Energetics,Conformation, and Recognition of DNA Duplexes Modified by Methylated Analogues of [PtCl(dien)]+

Monodentate DNA binding of [PtCl(dien)]⁺ (dien=diethylenetriamine) complexes may considerably affect the biophysical properties of DNA and consequently downstream cellular processes as a result of a large increase in the bulkiness of the nonleaving ligand by multiple methylation (see illustration).

     

Solvating,manipulating, damaging,and repairing DNA in a computer

This work highlights four different topics in modeling of DNA: (i) the importance of water and ions together with the structure and function of DNA; the hydration structure around the ions appears to be the determining factor in the ion coordination to DNA, as demonstrated in the results of our MD simulations; (ii) how MD simulations can be used to simulate single molecule manipulation experiments as a complement to reveal the structural dynamics of the studied biomolecules; (iii) how damaged DNA can be studied in computer simulations; and (iv) how repair of damaged DNA can be studied theoretically. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Synthesis,crystal structure,DNA binding,and DNA cleavage of a zinc complex containing N,N-bis(2-pyridylmethyl)amine

A water-soluble zinc complex, [Zn(bpea)Cl₂] (1) (bpea?=?N,N-bis(2-pyridylmethyl)ethylamine), was prepared to serve as a nuclease mimic. The complex was characterized by X-ray, infrared, and UV spectroscopy. Interactions of the complex with calf thymus-DNA (ct-DNA) have been investigated by UV absorption and fluorescence spectroscopies; the mode of ct-DNA binding for 1 has been proposed. DNA cleavage activities by 1 were performed in the absence of external agents. The influences of different complex concentrations or reaction times on DNA cleavage were studied.     

Programmable DNA Nanoflowers for Biosensing,Bioimaging, and Therapeutics

DNA nanostructures have shown excellent prospects in biomedical applications owing to their unique sequence programmability, function designability, and biocompatibility. As a type of unique DNA–inorganic hybrid nanostructures, DNA nanoflowers (DNFs) have attracted considerable attention in the past few years. Precise design of the DNA sequence enables the functions of DNFs to be customized. Specifically, DNFs exhibit high physiological stability and more diverse properties by virtue of the incorporation of inorganic materials, which in turn have been applied in an assortment of biomedical fields. In this review, the design, synthesis, and biomedical applications of programmable DNFs are discussed. First, the background of DNA-based materials and the fundamentals of DNFs are briefly introduced. In the second part, two synthetic methods of DNFs are categorized as the rolling circle amplification and salt aging method, focusing on the formation mechanism of DNFs and differences between the synthetic methods. In the third part, the biomedical applications of DNFs functional materials are summarized, including biosensing, bioimaging, and therapeutics. Finally, the challenges and future opportunities of DNFs are discussed toward more widespread applications.     

Synthesis,crystal structure,spectroscopy, and nuclease activity of copper(II) complexes containing N,N-bis(2-pyridylmethyl)amine ligand

[Cu(bpea)Cl]ClO₄ (1) and a new copper(II) complex [Cu(bpma)(Ph-COO)(H₂O)]ClO₄ (2) [bpea?=?N,N-bis(2-pyridylmethyl)ethylamine; bpma?=?N,N-bis(2-pyridylmethyl)methylamine] have been synthesized. Complex 2 was crystallized in monoclinic space group P2₁/c with unit cell parameters a ?=?16.460(6)?Å, b ?=?11.222(4)?Å, c?=?12.522(5)?Å, and β?=?97.985(6)°. Interactions of the complexes with calf thymus DNA (CT-DNA) have been investigated by UV absorption, fluorescence, and cyclic voltammetry; thus, modes of CT-DNA binding for the complexes have been proposed. Furthermore, DNA cleavage activities by the complexes were performed in the absence of any external agents. The influence of complex concentration or reaction time on the DNA cleavage was studied.     

“Printing” DNA Strand Patterns on Small Molecules with Control of Valency,Directionality, and Sequence

The incorporation of synthetic molecules as corner units in DNA structures has been of interest over the last two decades. In this work, we present a facile method for generating branched small molecule‐DNA hybrids with controllable valency, different sequences, and directionalities (5′–3′) using a “printing” process from a simple 3‐way junction structure. We also show that the DNA‐imprinted small molecule can be extended asymmetrically using polymerase chain reaction (PCR) and can be replicated chemically. This strategy provides opportunities to achieve new structural motifs in DNA nanotechnology and introduce new functionalities to DNA nanostructures.     

