Photocrosslinking between nucleic acids and proteins: general discussion (original) (raw)
Related papers
Bi-photonic Ionization of DNA: From Model Studies to Cell
Photochemistry and Photobiology
Oxidation reactions triggered by low-intensity UV photons represent a minor contribution with respect to the overwhelming pyrimidine base dimerization in both isolated and cellular DNA. The situation is totally different when DNA is exposed to high-intensity UVC radiation under conditions where biphotonic ionization of the four main purine and pyrimidine bases becomes predominant at the expense of singlet excitation processes. The present review article provides a critical survey of the main chemical reactions of the base radical cations thus generated by one-electron oxidation of nucleic acids in model systems and cells. These include oxidation of the bases with the predominant formation of 8-oxo-7,8-dihydroguanine as the result of preferential hole transfer to guanine bases that act as sinks in isolated and cellular DNA. In addition to hydration, other nucleophilic addition reactions involving the guanine radical cation give rise to intra-and interstrand cross-links together with DNA-protein cross-links. Information is provided on the utilization of high-intensity UV laser pulses as molecular biology tools for studying DNA conformational features, nucleic acid-protein interactions and nucleic acid reactivity through DNA-protein cross-links and DNA footprinting experiments.
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 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.
Quantum Mechanics in Biology: Photoexcitations in DNA
2009
We consider here the theoretical and quantum chemical description of the photoexcitated states in DNA duplexes. We discuss the motivation and limitations of an exciton model and use this as the starting point for more detailed excited state quantum chemical evaluations. In particular, we focus upon the role of interbase proton transfer between Watson/Crick pairs in localizing an excitation and then quenching it through intersystem crossing and charge transfer.
Photochemistry and Photobiology, 2002
The 266 nm nanosecond laser photolysis of various purine and pyrimidine derivatives results in their photoionization (PI) as one of the primary photochemical pathways. Electron photoejection occurs through a combination of one-and two-photon mechanisms. The PI values depend on the substituents attached to the chromophore of the base. The net PI of the purine bases at 266 nm are of the same order of magnitude (10 Ϫ2 ) as those of the pyrimidine bases under similar experimental conditions. The monophotonic component is approximately one-third of the net PI yield of the bases. A nonrelaxed singlet excited state intermediate is tentatively proposed for this pathway. It is proposed that this state is significantly stabilized by water solvation, transforming it into a charge transfer to solvent state from which the hydrated electron evolves.
Journal of the American Chemical Society, 2007
DNA multiply charged anions stored in a quadrupole ion trap undergo one-photon electron ejection (oxidation) when subjected to laser irradiation at 260 nm (4.77 eV). Electron photodetachment is likely a fast process, given that photodetachment is able to compete with internal conversion or radiative relaxation to the ground state. The DNA [6-mer] 3ions studied here show a marked sequence dependence of electron photodetachment yield. Remarkably, the photodetachment yield (dG6 > dA6 > dC6 > dT6) is inversely correlated with the base ionization potentials (G < A < C < T). Sequences with guanine runs show increased photodetachment yield as the number of guanine increases, in line with the fact that positive holes are the most stable in guanine runs. This correlation between photodetachment yield and the stability of the base radical may be explained by tunneling of the electron through the repulsive Coulomb barrier. Theoretical calculations on dinucleotide monophosphates show that the HOMO and HOMO-1 orbitals are localized on the bases. The wavelength dependence of electron detachment yield was studied for dG 6 3-. Maximum electron photodetachment is observed in the wavelength range corresponding to base absorption (260-270 nm). This demonstrates the feasibility of gas-phase UV spectroscopy on large DNA anions. The calculations and the wavelength dependence suggest that the electron photodetachment is initiated at the bases and not at the phosphates. This also indicates that, although direct photodetachment could also occur, autodetachment from excited states, presumably corresponding to base excitation, is the dominant process at 260 nm. Excited-state dynamics of large DNA strands still remains largely unexplored, and photo-oxidation studies on trapped DNA multiply charged anions can help in bridging the gap between gas-phase studies on isolated bases or base pairs and solution-phase studies on full DNA strands.
Theoretical ionization and capture cross sections for DNA nucleobases impacted by light ions
International Journal of Radiation Biology, 2012
Although DNA lesions are considered of prime importance for describing the post-irradiation cellular survival, they still remain rarely studied on both experimental and theoretical sides. Under these conditions, we here propose different theoretical models for predicting the single ionization and single capture total cross sections for DNA bases impacted by protons. Three theoretical approaches are developed: a first classical one based on a classical trajectory Monte Carlo (CTMC) model and two quantum mechanical ones, namely, a Coulomb Born (CB1) and a continuum-distorted wave eikonal-initial-state (CDW-EIS) model. Ionization and capture processes induced by protons on DNA bases (adenine, cytosine, thymine and guanine) are here studied in terms of total cross sections. A very good agreement is obtained between the different models at high enough impact velocities but discrepancies are observed between them at low impact energies (E(i) ≤ 100 keV). Furthermore, it is shown that the theoretical cross sections underestimate the rare existing experimental data in particular for adenine and thymine whereas a reasonable agreement is found for cytosine.