Synthesis, Spectroscopy Characterization and Biological Evaluation of La(III), Eu(III) and Gd(III) Complexes with Ampicillin: In Vitro Antimicrobial, Cytotoxic and Antiproliferative Activities and Theoretical Frameworks.

This study reports the synthesis, characterization, DFT calculations and in vitro antimicrobial, cytotoxic and antiproliferative evaluation of La(III), Eu(III), and Gd(III) metal complexes with ampicillin. The compounds were characterized by Thermal Gravimetric Analysis (TGA), elemental analysis, ultraviolet-visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance (1H NMR), indicating a 2:1 metal-to-ligand ratio with ampicillin, and likely, a coordination through carbonyl, carboxylic and β-lactam groups, with the general formula [Ln2(L)(Cl)5(H2O)x] (Ln = La(III), Eu (III), Gd (III), and x = 2 for La(III), 5 for Eu(III) and Gd(III), L-ampicillin anion). Antimicrobial studies showed activity against ampicillin-resistant Staphylococcus aureus (MIC = 15.6 µg·mL-1) but no activity against Escherichia coli. In cytotoxicity studies, all complexes inhibited B16-F10 (murine melanoma) proliferation, with GI50 values around 140 µg·mL-1. Against U251 (glioma) cell line, only [Eu2(L)(Cl)5(H2O)5] exhibited cytotoxicity activity, GI50 = 104 µg·mL-1, and notably, [Eu2(L)(Cl)5(H2O)5] was active against MCF7 (breast carcinoma) with a GI50 = 8.1 µg·mL-1. However, all complexes exhibited high cytotoxicity in NIH-3T3 cells (GI50 = 0.030-2.90 µg·mL-1), indicating limited selectivity between normal and cancer cells. Nevertheless, except for the La complex, most compounds were less cytotoxic than doxorubicin, highlighting the need for further optimization to improve selectivity.