Synthesis, Crystal Structure, and Characterization of three New Letrozole Complexes

Abstract

Three new letrozole complexes {[Cu(Le)4Cl2]·(H2O)} (1), {[Ni(Le)4Cl2]·(H2O)}(2) and {[Co(Le)4Cl2]·(H2O)} (3) (Le = letrozole = 1‐[bis(4‐cyanophenyl)methyl]‐1, 2, 4‐triazole) were obtained from self‐assembly of CuCl2, NiCl2·6H2O, and CoCl2·6H2O with medicine letrozole. All compounds were characterized by IR spectroscopy, elemental, single‐crystal as well as powder X‐ray diffraction, and thermogravimetric analyses. The analyses of the structures indicate that all crystals belong to monoclinic system, space group C2/c, for complex 1 with crystal data a = 34.501(18) Å, b = 12.724(7) Å, c = 16.116(9) Å, β = 114.958(7) °, V = 6414(6) Å 3, Z = 4, F(000) = 2660, R1 = 0.0668, wR2 = 0.1574; for complex 2, a = 34.769(6) Å, b = 12.7267(18) Å, c = 16.046(2) Å, β = 115.281(3) °, V = 6420.1(16) Å 3, Z = 4, F(000) = 2656, R1 = 0.0510, wR2 = 0.0896; for complex 3, a = 35.063(8) Å,b = 12.658(3) Å, c = 16.056(4) Å, β = 115.387(3) °, V = 6438(2) Å3, Z = 4, F(000) = 2652, R1 = 0.0528, wR2 = 0.1205. The local arrangements around central metal atoms (CuII, NiII, and CoII) can be best described as distorted octahedra which are constructed by two chlorine atoms and four monodentate nitrogen atoms from different letrozole ligands. XRD results of 1–3 show that all peaks displayed in the measured patterns at room temperature closely match those in the simulated patterns generated from single‐crystal diffraction data, indicating single phases of 1–3 were formed.

New Ruthenium(II)–Letrozole Complexes as Anticancer Therapeutics

“…To our knowledge, this is the first example of the coordination of letrozole to a group 8 metal, which is of great importance to further understand how this drug might also coordinate to iron, a congener of ruthenium in the periodic table, which is the metal responsible for the catalytic activity of the aromatase enzyme. Only two reports of letrozole−metal 12 as observed in the present study. The nature of 2a was unambiguously confirmed by highresolution (and high-accuracy) mass spectrometry, as well as by elemental analysis.…”

“…To our knowledge, this is the first example of the coordination of letrozole to a group 8 metal, which is of great importance to further understand how this drug might also coordinate to iron, a congener of ruthenium in the periodic table, which is the metal responsible for the catalytic activity of the aromatase enzyme. Only two reports of letrozole−metal interactions were found in the literature; they showed that the enzyme inhibitor can coordinate to Cu(I) in a tetradentate fashion to afford a polymer, {[Cu(LTZ)](BF 4 )•CHCl 3 } n , 11 or can coordinate to Cu(II), Ni(II), or Co(II) by only one nitrogen of the triazole ring, 12 as observed in the present study. The nature of 2a was unambiguously confirmed by highresolution (and high-accuracy) mass spectrometry, as well as by elemental analysis.…”

Organoruthenium(II) Complexes Bearing an Aromatase Inhibitor: Synthesis, Characterization, in Vitro Biological Activity and in Vivo Toxicity in Zebrafish Embryos

“…Depriving ER+ cells of estrogens was also previously shown to sensitize them to cytotoxic agents. , Thus, investigating the anticancer properties arising from the coordination of aromatase inhibitors to metals could lead to the development of efficient drug/prodrug candidates that display more than one mode of action, which could potentially circumvent the emergence of drug resistance mechanisms, a common cause of mortality in ER+ breast cancer patients. It was recently reported that the coordination of hydroquinoline, aminoquinoline, and uracyl ligands to copper can lead to cytotoxic complexes with an aromatase inhibitory activity. , To our knowledge, only a few investigations from other groups involved the preparation of letrozole (Cu, Co, and Ni) , or anastrozole (Pt) metal complexes, and none of these studies reported an assessment of their aromatase inhibitory activity. Organoruthenium complexes are of particular interest for their activity against numerous types of cancer cells via multiple mechanisms and are often considered as interesting alternatives to currently used therapeutics. − Maysinger et al previously reported a preliminary account of the cytotoxicity of a series of ruthenium complexes bearing letrozole ligands .…”

“…It was recently reported that the coordination of hydroquinoline, aminoquinoline, and uracyl ligands to copper can lead to cytotoxic complexes with an aromatase inhibitory activity. 22,23 To our knowledge, only a few investigations from other groups involved the preparation of letrozole (Cu, Co, and Ni) 24,25 or anastrozole (Pt) 26 reported an assessment of their aromatase inhibitory activity.…”

Synthesis, Crystal Structure and Luminescent Property of Cd (II) Complex with N-Benzenesulphonyl-L-leucine

“…Investigation of the inorganic-organic hybrid materials with carboxylate ligands has gained considerable attention during the last decade due to their attractive structures and promising potential applications for catalysis, gas storage, magnetic, luminescence materials [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Structural studies have shown that the organic ligands containing multi-oxygen and nitrogen atoms can coordinate with metal ions in different ways, resulting in the formation of various metal-organic frameworks with specific topologies and useful properties.…”