Backbone-extended pyrrolidine peptide nucleic acids (bepPNA): design, synthesis and DNA/RNA binding studies

One-carbon extended conformationally constrained pyrrolidine PNA monomer (bepPNA) has been synthesized, incorporated into PNA sequences at predefined positions, and showed selective RNA binding properties.     

Thiol-derivatized porphyrins: synthesis and design of hybrid nanostructures

The review is devoted to the synthesis of thiol-derivatized porphyrins and hybrid nanostructures manufactured from them. Literature data on the main synthetic strategies towards these compounds are summarized, examples of application of thiol-derivatized porphyrins in nanotechnology are given.     

Organoruthenium(II) thiosemicarbazone complexes: synthesis, spectral characterization, DNA binding and DNA cleavage studies

A series of new ruthenium(II) complexes were synthesized with Schiff bases derived from salicylaldehyde / o-hydroxyacetophenone/ o-vanillin / 2-hydroxy-1-naphthaldehyde with thiosemicarbazide and acetyl furan. They are characterized by elemental analysis, IR, electronic, ¹H NMR, ¹³C NMR and mass spectral studies. The elemental analysis suggests the stoichiometry to be 1:1 (metal:ligand). Four of these complexes were tested for its binding with CT-DNA using absorption spectroscopic studies and two of these complexes exhibit efficient DNA cleavage activity.      

Novel Schiff base metal complexes: synthesis,characterization, DNA binding,DNA cleavage and molecular docking studies

A novel Schiff base, 3-(((1H-1,2,4-triazol-3-yl)imino)methyl)-4H-chromen-4-one (L) was synthesized and used as ligand for the synthesis of Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) complexes. The structural characterization of the ligand and its metal complexes was determined by using various physicochemical and spectroscopic methods. The IR data show that the Schiff base ligand acts as a bidentate donor coordinating through the oxygen atom of the chromone and nitrogen atom of the imine group. Based on all spectral data, tetrahedral geometry has been proposed for all the metal complexes except Cu(II) and Pd(II) complexes. However, square-planar geometry has been proposed for Cu(II) and Pd(II) complexes. DNA binding interaction of the ligand and its metal complexes was investigated by using UV–visible absorption, fluorescence and molecular docking studies. The binding constants were in the order of 10⁴ M^?1 suggesting good binding affinity towards CT-DNA. The DNA cleavage activity of the synthesized compounds was investigated by using agarose gel electrophoresis. In vitro antimicrobial activity of the synthesized compounds were screened against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureu) and two gram-negative bacteria (Escherichia coli, Proteus vulgaris) and one fungi strain Candida albicans using disc diffusion method. Antioxidant activity was carried out by DPPH radical scavenging method. In vitro anti-proliferative activity of the ligand and its metal complexes was also carried on the HEK-293, HeLa, IMR-32 and MCF-7 cancer cell lines using MTT assay.     

Nonequilibrium synthesis and assembly of hybrid inorganic-protein nanostructures using an engineered DNA binding protein

We show that a protein with no intrinsic inorganic synthesis activity can be endowed with the ability to control the formation of inorganic nanostructures under thermodynamically unfavorable (nonequilibrium) conditions, reproducing a key feature of biological hard-tissue growth and assembly. The nonequilibrium synthesis of Cu(2)O nanoparticles is accomplished using an engineered derivative of the DNA-binding protein TraI in a room-temperature precursor electrolyte. The functional TraI derivative (TraIi1753::CN225) is engineered to possess a cysteine-constrained 12-residue Cu(2)O binding sequence, designated CN225, that is inserted into a permissive site in TraI. When TraIi1753::CN225 is included in the precursor electrolyte, stable Cu(2)O nanoparticles form, even though the concentrations of [Cu(+)] and [OH(-)] are at 5% of the solubility product (K(sp,Cu2O)). Negative control experiments verify that Cu(2)O formation is controlled by inclusion of the CN225 binding sequence. Transmission electron microscopy and electron diffraction reveal a core-shell structure for the nonequilibrium nanoparticles: a 2 nm Cu(2)O core is surrounded by an adsorbed protein shell. Quantitative protein adsorption studies show that the unexpected stability of Cu(2)O is imparted by the nanomolar surface binding affinity of TraIi1753::CN225 for Cu(2)O (K(d) = 1.2 x 10(-)(8) M), which provides favorable interfacial energetics (-45 kJ/mol) for the core-shell configuration. The protein shell retains the DNA-binding traits of TraI, as evidenced by the spontaneous organization of nanoparticles onto circular double-stranded DNA.     

