Structure‐Based Design of Platinum(II) Complexes as c‐myc Oncogene Down‐Regulators and Luminescent Probes for G‐Quadruplex DNA

A series of platinum(II) complexes with tridentate ligands was synthesized and their interactions with G‐quadruplex DNA within the c‐myc gene promoter were evaluated. Complex 1 , which has a flat planar 2,6‐bis(benzimidazol‐2‐yl)pyridine (bzimpy) scaffold, was found to stabilize the c‐myc G‐quadruplex structure in a cell‐free system. An in silico G‐quadruplex DNA model has been constructed for structure‐based virtual screening to develop new Pt^II‐based complexes with superior inhibitory activities. By using complex 1 as the initial structure for hit‐to‐lead optimization, bzimpy and related 2,6‐bis(pyrazol‐3‐yl)pyridine (dPzPy) scaffolds containing amine side‐chains emerge as the top candidates. Six of the top‐scoring complexes were synthesized and their interactions with c‐myc G‐quadruplex DNA have been investigated. The results revealed that all of the complexes have the ability to stabilize the c‐myc G‐quadruplex. Complex 3 a ([Pt^II L2R ] ⁺ ; L2 =2,6‐bis[1‐(3‐piperidinepropyl)‐1H‐enzo[d]imidazol‐2‐yl]pyridine, R =Cl) displayed the strongest inhibition in a cell‐free system (IC₅₀=2.2 μM ) and was 3.3‐fold more potent than that of 1 . Complexes 3 a and 4 a ([Pt^II L3R ]⁺; L3 =2,6‐bis[1‐(3‐morpholinopropyl)‐1H‐pyrazol‐3‐yl]pyridine, R =Cl) were found to effectively inhibit c‐myc gene expression in human hepatocarcinoma cells with IC₅₀ values of ≈17 μM , whereas initial hit 1 displayed no significant effect on gene expression at concentrations up to 50 μM . Complexes 3 a and 4 a have a strong preference for G‐quadruplex DNA over duplex DNA, as revealed by competition dialysis experiments and absorption titration; 3 a and 4 a bind G‐quadruplex DNA with binding constants (K) of approximately 10⁶–10⁷ dm³ mol^?1, which are at least an order of magnitude higher than the K values for duplex DNA. NMR spectroscopic titration experiments and molecular modeling showed that 4 a binds c‐myc G‐quadruplex DNA through an external end‐stacking mode at the 3′‐terminal face of the G‐quadruplex. Intriguingly, binding of c‐myc G‐quadruplex DNA by 3 b is accompanied by an increase of up to 38‐fold in photoluminescence intensity at λ_max=622 nm.     

Polycyclic Azoniahetarenes: Assessing the Binding Parameters of Complexes between Unsubstituted Ligands and G‐Quadruplex DNA

Polycyclic azoniahetarenes were employed to determine the effect of the structure of unsubstituted polyaromatic ligands on their quadruplex‐DNA binding properties. The interactions of three isomeric diazoniadibenzo[b,k]chrysenes ( 4 a – c ), diazoniapentaphene ( 5 ), diazoniaanthra[1,2‐a]anthracene ( 6 ), and tetraazoniapentapheno[6,7‐h]pentaphene ( 3 ) with quadruplex DNA were examined by DNA melting studies (FRET melting) and fluorimetric titrations. In general, penta‐ and hexacyclic azoniahetarenes bind to quadruplex DNA (K_b≈10⁶ M ^?1) even in the absence of additional functional side chains. The binding modes of 4 a – c and 3 were studied in more detail by ligand displacement experiments, isothermal titration calorimetry, and CD and NMR spectroscopy. All experimental data indicate that terminal π stacking of the diazoniachrysenes to the quadruplex is the major binding mode; however, because of different electron distributions of the π systems of each isomer, these ligands align differently in the binding site to achieve ideal binding interactions. It is proposed that tetraazonia ligand 3 binds to the quadruplex by terminal stacking with a small portion of its π system, whereas a significant part of the bulky ligand most likely points outside the quadruplex structure, and is thus partially placed in the grooves. Notably, 3 and the known tetracationic porphyrin TMPyP4 exhibit almost the same binding properties towards quadruplex DNA, with 3 being more selective for quadruplex than for duplex DNA. Overall, studies on azonia‐type hetarenes enable understanding of some parameters that govern the quadruplex‐binding properties of parent ligand systems. Since unsubstituted ligands were employed in this study, complementary and cooperative effects of additional substituents, which may interfere with the ligand properties, were eliminated.     

