Antibactericidal Ir(III) and Ru(II) Complexes with Phosphine‐Alkaloid Conjugate and Their Interactions with Biomolecules: A Case of N‐Methylphenethylamine

• Published in: Chemistry : a European journal 2023-11, Vol.29 (62), p.e202301603-n/a
• Main Authors: Wojtala, Daria, Kozieł, Sandra, Witwicki, Maciej, Niorettini, Alessandro, Guz‐Regner, Katarzyna, Bugla‐Płoskońska, Gabriela, Caramori, Stefano, Komarnicka, Urszula K.
• Format: Article
• Language: English
• Subjects: Adducts; Adenine; Alkaloids; antibacterial agents; Antimicrobial activity; Ascorbic acid; Bacteria; Biomolecules; Chemical analysis; Chemistry; Cymene; Density functional theory; Deoxyribonucleic acid; DNA; Electron transfer; Electrons; Fluorescence; Glutathione; Iridium; iridium(III); NAD; Nicotinamide; Nicotinamide adenine dinucleotide; NMR; Nuclear magnetic resonance; Oxidation; Oxidation process; Phosphine; Phosphines; Plasmids; Ruthenium; Ruthenium compounds; ruthenium(II); Spectrometry; Spectroscopy; Two dimensional analysis
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202301603

The phosphine ligand (Ph2PCH2N(CH3)(CH2)2Ph, PNMPEA) obtained by the reaction of the (hydroxymethyl)diphenylphosphine with naturally occurring alkaloid N‐methylphenethylamine, was used to synthesize the half‐sandwich iridium(III) (Ir(η5‐Cp*)Cl2Ph2PCH2N(CH3)(CH2)2Ph, IrPNMPEA) and ruthenium(II) (Ru(η6‐p‐cymene)Cl2Ph2PCH2N(CH3)(CH2)2Ph, RuPNMPEA) complexes. They were characterized using a vast array of methods, including 1D and 2D NMR, ESI(+)MS spectrometry, elemental analysis, cyclic voltammetry (CV), electron spectroscopy in the UV‐Vis range (absorption, fluorescence) and density functional theory (DFT). The initial antimicrobial activity in vitro toward Gram‐positive and Gram‐negative bacterial strains was examined, indicating that both complexes are selective towards Gram‐positive bacteria, e. g., Staphylococcus aureus, where the IrPNMPEA has been more bactericidal compared to RuPNMPEA. Additionally, the interactions of these compounds with various biomolecules, such as DNA (ctDNA, plasmid DNA, 9‐ethylguanine (9‐EtG), and 9‐methyladenine (9‐MeA)), nicotinamide adenine dinucleotide (NADH), glutathione (GSH), and ascorbic acid (Asc) were described. The results showed that both Ir(III) and Ru(II) complexes accelerate the oxidation process of NADH, GSH and Asc that appeared to occur by an electron transfer mechanism. Interestingly, only IrPNMPEA leads to the formation of various biomolecule adducts, which can explain its higher activity. Furthermore, RuPNMPEA and IrPNMPEA have been interacting with the DNA through weak noncovalent interactions. The phosphine derived from natural alkaloid N‐methylphenethylamine was used to synthesize half‐sandwich iridium(III) and ruthenium(II) complexes. It turned out that they are selective towards Gram‐positive bacteria, whereas the Ir(III) complex was more bactericidal. The potential action mode was proposed, based on the interactions with various biomolecules (ctDNA, plasmid DNA, 9‐ethylguanine, and 9‐methyladenine, nicotinamide adenine dinucleotide, glutathione, and ascorbic acid).