title: The origin of efficient triplet state population in sulfur-substituted nucleobases.
abstract: Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. Although it has long been established that the phototherapeutic activity of thiobases is intimately linked to efficient intersystem crossing into reactive triplet states, the molecular factors underlying this efficiency are poorly understood. Herein we combine femtosecond transient absorption experiments with quantum chemistry and nonadiabatic dynamics simulations to investigate 2-thiocytosine as a necessary step to unravel the electronic and structural elements that lead to ultrafast and near-unity triplet-state population in thiobases in general. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases. These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero.
authors.affiliation: Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 17, Vienna 1090, Austria.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Mai
authors.affiliation: Center for Chemical Dynamics and Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors.forename: Marvin
authors.initials: M
authors.lastname: Pollum
authors.affiliation: Universidad Autónoma de Madrid, Departamento de Química, Cantoblanco, Madrid 28049, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Martínez-Fernández
authors.affiliation: Center for Chemical Dynamics and Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Dunn
authors.affiliation: Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 17, Vienna 1090, Austria.
authors.forename: Philipp
authors.identifier: http://orcid.org/0000-0002-8711-1533
authors.initials: P
authors.lastname: Marquetand
authors.affiliation: Universidad Autónoma de Madrid, Departamento de Química, Cantoblanco, Madrid 28049, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Corral
authors.affiliation: Center for Chemical Dynamics and Department of Chemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Crespo-Hernández
authors.affiliation: Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 17, Vienna 1090, Austria.
authors.forename: Leticia
authors.initials: L
authors.lastname: González
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D010778:Photochemotherapy; D010789:Phototherapy; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry; D026082:Singlet Oxygen / Q000737:chemistry*; D013053:Spectrophotometry; D013455:Sulfur / Q000737:chemistry*; D013816:Thermodynamics; D013941:Thymine
chemical_list: D000970:Antineoplastic Agents; D026082:Singlet Oxygen; C058511:2-thiocytosine; D012313:RNA; D013455:Sulfur; D003596:Cytosine; D004247:DNA; D013941:Thymine