Tridentate N-donor palladium(II) complexes as efficient coordinating quadruplex DNA binders

Fifteen complexes of palladium, platinum, and copper, featuring five different N‐donor tridentate (terpyridine‐like) ligands, were prepared with the aim of testing their G‐quadruplex–DNA binding properties. The fluorescence resonance energy transfer melting assay indicated a striking positive effect of palladium on G‐quadruplex DNA stabilization compared with platinum and copper, as well as an influence of the structure of the organic ligand. Putative binding modes (noncoordinative π stacking and base coordination) of palladium and platinum complexes were investigated by ESI‐MS and UV/Vis spectroscopy experiments, which all revealed a greater ability of palladium complexes to coordinate DNA bases. In contrast, platinum compounds tend to predominantly bind to quadruplex DNA in their aqua form by noncoordinative interactions. Remarkably, complexes of [Pd(ttpy)] and [Pd(tMebip)] (ttpy=tolylterpyridine, tMebip=2,2′‐(4‐p‐tolylpyridine‐2,6‐diyl)bis(1‐methyl‐1H‐benzo[d]imidazole)) coordinate efficiently G‐quadruplex structures at room temperature in less than 1 h, and are more efficient than their platinum counterparts for inhibiting the growth of cancer cells. Altogether, these results demonstrate that both the affinity for G‐quadruplex DNA and the binding mode of metal complexes can be modulated by modifying either the metal or the organic ligand.     

Template‐Assembled Synthetic G‐Quadruplex (TASQ): A Useful System for Investigating the Interactions of Ligands with Constrained Quadruplex Topologies

A new biomolecular device for investigating the interactions of ligands with constrained DNA quadruplex topologies, using surface plasmon resonance (SPR), is reported. Biomolecular systems containing an intermolecular‐like G‐quadruplex motif 1 (parallel G‐quadruplex conformation), an intramolecular G‐quadruplex 2 , and a duplex DNA 3 have been designed and developed. The method is based on the concept of template‐assembled synthetic G‐quadruplex (TASQ), whereby quadruplex DNA structures are assembled on a template that allows precise control of the parallel G‐quadruplex conformation. Various known G‐quadruplex ligands have been used to investigate the affinities of ligands for intermolecular 1 and intramolecular 2 DNA quadruplexes. As anticipated, ligands displaying a π‐stacking binding mode showed a higher binding affinity for intermolecular‐like G‐quadruplexes 1 , whereas ligands with other binding modes (groove and/or loop binding) showed no significant difference in their binding affinities for the two quadruplexes 1 or 2 . In addition, the present method has also provided information about the selectivity of ligands for G‐quadruplex DNA over the duplex DNA. A numerical parameter, termed the G‐quadruplex binding mode index (G4‐BMI), has been introduced to express the difference in the affinities of ligands for intermolecular G‐quadruplex 1 against intramolecular G‐quadruplex 2 . The G‐quadruplex binding mode index (G4‐BMI) of a ligand is defined as follows: G4‐BMI=K_D^intra/K_D^inter, where K_D^intra is the dissociation constant for intramolecular G‐quadruplex 2 and K_D^inter is the dissociation constant for intermolecular G‐quadruplex 1 . In summary, the present work has demonstrated that the use of parallel‐constrained quadruplex topology provides more precise information about the binding modes of ligands.     

