Model studies of the (6–4) photoproduct photoreactivation: efficient photosensitized splitting of thymine oxetane units by covalently linked tryptophan in high polarity solvents

Abstract

Three covalently linked tryptophan-thymine oxetane compounds used as a model of the (6-4) photolyase-substrate complex have been prepared. Under 290 nm light, efficient splitting of the thymine oxetane with aromatic carbonyl compounds gives the thymine monomer and the corresponding carbonyl compounds by the covalently linked tryptophan via an intramolecular electron transfer, and exhibits a strong solvent dependence: the quantum yield (Phi) is ca. 0.1 in dioxane, and near 0.3 in water. Electron transfer from the excited tryptophan residue to the oxetane unit is the origin of fluorescence quenching of the tryptophan residue, and is more efficient in strong polar solvents. The splitting efficiency of the oxetane radical anion within the tryptophan.+-oxetane.- species is also solvent-dependent, ranging from ca. 0.2 in dioxane to near 0.35 in water. Thus, the back electron transfer reaction in the charge-separated species would be suppressed in water, but is still a main factor causing low splitting efficiencies in the tryptophan-oxetane systems. In contrast to the tryptophan-oxetane system, fast nonradiation processes are the main causes of low efficiency in the flavin-oxetane system. Hence, nonradiative processes of the excited FADH-, rather than electron transfer to oxetane, may be an important factor for the low repair efficiency of (6-4) photolyase.

Cytotoxicity Induced by Tetracyclines via Protein Photooxidation

“…Literature reports that tryptophan is the most susceptible residue to photooxidation on BSA, while tyrosine is the main photo-damaged residue in RNase A. Results, herein presented, are in perfect accord with the data available in literature [33][34][35].…”

“…Reference [38,48] Reference [3,[27][28][29] Reference [4,[35][36][37][38][39] Reference [6,41] Scheme 2: Strategy of experiment. The four assays chosen were (a) the relative rates of TCs photodegradation, (b) the relative phototoxicity of TCs to human keratinocytes, (c) the binding to model proteins (BSA and RNase A), and (d) the photoreaction with specific amino acids and the relative amount of photo oxidation.…”

Investigation of the Pathways of Excess Electron Transfer in DNA with Flavin‐Donor and Oxetane‐Acceptor Modified DNA Hairpins

“…Similar to the repair of (6-4) lesions by the flavin containing (6-4) photolyases [38][39][40] the cleavage involves an excess electron transfer from the flavin to the oxetane. [25,26,28,32] The presence of a reductive cleavage mechanism is supported by the fact that the flavin was required in the reduced and deprotonated state in which it can only donate and not accept an electron. Secondly, the observed sequence and distance dependence of the cleavage process is in accord with other systems that depend on electron donation into the duplex rather than electron abstraction and hole transfer.…”

“…[26,28,32] The hairpin series 2 a-d contains an oxetane, which is positioned close to the duplex. The assumed structure of the hairpins containing acceptor 2 is depicted as the result of a modeling study in Figure 2a.…”

Hetero-cycloreversions Mediated by Photoinduced Electron Transfer

“…1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 concentration and solvent-dependent; they are much higher for the oxetane-indole supramolecular systems than for the equivalent covalently-linked models ( Figure 6). 42 .…”