Ruthenium(II) complexes containing PEGylated N-heterocyclic carbene ligands for tunning biocompatibility in the fight against cancer

• Published in: Journal of inorganic biochemistry 2025-01, Vol.262, p.112765, Article 112765
• Main Authors: Barrios, Oscar, Inclán, Claudia, Herrera, Pablo, Bort, Alicia, Martín, Avelino, Cano, Jesús, Díaz-Laviada, Inés, Gómez, Rafael
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; cancer; Cell Line, Tumor; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Heterocyclic Compounds - chemistry; Heterocyclic Compounds - pharmacology; Humans; Imidazolium; Ligands; Methane - analogs & derivatives; Methane - chemistry; Methane - pharmacology; Neoplasms - drug therapy; NHC; PEG; Polyethylene Glycols - chemistry; Ruthenium; Ruthenium - chemistry; Silver
• ISSN: 0162-0134; 1873-3344; 1873-3344
• DOI: 10.1016/j.jinorgbio.2024.112765

A synthetic procedure was designed for the preparation and characterization of Ag and Ru complexes containing NHC ligands functionalized with PEG fragments. Stability studies were conducted to gain insight of the species in water and other solvents like DMSO, or with reagents like imidazole as representative group for histidine amino acid. The presence of Cl atoms instead of H in the 4,5 positions of the N-heterocyclic carbene afforded higher water stability. The complexes containing PEG units must be considered inactive as anticancer agents. To enhance the anticancer activity of PEG-containing complexes, the balance between hydrophilicity and hydrophobicity was adjusted using a silane moiety, and an anionic carbosilane dendrimer as a lipophilic carrier. Ru complexes containing NHC ligands functionalized with PEG fragments have been prepared. The hydrophilic-hydrophobic balance was adjusted to understand their anticancer properties. [Display omitted] •Synthetic protocol for pegilated N-heterocyclic carbene complexes.•Stability studies in water show formation of cationic species.•Hydrophilic-hydrophobic balance for cell viability of PEG-containing complexes.•Electrostatic versus covalent interaction in dendriplex formation.