Synthesis, characterization and incorporation of two phosphine-based ruthenium(II) complexes into lipid nanocarriers as potential antimicrobial agents

Abstract

The reaction of RuCl₃ with dppb = 1,4-bis(diphenylphosphino)butane yielded the binuclear complex [Ru₂(dppb)₃Cl₄] (I), which was used as a precursor in the preparation of the [Ru(dppb)(Spym)₂] (II) (Spym = 2-mercaptopyrimidine). These compounds were characterized using spectroscopic and electrochemical techniques, X-ray crystallography, and elemental analysis. Despite their promising biological profiles, they exhibit poor water solubility (<0.005 mg mL⁻¹), which limits their potential use as antimicrobial agents. To overcome this issue, we employed an encapsulation strategy that incorporated these metal complexes into lipid nanoparticles to improve their solubility and enhance their potential therapeutic action. This nanoformulation containing Pluronic F-127 and Capryol 90 showed the best profile with an enhancement of solubility of up to 4,900-fold. Additionally, preliminary in vitro antibacterial assays against Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) were carried out with free and nanoencapsulated metal compounds along with empty lipid nanoparticle as well. Surprisingly, the empty-nanoformulation also showed bacteriostatic activity, which highlights an issue that must be carefully addressed during the use of any nanostructure. Nevertheless, this nanoformulation required the metal compound II for biocidal action (MBC of 128 μg mL⁻¹), which should be further investigated.