DNA Interaction,DNA Photocleavage,Photocytotoxicity In Vitro,and Molecular Docking of Naphthyl-Appended Ruthenium Complexes

With the development of metal-based drugs, Ru(II) compounds present potential applications of PDT (photodynamic therapy) and anticancer reagents. We herein synthesized two naphthyl-appended ruthenium complexes by the combination of the ligand with naphthyl and bipyridyl. The DNA affinities, photocleavage abilities, and photocytotoxicity were studied by various spectral methods, viscosity measurement, theoretical computation method, gel electrophoresis, and MTT method. Two complexes exhibited strong interaction with calf thymus DNA by intercalation. Production of singlet oxygen (¹O₂) led to obvious DNA photocleavage activities of two complexes under 365 nm light. Furthermore, two complexes displayed obvious photocytotoxicity and low dark cytotoxicity towards Hela, A549, and A375 cells.     

Synthesis and Photocytotoxicity of Mono-functionalised Porphyrin with Valine Moiety

A mono-funtionalised tetraphenylporphyrin (TPP) bearing valine moiety at the phenyl ring was synthesized for photocytotoxicity examination in four steps, starting from regiospecific mono-nitration of TPP at the phenyl ring. The in vitro photocytotoxicitic effect against SPC-Al adenocarcinona cell line was tested.     

Investigation on Optical and Biological Properties of 2-(4-Dimethylaminophenyl)benzothiazole Based Cycloplatinated Complexes

The optical and biological properties of 2-(4-dimethylaminophenyl)benzothiazole cycloplatinated complexes featuring bioactive ligands ([{Pt(Me₂N-pbt)(C₆F₅)}L] [L=Me₂N-pbtH 1 , p-dpbH (4-(diphenylphosphino)benzoic acid) 2 , o-dpbH (2-(diphenylphosphino)benzoic acid) 3 ), [Pt(Me₂N-pbt)(o-dpb)] 4 , [{Pt(Me₂N-pbt)(C₆F₅)}₂(μ-PR_nP)] [PR₄P=O(CH₂CH₂OC(O)C₆H₄PPh₂)₂ 5 , PR₁₂P=O{(CH₂CH₂O)₃C(O)C₆H₄PPh₂}₂ 6 ] are presented. Complexes 1 – 6 display ¹ILCT and metal-perturbed ³ILCT dual emissions. The ratio between both bands is excitation dependent, accomplishing warm-white emissions for 2 , 5 and 6 . The phosphorescent emission is lost in aerated solutions owing to photoinduced electron transfer to ³O₂ and the formation of ¹O₂, as confirmed in complexes 2 and 4 . They also exhibit photoinduced phosphorescence enhancement in non-degassed DMSO due to local oxidation of DMSO by sensitized ¹O₂, which causes a local degassing. Me₂N-pbtH and the complexes specifically accumulate in the Golgi apparatus, although only 2 , 3 and 6 were active against A549 and HeLa cancer cell lines, 6 being highly selective in respect to nontumoral cells. The potential photodynamic property of these complexes was demonstrated with complex 4 .     

Photocytotoxicity and G‐quadruplex DNA interaction of water‐soluble gallium(III) tris(N‐methyl‐4‐pyridyl)corrole complex

A water‐soluble cationic gallium corrole, 5,10,15‐tris(N‐methyl‐4‐pyridyl)corrolatogallium(III) ( 3 ), was prepared and characterized. The photocytotoxicity of 3 was investigated using Hep G2 cancer cell line. Upon treatment with corrole 3 and irradiation, fragmentation of tumor cell nuclei was observed, which led to apoptosis. Flow cytometric analysis clearly showed the efficient induction of apoptotic cell death, and corrole 3 exhibited high photocytotoxicity towards Hep G2 cancer cells (IC₅₀ = 60 nM). Furthermore, the binding behavior of corrole 3 with c‐MYC G‐quadruplex DNA, a potent target for antitumor drugs, was investigated using spectroscopic methods and molecular docking simulation. Copyright © 2015 John Wiley & Sons, Ltd.     

