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

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 mu M), 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).

Automated summary

In this study, the synthesis and characterization of three heterocyclic curcuminoid ligands and their corresponding metal complexes with magnesium and copper were reported. The first N-methyl-2-pyrrole curcuminoid and its Mg(II) complex were newly discovered. The curcuminoid ligands and metal complexes were characterized using various techniques such as infrared spectroscopy, liquid state nuclear magnetic resonance, electron paramagnetic resonance, mass spectrometry, and single crystal X-ray diffraction. The metal complexes of FuranCurc-Mg and ThiopheneCurc-Cu exhibited a strong antioxidant effect and showed significant cytotoxicity against colon cancer adenocarcinoma cell line HCT-15.