Molecular design, chemical synthesis and biological evaluation of quinoxaline-carbohydrate hybrids as novel and selective photo-induced DNA cleaving and cytotoxic agents

The quinoxaline moiety in antitumor quinoxaline antibiotics cleaved double stranded DNA at the 5′ side guanine of the 5′-GG-3′ site upon irradiation with UV light with a long wavelength and without any additive. The quinoxaline-carbohydrate hybrid system was very effective for the DNA cleavage. Furthermore, the quinoxaline-carbohydrate hybrids exhibited strong and selective cytotoxicity against cancer cells with photoirradiation.     

Design, synthesis and binding studies of a novel quadruple ADDA hydrogen-bond array

The design and synthesis of a novel ADDA hydrogen-bond array is described. The ureidodiimidazole motif (UDIM) 2 engages in interactions with complementary diamidonaphthyridine (DAN) 3 motifs with an association constant K(a) = 825 ± 16 M(-1) in chloroform. (1)H NMR and molecular modelling studies were carried out in order to explain the unexpected behaviour of this new supramolecular motif. These revealed that a combination of effects including; an energetic bias for the folded conformer, subtle differences in shape complementarity between the two components and the potential for self-association of UDIM 2 disfavour higher affinity interactions between the two components.     

Discrete DNA three-dimensional nanostructures: the synthesis and applications

Structural DNA nanotechnology, an emerging technique that utilizes the nucleic acid molecule as generic polymer to programmably assemble well-defined and nano-sized architectures, holds great promise for new material synthesis and constructing functional nanodevices for different purposes. In the past three decades, rapid development of this technique has enabled the syntheses of hundreds and thousands of DNA nanostructures with various morphologies at different scales and dimensions. Among them, discrete three-dimensional (3D) DNA nanostructures not only represent the most advances in new material design, but also can serve as an excellent platform for many important applications. With precise spatial addressability and capability of arbitrary control over size, shape, and function, these nanostructures have drawn particular interests to scientists in different research fields. In this review article, we will briefly summarize the development regarding the synthesis of discrete DNA 3D nanostructures with various size, shape, geometry, and topology, including our previous work and recent progress by other groups. In detail, three methods majorly used to synthesize the DNA 3D objects will be introduced accordingly. Additionally, the principle, design rule, as well as pros and cons of each method will be highlighted. As functions of these discrete 3D nanostructures have drawn great interests to researchers, we will further discuss their cutting-edge applications in different areas, ranging from novel material synthesis, new device fabrication, and biomedical applications, etc. Lastly, challenges and outlook of these promising nanostructures will be given based on our point of view.     

Isoquino[4,5-bc]acridines: design, synthesis and evaluation of DNA binding, anti-tumor and DNA photo-damaging ability

Several novel isoquino[4,5-bc]acridine derivatives have been designed and synthesized. Their DNA-binding, anti-tumor and DNA-photo-damaging properties were investigated. A4 exhibited the highest anti-tumor activities against both A 549 (human lung cancer cell) and P388 (murine leukemia cells). All these compounds were found to be more cytotoxic against P388 than against A549. Under 365-nm light irradiation, A3 damaged plasmid DNA pBR322 at <2 microM and cleaved DNA from form I to 100% form II by 50 microM. The mechanism studies revealed that A3 damaged DNA by electron transfer mechanism and singlet oxygen species.     

