Design of new heteroscorpionate ligands and their coordinative ability toward Group 4 transition metals; an efficient synthetic route to obtain enantiopure ligands

Abstract

The reaction of different types of bis(pyrazol-1-yl)methane derivatives with Bu(n)Li and alkyl or aryl-containing-isocyanates or isothiocyanates, some of these as chiral reagents, gives rise to the preparation of new heteroscorpionate ligands in the form of the lithium derivatives [Li(NNE)]2 (1-10), although a similar process with trimethylsilyl isocyanate or isothiocyanate gave the complexes [Li(NCX)(bdmpzs)(THF)](X = O, 11; X = S, 12)[bdmpzs = bis(3,5-dimethylpyrazol-1-yl)trimethylsilylmethane]. Compounds 1-8 reacted with [TiCl4(THF)2] or [MCl4](M = Zr, Hf) to give a series of cationic complexes [MCl3{kappa3-NNE(H)}]Cl (13-36) where the heteroscorpionate ligand contains either an acetamide or thioacetamide group resulting from the protonation of the corresponding acetamidate or thioacetamidate. However, under appropriate experimental conditions neutral Ti complexes were isolated-namely [TiClx(NMe2)3-x(S-mbbpam)](37-39)[S-mbbpam =(S)-(-)-N-alpha-methylbenzyl-2,2-bis(3,5-dimethylpyrazol-1-yl)acetamidate]. Finally, two alkoxide-containing titanium complexes [TiClx(OR)3-x(S-mbbpamH)]Cl (40-41) were also prepared. The structures of these complexes have been determined by spectroscopic methods and, in addition, the X-ray crystal structures of 1, 12, and 19 were also established.

New multidentate heteroscorpionate ligands: N-Phenyl-2,2-bis(pyrazol-1-yl)thioacetamide and ethyl 2,2-bis(pyrazol-1-yl)dithioacetate as well as their derivatives

“…Herein we report the modification of bis(pyrazol-1-yl)methane by phenyl isothiocyanate and CS 2 on the bridging carbon atom to yield N-phenyl-2,2-bis(pyrazol-1-yl)thioacetamide and bis(pyrazol-1-yl)dithioacetate, which have the attractive character of being able to act as a monodentate, bidentate, or tridentate ligand, depending on different metal atoms. Very recently, the modification of bis(pyrazol-1-yl)methane by enantiopure isocyanate and isothiocyanate fragments has been reported [14,15].…”

Synthesis and Cytotoxic Activity Evaluation of New Cu(I) Complexes of Bis(pyrazol-1-yl) Acetate Ligands Functionalized with an NMDA Receptor Antagonist

“…In the search for copper-based anticancer agents [1], over the last few decades, our attention was focused on the design and synthesis of copper complexes of bis(azol-1-yl) carboxylate heteroscorpionate ligands [24][25][26] of general formula [HC(COOH)(az) 2 ], with az = pyrazole or 1,2,4-triazole [27][28][29][30]. Bis(azol-1-yl) carboxylic acids are convenient starting materials for the preparation of conjugated heteroscorpionate systems, due to the κ 3 -NNO coordination behavior of bis(azol-1-yl) methanes and to the presence of a carboxylic function suitable for the coupling with bioactive molecules [31][32][33][34][35][36]. We recently reported the synthesis and characterization of glucosamine and 5-nitroimidazole bifunctional ligands and the related Cu(I) and Cu(II) complexes, as well as a brief investigation of their cytotoxic activity toward human tumor cell lines [37][38][39].…”

Syntheses and Biological Studies of Cu(II) Complexes Bearing Bis(pyrazol-1-yl)- and Bis(triazol-1-yl)-acetato Heteroscorpionate Ligands

“…During the last decades, in our quest to find suitable ligands in the development of metal-based anticancer agents [1], we designed and synthesized new bis(azol-1-yl)carboxylate ligands with pyrazole, triazole, imidazole or pyridine scaffolds [59,60,61,62,63]. Bis(azol-1-yl)carboxylic acids are useful starting materials to yield neutral heteroscorpionate ligands functionalized with acetamide or thioacetamide groups [64,65,66,67,68,69]. In recent works, they have been conjugated with glucosamine, 5-nitroimidazole and a N -methyl- d -aspartate (NMDA) receptor antagonist and the related Cu(I) and Cu(II) complexes have been investigated for their cytotoxic activity towards several human tumor cell lines [43,44,45,46].…”