We describe the synthesis, 3D-derived quantitative structure-activity relationship (QSAR), antiproliferative activity and DNA binding properties of a series of 2-amino, 5-amino and 2,5-diamino substituted benzimidazo[1,2-a]quinolines prepared by environmentally friendly uncatalyzed microwave assisted amination. The antiproliferative activities were assessed in vitro against colon, lung and breast carcinoma cell lines; activities ranged from submicromolar to micromolar. The strongest antiproliferative activity was demonstrated by 2-amino-substituted analogues, whereas 5-amino and or 2,5-diamino substituted derivatives resulted in much less activity. Derivatives bearing 4-methyl- or 3,5-dimethyl-1-piperazinyl substituents emerged as the most active. DNA binding properties and the mode of interaction of chosen substituted benzimidazo[1,2-a]quinolines prepared herein were studied using melting temperature studies, a series of spectroscopic studies (UV/Visible, fluorescence, and circular dichroism), and biochemical experiments (topoisomerase I-mediated DNA relaxation and DNase I footprinting experiments). Both compound 36 and its bis-quaternary iodide salt 37 intercalate between adjacent base pairs of the DNA helix while compound 33 presented a very weak topoisomerase I poisoning activity. A 3D-QSAR analysis was performed to identify hydrogen bonding properties, hydrophobicity, molecular flexibility and distribution of hydrophobic regions as these molecular properties had the highest impact on the antiproliferative activity against the three cell lines.

Reactions of copper­(II) sulfate with 1,10-phenanthroline, l-serine, and a base were investigated under different solution-based and mechanochemical synthetic procedures. Six complexes with serine were obtained: [Cu­(l-ser)­(H2O)­(phen)]2SO4­·xH2O (x = 4, 6, or 10; 1·4H 2 O, 1·6H 2 O, and 1·10H 2 O), [Cu­(l-ser)­(H2O)­(phen)]­[Cu­(l-ser)­(CH3OH)­(phen)]­SO4·3H2O­·CH3OH (1·2·3H 2 O­·CH 3 OH), [Cu­(l-ser)­(CH3OH)­(phen)]2SO4­·xCH3OH (x = 2 or 2.5; 2·2CH 3 OH and 2·2.5CH 3 OH), and two without serine: [Cu­(SO4)­(phen)2]­·xH2O (x = 4.5 or 6.75; 3·4.5H 2 O and 3·6.75H 2 O) (phen = 1,10-phenanthroline, l-ser = l-serinato). The X-ray crystal structure analysis of serine-containing complexes revealed extensive hydrogen bonding and π-interactions that link complex cations, sulfate anions, and solvent molecules into three-dimensional architectures. Most of the water/methanol solvent molecules in these porous compounds are found in channels, some in pockets connected to channels, and can be exchanged in vapors of the other solvent. Along with the solvent exchange, the solvent molecule apically coordinated to copper­(II) is also exchanged in some transformations. By neat grinding, all serine-containing complexes transform into 1·6H 2 O. Quantum chemical calculations were done for compounds 1·4H 2 O and 1·6H 2 O in the gas phase and an aqueous (or methanol) surrounding. 1·6H 2 O and 3·4.5H 2 O showed pronounced antiproliferative activity toward human breast and lung tumor cell lines.

Four new complexes of copper(II) with D-allo,Lisoleucine were prepared by solution and mechanochemical synthesis: three complexes of aqua cis isomers, cis-[Cu(D-allo- 4), and anhydrous trans-[Cu(D-allo-Ile)(L-Ile)] ( 5). The previously characterized orthorhombic cis-[Cu(L-Ile) 2 (H 2 O)] (1a) cocrystallized with 3 and either 2 or 4, depending on the synthetic conditions. In 2, a disorder of the side chain was found, while 3 and 4 had a rare positional disorder of two diastereomers, namely, D-allo-Ile and L-Ile, resulting in two positions of the C α chiral center in their crystal structures. The complexes were analyzed by X-ray diffraction methods, solid-state NMR spectroscopy, and density functional theory calculated 13 C and 1 H Fermi contact shifts. Roomtemperature solid-state cis-to-trans isomerization of Cu(D-allo-Ile)(L-Ile) occurred by liquid-assisted grinding (LAG) of 3 with methanol, by aging in methanol vapor, and by soaking 3 in methanol. The latter was a fast process. The isomerization also happened in the 140−160 °C temperature interval. Reverse trans-to-cis isomerization occurred by LAG of 5 with water and very slowly by aging in water vapor. Low activation energy for the Cu(D-allo-Ile)(L-Ile) cis−trans isomerization in the solid state could explain why subtle changes in the experimental conditions affected the final product.

We report the crystal structures and magnetic properties of nine mononuclear complexes and one 1D coordination polymer containing CuII/CuI ions.