This work presents the synthesis, spectroscopic properties and single-crystal X-ray examination of the structure of 3-hydroxyiminoflavanone and its palladium complex. It presents the results of NMR (Nuclear Magnetic Resonance) spectroscopy, electron-density studies based on X-ray wavefunction refinement and theoretical calculations combined with QTAIM (Quantum Theory of Atoms in Molecules) and ELI-D (Electron Localizability Indicator) analyses. These offer an interesting new insight into the

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... uctures and behavior of flavanone and its complex, in solid state and in solution. The study also examines the cytotoxicity of the ligand and its complex against three human ovarian and lung cancer cell lines. Molecules 2016, 21, 455 2 of 17 antibacterial and antiallergenic properties. Furthermore, beneficial synergistic interactions have been found between flavonoids and metal ions [9, 10] . In addition, complexes with nitrogen-containing ligands are the subject of intensive biological evaluation in the search for less toxic and more selective anticancer agents [11] . Although our present study on 3-hydroxyiminoflavanone (1) and its Pd(II) complex (2) is a continuation of our preliminary studies on these compounds [12, 13] , it introduces novel, interesting findings which contrast with those obtained previously. For instance, while 3-hydroxyiminoflavanone was previously claimed to have 3Z(syn) geometry in solid state and in solutions [13], our present observations indicate it to have 3E(anti) geometry in solid and in polar solvents. It was also found that 3-HIF only has 3Z(syn) geometry when dissolved in chloroform, and this exists in equilibrium with the 3E(anti) isomer. Additionally, whereas an earlier study proposes that the coordination mode of the palladium complex of 3-HIF was via 4-carbonyl and 3-oxime oxygen atoms [12], our present findings indicate that the ligand chelates the Pd(II) ion via a 4-carbonyl group and a 3-nitrogen atom, while the oxime proton is lost and the ligand eventually becomes 3-nitrosoflavanone in the complex. This new evidence is confirmed by NMR (Nuclear Magnetic Resonance) spectroscopy, single crystal X-ray studies and electron-density studies. This study is the first to compare cytotoxic properties of 3-hydroxyiminoflavonone and its Pd(II) complex with cisplatin towards three cancer cell lines. Results and Discussion Synthesis of the Compounds 1 and 2 The synthesis of 1 was described elsewhere [13] and reproduced here. In a molecule of flavanone, the carbon atom C3 (adjacent to carbonyl group) is nitrosated with isoamyl nitrate(III) in acidic environment, and the 3-oxime is formed (See Scheme 1). The resulting compound was obtained with good yield and purity (see the Materials and Methods Section), and purified by recrystallization. Molecules 2016, 21, 455 2 of 17 between flavonoids and metal ions [9, 10] . In addition, complexes with nitrogen-containing ligands are the subject of intensive biological evaluation in the search for less toxic and more selective anticancer agents [11] . Although our present study on 3-hydroxyiminoflavanone (1) and its Pd(II) complex (2) is a continuation of our preliminary studies on these compounds [12, 13] , it introduces novel, interesting findings which contrast with those obtained previously. For instance, while 3-hydroxyiminoflavanone was previously claimed to have 3Z(syn) geometry in solid state and in solutions [13], our present observations indicate it to have 3E(anti) geometry in solid and in polar solvents. It was also found that 3-HIF only has 3Z(syn) geometry when dissolved in chloroform, and this exists in equilibrium with the 3E(anti) isomer. Additionally, whereas an earlier study proposes that the coordination mode of the palladium complex of 3-HIF was via 4-carbonyl and 3-oxime oxygen atoms [12], our present findings indicate that the ligand chelates the Pd(II) ion via a 4-carbonyl group and a 3-nitrogen atom, while the oxime proton is lost and the ligand eventually becomes 3-nitrosoflavanone in the complex. This new evidence is confirmed by NMR (Nuclear Magnetic Resonance) spectroscopy, single crystal X-ray studies and electron-density studies. This study is the first to compare cytotoxic properties of 3-hydroxyiminoflavonone and its Pd(II) complex with cisplatin towards three cancer cell lines. Results and Discussion Synthesis of the Compounds 1 and 2 The synthesis of 1 was described elsewhere [13] and reproduced here. In a molecule of flavanone, the carbon atom C3 (adjacent to carbonyl group) is nitrosated with isoamyl nitrate(III) in acidic environment, and the 3-oxime is formed (See Scheme 1). The resulting compound was obtained with good yield and purity (see the Materials and Methods Section), and purified by recrystallization. Scheme 1. Synthesis of 3-hydroxyiminoflavanone (1).