Novel Cyclometalated Fe(II) Complex with NCN Pincer and BODIPY‐Appended 4'‐Ethynyl‐2,2':6',2”‐terpyridine as Mitochondria‐Targeted Photodynamic Anticancer Agents

BODIPY (boron dipyrromethene) derivatives and iron complexes are two types of functional compounds that have found wide applications in the fields of biology and medicine. The new class of cyclometalated Fe(II) complex with NCN pincer and meso‐phenyl‐4'‐ethynyl‐2,2':6',2”‐terpyridine BODIPY ligands of formula [Fe(L)(tpy‐BODIPY)] , 1, in which HL:5‐methoxy‐1,3‐bis (1‐methyl‐1H‐benzo[d]imidazol‐2‐yl)benzene, tpy‐BODIPY: 8‐(4‐phenyl‐4'‐ethynyl‐2,2':6',2”‐terpyridine) BODIPY, has been synthesized and studied as mitochondria‐targeted photodynamic therapy (PDT). Complex 1 showed photocytotoxicity in HeLa cells at 500 nm with low dark toxicity. The phototoxicity of complex 1 on the nontumorigenic MRC‐5 cell line showed the same trend observed for HeLa cells, that is moderately photocytotoxic against the nontumorigenic MRC‐5 cell line (IC₅₀ = 36.21 μM). Moreover, complex 1 selectively localizes into mitochondria of the HeLa cells. The photophysical properties, cellular uptake, reactive oxygen species (ROS) generation, and cellular apoptosis of complex 1 have also been studied.Overall, the new Fe(II) complex with BODIPY moiety is significantly photocytotoxic in HeLa cells when irradiated with visible light of 500 nm giving as mitochondria targeting. Therefore, we present cyclometalated Fe(II) pincer complex induced mitochondria‐targeted PDT involving the BODIPY moiety that develops persuasively designed photoactivatable Fe(II) complexes.     

Flexible RuII Schiff Base Complexes: G-Quadruplex DNA Binding and Photo-Induced Cancer Cell Death

A series of new Ru^II Schiff base complexes built on the salphen moiety has been prepared. This includes four flexible monometallic Ru^II compounds and six rigid bimetallic analogues that contain Ni^II, Pd^II or Pt^II cations into the salphen complexation site. Steady state luminescence titrations illustrated the capacity of the compounds to photoprobe G-quadruplex (G4) DNA. Moreover, the vast array of the Schiff base structural changes allowed to extensively assess the influence of the ligand surface, flexibility and charge on the interaction of the compounds with G4 DNA. This was achieved thanks to circular dichroism melting assays and bio-layer interferometry studies that pointed up high affinities along with good selectivities of Ru^II Schiff base complexes for G4 DNA. In cellulo studies were carried out with the most promising compounds. Cellular uptake with location of the compounds in the nucleus as well as in the nucleolus was observed. Cell viability experiments were performed with U2OS osteosarcoma cells in the dark and under light irradiation which allowed the measurements of IC₅₀ values and photoindexes. They showed the substantial role played by light irradiation in the activity of the drugs in addition to the low cytotoxicity of the molecules in the dark. Altogether, the reported results emphasize the promising properties of Ru^II Schiff base complexes as a new class of candidates for developing potential G4 DNA targeting diagnostic or therapeutic compounds.     

Photocytotoxic Activity of Ruthenium(II) Complexes with Phenanthroline-Hydrazone Ligands

This paper reports on the synthesis and characterization of two new polypyridyl-hydrazone Schiff bases, (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)thiophene-2-carbohydrazide (L¹) and (E)-N′-(6-oxo-1,10-phenanthrolin-5(6H)-ylidene)furan-2-carbohydrazide (L²), and their two Ru(II) complexes of the general formula [RuCl(DMSO)(phen)(Lⁿ)](PF6). Considering that hydrazides are a structural part of severa l drugs and metal complexes containing phenanthroline derivatives are known to interact with DNA and to exhibit antitumor activity, more potent anticancer agents can be obtained by covalently linking the thiophene acid hydrazide or the furoic acid hydrazide to a 1,10-phenanthroline moiety. These ligands and the Ru(II) complexes were characterized by elemental analyses, electronic, vibrational, ¹H NMR, and ESI-MS spectroscopies. Ru is bound to two different N-heterocyclic ligands. One chloride and one S-bonded DMSO in cis-configuration to each other complete the octahedral coordination sphere around the metal ion. The ligands are very effective in inhibiting cellular growth in a chronic myelogenous leukemia cell line, K562. Both complexes are able to interact with DNA and present moderate cytotoxic activity, but 5 min of UV-light exposure increases cytotoxicity by three times.     