Development of novel antioxidants: design,synthesis, and reactivity

We are attempting to develop novel synthetic antioxidants aimed at retarding the effects of free-radical induced cell damage. In this paper we discuss the design strategy and report the synthesis of seven novel antioxidants, including six catechols and a benzylic phenol. The bond dissociation enthalpy (BDE) for the most active (weakest) OH bond in each molecule was calculated by theoretical methods, as well as the BDE for the semiquinone radical. Reaction rates with the nitrogen-centered free radical DPPH(*) were measured in ethyl acetate. The log of k(DPPH) for bimolecular reaction correlated well with the primary BDE. The correlation between rate constants and calculated BDEs shows that the BDE is a good predictor of antioxidant activity with DPPH(*), suggesting that our design criteria are useful and that these compounds should undergo further testing in cell cultures and in animal models.     

Metal(II) complexes of bioactive aminonaphthoquinone-based ligand: synthesis,characterization and BSA binding,DNA binding/cleavage,and cytotoxicity studies

An aminonaphthoquinone ligand, L, and its metal complexes of general formula [MLCl₂] {M = Co(II), Ni(II), Cu(II) and Zn(II)} have been synthesized and characterized by analytical and spectral techniques. Tetrahedral geometry has been assigned to Ni(II) and Zn(II) complexes and square planar geometry to Co(II) and Cu(II) complexes on the basis of electronic spectral and magnetic susceptibility data. The binding of complexes with bovine serum albumin (BSA) is relatively stronger than that of free ligand and alters the conformation of the protein molecule. Interaction of these complexes with CT-DNA has been investigated using UV-Vis and fluorescence quenching experiments, which show that the complexes bind strongly to DNA through intercalative mode of binding (K_app 10⁵ M^?1). Molecular docking studies reiterate the mode of binding of these compounds with DNA, proposed by spectral studies. The ligand and its complexes cleave plasmid DNA pUC18 to nicked (Form II) and linear (Form III) forms in the presence of H₂O₂ oxidant. The in vitro cytotoxicity screening shows that Cu(II) complex is more potent against MCF-7 cells and Zn(II) complex exhibits marked cytotoxicity against A-549 cells equal to that of cisplatin. Cell imaging studies suggested apoptosis mode of cell death in these two chosen cell lines.     

Synthesis and DNA binding studies of bis-intercalators with a novel spiro-cyclic linker

Threading polyintercalation has been demonstrated as a unique DNA binding mode in which a polyintercalating moiety threads back and forth through the DNA double helix. This binding topology necessitates linkers residing in both the minor and major grooves in an alternating fashion. In the present work, two novel, rigid, cis and trans oriented spiro-cyclic linkers were synthesized as potential groove binding elements in the context of threading bis-intercalation. Analysis of dissociation kinetics indicated that the cis oriented dimer has dramatically slower dissociation from poly(dGdC) and calf thymus (CT) DNA compared to the trans oriented dimer and a linear dimer control.     

Oxovanadium phenanthroimidazole derivatives: synthesis,DNA binding and antitumor activities

Four unsymmetrical oxovanadium phenanthroimidazole complexes, [VO(hntdtsc)(NPIP)] (1), [VO(hntdtsc)(CPIP)] (2), [VO(hntdtsc)(MEPIP)] (3) and [VO(hntdtsc)(HPIP)] (4) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, NPIP = 2-(4-nitrophenyl)-imidazo[4,5-f]1,10-phenanthroline, CPIP = 2-(4-chlorphenyl)-imidazo[4,5-f]1,10-phenanthroline), MEPIP = 2-(4-methylphenyl)-imidazo[4,5-f]1,10-phenanthroline), HPIP = 2-(4-hydroxylphenyl)-imidazo[4,5-f] 1,10-phenanthroline), have been synthesized and characterized. Their DNA binding and antitumor activities were determined by biochemical methods. All four oxovanadium complexes can bind with CT-DNA by an intercalation model and can also cleave supercoiled plasmid DNA in the presence of H₂O₂. The antitumor properties and mechanism of the complexes have been analyzed by MTT assay, cell cycle analysis, apoptosis assay and Western blot analysis. The results showed that the free ligands and their corresponding complexes all possess antiproliferative activities with very low IC₅₀ values against Hela, BIU-87 and SPC-A-1 cell lines. Complex 1, which has a strongly electron-withdrawing nitro group, exhibited the best antiproliferative activities. Complex 1 caused G₀/G₁ phase arrest of the cell cycle and induced apoptosis in Hela cells. Additionally, complex 1 attenuated the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2).This indicates that inhibition of the ERK1/2 signaling pathway may contribute to the antitumor effects of these complexes.     

