BECAS FULBRIGHT / FUNDACIÓN BUNGE Y BORN / FUNDACIÓN WILLIAMS

Concurso

2016

Photochemical and photophysical properties of novel Re(I)-Betacarbolines (βCs) complexes and their interaction with DNA

Iván Maisuls

University of Notre Dame

This project aims to understand the photochemical and photophysical behavior of novel transition metal complexes with natural alkaloids (β-Carbolines). These alkaloids are endogenously synthesized in mammals, and are involved in many biological processes. Also, a large spectrum of psychopharmacological, biological and toxicological activities has been reported for some derivatives, acting as antioxidants, antitumor and antimicrobial agents. These alkaloids have an active role in different photosensitizing processes For example; under UVA irradiation some derivatives can damage plasmidic DNA (bacterial DNA). Also some derivatives, under UVA irradiation have antiviral properties. In plants, it has been demonstrated that these alkaloids would have a specific participation in defense mechanisms, mediated by phototoxic effects, against insects, worms and other invasive agents. Also, responsibility in various neurodegenerative pathologies, such as Alzheimer has been proposed. This reduces the applicability of using these alkaloids as systemic drugs. Therefore the search of novel βCs derivatives with no toxic effects on DNA is of keen importance. Being that Re(I) tricarbonyl complexes, XRe(CO)3L, continue to attract the attention of researchers due to their applicability in several areas , there are good candidates to evaluate as novel βCs derivatives. As these Re(I) tricarbonyl complexes show exceptionally rich excited-state behavior and redox chemistry as well as thermal and photochemical stability. In our laboratory we have synthesized and full characterized several βC derivatives as well as five Rhenium complexes with βCs as ligands. Although these novel complexes show interesting properties, the full photophysical characterization is still needed. In our research group we recently discovered that some derivatives of βCs can interact and produce photoinduced damage to DNA. Therefore, is important to characterize the Re(I)-βCs complexes as well as the adducts formed with them and DNA in order to understand this mechanism. We suggest that rhenium complexes with norharmane (or another βC) will enhance the properties of the free βCs, nevertheless the possible mechanisms involved in these processes are not known. Using techniques as Laser Flash Photolysis, Pulse Radiolysis, and Electron Paramagnetic Resonance is going to be possible to deeply understand the photochemistry behavior of the Re(I)-βCs complexes, as well as the adducts with DNA fragments. The latter studies would contribute to further understand and evaluate the potential use of these compounds in photodynamic therapy, the medical procedure where light is used as a tool to destroy unwanted tissue (e.g., cancer cells), among others.

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