Structure and cytotoxicity of zinc (II) and cobalt (II) complexes based on 1,3,5‐tris(1‐imidazolyl) benzene

Three novel complexes, [Zn (tib)₂·(H₂O)₂]·(NO₃)₂ ( 1 ), [Co (tib)₂]·2NO₃ ( 2 ) and [Co₂(tib)₂(btc)]·H₂O ( 3 ) [H₄btc = 1,2,4,5‐benzenetetracarboxylic acid; H₂tib = 1,3,5‐tris(1‐imidazolyl)benzene], were synthesized and characterized by single‐crystal X‐ray, IR and elemental analysis. The interaction of these complexes with FS‐DNA (fish sperm DNA) was monitored, and binding constants were determined using UV/Vis, which revealed that they have the ability to bind to FS‐DNA. DNA‐binding constants (K) for the three complexes were 2.2 × 10⁴ m ^?1, 0.7 × 10⁴ m ^?1 and 0.09 × 10⁴ m ^?1, respectively. The interaction capacity of the complexes with FS‐DNA has been investigated by fluorescence spectroscopy. Stern–Volmer quenching plot values for complexes 1 , 2 and 3 were 0.3784, 0.1028 and 0.076, respectively. The viscosity measurement suggested that complexes 1 , 2 and 3 interact with DNA in an intercalation mode. In addition, anti‐cancer activities of these complexes investigated through MTT assays in vitro indicated that the complexes showed good cytotoxic activity against cancer cell lines. Cytotoxic activity of test complexes against two different cancer cell lines (HeLa and KB cells) showed significant cancer cell inhibition rates. Flow cytometry experiments and morphological apoptosis studies showed that the complexes induced apoptosis of HeLa tumor cell lines. Finally, a further molecular docking technique was employed to confirm the binding of the complexes toward the molecular target DNA.     

Synthesis,Characterization, and DNA Interaction Studies of the Ruthenium(II) Complexes [Ru(bpy)2(ipbp)]2+ and [Ru(ipbp)(phen)2]2+ (ipbp=3‐(1H‐Imidazo[4,5‐f][1,10]phenanthrolin‐2‐yl)‐4H‐1‐benzopyran‐2‐one; bpy=2,2′‐Bipyridine; phen=1,10‐Phenanthroline)

A novel ligand 3‐(1H‐imidazo[4,5‐f][1,10]phenanthrolin‐2‐yl)‐4H‐1‐benzopyran‐4‐one (ipbp) and its ruthenium(II) complexes [Ru(bpy)₂(ipbp)]²⁺ ( 1 ) and [Ru(ipbp)(phen)₂]²⁺ ( 2 ) (bpy=2,2′‐bipyridine, phen=1,10‐phenanthroline) were synthesized and characterized by elemental analysis and mass, ¹H‐NMR, and electronic‐absorption spectroscopy. The electrochemical behavior of the complexes was studied by cyclic voltammetry. The DNA‐binding behavior of the complexes was investigated by spectroscopic methods and viscosity measurements. The results indicate that complexes 1 and 2 bind with calf‐thymus DNA in an intercalative mode. In addition, 1 and 2 promote cleavage of plasmid pBR 322 DNA from the supercoil form I to the open circular form II upon irradiation.     

Hydrogen‐bonding and π–π stacking interactions in aquachloridobis(1,10‐phenanthroline)cobalt(II) chloride dichloridobis(1,10‐phenanthroline)cobalt(II) hexahydrate

The title compound, [CoCl(C₁₂H₈N₂)₂(H₂O)]Cl·[CoCl₂(C₁₂H₈N₂)₂]·6H₂O, is the first example of a new 1:1 cocrystal of the octahedral [CoCl₂(phen)₂] and [CoCl(phen)₂(H₂O)]⁺·Cl⁻ complexes (phen is 1,10‐phenanthroline). The latter form heterochiral dimers held by strong π–π stacking interactions via their phenathroline ligands, which confirms that π stacking is an important and reliable synthon in supramolecular design. In addition, the crystal structure is networked by H₂O...H₂O, H₂O...Cl⁻ and H₂O...Cl hydrogen bonds, which interconnect the different units of the cobalt complexes.     

