Design, Synthesis, and Anticancer Studies of a p -Cymene-Ru(II)-Curcumin Organometallic Conjugate Based on a Fluorescent 4-Amino-1,8-naphthalimide Tröger's Base Scaffold.

A unique V-shaped "chiral" supramolecular scaffold, N -(4-pyridyl)-4-amino-1,8-naphthalimide Tröger's base ( TBNap ), was synthesized in good yield from a precursor N -(4-pyridyl)-4-amino-1,8-naphthalimide ( Nap ). TBNap was characterized using different spectroscopic methods and the molecular structure was elucidated by diffraction analysis. A new p -cymene-Ru(II)-curcumin conjugate ( TB-Ru-Cur ) was designed by reacting TBNap dipyridyl donor and ruthenium-curcuminato acceptor [ RuCur = ( p -cymene)Ru-(curcuminato)Cl] in the presence of silver triflate. TB-Ru-Cur was isolated in quantitative yield and characterized using Fourier transform infrared (FT-IR), NMR ( 1 H, 13 C, and 19 F), and electrospray ionization mass spectrometry (ESI-MS), and the molecular structure has been predicted using a computational study. Both TBNap and TB-Ru-Cur exhibited intramolecular charge transfer (ICT)-based fluorescence emission. Furthermore, the anticancer properties of TBNap , Ru-Cur , and TB-Ru-Cur were assessed in different cancer cell lines. Gratifyingly, the conjugate TB-Ru-Cur displayed fast-cellular internalization and good cytotoxicity against HeLa, HCT-116, and HepG2 cancer cells and the estimated IC 50 value was much lower than that of the precursors ( TBNap and Ru-Cur) and the well-known chemotherapeutic drug cisplatin.