Naphthalimide-thiazoles as novel photonucleases: molecular design, synthesis, and evaluation

A new family of photonucleases, naphthalimide-thiazoles was synthesized and evaluated. These compounds intercalated into DNA efficiently and damaged DNA photochemically at concentrations as low as 5 μM. Mechanistic experiment suggests that a novel naphthalimide-thiazole radical produced via an excited triple state might be involved in the DNA photodamage. Different activity may arise from the impact of substituents at 2-phenyl ring of thiazole on the electron population of excited triple state according to AM1 semi-empirical calculation.     

Addressing association entropy by reconstructing guanidinium anchor groups for anion binding: design, synthesis, and host-guest binding studies in polar and protic solutions

The bicyclic hexahydropyrimidino[1,2a]pyrimidine cationic scaffold has a well-known capacity to bind a variety of oxoanions (phosphates, carboxylates, squarates, phosphinates). Based on this feature, the parent host was supplemented with sec-carboxamido substituents to generate compounds 1-3 in an effort to improve the anion-binding affinity and selectivity and to learn about the role and magnitude of entropic factors. Bicyclic guanidinium compounds were prepared by a convergent strategy via the corresponding tetraester 22 followed by catalytic amidation. Host-guest binding studies with isothermal titration calorimetry in acetonitrile probed the behavior of artificial hosts 1-3 in comparison with the tetraallylguanidinium compound 4 on binding p-nitrobenzoate, dihydrogenphosphate, and 2,2'-bisphenolcyclophosphate guests that showed enhanced affinities in the 10(5)-10(6) M(-1) range. Contrary to expectation, better binding emerges from more positive association entropies rather than from stronger enthalpic interactions (hydrogen bonding). In an NMR spectroscopy titration in DMSO, o-phthalate was sufficiently basic to abstract a proton from the guanidinium function, as confirmed by an X-ray crystal structure of the product. The novel carboxamide-appended anchor groups also bind carboxylates and phosphates, but not hydrogen sulfate in methanol with affinities in excess of 10(4) M(-1). The energetic signature of the complexation in methanol is inverted with respect to acetonitrile solvent and shows a pattern of general ion pairing with strong positive entropies overcompensating endothermic binding enthalpies. This study provides an example of the fact that bona fide decoration of a parent guanidinium anchor function with an additional binding functionality may provide the desired enhancement of the host-guest affinity, yet for a different reason than that implemented by design as guided by standard molecular modeling.     

Synthesis,DNA binding,and antimicrobial studies of novel metal complexes containing a pyrazolone derivative Schiff base

A novel series of Co(II), Ni(II), Cu(II), Zn(II), and VO(IV) complexes has been synthesized from the Schiff base derived from 4-[(3,4-dimethoxybenzylidene)amino]-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one and 1,2-diaminobenzene. Structural features were determined by analytical and spectral techniques. Binding of synthesized complexes with calf thymus DNA (CT DNA) was studied by spectroscopic methods and viscosity measurements. Experimental results indicate that the complexes are able to form adducts with DNA and to distort the double helix by changing the base stacking. Lower DNA affinity of the VO(IV) complex is caused by the change of coordination geometry by the vanadyl ion resulting in a somewhat unfavorable configuration for the DNA binding. Oxidative DNA cleavage activities of the complexes were studied with supercoiled (SC) pUC19 DNA using gel electrophoresis; the mechanism studies revealed that the hydroxyl radical is likely to be the reactive species responsible for the cleavage of pUC19 DNA by the synthesized complexes. The in vitro antimicrobial screening effects of the investigated compounds were monitored by the disc diffusion method. The synthesized Schiff base complexes exhibit higher antimicrobial activity than the respective free Schiff base.     