Functional tuning of nucleic acids by chemical modifications: tailored oligonucleotides as drugs,devices, and diagnostics

Chemical modifications of nucleic acids present vast opportunities for extending the functions and properties of these biomolecules. In general, efforts invested in this direction pertain to the introduction of reactive functional groups for further derivatizations of oligonucleotides with numerous reporter groups and for equipping nucleic acids with catalytic chemical moieties. This review deals with representative chemical modifications in the nucleobases, sugars, and the phosphate ester backbone and their application from novel catalytic RNA selection to nucleic acid-based biosensors.     

Energetics,Conformation, and Recognition of DNA Duplexes Modified by Monodentate RuII Complexes Containing Terphenyl Arenes

We studied the thermodynamic properties, conformation, and recognition of DNA duplexes site‐specifically modified by monofunctional adducts of Ru^II complexes of the type [Ru^II(η⁶‐arene)(Cl)(en)]⁺, in which arene=para‐, meta‐, or ortho‐terphenyl (complexes 1 , 2 , and 3 , respectively) and en=1,2‐diaminoethane. It has been shown (J. Med. Chem. 2008 , 51, 5310) that 1 exhibits promising cytotoxic effects in human tumor cells, whereas 2 and 3 are much less cytotoxic; concomitantly with the high cytotoxicity of 1 , its DNA binding mode involves combined intercalative and monofunctional (coordination) binding modes, whereas less cytotoxic compounds 2 and 3 bind to DNA only through a monofunctional coordination to DNA bases. An analysis of conformational distortions induced in DNA by adducts of 1 and 2 revealed more extensive and stronger distortion and concomitantly greater thermodynamic destabilization of DNA by the adducts of nonintercalating 2 . Moreover, affinity of replication protein A to the DNA duplex containing adduct of 1 was pronouncedly lower than to the adduct of 2 . On the other hand, another damaged‐DNA‐binding protein, xeroderma pigmentosum protein A, did not recognize the DNA adduct of 1 or 2 . Importantly, the adducts of 1 induced a considerably lower level of repair synthesis than the adducts of 2 , which suggests enhanced persistence of the adducts of the more potent and intercalating 1 in comparison with the adducts of the less potent and nonintercalating 2 . Also interestingly, the adducts of 1 inhibited DNA polymerization more efficiently than the adducts of 2 , and they could also be bypassed by DNA polymerases with greater difficulty. Results of the present work along with those previously published support the view that monodentate Ru^II arene complexes belong to a class of anticancer agents for which structure–pharmacological relationships might be correlated with their DNA‐binding modes.     

DNA浓度及序列检测的电化学传感器研究

综述近期本课题组有关DNA在化学修饰电极上的电化学行为、识别和检测方面的工作。     

Synthesis,structure, DNA binding and cleavage ability of a new copper ciprofloxacin complex

The structure of 1 consists of [Cu(HCp)(phen)(H₂O)]²⁺ (HCp is ciprofloxacin and phen is 1,10-phenanthroline), two acetates, and four free water molecules. In each cation, copper displays a distorted square pyramid, coordinated to ring 3-carboxylate and 4-oxo oxygen from HCp, two nitrogens from phen, and one water molecule. There are five water molecules in each discrete complex with one coordinated to Cu center, and the other four linked to each other by intermolecular hydrogen bonds. Two uncoordinated acetates make the compound neutral. The complex exhibits higher DNA binding compared to HCp at the same conditions by fluorescence and viscosity measurements. Combining its structure with the DNA-binding result, the binding mechanism may be explained by intercalation. Moreover, 1 shows significant cleavage of DNA in the presence of a reducing agent, such as ascorbate by gel electrophoresis using supercoiled pBR322 DNA in Tris-HCl buffer (pH 7.4). The complex also has a higher activity against Gram-positive bacteria Staphylococcus aureus and Gram-negative bacteria Klebsiella pneumoniae than HCp.     

