(4‐Acyl‐5‐pyrazolonato)titanium Derivatives: Oligomerization, Hydrolysis, Voltammetry, and DFT Study

Abstract

Twenty 4‐acyl‐5‐pyrazolonato (Q) titanium derivatives of varied nuclearity have been synthesized from Ti(OR)4 or TiCl4 and characterized with spectroscopic methods (IR, NMR, ESI‐MS). While Ti−(β‐diketonato) cleavage is not seen in isolated solids, Ti−O(alkoxy) (or Ti−Cl) bonds cleave upon hydrolysis, leading to several structural forms, including oligomers. Ionic Q species with no Ti, i.e., obtained after Ti−Q cleavage, are seen for some Ti−Q derivatives by ESI‐MS, which also indicates a varied nuclearity for a given species, e.g., the isolated polynuclear [Q2Ti‐μ‐O]n has several “n” values. Mononuclear Ti complexes are obtained under rigorous anhydrous conditions. The cis structures of the mononuclear species (QT)2Ti(OCH3)2, QT = 3‐methyl‐4‐(neopentylcarbonyl)‐1‐phenylpyrazol‐5‐onato have been analyzed with DFT methods. A trans influence is a major driving force that accounts for several sets of Ti−O bonds. One of the cis stereoisomers is 56 kcal/mol higher in energy than the other two. In contrast, all (QT)2TiCl2 cis isomers show similar energies. Voltammetry of the mononuclear species (QT)2Ti(OnPr)2 and the antitumor tetranuclear compound [(QB)2Ti‐μ‐O]4, (QB = 4‐benzoyl‐3‐methyl‐1‐phenylpyrazol‐5‐onato) indicate that the TiIV is less prone to reduction to TiIII in the latter (Epc for the TiIV/TiIII couple is −1.71 V and −1.46 V versus Fc+/Fc, respectively). Potential antitumor compounds having a Ti/Q ratio of 1:1 do not disproportionate, unlike the equivalent acetylacetonato derivatives, and are water‐soluble. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Cytotoxic Titanium(IV) Complexes: Renaissance

“…[19,21,34] This result is also in agreement with our observation that only complexes that yield a stable polynuclear complex upon water addition are cytotoxic, as this process involves the hydrolysis of the isopropoxo groups. Nevertheless, the correlation between polynuclear complex formation and cytotoxic activity raises the possibility of the cluster itself being the active species, consistently with the results observed with budotitane derivatives such as 17 (Scheme 6), [22,99] and 20 (Scheme 7). [74] Therefore, to further establish the importance of somewhat labile X groups and to inquire about the activity of the highly stable clusters forming upon hydrolysis, we measured the cytotoxicity of the trinuclear complex L (Figure 10), unlike the observations with 17 and 20.…”

Synthesis, Characterization, Cytotoxicity, and Hydrolytic Behavior of C2‐ and C1‐Symmetrical TiIV Complexes of Tetradentate Diamine Bis(Phenolato) Ligands: A New Class of Antitumor Agents

“…The nature of the active species, therefore, remains unknown, as does the identity of the biological target, the nature of the participation of the ligands, and the role of their particular lability. [20,[22][23][24][25] Thus, the development of new Ti IV -based cytotoxic compounds of defined hydrolytic behavior that may shed some light on this enigmatic process remains a significant challenge of immense value.…”

Titanium complexes with modifiable pyrazolonato and pyrazolonato-ketimine ligands: Synthesis, characterization and ethylene polymerization behavior

“…Pyrazolonato ligand precursors 1-2 and corresponding b-diketonato complexes 1-Ti and 2-Ti were prepared according to known literature procedures [41,42]. To introduce desirable imine function into the ligand back-bone, new pyrazolonato-ketimine ligand precursors 3-6 were synthesized using an autoclave method we have previously reported [35].…”

“…Two of these complexes have been previously synthesized (1-Ti and 2-Ti) [41] but to the best of our knowledge no polymerization experiments have been carried out with these compounds. Our interest towards these complexes arouse from the fact that their ligand structures offer many sites that can be altered and thus afford possibilities to effect the catalytic performance of these complexes.…”