Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6-Mercaptopurine†,Photochemistry and Photobiology

当前位置： X-MOL 学术 › Photochem. Photobiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6-Mercaptopurine†
Photochemistry and Photobiology ( IF 2.6 ) Pub Date : 2021-09-04 , DOI: 10.1111/php.13513
Luis A Ortiz-Rodríguez ₁ , Glesmarie Ortiz-Zayas ₁ , Marvin Pollum ₁ , Sean J Hoehn ₁ , Steffen Jockusch ₂ , Carlos E Crespo-Hernández ₁

Affiliation

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.

中文翻译：

硫唑嘌呤前药中的分子内电荷转移可淬灭 6-巯基嘌呤中的系统间交叉至反应性三重态†

硫嘌呤前药 6-巯基嘌呤和硫唑嘌呤是世界上治疗急性淋巴细胞白血病、免疫抑制和几种自身免疫疾病的必需药物。硫嘌呤前体药物是有效的 UVA 吸收剂和单线态氧发生器，长期使用这些前体药物治疗与患者日光诱发皮肤癌的高发病率相关。在这项贡献中，我们表明硫唑嘌呤的电子弛豫机制和光化学性质在吸收 UVA 辐射时与 6-巯基嘌呤的电子弛豫机制和光化学性质显着不同。6-巯基嘌呤的 UVA 激发导致近 100% 三重态产率和高达 30% 的单重态氧产生，而硫唑嘌呤与 UVA 的激发导致三重态产率 15-3%，具体取决于水溶液的 pH 值和 < 1% 单线态氧生成。虽然 6-巯基嘌呤和其他硫嘌呤前药的光激发可以促进氧化产生的细胞损伤，但硫唑嘌呤较差的光敏能力揭示了使用发色团间电荷转移相互作用来设计光稳定前药的分子设计，从而在药物代谢前显着降低光细胞毒性副作用。

更新日期：2021-09-04

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11