Stretching,Tearing, and Dissecting Single Molecules of DNA

Optical tweezers, bendable microneedles, and scanning force microscope probes make it possible to play with individual molecules of DNA, to stretch them beyond their natural length, to unzip and pull apart their strands (see schematic diagram), and to dissect them to create new molecules in situ. Depending on the method of measurement, the mechanical force necessary to separate the strands was in the range of 10–50 pN per base pair.     

Minimalist Design of Wireframe DNA Nanotubes: Tunable Geometry,Size, Chirality,and Dynamics

DNA nanotubes (NTs) have attracted extensive interest as artificial cytoskeletons for biomedical, synthetic biology, and materials applications. Here, we report the modular design and assembly of a minimalist yet robust DNA wireframe nanotube with tunable cross-sectional geometry, cavity size, chirality, and length, while using only four DNA strands. We introduce an h-motif structure incorporating double-crossover (DX) tile-like DNA edges to achieve structural rigidity and provide efficient self-assembly of h-motif-based DNA nanotube ( H-NT ) units, thus producing programmable, micrometer-long nanotubes. We demonstrate control of the H-NT nanotube length via short DNA modulators. Finally, we use an enzyme, RNase H, to take these structures out of equilibrium and trigger nanotube assembly at a physiologically relevant temperature, underlining future cellular applications. The minimalist H-NTs can assemble at near-physiological salt conditions and will serve as an easily synthesized, DNA-economical modular template for biosensors, plasmonics, or other functional materials and as cost-efficient drug-delivery vehicles for biomedical applications.     

1,4-二氢吡啶衍生物与DNA相互作用的电化学与圆二色谱研究

用电化学和圆二色谱(CD)技术研究了5个1,4-二氢吡啶(1,4-DHP)衍生物与小牛胸腺DNA(CT-DNA)的相互作用.结果表明,1,4-DHP衍生物与CT-DNA相互作用是通过嵌入的方式进行的,相互作用的强弱与1,4-DHP衍生物的立体结构有关.1,4-DHP衍生物4-取代基空间位阻越小,嵌入到CT-DNA的程度越大.相反,空间位阻较大的1,4-DHP衍生物嵌入CT-DNA程度较小.非平面结构的1,4-DHP衍生物使CT-DNA双螺旋链结构松散程度增大.     

The role of cobalt,copper, nickel,and zinc in the DNA replication inhibitory activity of p‐aminophenyl triphenylporphyrin

Cationic porphyrins have been widely used as tumor localizers in cancer therapies. When cationic porphyrins are flat they intercalate with double‐stranded DNA, duplexes of RNA or RNA–DNA. The antitumor activity of some cationic porphyrins depends on their interaction with human telomeric quadruplexes. Here, we report that noncationic meso‐(4‐aminophenyl)triphenylporphyrin (H₂TPPNH₂) ( 3 ) and its cobalt, copper, nickel, and zinc metallo derivatives ( 4 – 7 ) have DNA replication inhibitory activity in B16 mouse melanoma line cells. By means of quantification of ³HdTT radio‐labeled DNA, we observed that the nonplanar porphyrin [CoTPPNH₂] has the highest activity against carcinogenic DNA replication. Copyright © 2004 John Wiley & Sons, Ltd.     

水溶性不对称卟啉及其金属配合物合成及与DNA的 作用

合成并表征了三(4-N-甲基吡啶基)卟啉为母体,带有乙氧羰基甲氧基或羧基甲氧基侧链的水溶正电性卟啉及其金属配合物(M=Cu,Ni),并研究了它们与DNA的相互作用。卟啉对EB－DNA荧光猝灭研究表明：卟啉与DNA作用存在单一结合模式。EB荧光竞争法测得它们与DNA作用的结合常数介于3×10^5～3×10^6L·mol^-1。电子吸收研究谱表明：DNA引起卟啉Soret带的不同程度的红移(≤9nm)和减色(≤35%)。卟啉及其金属配合物都引起DNA的熔点升高(≤2.5℃)和DNA粘度的略微下降。所有这些研究表明：这些带较长侧链的水溶性卟啉及其金属配合物与DNA作用不存在插入作用模式,只是在DNA的外部结合。     

Synthesis,crystal structure,magnetic property,and nuclease activity of a binuclear iron(III) complex

