Planar Aromatic Ligands Research Articles

G-quadruplex microspheres-based optical RNA biosensor for arthropod-borne virus pathogen detection: A proof-of-concept with dengue serotype 2

Dengue virus (DENV) is a positive-sense single-stranded RNA virus and that the detection of viral RNA itself is highly desirable, which can be achieved by using RNA biosensor diagnostic method. Herein, acrylic micropolymer-based optical RNA biosensor was developed by binding anionic copper(II) phthalocyanine (CPC) planar aromatic ligand to the G-quadruplex DNA probe via end-stacking with π-system of the guanine (G) quartet, and a blue coloration was developed on the G-quadruplex microspheres. Hybridization of G-quadruplex DNA probe with target DENV serotype 2 (DENV2) RNA unfolded the G-quadruplex, and rendering release of the CPC planar optical label, causing discoloration of the G-quadruplex microbiosensor. Optical characterization of the RNA biosensor was performed by means of fiber optic reflectance spectrophotometer at maximum reflectance wavelength of 774 nm. The reflectance response enhancement of the RNA-responsive G-quadruplex-based reflectometric biosensor was linearly proportional to the target oligo DENV2 RNA concentration in the range of 2 zM–2 μM, with a 0.447 zM limit of detection and a rapid response time of 30 min. Heightening in the reflectance signal based on structural transition of G-quadruplex in response to target RNA was successfully implemented in real-time DENV2 detection in non-invasive human fluid samples (i.e. saliva and urine) under informed consent.

Investigation on water soluble copper(II) mono-anionic glutamate complexes with planar aromatic ligands: synthesis, crystal structures, biomacromolecular interactions and radical scavenging activities

Two water soluble copper(II) mono-anionic glutamatecomplexes -[Cu(phen)(glu)(H2O)]NO3·H2O (1) and [Cu(py-phen)(glu)(H2O)]NO3·H2O (2) - (phen: 1,10-phenanthroline, py-phen: pyrazino[2,3-f][1,10]phenanthroline, glu: glutamic acid), have been synthesized and characterized by CHN analysis, ESI-MS, FTIR and single-crystal X-ray diffraction techniques. Interaction of the complex with biomacromolecules {calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)} has been investigated by electronic absorption and fluorescence spectroscopy methods. The experimental outcomes displays that the complexes 1 and 2 bind to CT-DNA by means of a moderate intercalation mode. Furthermore, the fluorescence quenching mechanism between BSA and the complexes 1 and 2 is a static quenching process. The Stern-Volmer constants, binding constants, binding sites and the corresponding thermodynamic parameters (ΔG, ΔH, ΔS) of BSA+ the complexes 1 and 2 systems were determined at different temperatures. The binding distance between BSA and the complexes 1 and 2 was calculated according to Förster non-radiation energy transfer theory (FRET). The effect of the complexes 1 and 2 on the conformation of BSA was also examined using synchronous, two dimensional (2D) and three dimensional (3D) fluorescence spectroscopy. Radical scavenging activity of the complexes 1 and 2 was determined in terms of IC50, using the DPPH and H2O2 method. In biomacromolecules interactions and radical activity studies, the complexes 1 and 2 were found to give good results.

Anticancer activity, DNA binding and cell mechanistic studies of estrogen-functionalised Cu(II) complexes.

Four estrogen-functionalised copper complexes were synthesised and investigated as electrochemical active DNA binding and cleavage agents. These complexes strategically contain a biocompatible metal centre [Cu(II)], a planar aromatic ligand as DNA intercalative agent and an estradiol-derivative moiety which acts as delivery vector to target estrogen-receptor-positive (ER+) cancer cells. Cytotoxic activity was studied over a panel of estrogen-receptor-positive (ER+) and negative (ER-) human cancer cell lines by means of both 2D and 3D cell viability studies. The complexes showed high in vitro intercalative interaction with nuclear DNA and demonstrated to be strong DNA cleaving agents. This series of Cu compounds are potent anticancer agents with low and sub-micromolar IC50 values and the cellular uptake follows the lipophilicity order meaning that the internalisation mainly happened via passive diffusion. Finally, the estrogen-complexes are involved in the cellular redox stress by stimulating the production of ROS (reactive oxygen species).

