Differential impact on oral cancer cell viability for three carboxylate-stabilized rhenium(I) tricarbonyl centers supported by 2,2′-bipyridine: One-pot synthesis, a structure, and proton-catalyzed carboxylate ligand substitution

• Published in: Inorganica Chimica Acta Vol. 568; p. 122105
• Main Authors: Buren, Lyndsey, Tumbaco, Emily, Piesco, Alyssa, Irvin, Justin, Emge, Thomas J., Weisburg, Jeffrey H., Moehring, Gregory A., Naik, Datta V.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.08.2024
• Subjects: Carboxylate ligand substitution; Crystal structure; Cytotoxicity; HSC-2 oral cancer cells; One-pot synthesis; Rhenium; Carboxylate ligand substitution; One-pot synthesis; Cytotoxicity; HSC-2 oral cancer cells; Rhenium; Crystal structure
• ISSN: 0020-1693; 1873-3255
• DOI: 10.1016/j.ica.2024.122105

Proton NMR experiments on carboxylate-stabilized rhenium(I) tricarbonyl 2,2’-bipyridine-supported complexes indicate that carboxylate ligand substitution is proton catalyzed. The amount of substitution and its product(s) depend on Kb for the carboxylate and the matrix for the substitution. The differential cytotoxicity, measured as IC50 values, for the complexes Re(O2CR)(CO)3(2,2’-bipyridine) (R = H, CH3, or CHF2) towards HSC-2 oral cancer cells correlates positively with the values of Kb for the carboxylate ligand that is replaced. [Display omitted] •Carboxylate-stabilized rhenium(I) cytotoxicity for oral cancer cells.•One-pot prep of carboxylate-stabilized rhenium tricarbonyl complexes.•Chiral-carboxylate rhenium(I) tricarbonyl complex crystal structure.•Proton-catalyzed carboxylate ligand substitution at rhenium(I) center.•Eventual carboxylate ligand substitution by pyridine in water/DMSO. A set of six carboxylate-stabilized rhenium(I) tricarbonyl complexes supported by a 2,2′-bipyridine (bpy) ligand, Re(O2CR)(CO)3(bpy) (R = H, CH3, CHF2, R- or S-CHBrCH(CH3)2, and C5H11), were prepared by acidolysis of the complex Re(OCO2C5H11)(CO)3(bpy) with the appropriate carboxylic acid and characterized by 1H and 13C-{1H} NMR and IR spectroscopy. The crystal structure of the complex, Re[R-O2CCHBrCH(CH3)2](CO)3(bpy), was determined by X-ray crystallography. An alternate one-pot route to the carboxylate-stabilized rhenium(I) complexes Re(O2CR’)(CO)3(bpy) (R’ = CH3 or C6H5) and Re(O2CCH3)(CO)3(1,10-pheanthroline), which starts with Re2(CO)10 and in which an ester solvent serves as the source of the carboxylate ligand, was also developed. Cell viability tests on three carboxylate-stabilized rhenium(I) complexes (R = H, CH3, or CHF2), using the HSC-2 oral cancer cell line, found different levels of cytotoxicity for each complex. NMR studies of the carboxylate ligand substitution reaction found that the reaction is catalyzed by protons. In a chloride-rich NMR solution, substitution of the carboxylate ligand leads to either a chloride-stabilized neutral complex (major product) or to a water-stabilized cation (minor product). Cytotoxicity results correlate positively with the Kb value of the carboxylate ligand. Apparently, the more substitutionally inert the carboxylate-stabilized complex is in a chloride-rich environment (similar to extracellular fluid) the greater the amount of cytotoxic [Re(CO)3(bpy)(H2O)]+ that forms in the cytosol.