Solid,Solution, and Theoretical Approach of [Cu(CN‐acac)(dmeen)]+

The reaction of bis(3‐cyano‐2,4‐pentanedionato)copper(II), [Cu(NC‐acac)₂] with the nitrogenous base N,N‐dimethyl, N′‐ethyl‐1,2‐ethylenediamine (dmeen) in the presence of Cu(ClO₄)₂ · 6H₂O, afforded a new cationic mixed‐ligand chelate [Cu(CN‐acac)(dmeen)]⁺. Its structure was characterized spectroscopically (IR, UV/Vis, EPR) and verified by X‐ray diffraction studies as [Cu(CN‐acac)(dmeen)(H₂O)]ClO₄. The coordination of CN‐acac^– as bridging ligand leads to a polymeric helical chain, which extends in the crystallographic c axis. Density functional theory (DFT) calculations suggest that in the solid state the anion CN‐acac^– binding is envisaged through the nitrogen atom of the cyanido group, establishing an octahedral arrangement around copper, whereas in solution, the square‐planar arrangement is prevailed, in accordance with the EPR findings.     

DNA Binding and Cleavage Activity of cis‐Cobalt Aromatic Oxime Complexes and Its Pyridine/imidazole Adducts

cis‐Cobalt complexes with salicycaldoxime(SAO), (Z)‐1‐(2‐hydroxyphenyl)ethanonoxime (HEO), (Z)‐1‐(2,5‐dihydroxyphenyl)ethanonoxime (DEO), (Z)‐1‐(2,5‐dihydroxyphenyl)(phenyl)methanonoxime (DPO) and their adducts with pyridine (Py) and imidazole (Im) were synthesized and characterized by elemental analysis, magnetic susceptibility, UV‐Vis and IR spectra. The electrochemical studies were carried by cyclic voltammeter, the peak potential separation and formal potential of complexes were independent of sweep rate or scan rate (ν) indicating a quasi reversible one‐electron redox process. Absorption studies and thermal denature studies revealed that each of these octahedral complexes is an avid binder of calf thymus DNA. The apparent binding constants for mixed ligand complexes are in order of ～10³‐10³ M^?1. Based on the data obtained in the DNA binding studies a partial intercalative mode of binding is suggested for these complexes. The nucleolytic cleavage activity of parent complexes and their pyridine adduct were carried out on double stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment in the presence and absence of oxidant (H₂O₂). All the metal complexes show enhanced cleavage activity in presence of oxidant. The hydrolytic cleavage of DNA of Co(DEO)₂ and Co(DPO)₂ is evidenced from the control experiments showing discernable cleavage inhibition in the presence of the hydroxyl radical inhibitor DMSO and EDTA.     

Stabilization of G‐Quadruplex DNA with Platinum(II) Schiff Base Complexes: Luminescent Probe and Down‐Regulation of c‐myc Oncogene Expression

The interactions of a series of platinum(II) Schiff base complexes with c‐myc G‐quadruplex DNA were studied. Complex [PtL ^1a ] ( 1 a ; H₂L ^1a =N,N′‐bis(salicylidene)‐4,5‐methoxy‐1,2‐phenylenediamine) can moderately inhibit c‐myc gene promoter activity in a cell‐free system through stabilizing the G‐quadruplex structure and can inhibit c‐myc oncogene expression in cultured cells. The interaction between 1 a and G‐quadruplex DNA has been examined by ¹H NMR spectroscopy. By using computer‐aided structure‐based drug design for hit‐to‐lead optimization, an in silico G‐quadruplex DNA model has been constructed for docking‐based virtual screening to develop new platinum(II) Schiff base complexes with improved inhibitory activities. Complex [PtL ³ ] ( 3 ; H₂L ³ = N,N′‐bis{4‐[1‐(2‐propylpiperidine)oxy]salicylidene}‐4,5‐methoxy‐1,2‐phenylenediamine) has been identified with a top score in the virtual screening. This complex was subsequently prepared and experimentally tested in vitro for its ability to stabilize or induce the formation of the c‐myc G‐quadruplex. The inhibitory activity of 3 (IC₅₀=4.4 μM ) is tenfold more than that of 1 a . The interaction between 1 a or 3 with c‐myc G‐quadruplex DNA has been examined by absorption titration, emission titration, molecular modeling, and NMR titration experiments, thus revealing that both 1 a and 3 bind c‐myc G‐quadruplex DNA through an external end‐stacking mode at the 3’ terminal face of the G‐quadruplex. Such binding of G‐quadruplex DNA with 3 is accompanied by up to an eightfold increase in the intensity of photoluminescence at λ_max=652 nm. Complex 3 also effectively down‐regulated the expression of c‐myc in human hepatocarcinoma cells.     

