Strong impact of the solvent on the photokinetics of a 2(1H)-pyrimidinone (original) (raw)
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Pyrimidinone: versatile Trojan horse in DNA photodamage?
Photochemical & Photobiological Sciences, 2015
Photolesions between adjacent pyrimidine DNA bases are prone to secondary photochemistry. It has been shown that singlet excited (6-4) moieties form Dewar valence isomers as well as triplet excitations. We here report on the triplet state of a minimal model for the (6-4) photolesion, 1-methyl-2(1H)pyrimidinone. Emphasis is laid on its ability to abstract hydrogen atoms from alcohols and carbohydrates. Steady-state and time-resolved experiments consistently yield bimolecular rate constants of ∼10 4 M −1 s −1 for the hydrogen abstraction. The process also occurs intramolecularly as experiments on zebularine (1-(β-D-ribofuranosyl)-2(1H)-pyrimidinone) show.
Photochemical & Photobiological Sciences, 2014
Excited state dynamics of four azinium salts were studied in buffered water and in the presence of salmon testes DNA. Complexation with DNA changes the photobehaviour of the free ligands lowering the photoreactivity and emission in favor of internal conversion. The interaction of these four dyes with DNA was studied with different techniques with the aim to establish the affinity and the type of binding between the ligands and DNA. The results from spectrophotometric and fluorimetric titrations provided evidence of a strong interaction between the azinium salts and the polynucleotide, with a binding constant of about 10 6 M −1 , making them interesting for therapeutical applications. Dichroic measurements allowed us to determine the possible modes of binding for each complex. Short living excited states of the free dyes were detected and characterized by ultrafast absorption spectroscopy. A further decrease of transient lifetimes was observed upon interaction with DNA. The bicationic pyridinium iodide was found to act as a bisintercalative agent, potentially increasing the cytotoxicity with low dose and less collateral effects. † Electronic supplementary information (ESI) available. See
Chemistry - A European Journal, 2015
The main chromophore of (6-4) photoproducts, namely, 5-methyl-2-pyrimidone (Pyo), is an artificial noncanonical nucleobase. This chromophore has recently been reported as a potential photosensitizer that induces triplet damage in thymine DNA. In this study, we investigate the spectroscopic properties of the Pyo unit embedded in DNA by means of explicit solvent molecular-dynamics simulations coupled to time-dependent DFT and quantum-mechanics/ molecular-mechanics techniques. Triplet-state transfer from the Pyo to the thymine unit was monitored in B-DNA by probing the propensity of this photoactive pyrimidine analogue to induce a Dexter-type triplet photosensitization and subsequent DNA damage. Scheme 1. Molecular formula of the (6-4)PP and dPyo subunits.
Photorelaxation and Photorepair Processes in Nucleic and Amino Acid Derivatives
Molecules, 2017
Understanding the fundamental interaction between electromagnetic radiation and matter is essential for a large number of phenomena, with significance to civilization. On the most fundamental level, through the molecular origins of life, photosynthesis, and vision, the interaction between sunlight and matter has played an essential role in nature. Many applications of these interactions continue to revolutionize society through advances in medicine, communications, technology, and entertainment. Electromagnetic radiation is also capable of inducing a myriad of chemical transformations, as illustrated by the photodegradation of DNA and proteins [1-4]. These light-induced reactions have been associated with cancer and other diseases in living organisms [5-7], and photochemical investigations of nucleic and amino acids continue to be at the forefront of research. Photochemical investigations of modified nucleobases are also at the center of research because of their potential role as prebiotic materials of the building blocks of life [8-10] and their prospective applications as phototherapeutic agents [11-13]. Studying the basic interactions of these biological molecules with light may hold the key for a complete understanding of the mechanisms responsible for their photostability and photochemistry. It may also provide fundamental insight for a molecular-level understanding of the mechanisms tied to DNA photorepair. Absorption of ultraviolet or visible radiation by the ground state of a molecule populates electronic states, either directly to an excited singlet state or indirectly to a triplet state after intersystem crossing from the singlet manifold [14]. In both singlet and triplet manifolds, ultrafast internal conversion usually leads to the population of the lowest-energy excited state-the S 1 and T 1 states, respectively. These excited states, although relatively short lived (ca. ≤10 −9 s and ≤10 −6 s for singlet and triplet states, respectively), may live long enough that chemical reactions can compete with radiative or nonradiative decay to the ground state. Energy or charge transfer from an excited singlet/triplet state of a molecule (a.k.a., sensitizer) may also populate an excited singlet/triplet state of another molecule by a photochemical process known as photosensitization. In contemporary organic photochemistry, a microscopic description of the electronic