Zinc complexes of chloroquine and hydroxychloroquine versus the mixtures of their components: Structures, solution equilibria/speciation and cellular zinc uptake.

The zinc complexes of chloroquine (CQ; [Zn(CQH+)Cl3]) and hydroxychloroquine (HO-CQ; [Zn(HO-CQH+)Cl3]) were synthesized and characterized by X-Ray structure analysis, FT-IR, NMR, UV-Vis spectroscopy, and cryo-spray mass spectrometry in solid state as well as in aqueous and organic solvent solutions, respectively. In acetonitrile, up to two Zn2+ ions bind to CQ and HO-CQ through the tertiary amine and aromatic nitrogen atoms (KN-aminCQ = (3.8 ±â€¯0.5) x 104 M-1 and KN-aromCQ = (9.0 ±â€¯0.7) x 103 M-1 for CQ, and KN-aminHO-CQ = (3.3 ±â€¯0.4) x 104 M-1 and KN-aromHO-CQ = (1.6 ±â€¯0.2) x 103 M-1 for HO-CQ). In MOPS buffer (pH 7.4) the coordination proceeds through the partially deprotonated aromatic nitrogen, with the corresponding equilibrium constants of KN-arom(aq)CQ = (3.9 ±â€¯1.9) x 103 M-1and KN-arom(aq)HO-CQ = (0.7 + 0.4) x 103 M-1 for CQ and HO-CQ, respectively. An apparent partition coefficient of 0.22 was found for [Zn(CQH+)Cl3]. Mouse embryonic fibroblast (MEF) cells were treated with pre-synthesized [Zn((HO-)CQH+)Cl3] complexes and corresponding ZnCl2/(HO-)CQ mixtures and zinc uptake was determined by application of the fluorescence probe and ICP-OES measurements. Administration of pre-synthesized complexes led to higher total zinc levels than those obtained upon administration of the related zinc/(hydroxy)chloroquine mixtures. The differences in the zinc uptake between these two types of formulations were discussed in terms of different speciation and character of the complexes. The obtained results suggest that intact zinc complexes may exhibit biological effects distinct from that of the related zinc/ligand mixtures.

Hydrogen Evolution by FeIII Molecular Electrocatalysts Interconverting between Mono and Di-Nuclear Structures in Aqueous Phase.

A new FeL/Fe2 L2 manifold, with HL=2-({[di(2-pyridyl)methyl](methyl)amino}methyl)phenol, was prepared in gram scale (>50 % yield) and characterized in solution and solid state. The monomer/dimer interconversion is controlled in aqueous phase, upon varying the pH conditions. The electrocatalytic hydrogen evolution reaction (HER) occurs through the FeL monomer with added trifluoroacetic acid (TFA) and through the Fe2 L2 µ-oxo dimer in acetate buffer (pH 4.9), with an overpotential of about 1 V and faradaic yield up to 75 %. The resulting icat /ip values in the range 15-28 are among the highest reported for Fe-based electrocatalysts (icat is the catalytic current, whereas ip is the current of an Fe-based redox event).