Homoleptic Complexes of Heterocyclic Curcuminoids with Mg(II) and Cu(II): First Conformationally Heteroleptic Case, Crystal Structures, and Biological Properties

Abstract

We report herein the synthesis and characterization of three heterocyclic curcuminoid ligands and their homoleptic metal complexes with magnesium and copper. Thus, N-methyl-2-pyrrolecarboxaldehyde, Furan-2-carboxaldehyde, and 2-Thiophenecarboxaldehyde were condensed with 2,4-pentanedione-boron trioxide complex. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex are reported. All curcuminoid ligands and their corresponding metal complexes were characterized by infrared spectroscopy (IR), liquid state nuclear magnetic resonance (LSNMR), electron paramagnetic resonance (EPR), mass spectrometry (MS) and single crystal X-ray diffraction (SCXRD). The ThiopheneCurc-Cu (9) constitutes the first case of a “conformationally-heteroleptic” complex. The unique six-peaks star arrangement for the ThiopheneCurc ligand derived from the supramolecular description is reported. The metal complexes of FuranCurc-Mg (5) and ThiopheneCurc-Cu (9) have a good antioxidant effect (IC50 = 11.26 ± 1.73 and 10.30 ± 0.59 μM), three and two times higher than their free ligands respectively. Additionally, (5) shows remarkable cytotoxicity against colon cancer adenocarcinoma cell line HCT-15, comparable to that of cisplatin, with a negligible toxic effect in vitro towards a healthy monkey kidney cell line (COS-7).

The Homoleptic Curcumin–Copper Single Crystal (ML2): A Long Awaited Breakthrough in the Field of Curcumin Metal Complexes

“…Antioxidant activity of curcumin and curcumin–copper complex were tested by Thiobarbituric Acid Reactive Substances (TBARS) method and were measured using rat brain homogenates according to the method described by Ng and co-workers [ 75 ], with some modifications as previously was recorded [ 76 ]. The concentration of TBARS was calculated by interpolation on a standard curve of tetra-methoxypropane (TMP) as a precursor of MDA [ 77 ].…”

First Gallium and Indium Crystal Structures of Curcuminoid Homoleptic Complexes: All-Different Ligand Stereochemistry and Cytotoxic Potential

“…The curcuminoid complexes of Zn we recently reported provide an example of different geometries, including octahedral, trigonal pyramidal, and trigonal bipyramidal [15]. The heterocyclic curcuminoid complexes with Mg and Cu provide an example of the first conformationally heteroleptic complexes [16]. To the best of our knowledge, no theoretical approach has predicted any of the experimental cases mentioned.…”

“…On the other hand, In 3+ has ionic radii ranging from 62 pm to 92 pm, leading to tetracoordinate, hexacoordinate, and octacoordinated complexes [13]. In our previous work [14][15][16], we have found that the X-ray structure determinations are critical for establishing the stoichiometric relationships to the metal, geometry, and the conformations of ligands. The curcumin-copper complex recently reported provides a suitable ML 2 example [14].…”

Synthesis and Investigations of the Antitumor Effects of First-Row Transition Metal(II) Complexes Supported by Two Fluorinated and Non-Fluorinated β-Diketonates

“…The β-diketone scaffold is not very common in nature, though it is the main feature of curcumin and its derivatives [11][12][13] and, in recent years, many metal complexes of curcumin and curcuminoids have been reported and evaluated as anticancer agents [14][15][16][17][18][19][20][21][22][23][24][25][26]. In fact, β-diketones are known to form complexes with almost every metal, and they have been used as supporting ligands for Ti(IV)- [27,28], Ru(II)- [29][30][31][32][33][34][35], Pd(II)- [36] and Ptbased anticancer agents [37][38][39][40][41][42][43].…”