Structural study of ribonucleotide reductase inhibitor hydrazones. Synthesis and X-ray diffraction analysis of a copper(II)-benzoylpyridine-2-quinolinyl hydrazone complex.
Single crystals as yellow needles of N-(4,8-dimethyl-quinolin-2-yl)-N'-(1-pyridin-2-yl-ethylidene)-hydrazine, HL(1), 1, and N-(4-methyl-quinolin-2-yl)-N'-(phenyl-pyridin-2-yl-methylene)-hydrazine, HL(2), 2, were obtained from methanol (MeOH) and analyzed via X-ray diffraction (XRD). HL(2) reacted with copper(II) acetate to produce a dark red powder that gave single crystals of [Cu(L(2))(OOCCH(3))].0.9C(6)H(5)CH(3), 3.0.9C(6)H(5)CH(3) when recrystallized from toluene. The conformation of the N(quinolinyl,q)-C(q)-N(H)-N(imine,i)-C-C(pyridine,p)-N(p) grouping is trans,trans,trans,trans or tttt, and ttcc for 1 and 2, respectively, at the solid state, as revealed via single crystal X-ray diffraction. Thus, the structure of 1 has the methyl (hydrazone) group syn to the N-H bond and syn to the N(q) and N(p) atom. On the other side, the structure of 2 is stabilized by a strong intra-molecular N-H...N hydrogen bond which involves the pyridyl nitrogen atom. The molecule 1 is almost planar, the torsion angles do not deviate more than 4 degrees from the idealized values of 0 degrees and 180 degrees . In the structure of 2 the pyridyl ring is almost coplanar with the N(q)-C(q)-NH-N(i)-C system, whereas the phenyl (Ph) ring is twisted by ca. 55 degrees . The structure of 3 has the L(2) ligand as deprotonated at the N-N function and in a cttc conformation as opposite to the ttcc one found for pure 2. The metal center is coordinated through N(q), N(i), N(p) and through an oxygen atom from a carboxylate anion. The molecular modeling analysis of 1 and 2 (semi-empirical molecular orbital at Zerner's intermediate neglect of differential overlap (ZINDO/1) level and density functional theory (DFT) methods) gave good agreement with the X-ray structures. Semi-empirical quantum mechanics analysis of 3 allowed to assign the UV-Vis spectrum that is characterized by strong absorptions in the visible, UVA and UVB regions. Owing to the ribonucleotide reductase inhibitory activity of the ligand, to the ascertained anticancer activity shown previously by related copper(II)-hydrazone complexes, and to the oxygen radical scavenger activity of several copper(II)-complexes, 3 is potentially anticancer and anti-inflammatory.
Tamasi
Gabriella
G
Department of Chemical and Biosystem Sciences and Technologies, University of Siena, Via Aldo Moro 2, I-53100 Siena, Italy.
Chiasserini
Luisa
L
Savini
Luisa
L
Sega
Alessandro
A
Cini
Renzo
R
D000818:Animals; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared
D004791:Enzyme Inhibitors; D006835:Hydrazones; D009942:Organometallic Compounds; D011725:Pyridines; D012264:Ribonucleotide Reductases