An Azelaato‐bridged Dinuclear Copper(II) Complex, [Cu2(phen)2(C9H14O4)2] · 6 H2O (phen = 1,10‐phenanthroline)

The title compound [Cu₂(phen)₂(C₉H₁₄O₄)₂] · 6 H₂O was prepared by the reaction of CuCl₂ · 2 H₂O, 1,10‐phenanthroline (phen), azelaic acid and Na₂CO₃ in a CH₃OH/H₂O solution. The crystal structure (monoclinic, C2/c (no. 15), a = 22.346(3), b = 11.862(1), c = 17.989(3) Å, β = 91.71(1)°, Z = 4, R = 0.0473, wR² = 0.1344 for 4279 observed reflections) consists of centrosymmetric dinuclear [Cu₂(phen)₂(C₉H₁₄O₄)₂] complexes and hydrogen bonded H₂O molecules. The Cu atom is square‐planar coordinated by the two N atoms of the chelating phen ligand and two O atoms of different bidentate bridging azelaate groups with d(Cu–N) = 2.053, 2.122(2) Å and d(Cu–O) = 1.948(2), 2.031(2) Å. Two azelaate anions bridge two common Cu atoms via the terminal O atoms (d(C–O) = 1.29(2) Å; d(C–C) = 1.550(4)–1.583(4) Å). Phen ligands of adjacent complexes cover each other at distances of about 3.62 Å, indicating π‐π stacking interaction, by which the complexes are linked to 1 D bands.     

Syntheses,Crystal Structures,and Photophysical Properties of Heteronuclear Zinc(II)/Cadmium(II)‐Lanthanide(III) Coordination Complexes based on Benzoic Acid

The heteronuclear d‐f coordination complexes [Er₂Zn₂(C₆H₅COO)₁₀(phen)₂] (1), [Ho₂Zn₂(C₆H₅COO)₁₀(phen)₂] ( 2 ), [Pr₃Zn₆(C₆H₅COO)₂₁(phen)₃] ( 3 ), [ErCd(C₆H₅COO)₅(phen)·H₂O] ( 4 ), [Ho₂Cd₃(C₆H₅COO)₁₂(phen)₂] ( 5 ), [EuCd₂(C₆H₅COO)₇(phen)₂] ( 6 ) (C₆H₅COOH = benzoic acid;phen = 1,10‐phenanthroline) were synthesized by hydrothermal methods, and their structures were studied by single‐crystal X‐ray diffraction. Complexes 1 , 2 , 4 , and 5 crystallize in the triclinic space group P$\bar{1}$ and complexes 3 and 6 in the monoclinic space group C2/c. The room temperature IR, UV/Vis/NIR absorption, and emission spectra of the six complexes were determined and assigned. In the visible and NIR regions, the emission spectra of complexes show characteristic bands of corresponding Ln^III ions, which are attributed to the sensitization from the d block (Zn/Cd‐ligand section) and ligands. In comparison with isolated Ln^III ions, the NIR emission bands of complexes 1 – 5 exhibit shifting, broadening and splitting, which are also present in their UV/Vis/NIR absorption spectra. Thus, the two spectra of complexes can evidence each other.     

Di­aqua­bis(1,10‐phenanthroline‐κ2N,N′)­manganese(II) thiodiglycolate bis(1,10‐phenanthroline‐κ2N,N′)(thiodiglycolato‐κ2O,O′)­manganese(II) tridecahydrate

The title compound, [Mn(C₁₂H₈N₂)₂(H₂O)₂](C₄H₄O₄S)·[Mn(C₄H₄O₄S)(C₁₂H₈N₂)₂]·13H₂O, contains one dianion of thio­diglycolic acid (tdga²⁻) and two independent man­ganese(II) moieties, viz. [Mn(phen)₂(H₂O)₂]²⁺ and [Mn(tdga)(phen)₂], where phen is 1,10‐phenanthroline. The Mn^II atoms are octahedrally coordinated by four N atoms of two bidentate phen ligands [Mn—N = 2.240 (2)–2.3222 (19) Å] and either two water O atoms or two tdga carboxyl O atoms [Mn—O = 2.1214 (17)–2.1512 (17) Å]. The tdga ligand chelates as an O,O′‐bidentate ligand, forming an eight‐membered ring with one Mn atom. The free tdga²⁻ dianion is hydrogen bonded to an [Mn(phen)₂(H₂O)₂]²⁺ ion, with O⋯O distances of 2.606 (2) and 2.649 (2) Å. The crystal structure is further stabilized by an extensive network of hydrogen bonds involving 13 water mol­ecules.     

