•Two planar Pt complexes efficiently stabilize both DNA and RNA G-quadruplexes (GQ).•Pt complexes have the stabilizing preference towards antiparallel GQ topology.•Alkyl tail from coordination core interacted with GQ loops to recognize topology.•The Pt complexes exhibited high potential cytotoxicity towards cancer cells.Two platinum complexes with an aza-bridged bis(1,10-phenanthrolin-2-yl)amine (bpa) were synthesized. The two phenanthrolines in bpa entered a flat plane prior to binding of nucleic acids, which bestowed on the two Pt complexes a significantly high stabilizing ability on both DNA and RNA G-quadruplexes. Further extending alkyl tail from aromatic coordination core enabled the complexes to distinguish GQ sequence based upon the topological folding structures and enhanced the selectivity of the complex against duplex DNA. This study paved the way to develop Pt complexes as GQ stabilizers for specific folding topology and the applications to disease and/or personalized anticancer medicine/therapy.The two (1,10‐phenanthrolin‐2‐yl)amine (bpa) ligands in [Pt(bpa)]2+ complexes entered a flat plane prior to binding nucleic acids, bestowing the two Pt complexes with a high stabilizing ability on DNA and RNA G‐quadruplexes. The aromatic coordination core with extending alkyl tail can distinguish G‐quadruplex sequences based upon the topological folding structures.

A series of octahedral Ru(II) complexes with an x–y planar tetradentate and two trans-z-axis ammonia ligands were synthesized. High stabilization of G-quadruplexes was achieved upon π-stacking with aromatic planar ligands. Unique interaction from z-axis ligands bestowed both excellent binding resistance to duplex DNA and selectivity towards the antiparallel topology.

The unfolding pathway of human telomeric i-motifs was monitored by both monomer and exciplex fluorescence of in-stem thiazole orange. A uniform triplex intermediate was observed upon unfolding i-motifs against either pH or thermal denaturation.

Multi-interlocked circular DNA structures have been in high demand for fabricating complicated functional DNA architectures and nanodevices such as molecular switches, shuttles, and motors. Even though various innovative methods have been developed in the past, creation of multi-interlocked circular DNA structures with defined numbers of DNA molecules and linking patterns is still a challenging task nowadays. Here, we propose a top-down decatenation of kinetoplast DNA as a new approach for creating multi-interlocked circular DNA structures. Through optimizing the amount and reaction time of topoisomerase II, we synthesized completely mutually interlocked tricircular, tetra-circular, and oligo-circular DNA structures, which have not yet been acquirable through any other existing synthetic means. The catenation structures of multiple circular DNA were further verified through atomic force microscopic analysis of the backbone overlapping patterns and the circumference. It accordingly is our expectation that the top-down enzymatic approaches could offer a highly interlocked network with defined numbers of circular DNA with simple protocols, and could consequently be beneficial to the design and fabrication of sophisticated functional molecules and nanodevices in the areas of supramolecular chemistry, DNA nanotechnology, and material science.

Thermodynamic stability of hydroxymethylcytosine (hmC) containing CpG repeats showed that though hmC destabilizes hypomethylated CpG, this effect can be reversed in a heavily methylated duplex. This dual-epigenetic modulation on duplex stability was also observed in cellular-mimic crowding conditions for both A-form DNA–RNA hybrids and B-form DNA–DNA duplexes.

Electron conductivity of duplex DNA has promising applications in fabricating DNA based biosensors and electronic devices for biomimic solar cells. However, in aqueous solution DNA-mediated electron transfer (ET) is often far from ideal for these applications. We reported here that in hydrated ionic liquids (IL) electron can propagate through 4 nm of duplex DNA, and higher ET efficiency was achieved over longer distance which yielded a noncanonical negative distance decay parameter (γ = −0.02 Å–1). Fluorescence studies and ET efficiency of duplex DNA in IL-D2O revealed that the binding of both cationic and anionic species of hydrated IL in DNA minor groove and the exclusion of water from the DNA hydration layer significantly improved base-pair stacking of duplex DNA to achieve efficient electric conductivity. As an oxidation reaction of nucleic acids, efficient DNA ET observed here suggested that IL could be a promising nonorganic and nonaqueous solvent for redox reactions of biomacromolecules.Keywords: Anthraquinone; Conductive biomolecule; Deuterium water; DNA minor groove binder; Electron transport; Ionic liquids;

The two important epigenetic markers in the human genome, 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC), are involved in gene regulation processes. As a major epigenetic target, cytosines in a C-rich DNA sequence were substituted with mC and hmC to investigate the thermal stability and pH sensitivity of the corresponding i-motifs. Circular Dichroism (CD) studies indicate the formation of i-motifs at acidic pH (<6.5) for mC- and hmC-modified DNA sequences. Thermal denaturation results suggest that DNA i-motifs are stabilized when modified with one or two mCs. However, hypermethylation with mC and single modification with hmC cause destabilization of the structure. A biomimetic crowding agent does not alter the stability effect trends resulting from mC and hmC modifications, though the corresponding i-motifs show elevated melting temperatures without significant changes in pKa values.

Exaggerated radical-induced DNA damage under magnetic fields is of great concern to medical biosafety and biomolecular electronic devices. In this report, the effects of an external magnetic field (MF) on DNA electronic conductivity were investigated by studying the efficiencies of photoinduced DNA-mediated charge transport (CT) via guanine damage. Under a static MF of 300 mT, positive enhancements in the decomposition of 8-cyclopropyldeoxyguanosine (8CPG) were observed at both the proximal and distal guanine doublets, indicating a more efficient propagation of radical cations and higher electronic conductivity of duplex DNA. MF-assisted CT has shown sensitivity to magnetic field strength, duplex structures, and the integrity of base pair stacking. Spin evolution of charge injection and the alignment of base pairs to the CT-active conformation during radical propagation were proposed to be the two major factors that MF contributes to facilitate DNA-mediated CT. Herein, MF-assisted CT may offer a new avenue for designing DNA-based electronic devices and unraveling MF effects on redox and radical relevant biological processes.