Determinants for Tight and Selective Binding of a Medicinal Dicarbene Gold(I) Complex to a Telomeric DNA G‐Quadruplex: a Joint ESI MS and XRD Investigation

The dicarbene gold(I) complex [Au(9‐methylcaffein‐8‐ylidene)₂]BF₄ is an exceptional organometallic compound of profound interest as a prospective anticancer agent. This gold(I) complex was previously reported to be highly cytotoxic toward various cancer cell lines in vitro and behaves as a selective G‐quadruplex stabilizer. Interactions of the gold complex with various telomeric DNA models have been analyzed by a combined ESI MS and X‐ray diffraction (XRD) approach. ESI MS measurements confirmed formation of stable adducts between the intact gold(I) complex and Tel 23 DNA sequence. The crystal structure of the adduct formed between [Au(9‐methylcaffein‐8‐ylidene)₂]⁺ and Tel 23 DNA G‐quadruplex was solved. Tel 23 maintains a characteristic propeller conformation while binding three gold(I) dicarbene moieties at two distinct sites. Stacking interactions appear to drive noncovalent binding of the gold(I) complex. The structural basis for tight gold(I) complex/G‐quadruplex recognition and its selectivity are described.     

Selective,pH-Dependent Colorimetric and Fluorimetric Detection of Quadruplex DNA with 4-Dimethylamino(phenyl)-Substituted Berberine Derivatives

The 9- and 12-dimethylaminophenyl-substituted berberine derivatives 3 a and 3 b were readily synthesized by Suzuki-Miyaura reactions and shown to be useful fluorescent probes for the optical detection of quadruplex DNA (G4-DNA). Their association with the nucleic acids was investigated by spectrometric titrations, CD and LD spectroscopy, and with DNA-melting analysis. Both ligands bind to duplex DNA by intercalation and to G4-DNA by terminal π stacking. At neutral conditions, they bind with higher affinity (K_b=10⁵−10⁶ M⁻¹) to representative quadruplex forming oligonucleotides 22AG , c-myc , c-kit , and a2 , than to duplex calf thymus (ct) DNA (K_b=5-7×10⁴ M⁻¹). At pH 5, however, the affinity of 3 a towards G4-DNA 22AG is higher (K_b=1.2×10⁶ M⁻¹), whereas the binding constant towards ct DNA is lower (K_b=3.9×10³ M⁻¹) than under neutral conditions. Notably, the association of the ligand with DNA results in characteristic changes of the absorption and emission properties under specific conditions, which may be used for optical DNA detection. Other than the parent berberine, the ligands do not show a noticeable increase of their very low intrinsic emission intensity upon association with DNA at neutral conditions. In contrast, a fluorescence light-up effect was observed upon association to duplex (Φ_fl=0.01) and quadruplex DNA (Φ_fl=0.04) at pH 5. This fluorimetric response to G4-DNA association in combination with the distinct, red-shifted absorption under these conditions provides a simple and conclusive optical detection of G4-DNA at lower pH.     

Effect of the Ancillary Ligands on the Spectral Properties and G‐Quadruplexes DNA Binding Behavior: A Combined Experimental and Theoretical Study

In an effort to explore the effect of ancillary ligands on the spectral properties and overall G‐quadruplex DNA binding behavior, two new ruthenium(II) complexes [Ru(phen)₂(dppzi)]²⁺ ( 1 ) and [Ru(dmp)₂(dppzi)]²⁺ ( 2 ) (phen=1,10‐phenanthroline, dmp=2,9‐dimethyl‐1,10‐phenanthroline, dppzi=dipyrido[3,2‐a:2′,3′‐c]phenazine‐10,11‐imidazole) were prepared. Complex 1 can emit luminescence in the absence and presence of G‐quadruplexes DNA. However, with ?CH₃ substituent on the 2‐ and 9‐positions of the phen ancillary ligand, no detectable luminescence is observed for complex 2 in any organic solvent or in the absence and/or presence of G‐quadruplex DNA. Experimental and molecular docking studies indicated that both complexes interacted with the human telomeric repeat AG3(T2AG3)3 (22AG) G‐quadruplex with the stoichiometric ratio of 1:1, but the two complexes showed different G‐quadruplex DNA binding affinity. Complex 1 binds to the G‐quadruplexes DNA more tightly than complex 2 does. Our results demonstrate that methyl groups on the phen ancillary ligand significantly affect the spectral properties and the overall DNA binding behavior of the complexes. Such difference in spectral properties and DNA binding affinities of these two complexes can be reasonably explained by DFT/TD‐DFT calculations. This work provides guidance not only on exploring the G‐quadruplexes DNA binding behavior of complexes, but also understanding the unique luminescence mechanism.     

