Structural and Biological Properties of Heteroligand Copper Complexes with Diethylnicotinamide and Various Fenamates: Preparation, Structure, Spectral Properties and Hirshfeld Surface Analysis

• Published in: Inorganics Vol. 11; no. 3; p. 108
• Main Authors: Piroš, Milan, Schoeller, Martin, Koňariková, Katarína, Valentová, Jindra, Švorc, Ľubomír, Moncoľ, Ján, Valko, Marian, Švorec, Jozef
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.03.2023
• Subjects: Acids; Analgesics; Analysis; Anticancer properties; Antitumor activity; Binding; Biological activity; Biological properties; Bovine serum albumin; Calf thymus; Cancer; Chemical synthesis; Coordination compounds; Copper; Copper compounds; copper(II) complexes; Crystal structure; Crystals; Cytotoxicity; Diffraction; Electron paramagnetic resonance spectroscopy; fenamates; Fluorescence; Hirshfeld atom refinement; Hydrocarbons; Infrared spectroscopy; interactions with DNA; Ligands; Methods; Niacinamide; Nonsteroidal anti-inflammatory drugs; Pharmaceuticals; Properties; Redox properties; Rheumatoid arthritis; Scavenging; Serum albumin; Single crystals; SOD mimetic activity; Spectra; Spectroscopy; Spectrum analysis; Stereochemistry; Structural analysis; Structure; Surface analysis (chemical); Tumor cell lines; Viscosity measurement; X-ray diffraction; X-rays; Slovakia
• DOI: 10.3390/inorganics11030108
• ISSN: 2304-6740

Herein, we discuss the synthesis, structural and spectroscopic characterization, and biological activity of five heteroligand copper(II) complexes with diethylnicotinamide and various fenamates, as follows: flufenamate (fluf), niflumate (nifl), tolfenamate (tolf), clonixinate (clon), mefenamate (mef) and N, N-diethylnicotinamide (dena). The complexes of composition: [Cu(fluf)2(dena)2(H2O)2] (1), [Cu(nifl)2(dena)2] (2), [Cu(tolf)2(dena)2(H2O)2] (3), [Cu(clon)2(dena)2] (4) and [Cu(mef)2(dena)2(H2O)2] (5), were synthesized, structurally (single-crystal X-ray diffraction) and spectroscopically characterized (IR, EA, UV-Vis and EPR). The studied complexes are monomeric, forming a distorted tetragonal bipyramidal stereochemistry around the central copper ion. The crystal structures of all five complexes were determined and refined with an aspheric model using the Hirshfeld atom refinement method. Hirshfeld surface analysis and fingerprint plots were used to investigate the intermolecular interactions in the crystalline state. The redox properties of the complexes were studied and evaluated via cyclic voltammetry. The complexes exhibited good superoxide scavenging activity as determined by an NBT assay along with a copper-based redox-cycling mechanism, resulting in the formation of ROS, which, in turn, predisposed the studied complexes for their anticancer activity. The ability of complexes 1–4 to interact with calf thymus DNA was investigated using absorption titrations, viscosity measurements and an ethidium-bromide-displacement-fluorescence-based method, suggesting mainly the intercalative binding of the complexes to DNA. The affinity of complexes 1–4 for bovine serum albumin was determined via fluorescence emission spectroscopy and was quantitatively characterized with the corresponding binding constants. The cytotoxic properties of complexes 1–4 were studied using the cancer cell lines A549, MCF-7 and U-118MG, as well as healthy MRC-5 cells. Complex 4 exhibited moderate anticancer activity on the MCF-7 cancer cells with IC50 = 57 μM.