Ligand Substitution Reactions on Aquapentachloro‐ and Hexachloroplatinic Acid — Synthesis and Characterization of Tetrachloroplatinum(IV) Complexes with Heterocyclic N,N Donors

Reactions of aquapentachloroplatinic acid, (H₃O)[PtCl₅(H₂O)]·2(18C6)·6H₂O ( 1 ) (18C6 = 18‐crown‐6), and H₂[PtCl₆]·6H₂O ( 2 ) with heterocyclic N, N donors (2, 2′‐bipyridine, bpy; 4, 4′‐di‐tert‐butyl‐2, 2′‐bipyridine, tBu₂bpy; 1, 10‐phenanthroline, phen; 4, 7‐diphenyl‐1, 10‐phenanthroline, Ph₂phen; 2, 2′‐bipyrimidine, bpym) afforded with ligand substitution platinum(IV) complexes [PtCl₄(N∩N)] (N∩N = bpy, 3a ; tBu₂bpy, 3b ; Ph₂phen, 5 ; bpym, 7 ) and/or with protonation of N, N donor yielding (R₂phenH)₂[PtCl₆] (R = H, 4a ; Ph, 4b ) and (bpymH)⁺ ( 8 ). With UV irradiation Ph₂phen and bpym reacted with reduction yielding platinum(II) complexes [PtCl₂(N∩N)] (N∩N = Ph₂phen, 6 ; bpym, 9 ). Identities of all complexes were established by microanalysis as well as by NMR (¹H, ¹³C, ¹⁹⁵Pt) and IR spectroscopic investigations. Molecular structures of [PtCl₄(bpym)]·MeOH ( 7 ) and [PtCl₂(Ph₂phen)] ( 6 ) were determined by X‐ray diffraction analyses. Differences in reactivity of bpy/bpym and phen ligands are discussed in terms of calculated structures of complexes [PtCl₅(N∩N)]^— with monodentately bound N, N ligands (N∩N = bpy, 10a ; phen, 10b ; bpym, 10c ).     

Methyl substituent effect on one‐dimensional copper(II) coordination polymers containing biologically active ligands: Synthesis,characterization, DNA interactions and cytotoxicities

Three novel water‐soluble copper(II) complexes – {[Cu(phen)(trp)]ClO₄·3H₂O}_n ( 1 ), {[Cu(4‐mphen)(trp)]ClO₄·3H₂O}_n ( 2 ) and [[Cu(dmphen)(trp)(MeOH)][Cu(dmphen)(trp)(NO₃)]]NO₃ ( 3 ) (phen: 1,10‐phenanthroline; 4‐mphen: 4‐methyl‐1,10‐phenanthroline; dmphen: 4,7‐dimethyl‐1,10‐phenanthroline; trp: l ‐tryptophan) – have been synthesized and characterized using various techniques. Complexes 1 and 2 are isostructural, and exist as one‐dimensional coordination polymers. Complex 3 consists of two discrete copper(II) complexes containing [Cu(trp)(dmphen)(MeOH)]⁺, [Cu(trp)(dmphen)(NO₃)] and one nitrate anion. The binding interaction of the complexes with calf thymus DNA (CT‐DNA) was investigated using thermal denaturation, electronic absorption and emission spectroscopic methods, revealing that the complexes could interact with CT‐DNA via a moderate intercalation mode. The binding activity of the complexes to CT‐DNA follows the order: 3  >  2 > 1 . The pUC19 DNA cleavage activity of the complexes was investigated in the absence and presence of external agents using the agarose gel electrophoresis method. Especially, in the presence of H₂O₂ as an activator, the pUC19 DNA cleavage abilities of the complexes are clearly enhanced at low concentration. Addition of hydroxyl radical scavenger dimethylsulfoxide shows a marked inhibition of the pUC19 DNA cleavage activity of the complexes. In vitro cytotoxic effect of the complexes was examined on human tumor cell lines (Caco‐2, A549 and MCF‐7) and healthy cells (BEAS‐2B). The potent cytotoxic effect of complex 3 , with IC₅₀ values of 1.04, 1.16 and 1.72 μM, respectively, is greater relative to clinically used cisplatin (IC₅₀ = 22.70, 31.1 and 22.2 μM) against the Caco‐2, A549 and MCF‐7 cell lines.     