Synthesis and EPR/UV/Vis‐NIR Spectroelectrochemical Investigation of a Persistent Phosphanyl Radical Dication

The reaction of the bis(imidazoliumyl)‐substituted P^I cation [(2‐Im^Dipp)P(4‐Im^Dipp)]⁺ ( 10 ⁺) (2‐Im=imidazolium‐2‐yl; 4‐Im=imidazolium‐4‐yl; Dipp=2,6‐di‐isopropylphenyl) with trifluoromethanesulfonic acid (HOTf) or methyl trifluoromethylsulfonate (MeOTf) yields the corresponding protonated [(2‐Im^Dipp)PH(4‐Im^Dipp)]²⁺ ( 11 ²⁺) and methylated [(2‐Im^Dipp)PMe(4‐Im^Dipp)]²⁺ ( 12 ²⁺) dications, respectively. EPR/UV/Vis‐NIR spectroelectrochemical investigation of the low‐coordinated P^I cation 10 ⁺ predicted a stable and “bottleable” P‐centered radical dication [(2‐Im^Dipp)P(4‐Im^Dipp)]^2+. ( 13 ^2+.). The reaction of 10 ⁺ with the nitrosyl salt NO[OTf] yields the persistent phosphanyl radical dication 13 ^2+. as triflate salt in crystalline form. Quantum chemical investigation revealed an exceptional high spin density at the P atom.     

Single component transparent free‐standing films based on polyhedral octasilicate‐core dendrimers bearing carbazole terminal groups and their emission properties

9H‐carbazole‐9‐ethyl and 9H‐carbazole‐9‐hexyl‐terminated polyhedral octasilicate (OS)‐core dendrimers, denoted as OS‐C2‐Cz and OS‐C6‐Cz, respectively, were prepared by ring‐opening reaction and subsequent condensation of octakis(propenyl succinicanhydrido)polyhedral octasilicate (OS‐SA) with 9H‐carbazole‐9‐ethanol (Cz‐C2‐OH) and 9H‐carbazole‐9‐hexanol (Cz‐C6‐OH), respectively. Both the dendrimers formed optical transparent coating films. In particular, the coating film of OS‐C2‐Cz was easily peeled off from a substrate and formed a free‐standing film. The results of X‐ray diffraction and differential scanning calorimeter suggest that the films of OS‐C2‐Cz and OS‐C6‐Cz were amorphous. Thermogravimetric analysis of OS‐C2‐Cz and OS‐C6‐Cz showed 10 wt % weight losses at 374 and 383 °C, respectively. Photoluminescence property revealed that the carbazole group in OS‐C2‐Cz is prevented the excimer formation, while the carbazole group in OS‐C6‐Cz formed the excimer. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 628–633     

Assembly of a Highly Stable Luminescent Zn5 Cluster and Application to Bio‐Imaging

