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.     

Self‐Assembly of a 3D DNA Crystal Structure with Rationally Designed Six‐Fold Symmetry

Programming self‐assembled designer DNA crystals with various lattices and functions is one of the most important goals for nanofabrication using nucleic acids. The resulting porous materials possess atomic precision for several potential applications that rely on crystalline lattices and cavities. Herein, we present a rationally designed and self‐assembled 3D DNA crystal lattice with hexagonal symmetry. In our design, two 21‐base oligonucleotides are used to form a duplex motif that further assembles into a 3D array. The interactions between the strands are programmed using Watson–Crick base‐pairing. The six‐fold symmetry, as well as the chirality, is directed by the Holliday junctions formed between the duplex motifs. The rationally designed DNA crystal provides a new avenue that could create self‐assembled macromolecular 3D crystalline lattices with atomic precision. In addition, the structure contains a highly organized array of well‐defined cavities that are suitable for future applications with immobilized guests.     

Structural and electronic property responses to the arsenic/phosphorus exchange in GC‐related DNA of the B‐form

The suggestion that phosphorus/arsenic replacement in DNA can play a role in living things has generated great controversy (Wolfe‐Simon et al., Science 2011, 332, 1163). Examined here theoretically are substitution effects on Watson–Crick base pairing and base stacking patterns in realistic DNA subunits. Using duplex DNA models deoxyguanylyl‐3′,5′‐deoxycytidine ([dGpdC]₂) and deoxycytidyly‐3′,5′‐deoxyguanosine ([dCpdG)]₂), this research reveals that the geometric variations caused by the As/P exchange are small and are limited to the phosphate/arsenate groups. As/P replacement leads to alterations of ～0.15 Å in P/As? O bond lengths and less than 1.5° variations in O? P/As? O angles. The Watson–Crick base pairing and base stacking patterns are independent of the As/P replacement. The vertical electron detachment energies are also largely unaffected. However, the electron capture ability of the DNA units is improved by the As substitution. The arsenate is found to be the main electron acceptor in As‐DNA. The results are relevant to the possible existence of viable As‐DNAs, at least in the guanine and cytosine (GC)‐related B‐form DNA. © 2012 Wiley Periodicals, Inc. J Comput Chem, 2012     

Bifacial Base‐Pairing Behaviors of 5‐Hydroxyuracil DNA Bases through Hydrogen Bonding and Metal Coordination

A novel bifacial ligand‐bearing nucleobase, 5‐hydroxyuracil ( U^OH ), which forms both a hydrogen‐bonded base pair ( U^OH –A) and a metal‐mediated base pair ( U^OH –M– U^OH ) has been developed. The U^OH –M– U^OH base pairs were quantitatively formed in the presence of lanthanide ions such as Gd^III when U^OH – U^OH pairs were consecutively incorporated into DNA duplexes. This result established metal‐assisted duplex stabilization as well as DNA‐templated assembly of lanthanide ions. Notably, a duplex possessing U^OH –A base pairs was destabilized by addition of Gd^III ions. This observation suggests that the hybridization behaviors of the U^OH ‐containing DNA strands are altered by metal complexation. Thus, the U^OH nucleobase with a bifacial base‐pairing property holds great promise as a component for metal‐responsive DNA materials.     

Binding Cofactors with Triplex‐Based DNA Motifs

Cofactors are pivotal compounds for the cell and many biotechnological processes. It is therefore interesting to ask how well cofactors can be bound by oligonucleotides designed not to convert but to store and release these biomolecules. Here we show that triplex‐based DNA binding motifs can be used to bind nucleotides and cofactors, including NADH, FAD, SAM, acetyl CoA, and tetrahydrofolate (THF). Dissociation constants between 0.1 μM for SAM and 35 μM for THF were measured. A two‐nucleotide gap still binds NADH. The selectivity for one ligand over the others can be changed by changing the sequence of the binding pocket. For example, a mismatch placed in one of the two triplets adjacent to the base‐pairing site changes the selectivity, favoring the binding of FAD over that of ATP. Further, changing one of the two thymines of an A‐binding motif to cytosine gives significant affinity for G, whereas changing the other does not. Immobilization of DNA motifs gives beads that store NADH. Exploratory experiments show that the beads release the cofactor upon warming to body temperature.     