A μ-oxo-di-μ-carboxylato-bridged iron(III) complex containing two tridentate nitrogen ligands, {[Fe₂(bpma)(bpea)(μ-CH₃COO)₂ μ-O)] · (ClO₄)₂ · 0.5CH₃OH} (1) (bpma = N, N-bis(2-pyridylmethyl)methyl-amine, bpea = N,N-bis(2-pyridylmethyl)ethylamine), has been synthesized and determined by X-ray diffraction. Complex 1 crystallizes in the monoclinic space group P2₁/c with a = 10.9434(12) Å, b = 23.118(3) Å, c = 15.8721(18) Å, β = 92.736(2)° and Z = 4. In 1, each Fe(III) has a distorted octahedral geometry with a N₃O₃ donor set. The Fe(III) atoms are bridged by two carboxyl groups and one μ-oxo oxygen with Fe1–Fe2 separation of 3.064 Å. Susceptibility data of 1 indicate strong intramolecular antiferromagnetic coupling of the high-spin Fe(III) atoms with J = ?121.0 cm^?1 and g = 2.04. The interaction with calf thymus DNA was investigated by UV absorption and fluorescent spectroscopy. Results show that the complex binds to ct-DNA with a moderate intercalative mode. The interaction between 1 and pBR322 DNA has also been investigated by submarine gel electrophoresis; the complex exhibits effective DNA cleavage activity in the absence of activating agents under similar physiological conditions.     

Crystallization of DNA‐Capped Gold Nanoparticles in High‐Concentration,Divalent Salt Environments

The multiparametric nature of nanoparticle self‐assembly makes it challenging to circumvent the instabilities that lead to aggregation and achieve crystallization under extreme conditions. By using non‐base‐pairing DNA as a model ligand instead of the typical base‐pairing design for programmability, long‐range 2D DNA–gold nanoparticle crystals can be obtained at extremely high salt concentrations and in a divalent salt environment. The interparticle spacings in these 2D nanoparticle crystals can be engineered and further tuned based on an empirical model incorporating the parameters of ligand length and ionic strength.     

两种三齿多吡啶铜(Ⅱ)配合物的合成、表征及其与DNA的作用

本文合成了2个三齿多吡啶铜(Ⅱ)配合物[Cu(phpi)Cl₂]·H₂O和[Cu(tpy)Cl₂]·2H₂O(phpi=2-(苯并咪唑基-2)-1，10-邻菲咯啉，tpy=2，2:6′，2″-三联吡啶)，并通过元素分析、摩尔电导率、红外光谱、紫外光谱对其进行了表征。应用电子吸收光谱、荧光光谱和粘度法研究了配合物与DNA的相互作用。在抗坏血酸存在下，利用琼脂糖凝胶电泳方法研究了配合物对pBR322 DNA的切割作用并对其作用机理作了初步探讨。     

Copper Coordination Polymers of N1,N4-Bis(pyridin-2-ylmethyl)terephthalamide: Synthesis,Structures, DNA Binding and Cleavage,and Catalytic Activity for Oxidation of 1-Phenylethanol

Two Cu coordination polymers [Cu(bpmt)Cl₂ · 2DMF]_n ( 1 ), [Cu(bpmt)(μ-Cl) · DMSO]_n ( 2 ) [bpmt = N¹,N⁴-bis(pyridin-2-ylmethyl)terephthalamide)], were synthesized and characterized. X-ray single-crystal diffractions revealed complex 1 exhibits a one-dimensional (1D) chain in which central Cu^II ions are located in a six-coordinate slightly distorted octahedral structure. Complex 2 features 1D chain composed of Cu^I–Cl bridges and all the central Cu^I ions are situated a twisted tetrahedral configurations. Multi-spectroscopic DNA interaction studies indicate that the two complexes may bind to DNA via groove binding modes, and the calculated binding constants are 1.42 × 10⁴ ( 1 -CT-DNA) and 1.41 × 10⁴ ( 2 -CT-DNA). Both complexes are also capable of efficiently cleaving plasmid pBR322 DNA in the presence of H₂O₂ via an oxidative mechanism. Furthermore, 1 and 2 are employed as catalysts for the oxidation of 1-phenylethanol to acetophenone. Complex 1 displays good catalytic potential with the conversion rate reaches 99 % using tert-butyl hydroperoxide (TBHP) as oxidant and CH₃CN as solvent at 60 °C for 2.0 h.     

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.