Mixed‐Ligand Complexes of Copper(II) with α‐Hydroxycarboxylic Acids and 1,10‐Phenanthroline

Eight new two‐ligand complexes of copper(II) with 1,10‐phenanthroline and one of four different α‐hydroxy‐carboxylic acids (glycolic, lactic, mandelic and benzylic) were prepared. The complexes of general formula [Cu(HL)₂(phen)] · nH₂O (HL = monodeprotonated acid) ( 1 – 4 ) were characterized by elemental analysis, IR, electronic and EPR spectroscopy, magnetic measurements and thermo‐gravimetric analysis. The complexes of general formulae [Cu(HL)(phen)₂](HL) · H₂L · nSolv [ 1 a (HL = HGLYO^–, n = 1, Solv = MeCN) and 3 a (HL = HMANO^–, n = 0)] and [Cu(L)(phen)(OH₂)] · nH₂O [ 2 a (L = LACO^2–, n = 4) and 4 a (L = BENO^2–, n = 2)] were characterized by X‐ray diffractometry. In all these latter a pentacoordinated copper atom has a basically square pyramidal coordination polyhedron, the distortion of which towards a trigonal bipyramidal configuration has been evaluated in terms of the parameter τ. In 1 a and 3 a there are three forms of α‐hydroxycarboxylic acid: a monodentate monoanion, a monoanionic counterion, and a neutral molecule lying in the outer coordination sphere; in 2 a and 4 a the α‐hydroxycarboxylic acid is a bidentate dianion coordinating through carboxyl and hydroxyl oxygens.     

Synthesis,Crystal Structures and Properties of Tetrametallic Complexes: [M2(phen)4(FCA)2](ClO4)2·(H2O)2 (M=Zn or Co,phen=1,10‐phenanthroline,FCA=anion of 3‐ferrocenyl‐2‐crotonic acid)

Two new complexes [Zn₂(phen)₄(FCA)₂](ClO₄)₂·(H₂O)₂ ( 1 ) and [Co₂(phen)₄ (FCA)₂](ClO₄)₂·(H₂O)₂ (2) (FCA=anion of 3‐ferrocenyl‐2‐crotonic acid, phen=1,10‐phenanthroline) have been synthesized, and characterized by elemental analysis, IR, UV‐Vis spectra, thermal analyses, and single‐crystal X‐ray diffraction. Two M(II) (M=Zn or Co) ions are bridged by two FCA anions with syn‐anti bridging ligands, leading to dimeric cores, [M₂(phen)₄(FCA)₂]²⁺, and each M(II) ion is six‐coordinated in a distorted octahedral geometry by two chelate phen ligands and two μ₂‐carboxylate oxygen atoms from two FCA groups. The M(II)…M(II) intradimer distances are 0.4391 and 0.4462 nm in 1 and 2 , respectively. Electrochemical properties of the complexes have been discussed.     

Copper(II) and Cadmium(II) Complexes Based on N,N‐Bis(3, 5‐dimethyl‐2‐hydroxybenzyl)‐N‐(2‐pyridylmethyl)amine Ligand: Syntheses,Structures, Magnetic,and Luminescent Properties

The reaction of the aryl‐oxide ligand H₂L [H₂L = N,N‐bis(3, 5‐dimethyl‐2‐hydroxybenzyl)‐N‐(2‐pyridylmethyl)amine] with CuSO₄ · 5H₂O, CuCl₂ · 2H₂O, CuBr₂, CdCl₂ · 2.5H₂O, and Cd(OAc)₂ · 2H₂O, respectively, under hydrothermal conditions gave the complexes [Cu(H₂L¹)₂] · SO₄ · 3CH₃OH ( 1 ), [Cu₂(H₂L²)₂Cl₄] ( 2 ), [Cu₂(H₂L²)₂Br₄] ( 3 ), [Cd₂(HL)₂Cl₂] ( 4 ), and [Cd₂(L)₂(CH₃COOH)₂] · H₂L ( 5 ), where H₂L¹ [H₂L¹ = 2, 4‐dimethyl‐6‐((pyridin‐2‐ylmethylamino)methyl)phenol] and H₂L² [H₂L² = 2‐(2, 4‐dimethyl‐6‐((pyridin‐2‐ylmethylamino)methyl)phenoxy)‐4, 6‐dimethylphenol] were derived from the solvothermal in situ metal/ligand reactions. These complexes were characterized by IR spectroscopy, elementary analysis, and X‐ray diffraction. A low‐temperature magnetic susceptibility measurement for the solid sample of 2 revealed antiferromagnetic interactions between two central copper(II) atoms. The emission property studies for complexes 4 and 5 indicated strong luminescence emission.     