Hetero‐Selective DNA‐Like Duplex Stabilized by Donor–Acceptor Interactions

We report on the characterization of a novel hetero‐selective DNA‐like duplex of pyrene and anthraquinone pseudo base pairs. The pyrene/anthraquinone pairs showed excellent selectivity in hetero‐recognition and even trimers were found to form a hetero‐duplex. Pyrene and anthraquinone moieties were tethered on acyclic D ‐threoninol linkers and linked to adjacent residues by using standard phosphoramidite chemistry. When pyrene and anthraquinone were incorporated at pairing positions in complementary strands of natural DNA oligonucleotides, the duplex was stabilized significantly. Moreover, a pyrene hexamer and an anthraquinone hexamer formed a stable artificial hetero‐duplex without the assistance of natural base pairs. The pyrene/anthraquinone pair was so stable that even trimers formed a hetero‐duplex under conditions in which natural DNA strands of three residues do not.     

Synthesis,Characterization, Crystal Structure,and Biological Activities of Transition Metal Complexes with 1‐Phenyl‐3‐methyl‐5‐hydroxypyrazole‐4‐methylene‐8′‐quinolineimine

The Schiff base ligand, 1‐phenyl‐3‐methyl‐5‐hydroxypyrazole‐4‐methylene‐8′‐quinolineimine, and its Cu^II, Zn^II, and Ni^II complexes were synthesized and characterized. The crystal structure of the Zn^II complex was determined by single‐crystal X‐ray diffraction, indicating that the metal ions and Schiff base ligand can form mononuclear six‐coordination complexes with 1:1 metal‐to‐ligand stoichiometry at the metal ions as centers. The binding mechanism and affinity of the ligand and its metal complexes to calf thymus DNA (CT DNA) were investigated by UV/Vis spectroscopy, fluorescence titration spectroscopy, EB displacement experiments, and viscosity measurements, indicating that the free ligand and its metal complexes can bind to DNA via an intercalation mode with the binding constants at the order of magnitude of 105–106 M ^–1, and the metal complexes can bind to DNA more strongly than the free ligand alone. In addition, antioxidant activities of the ligand and its metal complexes were investigated through scavenging effects for hydroxyl radical in vitro, indicating that the compounds show stronger antioxidant activities than some standard antioxidants, such as mannitol. The ligand and its metal complexes were subjected to cytotoxic tests, and experimental results indicated that the metal complexes show significant cytotoxic activity against lung cancer A 549 cells.     

The Spermine–Bisaryl Conjugate as a Potent Inducer of B‐ to Z‐DNA Transition

DNA containing alternating purine and pyrimidine repeats has the potential to adopt the Z‐DNA structure, one of the well‐studied structures besides A‐ and B‐DNA. Despite a number of molecular models that have been proposed to explain the mechanism for B→Z transition, there is continued discussion on the mechanism and physiological role of this transition. In this study, we have found that the bis(2‐naphthyl)‐maleimide–spermine conjugate ( 3 c ) exhibits a remarkable ability to cause the B→Z transition of d(CGCGCG)₂ at low salt concentrations. Using isothermal titration calorimetry (ITC) we show that the B→Z transition induced by 3 c is both enthalpically and entropically favorable. The ligand might effect the dehydration of B‐DNA, which leads to the B→Z transition. Interestingly, an intermediate CD between the B and Z forms was observed in the pH‐dependent transition in the presence of the ligand. The unique structure and characteristics of the ligand designed in this investigation will be useful for the study of Z‐DNA.     

