title: The Triplet State of 6-thio-2'-deoxyguanosine: Intrinsic Properties and Reactivity Toward Molecular Oxygen.
abstract: Thiopurine prodrugs are currently among the leading treatment options for leukemia, immunosuppression, and arthritis. Patients undergoing long-term thiopurine treatment are at a higher risk of developing sunlight-induced skin cancers than the general population. This side effect originates from the cellular metabolization of thiopurine prodrugs to form 6-thio-2'-deoxyguanosine, which can absorb UVA radiation, populating its reactive triplet state and leading to oxidatively generated damage. However, the photo-oxidation mechanism is not fully understood. In this contribution, the oxidation potential and the adiabatic triplet energy of 6-thio-2'-deoxyguanosine are estimated computationally, whereas the intrinsic rate of triple-state decay and the rate constant for triplet quenching by molecular oxygen are determined using time-resolved spectroscopic techniques. A singlet oxygen quantum yield of 0.24 ± 0.02 is measured in aqueous solution (0.29 ± 0.02 in acetonitrile). Its magnitude correlates with the relatively low percentage of triplet-O2collision events that generate singlet oxygen (SΔ= 37%). This behavior is rationalized as being due to the exergonic driving force for electron transfer between the triplet state of 6-thio-2'-deoxyguanosine and molecular oxygen (ΔGET= -69.7 kJ mol-1), resulting in the formation of a charge-transfer complex that favors nonradiative decay to the ground state over triplet energy transfer.
authors.affiliation: Department of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, OH.
authors.forename: Marvin
authors.initials: M
authors.lastname: Pollum
authors.affiliation: Department of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, OH.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Ortiz-Rodríguez
authors.affiliation: Department of Chemistry, Columbia University, New York, NY.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jockusch
authors.affiliation: Department of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, OH.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Crespo-Hernández
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D011355:Prodrugs; D013872:Thionucleosides / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D013872:Thionucleosides; C002062:alpha-2'-deoxythioguanosine; D003849:Deoxyguanosine; D010100:Oxygen