relaxation pathways that a photoexcited molecule explores through nuclear coordinate space usually begins with a representation of a reaction coordinate describing the evolution of reactants to products [15-19]. An important distinction between a photochemical and a photophysical relaxation pathway concerns the initial and final states that the reaction coordinate develops. In a photochemical reaction, these states are different, corresponding to the different structures of the reactant(s) and product(s). In a photophysical process, the relaxation pathway ends where it began-in the electronic ground state. In order to return the molecule to its ground state, the absorbed energy can be released radiatively (i.e., through photon emission; usually from the S 1 or T 1 state), or it can be transformed into vibrational energy that can dissipate nonradiatively into the environment. Internal conversion and intersystem crossing can occur at a higher rate than radiative decay when nuclear motions take a molecule into regions of nuclear configuration space where two or more potential energy hypersurfaces cross. The intersection between potential energy hypersurfaces often create crossing seams or conical intersections, where states of equal multiplicity or singlet/triplet
The Journal of Physical Chemistry Letters, 2022
Oxo and amino substituted purines and pyrimidines have been suggested as protonucleobases participating in ancient pre-RNA forms. Considering electromagnetic radiation as a key environmental selection pressure on early Earth, the investigation of the photophysics of modified nucleobases is crucial to determine their viability as nucleobases' ancestors and to understand the factors that rule the photostability of natural nucleobases. In this Letter, we combine femtosecond transient absorption spectroscopy and quantum mechanical simulations to reveal the photochemistry of 4-pyrimidinone, a close relative of uracil. Irradiation of 4pyrimidinone with ultraviolet radiation populates the S 1 (ππ*) state, which decays to the vibrationally excited ground state in a few hundred femtoseconds. Analysis of the postirradiated sample in water reveals the formation of a 6-hydroxy-5H-photohydrate and 3-(N-(iminomethyl)imino)propanoic acid as the primary photoproducts. 3-(N-(Iminomethyl)imino)propanoic acid originates from the hydrolysis of an unstable ketene species generated from the C4−N3 photofragmentation of the pyrimidine core.
The Journal of Physical Chemistry B, 2014
The photophysical and photochemical properties of 5benzyluracil and 5,6-benzyluracil, the latter produced by photocyclization of the former through irradiation with femtosecond UV laser pulses, are investigated both experimentally and theoretically. The absorption spectra of the two molecules are compared, and the principal electronic transitions involved are discussed, with particular emphasis on the perturbation induced on the two chromophore species (uracil and benzene) by their proximity. The photoproduct formation for different irradiation times was verified with high-performance liquid chromatography and nuclear magnetic resonance measurements. The steady-state fluorescence demonstrates that the fluorescence is a distinctive physical observable for detection and selective identification of 5-and 5,6benzyluracil. The principal electronic decay paths of the two molecules, obtained through TDDFT calculations, explain the features observed in the emission spectra and the photoreactivity of 5-benzyluracil. The order of magnitude of the lifetime of the excited states is derived with steady-state fluorescence anisotropy measurements and rationalized with the help of the computational findings. Finally, the spectroscopic data collected are used to derive the photocyclization and fluorescence quantum yields. In obtaining a global picture of the photophysical and photochemical properties of the two molecules, our findings demonstrates that the use of 5-benzyluracil as a model system to study the proximity relations of a DNA base with a close-lying aromatic amino acid is valid at a local level since the main characteristics of the decay processes from the excited states of the uracil/thymine molecules remain almost unchanged in 5-benzyluracil, the main perturbation arising from the presence of the close-lying aromatic group.
DNA photodamage: Study of cyclobutane pyrimidine dimer formation in a locked thymine dinucleotide
Spectroscopy, 2010
The cyclobutane pyrimidine dimer (CPD) formed between two adjacent thymine bases is the most abundant DNA photolesion induced by UV radiation. The quantum yield of this reaction is on the order of ∼1% in DNA. This small quantum yield hampers the study of damage formation in naturally occurring DNA. Investigations with increased accuracy become possible for a locked nucleotide model compound T L pT L which exhibits a quantum yield of about 10% for CPD formation. Time resolved IR spectroscopy on T L pT L and two other DNA model compounds (TpT and (dT) 18 ) reveals that: (i) The absorption changes after ∼1 ps are due to CPD photodamage. (ii) The quantum efficiency of CPD formation on the few picosecond time scale equals the quantum efficiency reported in stationary experiments. CPD photodamage formation in the investigated DNA constructs is thus predominantly formed from the primarily photoexcited singlet ππ * state, whereas the triplet channel does not play an essential role.