNA and in UVA-irradiated melanocytes. We conclude that (i) the delocalized pi electron cloud that stabilizes the electron-donating activity of many common antioxidants allows the same molecule to prevent an electronically excited species from transferring its triplet-state energy to targets such as DNA and (ii) the most effective class of triplet-state quenchers appear to operate by energy diversion instead of electron donation and dissipate that energy by isomerization. |
| first_indexed | 2024-03-09T22:44:35Z |
| format | Article |
| id | doaj.art-75e1a84de21d4d788a53be3d93a2d644 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T22:44:35Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-75e1a84de21d4d788a53be3d93a2d6442023-11-23T18:32:32ZengMDPI AGAntioxidants2076-39212022-02-0111235710.3390/antiox11020357Triplet-Energy Quenching Functions of Antioxidant MoleculesCarlos Angelé-Martínez0Leticia Christina Pires Goncalves1Sanjay Premi2Felipe A. Augusto3Meg A. Palmatier4Saroj K. Amar5Douglas E. Brash6Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USADepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USADepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USADepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USADepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USADepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USADepartment of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520-8040, USAUV-like DNA damage is created in the dark by chemiexcitation, in which UV-activated enzymes generate reactive oxygen and nitrogen species that create a dioxetane on melanin. Thermal cleavage creates an electronically excited triplet-state carbonyl whose high energy transfers to DNA. Screening natural compounds for the ability to quench this energy identified polyenes, polyphenols, mycosporine-like amino acids, and related compounds better known as antioxidants. To eliminate false positives such as ROS and RNS scavengers, we then used the generator of triplet-state acetone, tetramethyl-1,2-dioxetane (TMD), to excite the triplet-energy reporter 9,10-dibromoanthracene-2-sulfonate (DBAS). Quenching measured as reduction in DBAS luminescence revealed three clusters of 50% inhibitory concentration, ~50 μM, 200–500 μM, and >600 μM, with the former including sorbate, ferulic acid, and resveratrol. Representative triplet-state quenchers prevented chemiexcitation-induced “dark” cyclobutane pyrimidine dimers (dCPD) in DNA and in UVA-irradiated melanocytes. We conclude that (i) the delocalized pi electron cloud that stabilizes the electron-donating activity of many common antioxidants allows the same molecule to prevent an electronically excited species from transferring its triplet-state energy to targets such as DNA and (ii) the most effective class of triplet-state quenchers appear to operate by energy diversion instead of electron donation and dissipate that energy by isomerization.https://www.mdpi.com/2076-3921/11/2/357triplet-stateelectronic excitationchemiexcitationchemiluminescencedioxetaneenergy transfer |
| spellingShingle | Carlos Angelé-Martínez Leticia Christina Pires Goncalves Sanjay Premi Felipe A. Augusto Meg A. Palmatier Saroj K. Amar Douglas E. Brash Triplet-Energy Quenching Functions of Antioxidant Molecules Antioxidants triplet-state electronic excitation chemiexcitation chemiluminescence dioxetane energy transfer |
| title | Triplet-Energy Quenching Functions of Antioxidant Molecules |
| title_full | Triplet-Energy Quenching Functions of Antioxidant Molecules |
| title_fullStr | Triplet-Energy Quenching Functions of Antioxidant Molecules |
| title_full_unstemmed | Triplet-Energy Quenching Functions of Antioxidant Molecules |
| title_short | Triplet-Energy Quenching Functions of Antioxidant Molecules |
| title_sort | triplet energy quenching functions of antioxidant molecules |
| topic | triplet-state electronic excitation chemiexcitation chemiluminescence dioxetane energy transfer |
| url | https://www.mdpi.com/2076-3921/11/2/357 |
| work_keys_str_mv | AT carlosangelemartinez tripletenergyquenchingfunctionsofantioxidantmolecules AT leticiachristinapiresgoncalves tripletenergyquenchingfunctionsofantioxidantmolecules AT sanjaypremi tripletenergyquenchingfunctionsofantioxidantmolecules AT felipeaaugusto tripletenergyquenchingfunctionsofantioxidantmolecules AT megapalmatier tripletenergyquenchingfunctionsofantioxidantmolecules AT sarojkamar tripletenergyquenchingfunctionsofantioxidantmolecules AT douglasebrash tripletenergyquenchingfunctionsofantioxidantmolecules |