Gadolinium(III) Porpholactones as Efficient and Robust Singlet Oxygen Photosensitizers

Construction of Gd^III photosensitizers is important for designing theranostic agents owing to the unique properties arising from seven unpaired f electrons of the Gd³⁺ ion. Combining these with the advantages of porpholactones with tunable NIR absorption, we herein report the synthesis of Gd^III complexes Gd‐1 – 4 ( 1 , porphyrin; 2 , porpholactone; 3 and 4 , cis‐ and trans‐porphodilactone, respectively) and investigated their function as singlet oxygen (¹O₂) photosensitizers. These Gd complexes displayed ¹O₂ quantum yields (Φ_Δs) from 0.64–0.99 with the order Gd‐1 < Gd‐2 < Gd‐3 < Gd‐4 . The gradually enhanced ¹O₂ sensitization after β‐oxazolone moiety replacement was ascribed to the narrowing of the energy gap (ΔE) between the lowest triplet states (T₁) of the ligand and the energy level of the ¹Δ_g→³Σ_g transition of ¹O₂. In particular, Gd‐4 is capable of excitation in the visible to NIR region (400–700 nm) with a quantum yield near unity. These Gd complexes were first demonstrated as efficient photosensitizers in photocatalysis such as oxidative C?H bond functionalization of secondary or tertiary amines, and the oxygenation of the natural product cholesterol. Finally, after glycosylation, these water‐soluble Gd complexes showed potential applications in photodynamic therapy (PDT) in HeLa cells. This work revealed that Gd^III complexes of “bioinspired” β‐modified porpholactones are efficient NIR photosensitizers and form a chemical basis to construct appealing photocatalysts and theranostic agents based on lanthanides.     

Bioorthogonal Labeling,Bioimaging, and Photocytotoxicity Studies of Phosphorescent Ruthenium(II) Polypyridine Dibenzocyclooctyne Complexes

The synthesis, characterization, photophysics, lipophilicity, and cellular properties of new phosphorescent ruthenium(II) polypyridine complexes functionalized with a dibenzocyclooctyne (DIBO) or amine moiety [Ru(N^N)₂(L)](PF₆)₂ are reported (L=4‐(13‐N‐(3,4:7,8‐dibenzocyclooctyne‐5‐oxycarbonyl) amino‐4,7,10‐trioxa‐tridecanyl‐aminocarbonyl‐oxy‐methyl)‐4′‐methyl‐2,2′‐bipyridine bpy‐DIBO, N^N=2,2′‐bipyridine bpy ( 1 a ), 1,10‐phenanthroline phen ( 2 a ); L=4‐(13‐amino‐4,7,10‐trioxa‐tridecanylaminocarbonyl‐oxy‐methyl)‐4′‐methyl‐2,2′‐bipyridine bpy‐NH₂, N^N=bpy ( 1 b ), phen ( 2 b )). The strain‐promoted alkyne–azide cycloaddition (SPAAC) reaction of the DIBO complexes 1 a and 2 a with benzyl azide were studied. Also, the DIBO complexes 1 a and 2 a can selectively label N‐azidoglycans located on the surface of CHO‐K1 and A549 cells that were pretreated with 1,3,4,6‐tetra‐O‐acetyl‐N‐azidoacetyl‐D ‐mannosamine (Ac₄ManNAz). Additionally, the intracellular trafficking and localization of these biomolecules were monitored using laser‐scanning confocal microscopy. Interestingly, the biolabeling and cellular uptake efficiency of the DIBO complexes 1 a and 2 a were cell‐line dependent, as revealed by flow cytometry and ICP‐MS. Furthermore, the complexes showed good biocompatibility toward the Ac₄ManNAz‐pretreated cells in the dark, but exhibited photoinduced cytotoxicity due to the generation of singlet oxygen.     

可溶性多氟烷氧基取代金属酞菁 :新型肿瘤光动力治疗光敏剂(英文)

合成了 9个新的多氟烷氧基取代的金属酞菁衍生物 ,它们均可溶于多数有机溶剂 .光氧化能力和对DNA的光切断活性的研究表明 ,中心金属离子为锌和铝的酞菁衍生物 ,具有较好的产生单重态氧的能力 .在乳化剂F68的存在下 ,锌酞菁衍生物 2a对离体杂交瘤细胞表现出良好的光灭活作用