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ABSTRACT Criegee intermediates make up a class of molecules that are of significant atmospheric importance. Understanding their electronically excited states guides experimental detection and provides insight into whether solar photolysis plays a role in their removal from the troposphere. The latter is particularly important for large and functionalized Criegee intermediates. In this study, the excited state chemistry of two small Criegee intermediates, formaldehyde oxide (CH2OO) and acetaldehyde oxide (CH3CHOO), was modeled to compare their specific dynamics and mechanisms following excitation to the bright ππ* state and to assess the involvement of triplet states to the excited state decay process. Following excitation to the bright ππ* state, the photoexcited population exclusively evolves to form oxygen plus aldehyde products without the involvement of triplet states. This occurs despite the presence of a more thermodynamically stable triplet path and several singlet/triplet energy crossings at the Franck‐Condon geometry and contrasts with the photodynamics of related systems such as acetaldehyde and acetone. This work sets the foundations to study Criegee intermediates with greater molecular complexity, wherein a bathochromic shift in the electron absorption profiles may ensure greater removalviasolar photolysis.
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Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6‐Mercaptopurine †
Abstract The thiopurine prodrugs 6‐mercaptopurine and azathioprine are among the world’s essential medications for acute lymphoblastic leukemia, immunosuppression and several autoimmune conditions. Thiopurine prodrugs are efficient UVA absorbers and singlet oxygen generators and the long‐term treatment with these prodrugs correlates with a high incidence of sunlight‐induced skin cancer in patients. In this contribution, we show that the electronic relaxation mechanisms and photochemical properties of azathioprine are remarkably different from those of 6‐mercaptopurine upon absorption of UVA radiation. UVA excitation of 6‐mercaptopurine results in nearly 100% triplet yield and up to 30% singlet oxygen generation, whereas excitation of azathioprine with UVA leads to triplet yields of 15–3% depending on pH of the aqueous solution and <1% singlet oxygen generation. While photoexcitation of 6‐mercaptopurine and other thiopurine prodrugs can facilitate oxidatively generated cell damage, azathioprine's poor photosensitization ability reveals the use of interchromophoric charge‐transfer interactions for the molecular design of photostable prodrugs exhibiting a remarkable reduction in photocytotoxic side effects before drug metabolization.
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- Award ID(s):
- 1800052
- PAR ID:
- 10367668
- Publisher / Repository:
- Wiley-Blackwell
- Date Published:
- Journal Name:
- Photochemistry and Photobiology
- Volume:
- 98
- Issue:
- 3
- ISSN:
- 0031-8655
- Page Range / eLocation ID:
- p. 617-632
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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