An oxidation-based synthetic approach was developed for facile preparation of 5-formyl-2′-deoxycytidine and 5-hydroxymethyl-2′-deoxycytidine phosphoramidites. Upon introducing organic solvent components and copper catalysts, C5-methyl groups of 5-methyl-2′-deoxycytidine and thymidine were readily oxidized to formyl and hydroxyl functionality, respectively. Standard solid phase DNA synthesis and conventional deprotection methods were applicable to synthesize 5-formyl- or 5-hydroxymethyl-cytosine containing DNA oligonucleotides, which were used to study the effect of epigenetic modifications on DNA thermal dynamic stability.

A fluorescent exciplex of thiazole orange (TO) is formed in a single-dye conjugated DNA i-motif. The exciplex fluorescence exhibits a large Stokes shift, high quantum yield, robust response to pH oscillation and little structural disturbance to the DNA quadruplex, which can be used to monitor the folding of high-order DNA structures.

A new G-quadruplex (GQ) stabilizer, [Pt(Dip)2](PF6)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), is prepared by the microwave irradiation method. The complex can highly stabilize G-quadruplex, but has negligible interactions with duplex DNA. Aromatic anchors on the polypyridyl ligands bestow the stabilizer with a high binding preference towards parallel GQ.

We report stimuli-responsive core–satellite assemblies of binary gold nanoparticles, linked by i-motif DNA, for live cell plasmonic imaging of pH changes in the endocytic pathway.

It was demonstrated in our studies that norfloxacin, a representative member of quinolone antibiotics, can indeed stabilize the gyrase–DNA complex formed during enzymatic cycle. In addition, the formation of the drug-induced complex has been firstly visualized through our atomic force microscopic examination.

Human Topoisomerase I (hTopo I) have been known as a potential target for cancer therapy. A series of duplex DNA with different intrinsic curvatures have been designed as inhibitors to hTopo I. The activities of hTopo I on relaxing supercoiled plasmid pUC 19 are apparently diminished in the presence of the curved DNA. More potent inhibitions and smaller IC50 are achieved by duplex DNA with higher curvatures. EMSA indicates that hTopo I can recognize the curved DNA through binding interactions. Our studies demonstrate that the activity of hTopo I can be modulated by the intrinsic curvature of linear DNA and provide a new avenue to design curved DNA as hTopo I inhibitors with high therapeutic efficiency and low toxicity.Our studies demonstrate that the activity of hTopo I can be modulated by the intrinsic curvature of linear DNA and provide a new avenue to design curved DNA as hTopo I inhibitors with high therapeutic efficiency and low toxicity.

A series of forcible curved circular DNAs (cDNAs) were prepared to investigate the recognition features of human Topoisomerase I (hTopo I). The IC50 can be modulated by the curvature degrees of cDNA. In addition, preferential bindings of hTopo I to cDNA with high curvature have been observed by AFM and EMSA.

A series of forcible curved circular DNAs (cDNAs) were prepared to investigate the recognition features of human Topoisomerase I (hTopo I). The IC50 can be modulated by the curvature degrees of cDNA. In addition, preferential bindings of hTopo I to cDNA with high curvature have been observed by AFM and EMSA.

We report stimuli-responsive core–satellite assemblies of binary gold nanoparticles, linked by i-motif DNA, for live cell plasmonic imaging of pH changes in the endocytic pathway.

A series of octahedral Ru(II) complexes with an x–y planar tetradentate and two trans-z-axis ammonia ligands were synthesized. High stabilization of G-quadruplexes was achieved upon π-stacking with aromatic planar ligands. Unique interaction from z-axis ligands bestowed both excellent binding resistance to duplex DNA and selectivity towards the antiparallel topology.

A new G-quadruplex (GQ) stabilizer, [Pt(Dip)2](PF6)2 (Dip: 4,7-diphenyl-1,10-phenanthroline), is prepared by the microwave irradiation method. The complex can highly stabilize G-quadruplex, but has negligible interactions with duplex DNA. Aromatic anchors on the polypyridyl ligands bestow the stabilizer with a high binding preference towards parallel GQ.

A fluorescent exciplex of thiazole orange (TO) is formed in a single-dye conjugated DNA i-motif. The exciplex fluorescence exhibits a large Stokes shift, high quantum yield, robust response to pH oscillation and little structural disturbance to the DNA quadruplex, which can be used to monitor the folding of high-order DNA structures.

The two important epigenetic markers in the human genome, 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC), are involved in gene regulation processes. As a major epigenetic target, cytosines in a C-rich DNA sequence were substituted with mC and hmC to investigate the thermal stability and pH sensitivity of the corresponding i-motifs. Circular Dichroism (CD) studies indicate the formation of i-motifs at acidic pH (<6.5) for mC- and hmC-modified DNA sequences. Thermal denaturation results suggest that DNA i-motifs are stabilized when modified with one or two mCs. However, hypermethylation with mC and single modification with hmC cause destabilization of the structure. A biomimetic crowding agent does not alter the stability effect trends resulting from mC and hmC modifications, though the corresponding i-motifs show elevated melting temperatures without significant changes in pKa values.

The unfolding pathway of human telomeric i-motifs was monitored by both monomer and exciplex fluorescence of in-stem thiazole orange. A uniform triplex intermediate was observed upon unfolding i-motifs against either pH or thermal denaturation.