Photoreactivity of biologically active compounds. XVII. Influence of solvent interactions on spectroscopic properties and photostability of primaquine.

The influence of solvent interactions on absorption properties, fluorescence properties (emission spectra and quantum yields) and relative photochemical degradation rates of primaquine has been investigated, in order to evaluate photochemical reaction mechanisms and chemical properties of the compound. The first absorption band (n - π*) of primaquine is only slightly dependent on properties of the solvent, which can be ascribed to a strong, intramolecular hydrogen bond between the quinoline N and amine group in the ground state (So). Amphiprotic solvents with predominant acidic properties (water and methanol) will to some extent stabilize the molecule and initiate hypsochromic shifts of the absorption band by protic interactions, while the other solvents (amphiprotic, basic and neutral) influence the absorption spectrum by general solvent effects only. The excited singlet (S* 1 ) state of primaquine interacts more efficiently with the surrounding solvents than the So state, as evaluated by the Stokes shifts. The pKa value of the quinoline N is likely to increase in the S* 1 state, which is important for the observed protic interactions with amphiprotic solvents of predominant acidity. Specific solvent effects are highly important for the efficiency of the fluorescence (fluorescence quantum yields; Φ f ). The fluorescence is quenched by amphiprotic solvents, likely due to a rupture of the intramolecular bond and protonation of the quinolone N, and enhanced by polar, non-protic (basic) solvents, probably by stabilization of the 6 intramolecular hydrogen bond. The observed photochemical degradation rates of primaquine in amphiprotic media are positively correlated with Φ f , indicating that the photochemical degradation of primaquine is dependent on intramolecular hydrogen bonding and non protonated lone-pair electrons at the quinoline N. The intramolecular ring-formation with a subsequent increased lipophilic character and (lack of) interactions with the surroundings, are important factors for biological behavior as well as pharmaceutical properties of primaquine. Knowledge about solvent interactions with primaquine in the So and S* 1 states is essential for the proceeding evaluation of photostability and phototoxicity of the drug.