The assembly sequence of the coordination cluster [Zn₅(H₂Lⁿ)₆](NO₃)₄]⋅8 H₂O⋅2 CH₃OH ( Zn₅ , H₃Lⁿ=(1,2‐bis(benzo[d]imidazol‐2‐yl)‐ethenol) involves in situ dehydration of 1,2‐bis(benzo[d]imidazol‐2‐yl)‐1,2‐ethanediol (H₄L) through the formation of the [Zn(H₃L)₂]⁺ monomer, dimerization to [Zn₂(H₃L)₂]⁺, dehydration of the ligand to [Zn₂(H₂Lⁿ)₂]⁺, and the final formation of the pentanuclear cluster. The cluster has the following special characteristics: 1) high stability in both refluxing 37 % HCl and 27 % NH₃, 2) low cytotoxicity, and 3) pH‐sensitive fluorescence in the visible‐to‐near‐infrared (Vis/NIR) region in the solid state and in solution. We have applied it as a fluorescent probe both in vivo and in vitro. Its H‐bonding ability is the key to its affinity and selectivity for imaging lysosomes in HeLa cells and tumors in male BALB/C mice. It provides a new type of sensitive and biocompatible fluorescent probe for detecting small tumors (13.5 mm³).     

Competitive binding exchange between alkali metal ions (K+, Rb+, and Cs+) and Na+ ions bound to the dimeric quadruplex [d(G4T4G4)]2: a 23Na and 1H NMR study

A comparative study of the competitive cation exchange between the alkali metal ions K⁺, Rb⁺, and Cs⁺ and the Na⁺ ions bound to the dimeric quadruplex [d(G₄T₄G₄)]₂ was performed in aqueous solution by a combined use of the ²³Na and ¹H NMR spectroscopy. The titration data confirm the different binding affinities of these ions for the G‐quadruplex and, in particular, major differences in the behavior of Cs⁺ as compared to the other ions were found. Accordingly, Cs⁺ competes with Na⁺ only for the binding sites at the quadruplex surface (primarily phosphate groups), while K⁺ and Rb⁺ are also able to replace sodium ions located inside the quadruplex. Furthermore, the ¹H NMR results relative to the CsCl titration evidence a close approach of Cs⁺ ions to the phosphate groups in the narrow groove of [d(G₄T₄G₄)]₂. Based on a three‐site exchange model, the ²³Na NMR relaxation data lead to an estimate of the relative binding affinity of Cs⁺ versus Na⁺ for the quadruplex surface of 0.5 at 298 K. Comparing this value to those reported in the literature for the surface of the G‐quadruplex formed by 5′‐guanosinemonophosphate and for the surface of double‐helical DNA suggests that topology factors may have an important influence on the cation affinity for the phosphate groups on DNA. Copyright © 2009 John Wiley & Sons, Ltd.     

DNA/BSA binding interactions and VHPO mimicking potential of vanadium(IV) complexes: Synthesis,structural characterization and DFT studies

Vanadium(IV) Schiff base complexes (VOL¹‐VOL³) were synthesized and characterized by elemental analysis, various spectral methods and single crystal XRD studies. Structural analysis of VOL² reveals that the central vanadium ion in the complex is six coordinate with distorted octahedral geometry. Density functional theory (DFT) and time dependent (TD‐DFT) studies were used to understand the electronic transitions observed in the complexes in UV–Vis spectra. The electrochemical behavior of the complexes was investigated in acetonitrile medium exhibit quasi‐reversible one electron transfer. The DNA and BSA protein binding interaction of vanadium complexes has been explored by UV–Vis and fluorescence spectral methods and viscosity measurements reveal that the complexes interact with CT‐DNA through intercalation mode and follows the order VOL¹ < VOL³ < VOL². The complexes exhibit binding interactions with BSA protein. The complexes act as chemical nuclease and cleave DNA in the presence of H₂O₂. The 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) assay was used to evaluate the radical scavenging activity demonstrate the antioxidant property of the complexes. The antimicrobial activity was screened for several microorganisms, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli. The mimicking of vanadium haloperoxidase was investigated by the bromination of the organic substrate phenol red by vanadium complexes in the presence of bromide and H₂O₂.     

