Ruthenium (ii)[3+ 2+ 1] mixed ligand complexes: substituent effect on photolability, photooxidation of bases, photocytotoxicity and photonuclease activity (original) (raw)
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Synthesis and DNA-binding studies of two ruthenium(II) complexes of an intercalating ligand
European Journal of Medicinal Chemistry, 2009
Two new ruthenium(II) complexes [Ru(bpy) 2 (HBT)] 2þ (1) and [Ru(phen) 2 (HBT)] 2þ (2) (bpy ¼ 2,2 0bipyridine; phen ¼ 1,10-phenanthroline; HBT ¼ 11H, 13H-4, 5,9,10,12,14-hexaaza-benzo [b] triphenylene) have been synthesized and characterized by elemental analysis, mass spectra, 1 H NMR and cyclic voltammetry. The DNA binding property of the two complexes has been investigated employing absorption spectroscopy, fluorescence spectroscopy and viscosity measurements. Both complexes 1 and 2 have been found to prefer intercalative binding to DNA. The DNA binding constants for the two complexes have been measured to be 5.71 AE 0.20 Â 10 7 and 4.65 AE 0.20 Â 10 7 M À1 through ethidium bromide displacement method. Molecular modeling studies too indicate that both complexes 1 and 2 prefer intercalative binding to DNA and both these complexes exhibit similar DNA binding energies. Both complexes 1 and 2 bring about photocleavage of plasmid DNA when irradiated at 440 nm.
Inorganic chemistry, 2017
Ruthenium polypyridine complexes have shown promise as agents for photodynamic therapy (PDT) and tools for molecular biology (chromophore-assisted light inactivation). To accomplish these tasks, it is important to have at least target selectivity and great reactive oxygen species (ROS) photogeneration: two properties that are not easily found in the same molecule. To prepare such new agents, we synthesized two new ruthenium complexes that combine an efficient DNA binding moiety (dppz ligand) together with naphthyl-modified (1) and anthracenyl-modified (2) bipyridine as a strong ROS generator bound to a ruthenium complex. The compounds were fully characterized and their photophysical and photochemical properties investigated. Compound 2 showed one of the highest quantum yields for singlet oxygen production ever reported (ΦΔ= 0.96), along with very high DNA binding (log Kb = 6.78). Such photochemical behavior could be ascribed to the lower triplet state involving the anthracenyl-modif...
DNA-Binding Studies of Mixed-Ligand (Ethylenediamine)ruthenium(II) Complexes
Chemistry & Biodiversity, 2006
A series of mixed-ligand ruthenium(II) complexes of the type [Ru(en) 2 bpy] 2 þ (bpy ¼ 2,2-bipyridine; 1), [Ru(en) 2 phen] 2 þ (phen ¼ 1,10-phenantroline; 2), [Ru(en) 2 IP] 2 þ (IP ¼ imidazo[4,5-f][1,10]phenanthroline; 3), and [Ru(en) 2 PIP] 2 þ (PIP ¼ 2-phenylimidazo[4,5-f][1,10]phenanthroline; 4) have been isolated and characterized by UV/VIS, IR, and 1 H-NMR spectral methods. The binding of the complexes with calf thymus DNA has been investigated by absorption, emission spectroscopy, viscosity measurements, DNA melting, and DNA photo-cleavage. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (¼ calf thymus DNA) by groove mode. Complex 2 binds more avidly to CT DNA than complex 1, complexes 3 and 4 bind to CT DNA by intercalation mode, 4 binds more avidly to CT DNA than 3. Noticeably, the four complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.
Inorganica Chimica Acta, 2011
In our search for new DNA intercalating ligands, a novel bifunctional intercalator 11-(9-acridinyl)dipyrido[3,2-a:2 0 ,3 0 -c]phenazine, acdppz (has two potentially effective intercalators via dipyridophenazine(dppz) and acridine which are linked together via C-C bond) and its corresponding Ru(II) polypyridyl complex [Ru(phen) 2 (acdppz)] 2+ (where phen = 1,10-phenanthroline) have been synthesized and characterized. The electrochemical behaviors of the ligand and its complex have been thoroughly examined. The structure of acdppz and [Ru(phen) 2 (acdppz)] 2+ were determined by X-ray crystallography. From the crystal structure of the complex, we found that the dppz moiety is not coplanar with the acridine ring, having a dihedral angle of 64.79 in the acdppz. The selected bond lengths and angles for the crystal structure of [Ru(phen) 2 (acdppz)] 2+ were compared to the geometry-optimized molecular structure of [Ru(phen) 2 (acdppz)] 2+ derived by Gaussian. The interaction of [Ru(phen) 2 (acdppz)] 2+ with calfthymus (CT) DNA was investigated by absorption and viscometry titration, thermal denaturation studies. The above measurements indicated that the complex binds less strongly with the CT DNA due to the intercalation by the ruthenium bound acdppz with an intrinsic binding constant of 2.6 Â 10 5 M À1 . Molecular-modeling studies also support an intercalative mode of binding of the complex to the model duplex d(CGCAATTGCG) 2 possibly from the major groove with a slight preference for GC rich region. Additionally, the title complex promotes the cleavage of plasmid pBR322 DNA upon irradiation under aerobic conditions.
