title: Synthesis, molecular structure (X-ray and DFT), and solution behavior of titanium 4-Acyl-5-pyrazolonates. Correlations with related antitumor beta-diketonato derivatives.
abstract: Previously reported structure-activity relationships have shown two features for effective antitumor activity of titanium beta-diketone complexes: (a) ligand asymmetry and (b) the presence of planar substitutents on the ligand. Mono- and dinuclear derivatives, studied with diffraction and DFT methods show that (a) is consistent with different Ti-O(beta-diketonato) bond lengths, which are longer than Ti-O(oxo) and Ti-O(alkoxy) ones. pi-pi features observed in dinuclear derivatives correlate with strong reactivity of related complexes with DNA and support DNA intercalation by such planar groups, in agreement with (b). Large variation for Ti-O bond lengths and Ti-O-C bond angles in the ethoxy moiety is associated with the titanium withdrawing effect and oxygen bonding s character; it is confirmed through exploration of the Cambridge crystallographic database. This ethoxy geometrical flexibility also suggests versatile accommodation in protein pockets and/or other biological targets. Electrospray ionization mass spectrometry (ESI-MS) spectra show formation of di- and trinuclear Ti-4-acyl-5-pyrazolonato cationic oligomers. Hydrolysis/oligomerization is also described by NMR results.
authors: Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche (CNR), c/o University of Rome Istituto Chimico, Piazzale Aldo Moro 5, 00185 Rome, Italy. francesco.caruso@icb.cnr.it
authors: Francesco
authors: F
authors: Caruso
authors: Claudio
authors: C
authors: Pettinari
authors: Fabio
authors: F
authors: Marchetti
authors: Paolo
authors: P
authors: Natanti
authors: Christine
authors: C
authors: Phillips
authors: Joseph
authors: J
authors: Tanski
authors: Miriam
authors: M
authors: Rossi
mesh_terms: D000215:Acylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D006859:Hydrogen / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*; D014025:Titanium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D010880:Piperidines; D006859:Hydrogen; D014025:Titanium; D010100:Oxygen