Quadracyclic Adenine: A Non‐Perturbing Fluorescent Adenine Analogue

Fluorescent‐base analogues (FBAs) comprise a group of increasingly important molecules for the investigation of nucleic acid structure and dynamics as well as of interactions between nucleic acids and other molecules. Here, we report on the synthesis, detailed spectroscopic characterisation and base‐pairing properties of a new environment‐sensitive fluorescent adenine analogue, quadracyclic adenine (qA). After developing an efficient route of synthesis for the phosphoramidite of qA it was incorporated into DNA in high yield by using standard solid‐phase synthesis procedures. In DNA qA serves as an adenine analogue that preserves the B‐form and, in contrast to most currently available FBAs, maintains or even increases the stability of the duplex. We demonstrate that, unlike fluorescent adenine analogues, such as the most commonly used one, 2‐aminopurine, and the recently developed triazole adenine, qA shows highly specific base‐pairing with thymine. Moreover, qA has an absorption band outside the absorption of the natural nucleobases (>300 nm) and can thus be selectively excited. Upon excitation the qA monomer displays a fluorescence quantum yield of 6.8 % with an emission maximum at 456 nm. More importantly, upon incorporation into DNA the fluorescence of qA is significantly less quenched than most FBAs. This results in quantum yields that in some sequences reach values that are up to fourfold higher than maximum values reported for 2‐aminopurine. To facilitate future utilisation of qA in biochemical and biophysical studies we investigated its fluorescence properties in greater detail and resolved its absorption band outside the DNA absorption region into distinct transition dipole moments. In conclusion, the unique combination of properties of qA make it a promising alternative to current fluorescent adenine analogues for future detailed studies of nucleic acid‐containing systems.     

Synthesis,Characterization, and DNA Binding Studies of a Nickel(II) Complex Containing the 1,3‐Bis(1‐propylbenzimidazol‐2‐yl)‐2‐oxapropane

A complex of formula [Ni(pobb)₂](pic)₂, (pobb = 1,3‐bis(1‐propylbenzimidazol‐2‐yl)‐2‐oxapropane, pic = 2,4,6‐trinitrophenol), has been synthesized and structurally characterized by physico‐chemical and spectroscopic methods. The crystals crystallize in the monoclinic system, space group C2/c, a = 25.766(11) Å, b = 14.943(7) Å, c = 19.543(14) Å, α = 90°, β = 129.722(4)°, γ = 90°, Z = 4. The coordination environment around nickel(II) atom can be described as a distorted octahedral geometry. The interactions of the ligand pobb and the nickel (II) complex with calf thymus DNA (CT‐DNA) are investigated by using electronic absorption titration, ethidium bromide‐DNA displacement experiments and viscosity measurements. The experimental evidence indicated the compounds interact with calf thymus DNA through intercalation.     

Some divalent metal(II) complexes of novel potentially tetradentate Schiff base N,N′‐bis(2‐carboxyphenylimine)‐2,5‐thiophenedicarboxaldhyde: Synthesis,spectroscopic characterization and bioactivities

A novel tetradentate dianionic Schiff base ligand, N ,N ′‐bis(2‐carboxyphenylimine)‐2,5‐thiophenedicarboxaldhyde (H₂L) and some first row d‐transition metal chelates (Co(II), Cu(II), Ni(II) and Zn(II)) were synthesized and characterized using various physicochemical and spectroscopic methods. The spectroscopic data suggested that the parent Schiff base ligand coordinates through both deprotonated carboxylic oxygen and imine nitrogen atoms. The free Schiff base and its metal chelates were screened for their antimicrobial activities for various pathogenic bacteria and fungi using the agar well diffusion method. The antibacterial and antifungal activities of all the newly synthesized compounds are significant compared to the standard drugs ciprofloxacin and nystatin. The antioxidant activities of the compounds were determined by reduction of 1,1‐diphenyl‐2‐picrylhydrazyl and compared with that of vitamin C as a standard. DNA binding ability of the novel Schiff base and its complexes was investigated using absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and thermal denaturation. The obtained results clearly demonstrate that the binding affinity with calf thymus DNA follows the order: Cu(II) complex > Ni(II) complex > Zn(II) complex > Co(II) complex >H₂L. Furthermore, the DNA cleavage activity of the newly synthesized ligand and its metal complexes was investigated using supercoiled plasmid DNA (pUC18) gel electrophoresis.     

