title: Major impact of N-methylation on cytotoxicity and hydrolysis of salan Ti(IV) complexes: sterics and electronics are intertwined.
abstract: A series of Ti(IV) complexes containing diamino bis(phenolato) "salan" type ligands with NH coordination were prepared, and their hydrolysis and cytotoxicity were analyzed and compared to the N-methylated analogues. Substituting methyl groups on the coordinative nitrogen donor of highly active and stable Ti(IV) salan complexes with H atoms has two main consequences: the hydrolysis rate increases and the cytotoxic activity diminishes. In addition, the small modification of a single replacement of Me with H leads to a different major hydrolysis product, where a dinuclear Ti(IV) complex with two bridging oxo ligands is obtained, as characterized by X-ray crystallography, rather than a trinuclear cluster. A partial hydrolysis product containing a single oxo bridge was also crystallographically analyzed. Investigation of a series of complexes with NH donors of different steric and electronic effects revealed that cytotoxicity may be restored by fine tuning these parameters even for complexes of low stability.
authors.affiliation: Institute of Chemistry, The Hebrew University of Jerusalem, Israel. tshuva@chem.ch.huji.ac.il
authors.forename: Sigalit
authors.initials: S
authors.lastname: Meker
authors.forename: Cesar M
authors.initials: CM
authors.lastname: Manna
authors.forename: Dani
authors.initials: D
authors.lastname: Peri
authors.forename: Edit Y
authors.initials: EY
authors.lastname: Tshuva
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004581:Electronics; D019073:HT29 Cells; D006801:Humans; D006868:Hydrolysis; D008745:Methylation; D008958:Models, Molecular; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014025:Titanium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010636:Phenols; D014025:Titanium