Organoplatinum(II) Complexes Self-Assemble and Recognize AT-Rich Duplex DNA Sequences

Abstract

The specific recognition of AT-rich DNA sequences opens up the door to promising diagnostic and/or therapeutic strategies against generelated diseases. Here, we demonstrate that amphiphilic Pt II complexes of the type [Pt(dmba)(N∧N)]NO 3 (dmba = N,N-dimethylbenzylamine-κN, κC; N∧N = dpq (3), dppz (4), and dppn ( 5)) recognize AT-rich oligonucleotides over other types of DNA, RNA, and model proteins. The crystal structure of 4 shows the presence of significant π-stacking interactions and a distorted coordination sphere of the d 8 Pt II atom. Complex 5, containing the largest πconjugated ligand, forms supramolecular assemblies at high concentrations under aqueous environment. However, its aggregation can be promoted in the presence of DNA at concentrations as low as 10 μM in a process that "turns on" its excimer emission around 600 nm. Viscometry, gel electrophoresis, and theoretical calculations demonstrate that 5 binds to minor groove when self-assembled, while the monomers of 3 and 4 intercalate into the DNA. The complexes also inhibit cancer cell growth with low-micromolar IC 50 values in 2D tissue culture and suppress tumor growth in 3D tumor spheroids with a multicellular resistance (MCR) index comparable to that of cisplatin.

Terpyridine copper(ii) complexes as potential anticancer agents by inhibiting cell proliferation, blocking the cell cycle and inducing apoptosis in BEL-7402 cells

“…These results indicated that all of the compounds were stable at least for 48 h in the buffer solution. 31 HPLC was also used to study the stability and purity of the test compounds. HPLC analysis of the solutions at 0 h and 48 h was carried out at room temperature.…”

“…S10 †), indicating that the ligands and complexes were stable in the Tris-HCl solution for at least 48 h. The HPLC results were consistent with the UV-Vis analysis results. 31…”

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).…”

Novel arylplatinum complexes with 2,2′‐dimethyl‐4,4′‐bithiazole: Synthesis, characterization, single crystal structure determination, and investigation of CT‐DNA interaction

“…[12] The interesting point about arylplatinum complexes containing chelating ligands is the formation of square planar geometry, which can have appropriate interactions with DNA. [13][14][15][16] It was shown that some platinum complexes can interact with the double helix of DNA through various modes such as intercalation (binding between two base pairs), electrostatic interaction, and groove binding. [17] So, the pharmaceutical and biological properties of Pt complexes are attributed to the binding modes with DNA.…”