Journal of Fluorescence, 2014
The new cis-[Co(Phen)2(NPS)](ClO4)2. cobalt(II) complexes (phen = 1,10-phenanthroline, NPS= N-phenylsalicylaldimine) have been synthesized and characterized by CHN analysis, molar conductance, electronic absorption, IR & NMR studies. They have been tested for their in vitro DNA binding activities by the spectroscopic methods such as UV-Visible, Emission, Cyclic volumetric and viscosity measurements. Further complex 1 was tested for their antimicrobial activities and it was found to have good antimicrobial activities.
Helvetica Chimica Acta, 2008
Complexes [Ru(phen) 2 (ppd)] 2þ and [Ru(phen)(ppd) 2 ] 2þ (ppd ¼ Pteridino[6,7-f] [1,10]phenanthroline-11,13(10H,12H)-dione, phen ¼ 1,10-Phenanthroline)
Designing photoreactive Ruthenium(II) complexes for biomedical applications
2012
The development of therapeutic agents represents one of the main research objectives in the fight against cancer. In this context, the “laboratoire de Chimie Organique et Photochimie” focuses its interest in the design of photoreactive Ruthenium II complexes. The interesting photoreactivity is mainly due to the photooxidizing properties of complexes bearing deficient ligands. It has been demonstrated that a photo-induced electron transfer (PET) is indeed possible between a DNA guanine moiety and a Ru II complex containing at least two accepting ligands. This primary PET process can lead to the formation of a photoadduct, in which a covalent link is formed between the Ru II complex and a DNA strand. This covalent binding allows the development of gene silencing strategies where two complementary oligonucleotides (ODNs) are irreversibly photocrosslinked. The present work concerns the preparation and a first photophysical study of new Ru II
Coord Chem Rev, 2019
In this review we summarize our work on development of Ru complexes with potential antitumor activity , which was performed over the last few years. In order to establish the structure-activity relationship for Ru(II) compounds, we have designed, synthesized and thoroughly studied several Ru(II) complexes, which were divided in three main groups: i) organometallic Ru(II)-arene complexes, ii) Ru(II) half-sandwich coordination complexes bearing neutral face-capping macrocyclic ligands, such as 1,4,7-trithiacyclononane ([9]aneS3) and 1,4,7-triazacyclononane ([9]aneN3), and iii) Ru(II)-polypyridyl complexes. Our most recent experiments moved toward synthesis, chemistry and reactivity of the heteronu-clear ruthenium(II)/ferrocene complexes. The first part of the present review gives a brief overview of the structural features and anticancer activity of ruthenium complexes. The second part is focused mainly on the results obtained from the kinetic and mechanistic studies of the reactions between Ru(II) complexes and guanine derivatives, such as 9-methylguanine (9MeG), guanosine (Guo) and guanosine-5 0-monopho sphate (5 0-GMP), as well as on structural characterization of the final products of these reactions. In the final part we deal with the reactions of Ru(II) complexes with DNA, which is widely accepted as a potential target for cytotoxic ruthenium compounds. We have also described the interactions of Ru(II) compounds with the most abundant transport proteins from human serum: human serum albumin (HSA) and transferrin (Tf). We believe that a systematic review of the aforementioned studies will not only contribute to the future development of ruthenium complexes as potential antitumor agents, but will also help to understand the potential toxicity of ruthenium-based drugs. Abbreviations: 5 0-AMP, adenosine-5 0-monophosphate; A549, human lung carcinoma cell line; Bip, biphenyl; biphtpy, 4 0-biphenyl-2,2 0 :6,2 00-terpyridine; bpy, 2,2 0-bipyridine; biphbpy, 4,4 0-diphenyl-2,2 0-dipyridine; BSA, bovine serum albumin; CT DNA, calf thymus DNA, CT26, mouse colon carcinoma cell line; dach, 1,2-diaminocyclohexane; DNA, deoxyribonucleic acid; DNA-1, 5 0-CTT CTT GGT TCT CTT-3 0 /5 0-AAG AGA ACC AAG AAG-3 0 ; DNA-2, 5 0-TCT CCT TCT TGG TTC TCT TCT C-3 0 /5 0-GAA GAG AAC CAA GAA GGA GAG A-3 0 ; dppz, dipyrido(3,2-a:2 0 ,3 0-c]phenazine; dppt, 3-(1,10-phenanthrolin-2-yl)-5,6-diphenyl-as-triazine; en, 1,2-diaminoethane; 9EtG, 9-ethylguanine; Guo, guanosine; 5 0-GMP, guanosine-5 0-monophosphate; Cl-tpy, 4 0-chloro-2,2 0 :6 0 ,2 00-terpyridine; Cl-Ph-tpy, 4 0-(4-chlorophenyl)-2,2 0 :6 0 ,2 00-terpyridine; HSA, human serum albumin; HT DNA, herring testes DNA; HCT116, human colon carcinoma cell line; ICP-MS, inductively coupled plasma mass spectrometry; ICP-OES, inductively coupled plasma optical emission spectrometry; IgG, immunoglobulin G; KP1019, indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]; L-His, L-histidine; L-Cys, L-cysteine; L-Met, L-methionine; LC, liquid chromatography; Me 2 bpy, 4,4 0-dimethyl-2,2 0-bipyridine; 9MeG, 9-methylguanine; MCF-7, breast carcinoma cell line; MRC-5, human fetal lung fibroblast cell line; NAMI-A, imidazolium trans-[tetrachlorido(1H-imidazole)(dimethylsulfoxide)ruthenate(III)]