Photoelectron transfer processes leading to DNA cleavages

We have limited this section to the discussion of DNA cleavages resulting from direct photoelectron transfer processes from a DNA base to the excited state of a photosensitizer.46 By modulating the photosensitizer's absorption spectrum, the photo-oxidation can occur with genetic material situated at different depths in tissues. For example, some authors studied derivatives of RuII-2,3-naphthalocyanine (Figure 19.7) that are characterized by a huge absorption in the 'phototherapeutic window' (650-850 nm) where the depth of light penetration into mammalian tissues is maximum.45 RuII-2,3-naphthalocyanine compounds were shown to be active in vitro against cancer cells, most probably via an electron transfer process since singlet oxygen was not detected in solution.61

Figure 19.7 RuII-2,3-naphthalocyanine derivatives. L can be different ligands such as benzonitrile, pyridinesulfonate, aminoethanesulfonate, alanine, etc. The choice of these ligands influences the solubility of the complex as well as its physical and biological properties

Besides, it has been demonstrated that a photo-induced electron transfer takes place from a guanine (electron donor) to the 3MLCT excited state of some Ru11 complexes containing p-deficient ligands such as TAP (1,4,5,8-tetraazaphenanthrene) (Figure 19.8a), HAT (1,4,5,8,9,12-hexaazatriphenylene) (Figure 19.8b) or BPZ (2,2'-bipyrazine) (Figure 19.8c) (electron acceptors).48,49,62 64 Indeed, these ligands are known to stabilize the HOMO (highest occupied molecular orbital)

Figure 19.8 Photo-oxidizing Run complexes. (a) [RuII(TAP)3]2+, (b) [RuII(HAT)3]2+, (c) [RuII(BPZ)3]2+

and LUMO (lowest unoccupied molecular orbital) orbitals of the complex, which makes the complex much more oxidizing in the excited state.

For example, the reduction potential of [RuII(TAP)3]2+ (Figure 19.8a) in its ground state (addition of one electron to the LUMO orbital of the complex) is negative versus the saturated calomel electrode (SCE) (rather high in energy) and obviously not positive enough (not low enough in energy) to abstract an electron from a guanine moiety (Figure 19.9).

In contrast, in the excited state, the reduction potential of the complex becomes positive because the electron from the guanine moiety can be added in the semi-occupied HOMO of the complex. In this way, the charge transfer process becomes exergonic and the excited state of the complex is thus able to abstract an electron from the guanine donor (Figure 19.9). In agreement with this, the luminescence of the complex is quenched by the GMP (guanosine-50-monophosphate).65 The electron transfer corresponding to this luminescence extinction has been demonstrated by laser flash photolysis experiments. Indeed, the differential absorption spectrum obtained after the pulsed excitation (i.e. after reduction of the excited complex by GMP) is similar to that obtained when the complex is reduced by pulse radiolysis or electrochemically.65

Complex in the ground state

Complex

Electron donor

LUMO

HOMO dn

Complex in the excited state

LUMO

Complex

Electron donor

Mono-reduced complex

Mono-oxidized donor

HOMO dn

Figure 19.9 Schematic representation of the HOMO/LUMO orbitals of a Ru11 complex and an electron donor (GMP for example). When the complex is in the ground state, the electron transfer is endergonic; in the excited state the electron transfer becomes exer-gonic and leads to the formation of the mono-reduced complex and the mono-oxidized donor (GMP'+ for example)

[RuII(TAP)3]2+ + GMP -! [RuII(TAP)2(TAP-)]+ + GMP*+

Such an electron transfer has also been observed in the presence of DNA and with other complexes containing at least two p-deficient ligands.48,49,63 As in the case of singlet oxygen production, gel electrophoresis studies with plasmid DNA after illumination with this type of complex have shown that the formation of the radical cation on the guanine is the reason for efficient DNA cleavages.46,50,51,66

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