Binding Behaviors for Different Types of DNA G‐Quadruplexes: Enantiomers of [Ru(bpy)2(L)]2+ (L=dppz,dppz‐idzo)

Polymorphic DNA G‐quadruplex recognition has attracted great interest in recent years. The strong binding affinity and potential enantioselectivity of chiral [Ru(bpy)₂(L)]²⁺ (L=dipyrido[3,2‐a:2′,3′‐c]phenazine, dppz‐10,11‐imidazolone; bpy=2,2′‐bipyridine) prompted this investigation as to whether the two enantiomers, Δ and Λ, can show different effects on diverse structures with a range of parallel, antiparallel and mixed parallel/antiparallel G‐quadruplexes. These studies provide a striking example of chiral‐selective recognition of DNA G‐quadruplexes. As for antiparallel (tel‐Na⁺) basket G‐quadruplex, the Λ enantiomers bind stronger than the Δ enantiomers. Moreover, the behavior reported here for both enantiomers stands in sharp contrast to B‐DNA binding. The chiral selectivity toward mixed parallel/antiparallel (tel‐K⁺) G‐quadruplex of both compounds is weak. Different loop arrangements can change chiral complex selectivity for both antiparallel and mixed parallel/antiparallel G‐quadruplex. Whereas both Δ and Λ isomers bind to parallel G‐quadruplexes with comparable affinity, no appreciable stereoselective G‐quadruplex binding of the isomers was observed. In addition, different binding stoichiometries and binding modes for Δ and Λ enantiomers were confirmed. The results presented here indicate that chiral selective G‐quadruplex binding is not only related to G‐quadruplex topology, but also to the sequence and the loop constitution.     

Correspondence of RuIIIRuII and RuIVRuIII Mixed Valent States in a Small Dinuclear Complex

The diruthenium(III) compound [(μ‐oxa){Ru(acac)₂}₂] [ 1 , oxa^2?=oxamidato(2?), acac^?=2,4‐pentanedionato] exhibits an S=1 ground state with antiferromagnetic spin‐spin coupling (J=?40 cm^?1). The molecular structure in the crystal of 1? 2 C₇H₈ revealed an intramolecular metal–metal distance of 5.433 Å and a notable asymmetry within the bridging ligand. Cyclic voltammetry and spectroelectrochemistry (EPR, UV/Vis/NIR) of the two‐step reduction and of the two‐step oxidation (irreversible second step) produced monocation and monoanion intermediates (K_c=10^5.9) with broad NIR absorption bands (ε ca. 2000 M ^?1 cm^?1) and maxima at 1800 ( 1 ^?) and 1500 nm ( 1 ⁺). TD‐DFT calculations support a Ru^IIIRu^II formulation for 1 ^? with a doublet ground state. The 1 ⁺ ion (Ru^IVRu^III) was calculated with an S=3/2 ground state and the doublet state higher in energy (ΔE=694.6 cm^?1). The Mulliken spin density calculations showed little participation of the ligand bridge in the spin accommodation for all paramagnetic species [(μ‐oxa){Ru(acac)₂}₂]ⁿ, n=+1, 0, ?1, and, accordingly, the NIR absorptions were identified as metal‐to‐metal (intervalence) charge transfers. Whereas only one such NIR band was observed for the Ru^IIIRu^II (4d⁵/4d⁶) system 1 ^?, the Ru^IVRu^III (4d⁴/4d⁵) form 1 ⁺ exhibited extended absorbance over the UV/Vis/NIR range.     

Site-specific control of N7-metal coordination in DNA by a fluorescent purine derivative

A synthetic strategy that utilizes O6‐protected 8‐bromoguanosine gives broad access to C8‐guanine derivatives with phenyl, pyridine, thiophene, and furan substituents. The resulting 8‐substituted 2′‐deoxyguanosines are push–pull fluorophores that can exhibit environmentally sensitive quantum yields (Φ=0.001–0.72) due to excited‐state proton‐transfer reactions with bulk solvent. Changes in nucleoside fluorescence were used to characterize metal‐binding affinity and specificity of 8‐substituted 2′‐deoxyguanosines. One derivative, 8‐(2‐pyridyl)‐2′‐deoxyguanosine (2PyG), exhibits selective binding of Cu^II, Ni^II, Cd^II, and Zn^II through a bidentate effect provided by the N7 position of guanine and the 2‐pyridyl nitrogen atom. Upon incorporation into DNA, 2‐pyridine‐modified guanine residues selectively bind to Cu^II and Ni^II with equilibrium dissociation constants (K_d) that range from 25 to 850 nM ; the affinities depend on the folded state of the oligonucleotide (duplex>G‐quadruplex) as well as the identity of the metal ion (Cu>Ni?Cd). These binding affinities are approximately 10 to 1 000 times higher than for unmodified metal binding sites in DNA, thereby providing site‐specific control of metal localization in alternatively folded nucleic acids. Temperature‐dependent circular‐dichroism studies reveal metal‐dependent stabilization of duplexes, but destabilization of G‐quadruplex structures upon adding Cu^II to 2PyG‐modified oligonucleotides. These results demonstrate how the addition of a single pyridine group to the C8 position of guanine provides a powerful new tool for studying the effects of N7 metalation on the structure, stability, and electronic properties of nucleic acids.     