An Adamantane‐Based Building Block for DNA Networks

DNA governs the storage and transfer of genetic information through generations in all living systems with the exception of some viruses. Its physicochemical nature and the Watson–Crick base pairing properties allow molecular constructions at nanometer length, thereby enabling the design of desired structural motifs, which can self‐assemble to form large supramolecular arrays and scaffolds. The tailor‐made DNAs have been an interesting material for such designed nanoscale constructions. However, the synthesis of specific structures with a desired molecular function is still in its infancy and therefore has to be further explored. To add a new dimension to this approach, we have synthesized a rigid three‐way branched adamantane motif, which is capable of forming highly stable DNA networks. The moiety generated could serve as a useful building block for DNA‐based nanoconstructions.     

Thermodynamic and Mechanistic Insights into Translesion DNA Synthesis Catalyzed by Y‐Family DNA Polymerase Across a Bulky Double‐Base Lesion of an Antitumor Platinum Drug

To determine how the Y‐family translesion DNA polymerase η (Polη) processes lesions remains fundamental to understanding the molecular origins of the mutagenic translesion bypass. We utilized model systems employing a DNA double‐base lesion derived from 1,2‐GG intrastrand cross‐links of a new antitumor Pt^II complex containing a bulky carrier ligand, namely [PtCl₂(cis‐1,4‐dach)] (DACH=diaminocyclohexane). The catalytic efficiency of Polη for the insertion of correct dCTP, with respect to the other incorrect nucleotides, opposite the 1,2‐GG cross‐link was markedly reduced by the DACH carrier ligand. This reduced efficiency of Polη to incorporate the correct dCTP could be due to a more extensive DNA unstacking and deformation of the minor groove induced in the DNA by the cross‐link of bulky [PtCl₂(cis‐1,4‐dach)]. The major products of the bypass of this double‐base lesion produced by [PtCl₂(cis‐1,4‐dach)] by Polη resulted from misincorporation of dATP opposite the platinated G residues. The results of the present work support the thesis that this misincorporation could be due to sterical effects of the bulkier 1,4‐DACH ligand hindering the formation of the Polη–DNA–incoming nucleotide complex. Calorimetric analysis suggested that thermodynamic factors may contribute to the forces that governed enhanced incorporation of the incorrect dATP by Polη as well.     

Pentopyranosyl Oligonucleotide Systems,Communication No. 10 , The α‐L‐Lyxopyranosyl‐(4′→2′)‐oligonucleotide System

To determine whether the remarkable chemical properties of the pyranosyl isomer of RNA as an informational Watson‐Crick base‐pairing system are unique to the pentopyranosyl‐(4′→2′)‐oligonucleotide isomer derived from the RNA‐building block D ‐ribose, studies on the entire family of diastereoisomeric pyranosyl‐(4′→2′)‐oligonucleotide systems deriving from D ‐ribose, L ‐lyxose, D ‐xylose, and L ‐arabinose were carried out. The result of these extended studies is unambiguous: not only pyranosyl‐RNA, but all members of the pentopyranosyl‐(4′→2′)‐oligonucleotide family are highly efficient Watson‐Crick base‐pairing systems. Their synthesis and pairing properties will be described in a series of publications in this journal. The present paper describes the α‐L ‐lyxopyranosyl‐(4′→2′)‐system.     

