Photosensitized electron transfer within a self-assembled norharmane–2′-deoxyadenosine 5′-monophosphate (dAMP) complex

Abstract

Norharmane is a compound that belongs to a family of alkaloids called β-carbolines (βCs). These alkaloids are present in a wide range of biological systems, playing a variety of significant photo-dependent roles. Upon UV-A irradiation, βCs are able to act as efficient photosensitizers. In this work, we have investigated the photosensitized oxidation of 2'-deoxyadenosine 5'-monophosphate (dAMP) by norharmane in an aqueous phase, upon UV-A (350 nm) irradiation. The effect of the pH was evaluated on both the interactions between norharmane and dAMP in the ground and electronic excited states, and on the dAMP photosensitized oxidation. A quite strong static interaction between norharmane and dAMP was observed, especially under those pH conditions where the protonated form of the alkaloid is present (pH < 7). Theoretical studies were performed to further characterize the static complex structure. The participation of reactive oxygen species (ROS) in the photosensitized reaction was also investigated and the photoproducts were characterized by means of UV-LDI-MS and ESI-MS. All the data provided herein indicate that electron transfer (Type I) within a self-assembled norharmane-dAMP complex is the operative mechanism in the dAMP photosensitization.

Chemical and photochemical properties of chloroharmine derivatives in aqueous solutions

“…23 Despite their abundance, the main biological role of these alkaloids as well as many fundamental aspects of the mechanisms involved still remain poorly understood; as consequence the potential use of synthetically modified (halogenated) βCs still is not clearly known. Moreover, taking into account that non-halogenated βCs are photoactive compounds [24][25][26][27][28][29][30] and having in mind their abundance in nature (including phototrophic organisms), 11 the photochemical and photobiological properties of halogenated-βCs deserve to be explored in detail.…”

UVA Photoactivation of Harmol Enhances Its Antifungal Activity against the Phytopathogens Penicillium digitatum and Botrytis cinerea

“…Mechanistically, photodynamic effects can be a consequence of a direct reaction of the excited state of the photosensitizer with biomolecules and/or structural constituents of the fungi (i.e., Type-I reactions) or indirectly via ROS (i.e., Type-II reactions; Foote, 1991). Previous findings for other βC derivatives suggest that Type I reactions seem to be responsible for the damage generation (Gonzalez et al, 2010, 2012a). In the case of harmol, a similar pattern would be expected as the most probable mechanism of action.…”

“…Some βC alkaloids have been described as efficient photosensitizers in acidic conditions (Gonzalez et al, 2009b, 2012a). Thus, toxicity of electronically photoexcited harmol was screened at pH 5, exposing the treatments to UVA irradiation ( Table 1 ).…”

“…In agreement, cationic species guides antimicrobial properties of different molecules (Boman, 1994; Ladokhin et al, 1997; Matsuzaki et al, 1997; Muñoz et al, 2006). In addition, it has been reported that changes in βCs electronic ground state distribution at different pH have a strong effect on chemical and binding properties of these compounds (Gonzalez et al, 2010, 2012a,b, 2014; Vignoni et al, 2013). …”

“…They are also recognized as photochemically active substances. Upon UVA photoexcitation, these alkaloids are able to photoinduce damage on biologically relevant macromolecules (Hazen and Gutierrez-Gonzalvez, 1988; Gonzalez et al, 2010, 2012a,b; Vignoni et al, 2013, 2014) as well as to inactivate bacteria and viruses (McKenna and Towers, 1981; Hudson et al, 1986). …”