Photochemical Tuning of Tris-Bidentate Acridine- and Phenazine-Based Ir(III) Complexes.

Five new Ir(III) complexes of the type [Ir(ppy)2L]+ (where ppy = 2-phenylpyridine, L = bidentate N^N ligand) bearing linear and elbow-shaped acridine- and phenazine-based extended planar aromatic ligands have been successfully synthesized and characterized. The electrochemical and photochemical studies revealed that all complexes allow emission in the range 589-601nm from excited states corresponding to a charge transfer between an Ir-ppy fragment and the extended planar ligand. Luminescence quenching occurs in water for [Ir(ppy)2dpac]+ (Ir-DPAC), [Ir(ppy)2dpacF2]+ (Ir-DPACF 2 ), [Ir(ppy)2dpacF4]+ (Ir-DPACF 4 ) and [Ir(ppy)2bdppz]+ (Ir-BDPPZ), while solely partial quenching is observed for [Ir(ppy)2npp]+ (Ir-NPP). This "light-switch" effect has been ascribed to the possible formation of a non-emissive mono-hydrogen-bonded excited state for the four complexes. The "elbow shaped" of Ir-NPP is believed to prevent the non-chelating nitrogen atom of the npp ligand to form H-bond with solvent molecules. The results emphasized the potential of small chemical modifications of the extended planar ligand on the properties of the corresponding Ir(III) complexes. Their tunable properties make them ideal candidates for applications such as DNA photoprobes.

Design and Photophysical Studies of Acridine‐Based RuII Complexes for Applications as DNA Photoprobes

A series of new extended planar aromatic ligands based on an acridine core (dpac = dipyrido[3,2‐a:2′,3′‐c]acridine; dpacF2 = 7,8‐difluorodipyrido[3,2‐a:2′,3′‐c]acridine; dpacF4 = 6,7,8,9‐tetrafluorodipyrido[3,2‐a:2′,3′‐c]acridine) and their respective RuII complexes were synthesized and extensively studied. The photophysical and theoretical studies revealed that Ru‐DPAC and Ru‐DPACF2 allow emission from a 3MLCTphen/dpac excited state at 597 and 604 nm, respectively, whereas the lowest excited state for Ru‐DPACF4 shifts from a bright 3MLCTphen/dpac state towards a poorly luminescent 3MLCTdpac state (λem = 609 nm) owing to the formation of hydrogen bonds with water molecules in the excited state. These complexes exhibit up to sevenfold luminescence enhancement in the presence of complementary and mismatched DNA, demonstrating a strong binding to polynucleotides. The results emphasize the interest in RuII complexes bearing acridine derivatives as DNA interacting agents as a complement to the well‐known phenazine‐based derivatives.

DNA interaction with dipolar ruthenium(II) ammine complexes containing 4,4′-bipyridinium as photochemotherapeutic agents

The interaction of DNA with dipolar ruthenium(II) ammine complexes containing 4,4′-bipyridinium cations L+, [Ru(L+)(NH3)5]3+, has been investigated by spectroscopic and electrochemical methods. These ruthenium(II) complexes undergo strong stacking interactions of L+ with the base-pairs of DNA duplex in addition to the electrostatic and hydrogen binding modes. The phbp+ ([2]3+) and pymbp+ ([3]3+) complexes bind to DNA more strongly than the mebp+ ([1]3+) complex, due to the presence of extended planar aromatic ligands. [3]3+ which exhibited the strongest interaction with DNA can bind to supercoiled plasmid pBR322 DNA following photoinduced loss of ligands pymbp+ and NH3. The finding led to the photocleavage of supercoiled plasmid pBR322 DNA by [3]3+ with visible light under aerobic and unaerobic conditions. Since similar photolysis of [1]3+ and [2]3+ has been observed, all the dipolar ruthenium(II) ammine complexes bearing 4,4′-bipyridinium cations can function as O2-independent photochemotherapeutic agents.

