Palladium Complexes with Tridentate N-Heterocyclic Carbene Ligands: Selective “Normal” and “Abnormal” Bindings and Their Anticancer Activities

Abstract

A series of new imidazolium salts was synthesized by simple quaternization reactions of 1-benzyl-1H-imidazole or 1-benzyl-2-methyl-1H-imidazole and their derivatives with 2-chloro-N-(pyridin-2-ylmethyl)­acetamide. These resulting imidazolium salts were successfully employed as ligand precursors for the syntheses of novel palladium­(II) complexes bearing tridentate ligands of N-heterocyclic carbene, amidate, and pyridine donor moieties. Simple tuning of the reaction conditions allowed selective coordination of the N-heterocyclic carbene moiety in either “normal” or “abnormal” binding modes. An isomeric pair of palladium complexes with “normal” and “abnormal” N-heterocyclic carbenes was successfully characterized by single-crystal X-ray diffraction studies. Theoretical calculations indicated that the palladium complex with “normal” NHC coordination was more thermally stable than its isomeric complex with “abnormal” NHC binding. The potential of these two sets of palladium complexes as anticancer drugs was evaluated, and the results showed that some of these novel complexes exhibited promising inhibition activity against human ovarian cancer cell lines. The inhibition activity of these novel complexes was highly structurally dependent. While the nNHC complex bearing an N-3-methoxybenzyl group appeared to be the most active compound, its isomeric aNHC complex did not exhibit any inhibition activity toward TOV21G cells. In contrast, in the case of an isomeric pair of palladium complexes bearing N-4-fluorobenzyl groups, the aNHC complex showed activity superior to that of the nNHC complex.

Transition Metal Compounds of Pyridine‐Amide‐Functionalized Carbene Ligands: Synthesis, Structure, and Electrocatalytic Properties in Proton Reduction

“…The relatively high reactivity of the pendant pyridyl group resulted in the formation of oligomeric side products (Scheme ), giving relatively low yields of the desired products (30 %‐50 %). The reported imidazolium salt H 2 L3 Cl containing a benzyl group was synthesized following a literature procedure . The (benz)imidazolium salts were characterized by NMR spectroscopy and electrospray ionization mass spectrometry (ESI‐MS).…”

“…The compounds dichlorido(dimethoxyethane)nickel {[Ni(dme)Cl 2 ]} , 2‐chloro‐ N ‐(pyridin‐2‐ylmethyl)acetamide, and N ‐pyridin‐2‐ylmethyl(benz)imidazole were prepared following published procedures. The ligand precursor H 2 L3 Cl was synthesized following a literature method …”

Current Researches and Applications of Azole-BasedSupermolecules as Medicinal Agents

“…进一步研究发现, 苯环上没 有取代基或用吸电子基代替甲氧基得到的超分子抗癌 活性显著降低. 24 的动物实验也正在进行中 [97] . 随着贵金属抗癌药物的巨大成功和研究的深入, 许 多的研究自然地延伸到过度金属络合物超分子 [98,99] .…”

Formation of N‐Heterocyclic Carbenes by Tautomerization of Mesomeric Betaines: Cyclic Boron Adducts and Palladium Complexes From 2‐(Imidazolium‐1‐yl)phenolates

“…[1] Structural variations of the substitution pattern,aswell as variation of the heterocyclic ring system,t uning of the electronic properties by the substituents, and investigation of steric factors yielded ab road variety of distinct classes of NHCs with interesting properties. Meanwhile, classical or "normal" NHCs (nNHCs), remote NHCs (rNHCs), [2][3][4][5][6][7] and abnormal NHCs (aNHCs) [8][9][10][11][12][13][14] which are also sometimes called mesoionic carbenes (MIC) [15][16] -are distinguished. Ar eview of complexes of the distinct types of NHCs has appeared recently.…”

“…These molecules are the first representatives of an ew heterocyclic ring system. The boron atom appears between d = 0.94 and À1.17 ppm in the11 BNMR spectra. Single crystalso f22 c and 22 d were obtained by slow evaporation of concentrated solutionsi ne thyl acetate.…”