Intramolecular Charge Transfer in the Azathioprine Prodrug Quenches Intersystem Crossing to the Reactive Triplet State in 6-Mercaptopurine†.
Luis A Ortiz-RodríguezGlesmarie Ortiz-ZayasMarvin PollumSean J HoehnSteffen JockuschMaurizio PersicoPublished in: Photochemistry and photobiology (2021)
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.
Keyphrases
- energy transfer
- acute lymphoblastic leukemia
- quantum dots
- end stage renal disease
- aqueous solution
- skin cancer
- chronic kidney disease
- ejection fraction
- newly diagnosed
- drug induced
- multiple sclerosis
- prognostic factors
- risk factors
- oxidative stress
- high glucose
- stem cells
- single molecule
- radiation therapy
- emergency department
- allogeneic hematopoietic stem cell transplantation
- cancer therapy
- diabetic rats
- endothelial cells
- patient reported outcomes
- drug delivery
- mesenchymal stem cells
- drug release