Li-Na Zhu

Oxidative DNA cleavage by Schiff base tetraazamacrocyclic oxamido nickel(II) complexes

Nickel is considered a weak carcinogen. Some researches have shown that bound proteins or synthetic ligands may increase the toxic effect of nickel ions. A systematic study of ligand effects on the interaction between nickel complexes and DNA is necessary. Here, we compared the interactions between DNA and six closely related Schiff base tetraazamacrocyclic oxamido nickel(II) complexes NiL(1-3a,1-3b). The structure of one of the six complexes, NiL(3b) has been characterized by single crystal X-ray analysis. All of the complexes can cleave plasmid DNA under physiological conditions in the presence of H(2)O(2). NiL(3b) shows the highest DNA cleavage activity. It can convert supercoiled DNA to nicked DNA then linear DNA in a sequential manner as the complex concentration or reaction time is increased. The cleavage reaction is a typical pseudo-first-order consecutive reaction with the rate constants of 3.27+/-0.14h(-1) (k(1)) and 0.0966+/-0.0042h(-1) (k(2)), respectively, when a complex concentration of 0.6mM is used. The cleavage mechanism between the complex and plasmid DNA is likely to involve hydroxyl radicals as reactive oxygen species. Circular dichronism (CD), fluorescence spectroscopy and gel electrophoresis indicate that the complexes bind to DNA by partial intercalative and groove binding modes, but these binding interactions are not the dominant factor in determining the DNA cleavage abilities of the complexes.

Specific recognition and stabilization of monomeric and multimeric G-quadruplexes by cationic porphyrin TMPipEOPP under molecular crowding conditions

Ligands targeting telomeric G-quadruplexs are considered good candidates for anticancer drugs. However, current studies on G-quadruplex ligands focus exclusively on the interactions of ligands and monomeric G-quadruplexes under dilute conditions. Living cells are crowded with biomacromolecules, and the ∼200-nucleotide G-rich single-stranded overhang of human telomeric DNA has the potential to fold into multimeric G-quadruplex structures containing several G-quadruplex units. Studies on interactions between ligands and multimeric G-quadruplexes under molecular crowding conditions could provide a new route for screening specific telomeric G-quadruplex-targeting ligands. Herein, TMPipEOPP, a cationic porphyrin derivative designed by us, was demonstrated as a promising multimeric telomeric G-quadruplex ligand under molecular crowding conditions. It could highly specifically recognize G-quadruplexes. It could also promote the formation of G-quadruplexes and stabilize them. Detailed studies showed that TMPipEOPP interacted with monomeric G-quadruplexes in sandwich-like end-stacking mode of quadruplex/TMPipEOPP/quadruplex and interacted with multimeric human telomeric G-quadruplexes by intercalating into the pocket between two adjacent G-quadruplex units. The pocket size greatly affected TMPipEOPP binding. A larger pocket was advantageous for the intercalation of TMPipEOPP. This work provides new insights into the ligand-binding properties of multimeric G-quadruplexes under molecular crowding conditions and introduces a new route for screening anticancer drugs targeting telomeric G-quadruplexes.

Triphenylmethane dyes as fluorescent probes for G-quadruplex recognition

Triphenylmethane (TPM) dyes normally render rather weak fluorescence due to easy vibrational deexcitation. However, when they stack onto the two external G-quartets of a G-quadruplex (especially intramolecular G-quadruplex), such vibrations will be restricted, resulting in greatly enhanced fluorescence intensities. Thus, TPM dyes may be developed as sensitive G-quadruplex fluorescent probes. Here, fluorescence spectra and energy transfer spectra of five TPM dyes in the presence of G-quadruplexes, single- or double-stranded DNAs were compared. The results show that the fluorescence spectra of four TPM dyes can be used to discriminate intramolecular G-quadruplexes from intermolecular G-quadruplexes, single- and double-stranded DNAs. The energy transfer fluorescence spectra and energy transfer fluorescence titration can be used to distinguish G-quadruplexes (including intramolecular and intermolecular G-quadruplexes) from single- and double-stranded DNAs. Positive charges and substituent size in TPM dyes may be two important factors in influencing the binding stability of the dyes and G-quadruplexes.