Dinuclear platinum complexes containing planar aromatic ligands to enhance stacking interactions with proteins.

In an approach to design drugs with higher affinity for π-π stacking and electrostatic interactions with targeted biomolecules, complexes of the type [{cis-Pt(A)2 (L)}2 -μ-{trans-1,4-dach}](NO3 )4 ((A)2 =(NH3 )2 or ethylenediamine (en), L=quinoline (quin) or benzothiazole (bztz), dach=trans-1,4-diaminocyclohexane) were synthesized. The quinoline complex, [{cis-Pt(en)(quin)}2 -μ-(dach)](NO3 )4 (9) was synthesized from the precursor K[PtCl3 (quin)] (1), while the benzothiazole complexes, [{cis-Pt(A)2 (bztz)}2 -μ-(dach)](NO3 )4 ((A)2 =(NH3 )2 (10) and (A)2 =en (11)) were synthesized from the precursors cis-[Pt(A)2 Cl(bztz)] ((A)2 =(NH3 )2 (7) and (A)2 =en (8)). Their interactions with N-acetyltryptophan and a model pentapeptide (N-Ac-WLDSW-OH), modeled on the pentapeptide recognition sequence (FSDLW) of p53-mdm2 interaction, were examined by fluorescence spectroscopy. The dinuclear complexes were found to be significantly stronger at quenching the fluorescence of tryptophan than their mononuclear Pt-based analogues indicating stronger binding. Molecular modeling suggests a "sandwich" mode of binding, and the flexibility of the dinuclear motif can allow the design of more selective and stronger-binding complexes. Based on these results a further prototype, [{Pt(en)(9-EtGua)}2 μ-H2 N(CH2 )6 NH2 ](4+) , incorporating the purine 9-ethylguanine (9-EtG) as a stacking moiety, was prepared which showed good cytotoxicity in A2780 and OsACL tumor cell lines.

Two heptadentate Co(III) and Mn(III) complexes with partially deprotonated cyclen derivative bearing four hydroxypropyl pendants: structure, DNA binding and DNA cleavage

Two new complexes, (CoIII)2(H3L−)2(0.5H2O)2(ClO4)4 (I) and (MnIII)2(H3L−)2(0.5H2O)2 (ClO4)4 (II), were synthesized and crystallographically characterized [H4L = 1,4,7,10‐tetra‐(2‐hydroxypropyl)‐l,4,7,10‐tetraazacyclododecane] using electrospray ionization mass spectrometry and X‐ray photoelectron spectrometery. The characterizations confirmed that the valences of the metal ions increased from divalent to trivalent due to deprotonation of one OH group (H4L was in the form of H3L−). Owing to the instability of Co(III) and Mn(III) in both air and in solution, they preferred to exist in divalent form. The two heptadentate complexes are extraordinary in that the chiral pendants of the complexes are different in configuration. Spectroscopic studies, viscosity measurements, thermal denaturation experiments and circular dichroism spectra demonstrated that the complexes were prone to interact with DNA by groove binding. At micromolar concentrations and under physiological conditions, the two complexes were able to oxidatively cleave the supercoiled pUC19 plasmid DNA into its nicked and linear forms. Mechanistic studies using various additives suggest the complexes had structures different from those of other inorganic complexes. These are the first reported inorganic complexes not containing planar aromatic ligands and yet binding at the major groove. Copyright © 2012 John Wiley & Sons, Ltd.

