Photoinduced Intercalation and Coordination of a Dirhodium Complex to DNA: Dual DNA Binding

Abstract

Two new complexes, cis-H,H-[Rh2 (OCCH3 NH)2 (LL)(CH3 CN)2 ](2+) , where LL=bpy (2, bpy=2,2'-bipyridine) and dppz (3, dppz=dipyrido[3,2-a:2',3'-c]phenazine), were prepared from the reaction of cis-H,H-[Rh2 (OCCH3 NH)2 (CH3 CN)6 ](2+) (1) with the corresponding bidentate ligand. The bpy and dppz ligands chelate to the same rhodium atom and are positioned trans to the amidato N atoms, as determined by the single crystal X-ray structure of 2. Irradiation of 2 and 3 with visible light in water results in the exchange of one CH3 CNeq ligand for an H2 O molecule with quantum yields, Φ400 , of 0.040 and 0.044, respectively (λirr =400 nm). The identities of the photoproducts of 2 and 3 were determined to be cis-H,H-[Rh2 (OCCH3 NH)2 (L)(H2 O)(CH3 CN)](2+) , where L is bpy (4) and dppz (5), respectively. Mobility shift assays show that 4 crosslinks double-stranded DNA, and ESI-MS experiments indicate that both 4 and 5 form covalent adducts with single-stranded DNA. In addition, relative viscosity and 2D NMR experiments show that the dppz ligand of 5 also intercalates into DNA upon irradiation, making 3 a dual-binding agent that both intercalates and covalently binds to DNA upon the absorption of visible light.

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

“…The peak at ~520 nm apparent in 1 (ε ~ 200 M −1 cm −1 ) is characteristic of the Rh 2 (δ*)/amidato(π*)→Rh 2 (σ*) transition, also present in the related complex cis -H,H-[Rh 2 (OCCH 3 NH) 2 (bpy)(CH 3 CN) 2 ] 2+ (ε ~ 160 M −1 cm −1 ). This peak is also expected in 2 , but it cannot be observed due to the overlapping, intense tail of the 1 LC and 1 MLCT transitions [17,21,22]. …”

“…Cis - [Rh 2 (OCCH 3 NH) 2 (CH 3 CN) 6 ](BF 4 ) 2 [21], dppn [33], and 1 [22] were synthesized according to published procedures. D 2 O (99.9% D) and 3-(trimethylsilyl)-1-propanesulfonic acid sodium salt (DSS) was purchased from Sigma Aldrich, whereas ethidium bromide (EtBr), 1,3- diphenylisobenzofuran (DPBF), and polystyrene sulfonate (PSS) were obtained from Aldrich and used without further purification.…”

“…The replacement of the CH 3 CN ligands of the complex positioned trans to the N atoms with the dppz bidentate ligand resulted in the isolation of cis -H,H-[Rh 2 (OCCH 3 NH) 2 (dppz)(CH 3 CN) 4 ] 2+ ( 1 , Figure 1). Complex 1 was shown to intercalate and to covalently bind to ds-DNA following CH 3 CN photodissociation, but only upon irradiation with visible light [22]. …”

Photoinduced interactions of two dirhodium complexes with d(GTCGAC)2 probed by 2D NOESY

“…36 Moreover, the related complexes cis - H,H -[Rh 2 (OCCH 3 NH) 2 (L)(CH 3 CN) 2 ] 2+ , where L = 2,2′-bipyridine (bpy, 1 ) or dipyrido[3,2- a :2′,3′- c ]phenazine (dppz, 2 ), depicted in Figure 1, coordinate to DNA upon photoinduced CH 3 CN exchange when irradiated in H 2 O and, in the case of 2 , also intercalate between the base pairs of the duplex. 37 This dual activity of 2 is of interest because compounds with novel DNA binding modes, such as simultaneous intercalation and coordination, have been shown to overcome cisplatin resistance. 38,39 The light activated intercalation and covalent DNA binding with 2 provides spatiotemporal control not available with the previous dual-binding platinum compounds.…”

“…Previous work showed that both complexes undergo photoinduced covalent binding to the 12-mer duplex oligonucleotide d(5′-CTCTCAACTTCC-3′)•d(5′-GGAAGTTGAGAG-3′), but 2 also exhibits enhanced intercalation following irradiation. 37 To elucidate the specific binding sites of 1 and 2 , 2D 1 H− 1 H NOESY and thermal denaturation experiments were conducted with the shorter d(GTCGAC) 2 duplex both in the dark and upon irradiation with visible light.…”