A New Cationic Porphyrin Derivative (TMPipEOPP) with Large Side Arm Substituents: A Highly Selective G-Quadruplex Optical Probe

The discovery of uncommon DNA structures and speculation about their potential functions in genes has brought attention to specific DNA structure recognition. G-quadruplexes are four-stranded nucleic acid structures formed by G-rich DNA (or RNA) sequences. G-rich sequences with a high potential to form G-quadruplexes have been found in many important genomic regions. Porphyrin derivatives with cationic side arm substituents are important G-quadruplex-binding ligands. For example, 5,10,15,20-Tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TMPyP4), interacts strongly with G-quadruplexes, but has poor selectivity for G-quadruplex versus duplex DNA. To increase the G-quadruplex recognition specificity, a new cationic porphyrin derivative, 5,10,15,20-tetra-{4-[2-(1-methyl-1- piperidinyl)ethoxy]phenyl} porphyrin (TMPipEOPP), with large side arm substituents was synthesized, and the interactions between TMPipEOPP and different DNA structures were compared. The results show that G-quadruplexes cause large changes in the UV-Vis absorption and fluorescence spectra of TMPipEOPP, but duplex and single-stranded DNAs do not, indicating that TMPipEOPP can be developed as a highly specific optical probe for discriminating G-quadruplex from duplex and single-stranded DNA. Visual discrimination is also possible. Job plot and Scatchard analysis suggest that a complicated binding interaction occurs between TMPipEOPP and G-quadruplexes. At a low [G-quadruplex]/[TMPipEOPP] ratio, one G-quadruplex binds two TMPipEOPP molecules by end-stacking and outside binding modes. At a high [G-quadruplex]/[TMPipEOPP] ratio, two G-quadruplexes bind to one TMPipEOPP molecule in a sandwich-like end-stacking mode.

Analysis of factors governing the formation of single-stranded helical coordination polymers from a macrocyclic metalloligand and Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Pb2+

The high rigidity, asymmetric exoditopic coordination mode, angular orientations of the coordination tops and good coordination adaptability of the metalloligand, the π⋯π stacking between the adjacent metalloligands in the polymeric chains and the coordination characteristics of the nodes are responsible for the formation of the eight 1D helices.

A novel porous metal–organic framework from a new bis(acylhydrazone) ligand capable of reversibly adsorbing/desorbing water and small alcohol molecules

A porous metal–organic material of the doubly deprotonated form of a new bis(aroylhydrazone) ligand (L12−) was self-assembled from 2,3-butanedione, isonicotinoyl hydrazine and lead nitrate. X-ray single crystal analysis revealed that six L12− and six Pb2+ are arranged alternately to form a metallomacrocycle in the porous material. Weak coordination bonds together with π⋯π interactions connect the metallomacrocycle units rather strongly into two interpenetrating unique 3D networks. TG, PXRD and dehydration investigation showed that all of the coordination and guest water molecules in the material can be removed upon heating to give the activated structure with vacant pores and open Pb sites. The material can reversibly adsorb/desorb water and small alcohol molecules.

Three Single Stranded Helical Coordination Polymers of a Macrocyclic Metalloligand and Mg2+, Zr4+ and Pb2+ Nodes

Three new coordination polymers, {[Mg(NiL1)(H2O)3]·CH3CH2OH·2H2O}n (1), {[Zr2(NiL1)2(OH)4(H2O)2]·8H2O}n (2) and {[Pb(NiL1)(H2O)2]·3H2O}n (3), were prepared from a macrocyclic metalloligand NiL1. H2L1 denotes 1,4-dihydro-2,3-dioxo-5,6:- 9,10:13,14-tribenzo[1,4,8,11]tetraazacyclotetradeca-7,11-diene-7,12-dicarboxylate. Single crystal X-ray diffraction studies revealed that 1, 2 and 3 have infinite single stranded helical structures. In each of the three compounds, NiL1 plays the role of the bridging ligand by chelating one node via two oxamido carbonyls and binding to another through a carboxylate oxygen atom. 1D helical coordination polymers of macrocyclic metalloligands and those of Mg2+, Zr4+ and Pb2+ nodes are all not common. The generation of the three complexes manifests further that NiL1 is a bridging ligand unprecedentedly powerful in directing the formation of single stranded helical coordination polymers. It is the combination of multiple features of NiL1 that are responsible for its high powerfulness of inducing these helical structures. The outcome implies that combining multiple features surporting the formation of such helices into one ligand should be an effective strategy for the design and selection of bridging ligands powerful for the production of such structures.