Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands†

doi:10.7503/cjcu20180370

Abstract

Abstract:

Three novel arene-ruthenium complexes(1—3) were synthesized from 2-(4-pyridinyl)imidazo[4,5-f]-1,10-phenanthroline(L₁) and [(η⁶-cymene)Ru(μ-Cl)Cl]₂. A polypyridine-ruthenium complex(4) was synthesized from RuCl₃ and 2-(4-(1H-imidazol-1-yl)phenyl)-1H-imidazo[4,5-f]-1,10-phenanthroline(L₂). All the complexes were characterized by ¹H NMR, elemental analysis and ESI-MS. UV-Vis, circular dichroism and fluorescence techniques were used to study the interactions between complexes 1—4 and calf thymus DNA(CT-DNA) or BSA, respectively. Viscosity measurements were carried out to clarify further the interaction mode of complexes 1—4 with DNA. In addition, the interactions of complex 4 with pBR322 DNA were studied by gel electrophoresis, and the pH-related fluorescence spectra of complex 4 were recorded in various pH solutions. The results show that these complexes could interact with DNA via intercalation and disturbing the secondary structure of DNA. The static quenching for complexes 1—4 were observed when these complexes were titrated with BSA protein. Only one binding site was observed between these complexes and BSA and the binding constants were calculated. Under the UV light(365 nm), complex 4 could generate ¹O₂ and cleave pBR322-DNA efficiently and its fluorescencewere enhanced more than 56% when the solution pH was changed from 11.37 to 1.74.

Key words: Ruthenium-arene complex, ,10-Phenanthroline, Interaction with DNA, Interaction with BSA, Photocleavage

CLC Number:

O614

TrendMD:

ZHAO Yachen,LI Ji,ZHANG Peipei,LIU Shuxian,WEI Daina,SU Zhi,QIAN Yong,WANG Feili,Peter John Sadler,LIU Hongke. Synthesis, Characterization and DNA, BSA Interactions of Mononuclear Ruthenium Complexes with Modified 1,10-Phenanthrolines Ligands^†[J]. Chem. J. Chinese Universities, 2019, 40(1): 30.

Figures/Tables 11

Scheme 1 Synthesis of complexes 1—4

Fig.1 UV spectra of complexes 1(A), 2(B), 3(C) and 4(D) in DMSO/PBS[Complex]=50 μmol/L; DMSO/PBS volume ratio is 5:95; pH≈7.4.

Fig.2 UV-Vis absorption spectra of complexes 1(A), 2(B), 3(C) and 4(D)in the absence and in the presence of increasing concentration of CT-DNAThe arrows show the changes upon increasing amounts of CT-DNA; [Complex]=50 μmol/L, [DNA]=0—36 μmol/L.

Fig.3 CD spectra of CT-DNA in the absence and in the presence of complex 1(A), 2(B), 3(C) or 4(D)(A), (B), (C) [DNA]=100 μmol/L, [Complex]=0—70 μmol/L; (D) [DNA]=200 μmol/L, [Complex]=0—40 μmol/L.

Fig.4 Effect of the addition of increasing amounts of ethidium bromide(EB) or complexes 1—4 on the relative viscosity of CT-DNA(100 μmol/L) in PBS(pH=7.4) at 25 ℃

Fig.5 Agarose gel electrophoresis assay to investigate the DNA cleavage induced by complex 4Lanes 1: DNA alone; lanes 2—7: DNA + complex 4(with light); lane 8: DNA+complex 4(without light, [complex 4]=10 μmol/L). The DNA concentration is 10 μmol/L. The concentrations of complex 4 from lane 2 to lane 7 are 0.5, 1, 2.5, 5, 7.5, 10 μmol/L, respectively.

Fig.6 Fluorescence spectra of BSA with different concentrations of complexes 1—4The arrows show the changes upon increasing amounts of complex. (A—D) [BSA]=3 μmol/L, [complex]=0—20 mmol/L.

Table 1 KSV data, binding constant, and binding site of complexes 1—4 with BSA

System	K_SV/(L·mol^-1)	K_q/(L·mol^-1·s^-1)	K/(L·mol^-1)	n
1-BSA	5.04×10⁴	5.04×10¹²	5.06×10⁵	1.17
2-BSA	3.34×10⁴	3.34×10¹²	3.90×10⁵	1.22
3-BSA	3.85×10⁴	3.85×10¹²	3.02×10⁴	0.99
4-BSA	2.72×10⁵	2.72×10¹³	6.61×10⁶	1.32

Fig.7 Fluorescence spectra of complex 4 with different pH values [Complex 4]=10 μmol/L.

Fig.8 Fluorescence spectra of complex 4 with different pH values[Complex 4]=10 μmol/L.

Fig.9 Changes of DCF fluorescence intensity in complex 4-treated MCF-7 cell

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