Synthesis,characterization, DNA binding,cytotoxicity and molecular docking properties of Cu (II) and Mn (II) complexes with 1,4‐bis (pyrazol‐1‐yl) terephthalic acid

Two novel complexes, [Cu (L)(H₂O)]?H₂O ( 1 ) and [Mn (H₂O)₆] ?L ?H₂O ( 2 ) (L = 1,4‐bis (pyrazol‐1‐yl) terephthalic acid), were synthesized under hydrothermal conditions. They were characterized using elemental analysis, infrared spectroscopy and single‐crystal X‐ray diffraction. Intramolecular weak interactions, such as hydrogen bonds, and intermolecular interactions play important roles in the construction of the complexes. The interaction of these complexes with fish sperm DNA (FS‐DNA) was monitored and binding constants were determined using UV–visible spectroscopy, which revealed their ability to bind to FS‐DNA, with binding constants for the two complexes of 1.88 × 10⁴ M^?1 ( 1 ) and 1.06 × 10⁴ M^?1 ( 2 ). Viscosity experiments further demonstrated the binding of the complexes to DNA. The complexes were further studied using gel electrophoresis assay with supercoiled plasmid pBR322 DNA. In addition, anticancer activities of the metal complexes investigated through MTT assays in vitro indicated good cytotoxic activity against cancer cell lines. Flow cytometry and apoptosis experiments showed that these complexes induced apoptosis of two different cancer cell lines (HeLa and KB cells), demonstrating a significant cancer cell inhibitory rate. Finally, a further molecular docking technique was employed to confirm the binding of the complexes towards the molecular target DNA.     

Newly synthesized Cu(II) pyrazino[2,3‐f][1,10]phenanthroline complexes as potential anticancer candidates

New binary and ternary copper(II) complexes, [Cu(py‐phen)₂(NO₃)]NO₃ ( 1 ), [Cu₂(py‐phen)₂(gly)₂(NO₃)₂(H₂O)₂]?3H₂O ( 2 ) and [Cu₂(py‐phen)₂(tyr)₂(H₂O)₂](NO₃)₂?3H₂O ( 3 ) (py‐phen: pyrazino[2,3‐f][1,10]phenanthroline; gly: glycine; tyr: tyrosine), have been synthesized and characterized using CHN analysis, electrospray ionization mass spectrometry, Fourier transform infrared spectroscopy and single‐crystal X‐ray diffraction. Interaction of these complexes with calf thymus DNA has been investigated using absorption spectral titration, ethidium bromide and Hoechst 33258 displacement assay and thermal denaturation measurements. These complexes were found to be efficient cleaving agents and cleavage reactions were mediated by hydrolytic and oxidative pathways. The interaction between these complexes and bovine serum albumin (BSA) was investigated using electronic absorption and fluorescence spectroscopy. The experimental results show that the fluorescence quenching mechanism of these complexes and BSA is a static quenching process. Furthermore, in vitro cytotoxicities of these complexes against tumour cell lines (Caco‐2, MCF‐7 and A549) and healthy cell line (BEAS‐2B) showed that they exhibited anticancer activity with low IC₅₀ values. These complexes were markedly active against the cell lines and can be good drug candidates that are effective and safe for healthy tissue.     

Synthesis,Characterization, and Thermostability of Four Novel Cadmium(II) Coordination Polymers with Mixed Ligands

Four novel mixed‐ligand complexes were obtained from the reaction of maleic acid, diimine chelating ligands and Cd(OH)₂ or CdO in a mixed solvent of water and methanol. The complexes were characterized by IR spectroscopy, elemental analysis, and single‐crystal X‐ray diffraction. The results show that all the four complexes are coordination polymers. [Cd(phen)(H₂O)(male)]_n · 2nH₂O ( 1 ) and [Cd(bipy)(H₂O)(male)]_n · 2nH₂O ( 2 ) (male = maleate; phen = 1, 10‐phenanthroline, bipy = 2, 2′‐bipyridine) are isomorphic, and the asymmetric unit is constructed by one Cd^II atom, a maleate group, a diimine ligand and two crystal water molecules. Each maleate group links two Cd^II atoms in a bis(bidentate) chelating mode, resulting in a 1D helical chain. Within [Cd(phen)(H₂O)₂(male)]_n · 2nH₂O ( 3 ), the maleate group bridges two Cd^II atoms in a bis(monodentate) chelating mode into a 1D helical chain along the [100] direction. The helical chain is decorated by phen groups alternatively at the two sides, and each phen plane of one chain is inserted in the void space between two adjacent phen ligands from an adjacent chain, resulting in a double zipper‐like chain. The asymmetric unit of [Cd₂(phen)₂(male)₂]_n ( 4 ) contains a Cd^II cation, one phen molecule, and a maleate group, and one bridging maleate group links three Cd^II atoms resulting in a 2D layer extending in [011] plane. The 2D networks are constructed by four kinds of rings formed by the central metal atom and maleate dianion. The thermostabilities of the four complexes were investigated.     

