Development of P^N-Pd(II) Type Complexes Derived from Aliphatic Amines as Potential Antibacterial and Antifungal Agents

Background/Objectives: The development of new metallodrugs has represented an important milestone in recent years for their potential application in different therapeutic approaches. Therefore, the objective of this study was to synthesize a series of P^N iminophosphine Pd(II) complexes (1Pd–3Pd) incorporating different aliphatic amines. Methods: All complexes were characterized using several spectroscopic and analytical techniques, including 1H, 13C{1H}, and 31P{1H} NMR spectroscopy, mass spectrometry, FT-IR spectroscopy, and elemental analysis. In addition, complex 3Pd was unambiguously characterized by single-crystal X-ray diffraction. Results: Supramolecular studies allowed the main noncovalent interactions responsible for stabilizing the crystal lattice of complex 3Pd to be identified. These interactions were analyzed using Hirshfeld surface analysis, which revealed that C-H···π and C-H···Cl interactions contributed most significantly to the stabilization of the crystal lattice. All complexes exhibited stability in different solvents and positive lipophilicity values, with complex 3Pd displaying the highest hydrophobicity. Through in vitro studies, the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of all complexes were determined against different Gram-positive and Gram-negative bacterial strains, as well as fungal strains of Candida species. Complex 3Pd exhibited the highest activity, particularly against L. monocytogenes (1.17 µg/mL), P. aeruginosa (4.68 µg/mL), and all fungal strains (18.75 µg/mL), displaying both bactericidal and fungicidal activity. Furthermore, in silico studies enabled the identification of the potential modes of action of the complexes against different molecular targets present in the bacterial and fungal strains. Conclusions: These results demonstrate the efficacy of the three synthesized complexes against different virulent strains exhibiting resistance to broad-spectrum drugs. Furthermore, the presence of the metal center, together with the incorporation of increasingly longer aliphatic chains, appears to enhance the antibacterial and antifungal activity of the complexes.