Light Triggers the Antiproliferative Activity of Naphthalimide-Conjugated (η6-arene)ruthenium(II) Complexes

Abstract

We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N′)L][PF6]2 containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT).

Stimuli-responsive platinum and ruthenium complexes for lung cancer therapy

“…Monodentate ligand in a Ru(II) complex easily undergoes ligand substitution reaction, especially under light irradiation. Half-sandwich Ru(II)-arene complex 40 bearing pyridinyl naphthalimides ( Figure 10 ) as monodentate ligand were stable in the dark, and released the monodentate pyridyl ligand upon blue light irradiation ( Bisceglie et al, 2022 ). It exhibited high photocytotoxicity to A549 cells under blue light irradiation with an IC 50 value of 10.55 μM.…”