Synthesis,structure and in vitro antiproliferative activities of oxamido‐bridged dicopper(II) complexes: A comparative study of experimental evidence and molecular docking of DNA/protein binding

Two μ‐oxamido‐bridged dicopper(II) complexes, namely [Cu₂(hmpoxd)(H₂O)(phen)](ClO₄) ( 1 ) and [Cu₂(papo)(H₂O)(phen)](ClO₄)·2H₂O ( 2 ), where H₃hmpoxd and H₃papo represent N‐(2‐hydroxy‐5‐methylphenyl)‐N′‐[3‐(dimethylamino)propyl]oxamide and N‐(2‐hydroxylphenyl)‐N′‐(3‐aminopropyl)oxamide, respectively, and phen represents 1,10‐phenanthroline, were synthesized. Single‐crystal X‐ray crystallography and other methods revealed that the two copper(II) ions in complex 1 are bridged by the cis‐hmpoxd^3? with Cu···Cu separation of 5.1896(7) Å, in which the inner (Cu1) and outer (Cu2) copper(II) atoms are located in square‐planar and square‐pyramidal geometries, respectively. To evaluate the effects of bridging ligand hydrophobicity on DNA/protein binding and potential anticancer activities, comparative studies of the reactivity towards herring sperm DNA and protein bovine serum albumin (BSA) as well as cytotoxicity of complex 1 with our previously reported complex 2 were conducted theoretically and experimentally. The results indicate that the two complexes can interact interactively with DNA, and bind to BSA via the binding sites Trp213 for 1 and Trp134 for 2 . Interestingly, the in vitro anticancer activities and DNA/protein binding affinities consistently follow the order of 1 > 2 .     

Synthesis,DNA‐Binding and Photocleavage Studies of the Ruthenium(II) Complexes [Ru(phen)2(ppd)]2+ and [Ru(phen)(ppd)2]2+ (ppd=Pteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione,phen=1,10‐Phenanthroline)

Two new complexes, [Ru(phen)₂(ppd)]²⁺ ( 1 ) and [Ru(phen)(ppd)₂]²⁺ ( 2 ) (ppd=pteridino[6,7‐f] [1,10]phenanthroline‐11,13(10H,12H)‐dione, phen=1,10‐phenanthroline) were synthesized and characterized by ES‐MS, ¹H‐NMR spectroscopy, and elemental analysis. The intercalative DNA‐binding properties of 1 and 2 were investigated by absorption‐spectroscopy titration, luminescence‐spectroscopy studies, thermal denaturation, and viscosity measurements. The theoretical aspects were further discussed by comparative studies of 1 and 2 by means of DFT calculations and molecular‐orbital theory. Photoactivated cleavage of pBR322 DNA by the two complexes were also studied, and 2 was found to be a much better photocleavage reagent than 1 . The mechanism studies revealed that singlet oxygen and the excited‐states redox potentials of the complex may play an important role in the DNA photocleavage.     

Stabilization of G‐Quadruplex DNA,Inhibition of Telomerase Activity and Live Cell Imaging Studies of Chiral Ruthenium(II) Complexes