Introduction of axial chirality in a planar aromatic ligand results in chiral recognition with DNA

Dimerization of a hydroxycarbazole produces an axially chiral biaryl, BICOL (2). One enantiomer (R)-2, is capable of enantioselective binding to different polymorphs of DNA. The biaryl (R)-2 was shown by fluorescence and circular dichroism to induce a shift of Z-DNA to B-DNA. The opposite enantiomer (S)-2 shows no specific binding. The significant difference in behaviour between the two enantiomers (S)-2 and (R)-2 is in line with molecular modelling studies which show two very different binding geometries between the enantiomers with each polymorph of DNA.

Orthogonal non-covalent binding forces in solid state supramolecular herringbone-shaped “interlocked dimers”. Pseudopolymorphism in [(ppy)Pd(μ-pz)]2 (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) complex

The crystal structures of [(ppy)Pd(mu-pz)](2) (ppy = 2-(2-pyridyl)phenyl, pz = pyrazol-1-yl) (1) and two different solvatomorphs of it, [(ppy)Pd(mu-pz)](2) x 1/2 CH(2)Cl(2) (2) and [(ppy)Pd(mu-pz)](2) x 1/2 CHCl(3) (3) have been elucidated by powder (1 and 2) and single crystal (3) X-ray diffraction. In all of them two molecules fit together following a very similar pattern forming a "dimer". All neutral dinuclear square-planar complexes having mu-pz or related bridges and planar aromatic ligands completing the coordination spheres found in the CSD show a similar arrangement to those observed in compounds 1-3, consisting of "interlocked dimers" following a herringbone-like pattern. A DFT study reveals the simultaneous action of pi,pi- and T-stacking interactions occurring as two sets of orthogonally oriented binding forces, as well as anagostic bonds overlapped with the latter.

Metal–Metal Electronic Coupling in syn and anti Stereoisomers of Mixed‐Valent (FeCp)2‐, (RhL2)2‐, and (FeCp)(RhL2)‐as‐Indacenediide Ions

The extent of metal-metal electronic coupling was quantified for a series of syn and anti stereoisomers of (FeCp)(2)-, (RhL(2))(2)- and (FeCp)(RhL(2))- (L(2)=1,5-cyclooctadiene (cod), L=CO) as-indacenediide mixed-valent ions by spectroelectrochemical and DFT studies. The effect of the syn/anti orientation of the metal units with respect to the planar aromatic ligand indicates that electron transfer occurs through the bridge rather than through space. The nature of the metal was found to be crucial: while homobimetallic diiron species are localised valence-trapped ions (Class II), the dirhodium analogues are almost delocalised mixed-valent ions (borderline and Class III). Finally, despite their redox asymmetry, even in the heterobimetallic iron-rhodium as-indacenediide complexes, strong metal-metal coupling is present. In fact, oxidation of the iron centre is accompanied by electron transfer from rhodium to iron and formation of a reactive 17-electron rhodium site. syn and anti Fe-Rh as-indacenediide complexes are rare examples of heterobimetallic systems which can be classified as borderline Class II/Class III species.

Taspine: Bioactivity-Guided Isolation and Molecular Ligand−Target Insight of a Potent Acetylcholinesterase Inhibitor fromMagnoliaxsoulangiana

A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory agent in a Magnolia x soulangiana extract using a microplate enzyme assay with Ellman's reagent. This permitted the isolation of the alkaloids taspine (1) and (-)-asimilobine (2), which were detected for the first time in this species. Compound 1 showed a significantly higher effect on AChE than the positive control galanthamine and selectively inhibited the enzyme in a long-lasting and concentration-dependent fashion with an IC(50) value of 0.33 +/- 0.07 muM. Extensive molecular docking studies were performed with human and Torpedo californica-AChE employing Gold software to rationalize the binding interaction. The results suggested ligand 1 to bind in an alternative binding orientation when compared to galanthamine. While this is located in close vicinity to the catalytic amino acid triad, the 1-AChE complex was found to be stabilized by (i) sandwich-like pi-stacking interactions between the planar aromatic ligand (1) and the Trp84 and Phe330 of the enzyme, (ii) an esteratic site anchoring with the amino side chain, and (iii) a hydrogen-bonding network.