Synthesizing Palladium-Unnatural Amino Acid Complexes: Structural Analysis and Potential for Anti-Cancer Biological Activity

Cisplatin is a potent anticancer drug that has been widely used in the treatment of several cancers. The drug works by stopping the DNA replication process in cancer cells, preventing them from rapidly multiplying. Despite its effectiveness in treating many cancers, cisplatin has several toxic side effects that hinder its use. Platinum is the central metal in cisplatin, but research has not explored other transition metals, specifically palladium, as an alternative central metal in similar structural complexes. Palladium, being a more reactive species than platinum, offers the potential for a new and improved anticancer drug through the formation of palladium-non-natural amino acid complexes. This study aims to investigate palladium-based complexes synthesized with the non-natural amino acids: 3-(2'-Pyridyl)-L-alanine, 3-(3'-Pyridyl)-L-alanine dihydrochloride, and 3-(4'-Pyridyl)-L-alanine. The use of non-natural amino acids is intended to overcome synthetic challenges previously encountered with the natural amino acids, which have led to poor crystalline structures. Through synthesis the palladium complexes were successfully created as seen in the full analytical characterization that included ¹H Nuclear Magnetic Resonance (NMR) spectroscopy, Fourier Transform Infrared (FTIR) spectroscopy, and mass spectrometry. Due to solubility issues, the complex could not be tested against the NCI-60 cell line panel to ensure anti-cancer activity. This research represents a new approach in cancer treatment, as palladium-based complexes have not been widely studied and tested as new anticancer drugs. The findings from this study could contribute to the development of more effective cancer treatments, advancing research into metal-based drugs, and potentially overcoming some of the limitations associated with cisplatin.