Telomerase inhibition is an attractive strategy for cancer chemotherapy. In the current study, we have synthesized and characterized two chiral ruthenium(II) complexes, namely, Λ‐[Ru(phen)₂(p‐MOPIP)]²⁺ and Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺, where phen is 1,10‐phenanthroline and p‐MOPIP is 2‐(4‐methoxyphenyl)‐imidazo[4,5f][1,10]phenanthroline. The chiral selectivity of the compounds and their ability to discriminate quadruplex DNA were investigated by using UV/Vis, fluorescence spectroscopy, circular dichroism spectroscopy, fluorescence resonance energy transfer melting assay, polymerase chain reaction stop assay and telomerase repeat amplification protocol. The results indicate that the two chiral compounds could induce and stabilize the formation of antiparallel G‐quadruplexes of telomeric DNA in the presence or absence of metal cations. We report the remarkable ability of the two complexes Λ‐[Ru(phen)₂(p‐MOPIP)]²⁺ and Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺ to stabilize selectively G‐quadruplex DNA; the former is a better G‐quadruplex binder than the latter. The anticancer activities of these complexes were evaluated by using the MTT assay. Interestingly, the antiproliferative activity of Λ‐[Ru(phen)₂(p‐MOPIP)]²⁺ was higher than that of Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺, and Λ‐[Ru(phen)₂(p‐MOPIP)]²⁺ showed a significant antitumor activity in HepG2 cells. The status of the nuclei in Λ/Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺‐treated HepG2 cells was investigated by using real‐time living cell microscopy to determine the effects of Λ/Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺ on intracellular accumulation. The results show that Λ/Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺ can be taken up by HepG2 cells and can enter into the cytoplasm as well as accumulate in the nuclei; this suggests that the nuclei were the cellular targets of Λ/Δ‐[Ru(phen)₂(p‐MOPIP)]²⁺.     

Studies on the nuclease activity and interactions of the mixed‐polypyridyl [Ni2(1,3‐tpbd)(diimine)2(H2O)2]4+ complexes with thioredoxin reductase

Three new nickel(II) complexes formulated as [Ni₂(1,3‐tpbd)(diimine)₂(H₂O)₂]⁴⁺ [1,3‐tpbd = N,N,N′,N′‐tetrakis(2‐pyridylmethyl)benzene‐1,3‐diamine, where diimine is an N,N‐donor heterocyclic base like 1,10‐phenanthroline (phen),2,2′‐bipyridine (bpy), 4,5‐diazafluoren‐9‐one (dafo)], have been synthesized and structurally characterized by X‐ray crystallography: [Ni₂(1,3‐tpbd)(phen)₂(H₂O)₂]⁴⁺ (1), [Ni₂(1,3‐tpbd)(bpy)₂(H₂O)₂]⁴⁺(2) and [Ni₂(1,3‐tpbd)(dafo)₂(H₂O)₂]⁴⁺ (3). Single‐crystal diffraction reveals that the metal atoms in the complexes are all in a distorted octahedral geometry and in a trans arrangement around 1,3‐tpbd ligand. The interactions of the three complexes with calf thymus DNA (CT‐DNA) have been investigated by UV absorption, fluorescence spectroscopy, circular dichroism and viscosity. The apparent binding constant (K_app) values are calculated to be 1.91 × 10⁵ m ^?1 for 1, 1.18 × 10⁵ m ^?1 for 2, and 1.35 × 10⁵ m ^?1 for 3, following the order 1 > 3 > 2. The higher DNA binding affinity of 1 is due to the involvement in partial insertion of the phen ring between the DNA base pairs. A decrease in relative viscosities of DNA upon binding to 1–3 is consistent with the DNA binding affinities. These complexes efficiently display oxidative cleavage of supercoiled DNA in the presence of H₂O₂ (250 µ m ), with 3 exhibiting the highest nuclease activity. The rate constants for the conversion of supercoiled to nicked DNA are 5.28 × 10^?5 s^?1 (for 1), 6.67 × 10^?5 s^?1 (for 2) and 1.39 × 10^?4 s^?1 (for 3), also indicating that complex 3 shows higher catalytic activity than 1 and 2. Here the nuclease activity is not readily correlated to binding affinity. The inhibitory effect of complexes 1–3 on thioredoxin reductase has also been examined. The IC₅₀ values are calculated to be 26.54 ± 0.57, 31.03 ± 3.33 and 8.69 ± 2.54 µ m , respectively, showing a more marked inhibitory effect on thioredoxin reductase by complex 3 than the other two complexes. Copyright © 2012 John Wiley & Sons, Ltd.     

