Reaction mechanisms of bioactive molecules: nitrosation and alkylation processes
In recent years, the lowering of conceptual barriers among chemical, biological, medicinal, and environmental problems has been spectacular. Many of these problems
address analogous underlying mechanisms.
As Chemical Kinetics is a transversal field of research, the following aspects are currently under kinetic investigation by our group:
1. The reactivity of alkylating agents, in terms of their ability to form adducts with substrates such as 4-(p-nitrobenzyl)pyridine a molecule of nucleophilicity
similar to that of DNA bases as well as with nucleosides such guanosine, is being studied under biomimetic conditions. The reactivity of different electrophilic species
(lactones, alkylnitrosoureas, diketene) has revealed a correlation between the alkylating potential and the mutagenic/carcinogenic capacity.
The results achieved with alkylating agents such as alkylnitrosoureas, ethylnitrolic acid, and others, have shown that the effective alkylating agents can be intermediate
Our aim is to expand this research, not only in its experimental aspect but also with in silico treatments.
2. In order to gain a better understanding and possibly control of the alkylation mechanisms that may give rise to mutagenesis/carcinogenesis, reactions that
concur with the alkylation reaction itself such as the solvolysis of reagents and products and adduct stability are being investigated.
3.Since in previous stages of our work it was found that some nitrosation mechanisms (of aminoacids with an -NH2 group) are precursors to alkylating agents of
highly mutagenic character, we are now studying nitrosation mechanisms which, either per se (the nitrosation of taurine and derivatives, the nitrosation of minoxidil) or
through the concurrence of alkylating and nitrosating species (nitrites and sorbates used together as food preservatives), could give rise to the formation of mutagenic species.
Our ultimate goal is to achieve a closer approach to the in vivo alkylation mechanisms that give rise to mutagenic effects and to search for the conditions suitable to
block/inhibit them, not just interpretatively but also with prediction in mind.
With this aim, our group has promoted collaboration among scientists from diverse areas of specialization (chemistry, biology, engineering, environmental and medical
sciences) with a view to integrating their collective knowledge within a broad area of research.
We thank the European Union, the Spanish Ministerio de Economía y Competitividad, and the European Regional Development Fund for supporting the research efforts of our group.