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

Abstract

A unique V-shaped "chiral" supramolecular scaffold, N-(4-pyridyl)-4-amino-1,8-naphthalimide Troger'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 pcymene-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.

Design of 1,8‐Naphthalimide‐Based Fluorescent Functional Molecules for Biological Application: A Review

“…For example, they designed a unique V-shaped "chiral" functional molecule (36), p-cymene-Ru(II)-curcumin conjugate, built from N-(4pyridyl)-4-amino-1,8-naphthalimide Tröger's base dipyridyl donor and ruthenium-curcuminato acceptor (Figure 13). [74] The functional molecule displayed ICT-based fluorescence emission, and it exhibited fast-cellular internalization and good cytotoxicity against HeLa, HCT-116, and HepG2 cancer cells. Afterward, they introduced ruthenium polypyridyl complexes onto the Nposition of a 4-nitro-1,8-naphthalimide group, and then an effective light switch (37) with DNA binding ability was obtained (Figure 13).…”

Therapeutic potential and limitations of curcumin as antimetastatic agent

“…In addition, some of them (e.g., Cu 2+ , VO, La) display sometimes higher light toxicity than original curcumin, comparable with Photofrin. [352] In combination with structure motif of the curcumin and ruthenium complexes, this could lead to an increase in curcumin therapeutic effectivity [353][354][355][356]. In this case, IC 50 value for Ru(cym)(bdcurc)(PTA)]PF 6 (Fig.…”

Synthesis, characterization, and heparin-binding study of a self-assembled p-cymene-Ru(ii) metallocycle based on a 4-amino-1,8-naphthalimide Tröger's base supramolecular scaffold

“…The cleft-shaped structure of TBNaps also provides a large internal hydrophobic cavity that can be exploited in host–guest chemistry and chemosensing applications. 13…”

“…These supramolecular structures and functional materials were used in the chemosensing of anions, cations, and small molecules, fluorescence sensing and adsorption of chemical explosives, DNA binding, and bio-imaging. 11–13 Despite the extensive use of TBNaps in the area of supramolecular chemistry, there are no reports of finite metallosupramolecular coordination complexes based on the TBNap supramolecular scaffold. Herein, we report the very first example of a [2 + 2] coordination-self-assembled metallocycle ( TBNap-Ru-MC ) based on TBNap containing a di-4-pyridyl donor.…”

“…As we have demonstrated in our earlier publications, TBNap derivatives are highly fluorescent due to the ICT-based charge transfer from the electron-rich amine moiety to the electron-poor imide site. 11–13 Upon photo-excitation, TBNap derivatives generate an excited state dipole that is highly dependent on solvent polarity. 11 Therefore, we measured the absorption and emission spectra in different polar solvents from non-polar toluene to polar DMSO solvents.…”