Oxovanadium(IV) and ruthenium(II) carbonyl complexes of ONS‐donor ligands derived from dehydroacetic acid and dithiocarbazate: Synthesis,characterization, antioxidant activity,DNA binding and in vitro cytotoxicity

A series of new complexes of oxovanadium(IV) [VO(L)(B)] and ruthenium(II) [Ru(CO)(PPh₃)₂(L)] ( 1.1- 1.3,  2.1–2.3 ) (H₂L = dehydroacetic acid Schiff base of S‐methyldithiocarbazate, H₂smdha ( 1 ) or S‐benzyldithiocarbazate, H₂sbdha ( 2 ); B = 2,2′‐bipyridine (bpy) or 1,10‐phenanthroline (phen)) have been synthesized. The structure of these complexes was authenticated using elemental analyses and spectroscopic techniques, and their magnetic properties and electrochemical behaviour were studied. The molecular structures of oxovanadium(IV) complexes [VO(smdha)(bpy)]?CH₂Cl₂ ( 1.1 ) and [VO(sbdha)(phen)]?2H₂O ( 2.2 ) were confirmed using single‐crystal X‐ray crystallography. Analytical data showed that the ligands 1 and 2 are chelated to the metal centres in a bi‐negative tridentate fashion through azomethine N, thiol S and deprotonated hydroxyl group. The antioxidant activity of the synthesized compounds was tested against 2,2‐diphenyl‐1‐picrylhydrazyl) radical, which showed that the complexes demonstrate a better scavenging activity than their corresponding ligands. The cupric ion reducing antioxidant capacity method was also employed and the total equivalent antioxidant capacity values were found to be higher for the oxovandium(IV) complexes. DNA binding affinity of the compounds was determined using UV–visible and fluorescence spectra, revealing an intercalation binding mode. Higher cytotoxicity for the complexes compared to their ligands was found against human liver hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF7) cell lines using MTT assay.     

Crystal Structures and Solution Studies of Two Novel Zinc(II) Complexes of a Proton Transfer Compound Obtained from 2, 6‐Pyridinedicarboxylic Acid and 1, 10‐Phenanthroline: Observation of Strong Intermolecular Hydrogen Bonds

The proton transfer compound LH₂ , (phenH⁺)₂(pydc^2—), has been prepared from 1, 10‐phenanthroline, phen, and 2, 6‐pyridinedicarboxylic acid, (dipicolinic acid), pydcH₂. Characterization was performed using solution and solid phase CP/MAS ¹³C NMR and IR spectroscopy. The reactions of this adduct with ZnSO₄·7H₂O and Zn(NO₃)₂·4H₂O give the complexes, [Zn(pydc)₂][Zn(phen)₂(H₂O)₂]·7H₂O (1) and [Zn(phen)₃]₄(H(Hpydc)₂)(NO₃)₇·26H₂O (2) , respectively. These complexes were characterized by ¹H and ¹³C NMR spectroscopy and single crystal X‐ray analysis. The complexes crystallize in the triclinic space group P1 with Z = 2. The unit cell dimensions for complex 1 and 2 are: a = 9.9838(9) Å, b = 14.7483(13) Å, c = 14.8365(13) Å and a = 12.640(4) Å, b = 15.855(5) Å, c = 21.830(7) Å, respectively. In complex 1 (pydc^2—) and phen, are tri‐ and bidentate ligands, respectively, and an anionic [Zn(pydc)₂]^2— and cationic [Zn(phen)₂(H₂O)₂]²⁺ complex are formed simultaneously. In complex 2 , three phen participate in complexation leaving hydrogen‐bis(pyridine‐2‐carboxylate), (H(Hpydc)₂)^— as a supramolecular anion. The fragments (H(Hpydc)₂)^—, 7 NO₃^—, and 26 H₂O in complex 2 are joined together by extensive and strong H‐bonding; therefore, the structure is composed of [Zn(phen)₃]₄⁸⁺, and an anionic hydrogen bond supramolecular assembly with the formula, {(H(Hpydc)₂(NO₃)₇)^8— · 26H₂O}_n. The anionic species (H(Hpydc)₂)^— has a special position at the inversion center, as well as one of the NO₃^— anions, which is disordered over the inversion center. Most of the hydrogen bonds in complex 2 represent strong H‐bonding. The protonation constants of the building blocks of the pydc‐phen adduct, the equilibrium constants for the reaction of (pydc^2—) with phenanthroline and the stoichiometry and stability of the Zn^II complex with LH₂ on aqueous solution were determined by potentiometric pH titration. The solution study results support self‐association between (pydc^2—) and (phenH⁺) with a stoichiometry for the Zn(II) complex similar to that observed for the isolated crystalline complex.