Carbon-phosphorus stapled Au(I) anticancer agents via bisphosphine induced reductive elimination

• Published in: Dalton transactions : an international journal of inorganic chemistry
• Main Authors: Gilpatrick, Sean T, Obisesan, Oluwatosin A, Parkin, Sean, Awuah, Samuel G
• Format: Journal Article
• Language: English
• Published: England The Royal Society of Chemistry 20.08.2024
• Subjects: Chemistry
• ISSN: 1477-9234; 1477-9226; 1477-9234
• DOI: 10.1039/d4dt01929f

Towards the goal of generating new stabilized gold complexes as potent anticancer agents, we report here a novel class of Au(I) agents from Au(III)-mediated C -P bond formation captured within the same complex by reacting a C^N cyclometalated Au(III) complex with bisphosphines. Cyclometalated Au(III) complexes of the type [Au(C^N)Cl ], where C^N represent different aryl pyridine framework reacted with bis(2-diphenylphosphino)phenyl ether in refluxing methanol to access an unsymmetrical gold complex featuring C-P coupling and Au(I)-phosphine. The complexes were characterized by H-NMR, C-NMR, and P-NMR and mass spectrometry. The structures of the complexes were characterized by X-ray crystallography and purity ascertained by HPLC and elemental analysis. The complexes demonstrate promising anticancer activity in a broad panel of cancer cell lines of different tumor origin. Mechanistically, the complexes induce apoptosis, generate mitochondrial ROS, depolarize mitochondrial membrane potential and modulate mitochondrial respiration in cancer cells. Overall, we developed a new structural class of Au(I) complexes with promising anticancer potential with potential utility in other applications.