LAUSR

Tris(2-aminoethyl)amine (tren) coordinates to a Zn(II) ion to form the [Zn(tren)]2+ cation that accepts a monodentate favipiravir (FAV) anion. The results of this work show that the FAV anion is capable of binding to the [Zn(tren)]2+ cation through either a nitrogen or an oxygen atom (N/O-coordination). The energy decomposition analysis shows that, interestingly, both the strength and nature of the bonds between the [Zn(tren)]2+ cation and the N/O-coordinated FAV anion are almost the same. X-ray crystal structure determinations confirmed the existence of two types of cations in the solid state, [Zn(tren)(N-FAV)]+ and [Zn(tren)(O-FAV)]+. The NMR data, in a DMSO solution, were consistent with either the N-coordinated or the O-coordinated complex, but not a mixture of the two linkage isomers. The theoretical data indicated that the [Zn(tren)(N-FAV)]+ and [Zn(tren)(O-FAV)]+ cations have very similar stability in the gas phase, and in H2O, CH3OH, and DMSO solutions, and can also easily convert from one linkage isomer to the other. The experimental and theoretical data showed that, upon protonation of the above cations under acidic conditions (pH ≈ 3 to 5.5), the drug FAV will be easily released and replaced by a Cl- anion, or an H2O molecule, which will coordinate to the zinc atom showing the potential of [Zn(tren)]2+ as a safe drug vehicle. Molecular docking studies using two well-known molecular docking packages show the relatively strong binding interactions of the [Zn(tren)(N-FAV)]+ and [Zn(tren)(O-FAV)]+ cations with DNA and viral protein macromolecules.