Two‐ and Three‐Dimensional Molecular Organization of Schiff‐Base Derivatives

We have designed and synthesized a series of Schiff base derivatives, and studied their structural features in two‐dimensional (2D) and three‐dimensional (3D) states by combining scanning tunneling microscopy (STM) and X‐ray diffraction experiments. The Schiff‐base derivatives with short alkyl chains crystallize easily, which allows a detailed structural analysis by X‐ray diffraction. Due to the strong adsorbate–substrate interactions, those bases with long alkyl chains easily form 2D assemblies on highly oriented pyrolytic graphite (HOPG). The STM images indicate also that the introduction of two methoxy groups into the molecule can change the structure of these 2D assemblies as a result of the increased steric hindrances, for example: the Schiff‐base derivative, bearing both methoxy groups and C₁₆H₃₃ tails, forms 2D Moiré patterns, and an alignment of pairing Schiff‐base molecules may be easily resolved. Conversely, the Schiff base derivative, bearing solely C₁₆H₃₃ tails, forms 2D non‐Moiré patterns. It is demonstrated that the 3D structural features result from the compromise of intermolecular interactions of different molecular moieties. However, there is one more factor, which also governs the 2D structure: the adsorbate‐substrate interaction. The 3D crystal structure may thus help to understand many factors involved in the formation of 2D structures, and would be helpful for designing new molecular assemblies with tailoring functions.     

Ionic‐liquid‐assisted desorption of DNA from polyamidoamine‐grafted silica nanoparticles surface by a low‐salt solution

We studied the influences of imidazolium‐based ionic liquids as additives in low ionic strength phosphate solution on releasing DNA from polyamidoamine dendrimer‐grafted silica nanoparticle surfaces. The effects of the side‐chain length of the imidazolium group, the anion and the concentration of the ionic liquid, the generation of the dendrimer, and the pH and the concentration of the release solution were investigated. It was found that addition of 4 mM 1‐hexyl‐3‐methylimidazolium bromide to 5 mM phosphate at pH 11 could markedly promote the desorption of DNA fragments, with a desorption efficiency of 99.0%. Compared with the conventional strategies employing high‐salt solutions or elevated temperature for acceptable recoveries, the method described here enabled quick release of DNA fragments that permitted direct, accurate analysis, and further treatment without desalting.     

An Isosteric and Fluorescent DNA Base Pair Consisting of 4‐aminophthalimide and 2,4‐diaminopyrimidine as C‐Nucleosides

A 13mer DNA duplex containing the artificial 4‐aminophthalimide:2,4‐diaminopyrimidine (4AP:DAP) base pair in the central position was characterized by optical and NMR spectroscopy. The fluorescence of 4AP in the duplex has a large Stokes shift of Δλ =124 nm and a quantum yield of Φ _F=24 %. The NMR structure shows that two interstrand hydrogen bonds are formed and confirms the artificial base pairing. In contrast, the 4‐N ,N ‐dimethylaminophthalimide moiety prefers the syn conformation in DNA. The fluorescence intensity of this chromophore in DNA is very low and the NMR structure shows no significant interaction with DAP. Primer‐extension experiments with DNA polymerases showed that not only is the 4AP C nucleotide incorporated at the desired position opposite DAP in the template, but also that the polymerase is able to progress past this position to give the full‐length product. The observed selectivity supports the NMR results.     

A DNA Structure Containing AgI‐Mediated G:G and C:C Base Pairs

Metal‐mediated base pairs have been extensively utilized in many research fields, including genetic‐code extension, novel therapeutics development, and nanodevice design. Compared to other cations, Ag^I is more flexible in pairing with natural base pairs. Herein, we present a DNA structure containing two C‐Ag^I‐C pairs and the first reported G‐Ag^I‐G pair in a short 8mer DNA strand. This structure not only provides detailed insight into these Ag^I‐mediated base‐pairing patterns in DNA, but also represents the first nonhelical DNA structure driven by heavy‐metal ions, thus further contributing to the structural diversity of DNA. This unique complex structure is highly sequence‐dependent, thus implying functional potentials as a new DNA aptamer that can bind and recognize silver ions. These results not only advance our understanding of the interactions between Ag^I and nucleobases, but also provide a unique structural component for the rational design of new DNA nanodevices.