Synthesis and binding studies of novel diethynyl-pyridine amides with genomic promoter DNA G-quadruplexes

Herein, we report the design, synthesis and biophysical evaluation of novel 1,2,3-triazole-linked diethynyl-pyridine amides and trisubstituted diethynyl-pyridine amides as promising G-quadruplex binding ligands. We have used a Cu(I)-catalysed azide-alkyne cycloaddition click reaction to prepare the 1,2,3-triazole-linked diethynyl-pyridine amides. The G-quadruplex DNA binding properties of the ligands have been examined by using a F?rster resonance energy transfer (FRET) melting assay and surface plasmon resonance (SPR) experiments. The investigated compounds are conformationally flexible, having free rotation around the triple bond, and exhibit enhanced G-quadruplex binding stabilisation and specificity between intramolecular promoter G-quadruplex DNA motifs compared to the first generation of diaryl-ethynyl amides (J. Am. Chem. Soc. 2008, 130, 15950-15956). The ligands show versatility in molecular recognition and promising G-quadruplex discrimination with 2-50-fold selectivity exhibited between different intramolecular promoter G-quadruplexes. Circular dichroism (CD) spectroscopic analysis suggested that at higher concentration these ligands disrupt the c-kit2 G-quadruplex structure. The studies validate the design concept of the 1,3-diethynyl-pyridine-based scaffold and demonstrate that these ligands exhibit not only significant selectivity over duplex DNA but also variation in G-quadruplex interaction properties based on small chemical changes in the scaffold, leading to unprecedented differential recognition of different DNA G-quadruplex sequences.     

Structure design of polysaccharides: novel concepts,selective syntheses,high value applications

Using protecting silyl groups, catalyzed transesterification, and stereochemically controlled S_N2 mechanisms examples of well‐defined 2‐, 3‐, 6‐, and 2,6‐ethers, esters, resp. amino derivatives of cellulose, starch, and related polysaccharides have been synthesized and characterized by two‐dimensional NMR spectroscopy. Supramolecularly structured polymer matrices useful in biosensors could be developed by immobilization of enzymes like glucose oxidase and aromatic redox‐chromogenic structures at 6‐deoxy‐6‐(4‐aminophenyl)‐aminocellulose. Cellulose tubes “grown” biotechnologically from D‐glucose in the culture medium of Acetobacter xylinum represent novel types of artificial blood vessels because of their unique highly‐swollen nanofiber network‐structure.     

One-dimensional inorganic nanostructures: synthesis, field-emission and photodetection

One-dimensional inorganic nanostructures have drawn prime attention due to their potential for understanding fundamental physical concepts and constructing nanoscale electronic and optoelectronic devices. This critical review mainly focuses on our recent research progresses in 1D inorganic nanostructures, including their rational synthesis and potential applications, with an emphasis on field-emitter and photodetector applications. Firstly, we will discuss the rational design of synthetic strategies and the synthesis of 1D nanostructures via a vapour phase approach. Secondly, we will present our recent progresses with respect to several kinds of important inorganic nanostructures and their field-emission and photoconductivity characteristics. Finally, we conclude this review with some perspectives/outlook and future research in these fields (212 references).     

Thin metal nanostructures: synthesis,properties and applications

Two-dimensional nanomaterials, especially graphene and single- or few-layer transition metal dichalcogenide nanosheets, have attracted great research interest in recent years due to their distinctive physical, chemical and electronic properties as well as their great potentials for a broad range of applications. Recently, great efforts have also been devoted to the controlled synthesis of thin nanostructures of metals, one of the most studied traditional materials, for various applications. In this minireview, we review the recent progress in the synthesis and applications of thin metal nanostructures with a focus on metal nanoplates and nanosheets. First of all, various methods for the synthesis of metal nanoplates and nanosheets are summarized. After a brief introduction of their properties, some applications of metal nanoplates and nanosheets, such as catalysis, surface enhanced Raman scattering (SERS), sensing and near-infrared photothermal therapy are described.