Solvation and Protonation of Coumarin 102 in Aqueous Media - a Fluorescence Spectroscopic and Theoretical Study

The ground and excited state protonation of Coumarin 102 (C102), a fluorescent probe applied frequently in heterogeneous systems with an aqueous phase, has been studied in aqueous solutions by spectroscopic experiments and theoretical calculations. For the dissociation constant of the protonated form in the ground state, was obtained from the absorption spectra, for the excited state dissociation constant was obtained from the fluorescence spectra. These values were closely reproduced by theoretical calculations via a thermodynamic cycle – the value of also by calculations via the Förster cycle - using an implicit-explicit solvation model (polarized continuum model + addition of a solvent molecule). The theoretical calculations indicated that (i) in the ground state C102 occurs primarily as a hydrogen bonded water complex, with the oxo group as the binding site, (ii) this hydrogen bond becomes stronger upon excitation; (iii) in the ground state the amino nitrogen atom, in the excited state the carboxy oxygen atom is the protonation site. A comprehensive analysis of fluorescence decay data yielded the values kpr = 3.271010 M-1 s 1 for the rate constants of excited state protonation, and kdpr = 2.78108 s-1 for the rate constant of the reverse process (kpr and kdpr were treated as independent parameters). This, considering the relatively long fluorescence lifetimes of neutral C102 (6.02 ns) and its protonated form (3.06 ns) in aqueous media, means that a quasi-equilibrium state of excited state proton transfer is reached in strongly acidic solutions

Novel Naphthalene-Based Inhibitors of Trypanosoma brucei RNA Editing Ligase 1

African sleeping sickness is a devastating disease that plagues sub-Saharan Africa. Neglected tropical diseases like African sleeping sickness cause significant death and suffering in the world's poorest countries. Current treatments for African sleeping sickness either have high costs, terrible side effects, or limited effectiveness. Consequently, new medicines are urgently needed. RNA editing ligase 1 is an important protein critical for the survival of Trypanosoma brucei, the unicellular parasite that causes African sleeping sickness. In this paper, we describe our recent efforts to use advanced computer techniques to identify chemicals predicted to prevent RNA editing ligase 1 from functioning properly. We subsequently tested our predicted chemicals and confirmed that a number of them inhibited the protein's function. Additionally, one of the chemicals was effective at stopping the growth of the parasite in culture. Although substantial work remains to be done in order to optimize these chemicals so they are effective and safe to use in human patients, the identification of these parasite-killing compounds is nevertheless a valuable step towards finding a better cure for this devastating disease