Dual photoreactivity of a new Rh2(II,II) complex for biological applications

Abstract

A new Rh2(II,II) complex containing one dppn (benzo[i]dipyrido[3,2-a:2,3-c]phenazine) ligand with an extended π-system, cis-H,H-[Rh2(OCCH3NH)2(dppn)(CH3CN)2]2+ (2), was synthesized and characterized. The dppn ligand, which serves as a DNA base pair intercalator, chelates to a single Rh center and is positioned trans to the amidato N atoms of the bridging acetamide ligand. This ligand also possesses a low-lying dppn-centered 3ππ* state that is advantageous for the sensitization of singlet oxygen (1O2), which complex 2 produced with a quantum yield, Φ1O2 460, of 0.22(7) with 460 nm excitation. In addition, one equivalent of CH3CN is released from 2 upon irradiation with visible light, generating cis-H,H-[Rh2(OCCH3NH)2(dppn)(H2O)(CH3CN)]2+ in aqueous media with photoinduced ligand exchange quantum yield, ΦLE 450, of 0.0033(1). Thermal denaturation and relative viscosity studies are consistent with a π-stacking interaction of 2 with double-stranded DNA together with covalent binding to the duplex upon irradiation with visible light. Therefore, 2 exhibits dual photoreactivity towards DNA, making it potentially useful for photochemotherapy with enhanced activity relative to compounds able to achieve only one mode of cell death upon irradiation.

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

“… Remarkably, the release quantum yield measured upon irradiation at 550 nm exceeded unity (Φ r = 1.38), suggesting that a dark release follows the initial photoreaction. Another photoactivatable dirhodium complex, 182 , bearing a benzo­[ i ]­dipyrido­quinoxaline ligand (Figure ) was designed to serve as a DNA-intercalating singlet oxygen generator (Φ Δ = 0.22 at 477 nm) thanks to its low-lying dppn-centered 3 π,π* state . Upon irradiation in water, acetonitrile is released from this compound and replaced by H 2 O as a ligand (Φ r = 0.0033 at 450 nm).…”

Metal-mediated diradical tuning for DNA replication arrest via template strand scission

“…Metalloinserters and metallointercalators exploit noncovalent interactions of planar aromatic ligands to inhibit DNA repair because they show unwinding of DNA to π-stack between base pairs, groove binding, or insertion into a destabilized site (12,13). Covalent interactions can be used to directly bind complexes to the DNA duplex whereas the ligands may be functionalized for subsequent reactions such as radicalinduced DNA cleavage (14)(15)(16)(17)(18)(19). Complexes using these mechanisms often demonstrate inhibition of DNA replication, leading to G2 arrest to halt progression of the damaged DNA during the cell cycle; however, many suffer from lengthy reaction times of up to 48 h or inefficient DNA degradation.…”

Ruthenium(ii) polypyridyl complexes with π-expansive ligands: synthesis and cubosome encapsulation for photodynamic therapy of non-melanoma skin cancer

“…Indeed, this peculiar ligand has been largely exploited not only to improve the photobiological activity of the resulting compounds, via the population of long-lived dppn-centered 3 ππ* excited states, but also to shift their 1 MLCT absorption towards longer wavelengths 18 and, given its known DNA-intercalating properties, to strengthen their interaction with the nucleic acid. 19–21 A recent example of this was reported by Zhao and coworkers, who showed the benefits derived from the substitution of a bpy (bipyridine) unit by a dppn ligand in their tris-heteroleptic RPC-based PSs. 22…”

“…Indeed, this peculiar ligand has been largely exploited not only to improve the photobiological activity of the resulting compounds, via the population of long-lived dppn-centered 3 ππ* excited states, but also to shift their 1 MLCT absorption towards longer wavelengths 18 and, given its known DNA-intercalating properties, to strengthen their interaction with the nucleic acid. [19][20][21] A recent example of this was reported by Zhao and coworkers, who showed the benefits derived from the substitution of a bpy (bipyridine) unit by a dppn ligand in their tris-heteroleptic RPC-based PSs. 22 Notwithstanding the advantages derived from the use of dppn, it is surprising that PSs containing two dppn ligands simultaneously coordinated to a Ru(II) center have been only sparingly explored, 23,24 while numerous examples of dppn-containing RPCs for PDT are reported in the literature [25][26][27][28][29][30][31] (some of them have also been applied for compounds at the boundary between PDT and photoactivated chemotherapy PACT).…”