A New Samarium(III) Complex of Liriodenine: Synthesis,Crystal Structure,Antitumor Activity,and DNA Binding Study

A novel Sm^III complex [Sm^III(LA)₂(pic)₃] (Hpic = picric acid), in which LA is a natural‐derived alkaloid, liriodenine, was synthesized and characterized by IR, elemental analysis, and single‐crystal X‐ray diffraction analysis. This complex showed enhanced solubility compared with liriodenine and its metal complexes that have been previously reported. The interaction of the Sm^III complex with ct‐DNA was further investigated by various spectroscopic techniques, such as UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy (CD), and viscosity measurement. The results showed that the intrinsic binding constant K_b of the Sm^III complex with ct‐DNA was calculated to be 5.03 × 10³ L·mol^–1 by UV/Vis absorption spectral analysis. The thermodynamic fluorescent spectral analysis suggested that the fluorescence intensity of the Sm^III complex was weakened by ct‐DNA mainly through a dynamic quenching mechanism. The presence of Sm complex could increase the viscosity of DNA solution, so it was concluded that the complex bound with ct‐DNA via a moderate intercalative mode. Furthermore, this Sm^III complex exhibited significant growth inhibition on the three typical tumor cell lines, HepG2, T‐24, and SK‐OV‐3, with the corresponding IC₅₀ values, 10.76 ± 0.19, 8.85 ± 1.12, and 10.01 ± 0.55 μM, respectively. The in vitro antitumor activity was comparable with LA and cisplatin, which suggested that it might be a new broad spectrum antitumor agent with more satisfying solubility.     

New anthracene based Schiff base ligands appended Cu(II) complexes: Theoretical study,DNA binding and cleavage activities

New anthracene based Schiff base ligands L ¹ and H( L ² ), their Cu(II) complexes [Cu( L ¹ )Cl₂] ( 1 ) and [Cu( L ² )Cl] ( 2 ) , (where L ¹  = N¹,N²‐bis(anthracene‐9‐methylene)benzene‐1,2‐diamine, L ²  = (2Z,4E)‐4‐(2‐(anthracen‐9‐ylmethyleneamino)phenylimino)pent‐2‐en‐2‐ol) have been prepared and characterized by elemental analysis, NMR, FAB‐mass, EPR, FT‐IR, UV–Vis and cyclic voltammetry. The electronic structures and geometrical parameters of complexes 1 and 2 were analyzed by the theoretical B3LYP/DFT method. The interaction of these complexes 1 and 2 with CT‐DNA has been explored by using absorption, cyclic voltammetric and CD spectral studies. From the electronic absorption spectral studies, it was found that the DNA binding constants of complexes 1 and 2 are 8.7 × 10³ and 7.0 × 10⁴ M^?1, respectively. From electrochemical studies, the ratio of DNA binding constants K₊/K₂₊ for 2 has been estimated to be >1. The high binding constant values, K₊/K₂₊ ratios more than unity and positive shift of voltammetric E_1/2 value on titration with DNA for complex 2 suggest that they bind more avidly with DNA than complex 1 . The inability to affect the conformational changes of DNA in the CD spectrum is the definite evidences of electrostatic binding by the complex 1 . It can be assumed that it is the bulky anthracene unit which sterically inhibits these complexes 1 and 2 from intercalation and thereby remains in the groove or electrostatic. The complex 2 hardly cleaves supercoiled pUC18 plasmid DNA in the presence of hydrogen peroxide. The results suggest that complex 2 bind to DNA through minor groove binding.