Sequence-specific binding behavior of coralyne toward triplex DNA: An ultrafast time-resolved fluorescence spectroscopy study.

Triplex DNA structure has potential therapeutic application in inhibiting the expression of genes involved in cancer and other diseases. As a DNA-targeting antitumor and antibiotic drug, coralyne shows a remarkable binding propensity to triplex over canonical duplex and thus can modulate the stability of triplex structure, providing a prospective gene targeting strategy. Much less is known, however, about coralyne-binding interactions with triplex. By combining multiple steady-state spectroscopy with ultrafast fluorescence spectroscopy, we have investigated the binding behaviors of coralyne with typical triplexes. Upon binding with a G-containing triplex, the fluorescence of coralyne is markedly quenched owing to the photoinduced electron transfer (PET) of coralyne with the G base. Systematic studies show that the PET rates are sensitive to the binding configuration and local microenvironment, from which the coexisting binding modes of monomeric (full and partial) intercalation and aggregate stacking along the sugar-phosphate backbone are distinguished and their respective contributions are determined. It shows that coralyne has preferences for monomeric intercalation within CGG triplex and pure TAT triplex, whereas CGC+ triplex adopts mainly backbone binding of coralyne aggregates due to charge repulsion, revealing the sequence-specific binding selectivity. The triplex-DNA-induced aggregation of coralyne could be used as a probe for recognizing the water content in local DNA structures. The strong π-π stacking of intercalated coralyne monomer with base-triplets plays an important role in stabilizing the triplex structure. These results provide mechanistic insights for understanding the remarkable propensity of coralyne in selective binding to triplex DNA and shed light on the prospective applications of coralyne-triplex targeted anti-gene therapeutics.

Free-Radical-Mediated Photoinduced Electron Transfer between 6-Thioguanine and Tryptophan Leading to DNA-Protein-Like Cross-Link.

The nucleobase analog 6-thioguanine (6-TG) has emerged as important immunosuppressant, anti-inflammatory, and anticancer drug in the past few decades, but its unique photosensitivity of absorbing strongly ultraviolet UVA light elicits photochemical hazards in many ways. The particularly intriguing yet unresolved question is whether the direct photoreaction of 6-TG can promote DNA-protein cross-links (DPCs) formation, which are large DNA adducts blocking DNA replication and physically impede DNA-related processes. Herein, by real-time observation of radical intermediates using time-resolved UV-vis absorption spectroscopy in conjunction with product analysis by HPLC-MS, we discover that UVA excitation of 6-TG triggers direct covalent cross-linking with tryptophan (TrpH) via an exquisite radical mechanism of electron transfer. The photoexcitation prepares the redox-active triplet 36-TG*, which initiates electron transfer with TrpH, creating TrpH•+ and 6-TG•- in the first step. The deprotonated Trp• undergoes radical-recombination with its geminate partner 6-TG•- and eliminates a H2S, leading to the cross-linking product 6-TG-Trp. The photoadduct structures (two chiral isomers and one constitutional isomer) are identified unambiguously, validating further the mechanism. These findings pinpoint the exact amino acid that is vulnerable to photo-cross-linking with 6-TG and establish a mechanistic framework for understanding mutagenic DPCs formation and developing photoprobes based on this new type of photo-cross-linking.

Deprotonation of Guanine Radical Cation G•+ Mediated by the Protonated Water Cluster.

Proton transfer is regarded as a fundamental process in chemical reactions of DNA molecules and continues to be an active research theme due to the connection with charge transport and oxidation damage of DNA. For the guanine radical cation (G•+) derived from one-electron oxidation, experiments suggest a facile proton transfer within the G•+:C base pair, and a rapid deprotonation from N1 in free base or single-strand DNA. To address the deprotonation mechanism, we perform a thorough investigation on deprotonation of G•+ in free G base by combining density functional theory (DFT) and laser flash photolysis spectroscopy. Experimentally, kinetics of deprotonation is monitored at temperatures varying from 280 to 298 K, from which the activation energy of 15.1 ± 1.5 kJ/mol is determined for the first time. Theoretically, four solvation models incorporating explicit waters and the polarized continuum model (PCM), i.e., 3H2O-PCM, 4H2O-PCM, 5H2O-PCM, and 7H2O-PCM models are used to calculate deprotonation potential energy profile, and the barriers of 5.5, 13.4, 14.4, and 13.7 kJ/mol are obtained, respectively. It is shown that at least four explicit waters are required for properly simulating the deprotonation reaction, where the participation of protonated water cluster plays key roles in facilitating the proton release from G•+.

Solution-Processed Sensing Textiles with Adjustable Sensitivity and Linear Detection Range Enabled by Twisting Structure.

Wearable strain sensors are emerging rapidly for their promising applications in human motion detection for diagnosis, healthcare, training instruction, and rehabilitation exercise assessment. However, it remains a bottleneck in gaining comfortable and breathable devices with the features of high sensitivity, linear response, and tunable detection range. Textiles possess fascinating advantages of good breathability, aesthetic property, tailorability, and excellent mechanical compliance to conformably attach to human body. As the meandering loops in a textile can be extended in different directions, it provides plenty of room for exploring ideal sensors by tuning a twisting structure with rationally selected yarn materials. Herein, textile sensors with twisting architecture are designed via a solution-based process by using a stable water-based conductive ink that is composed of polypyrrole/polyvinyl alcohol nanoparticles with a mean diameter of 50 nm. Depending on the predesigned twisting models, the thus-fabricated textile sensors show adjustable performances, exhibiting a high sensitivity of 38.9 with good linearity and a broad detection range of 200%. Such sensors can be integrated into fabrics and conformably attached to skin for monitoring subtle (facial expressions, breathing, and speaking) and large (stretching, jumping, running and jogging, and sign language) human motions. As a proof-of-concept application, by integrating with a wireless transmitter, the signals detected by our sensors during exercise (e.g., running) can be remotely received and displayed on a smartphone. It is believed that the integration of our textile sensors with selected twisting models into a cloth promises full-range motion detection for wearable electronics and human-machine interfaces.

pH Controlled Intersystem Crossing and Singlet Oxygen Generation of 8-Azaadenine in Aqueous Solution.

Azabases are intriguing DNA and RNA analogues and have been used as effective antiviral and anticancer medicines. However, photosensitivity of these drugs has also been reported. Here, pH-controlled intersystem crossing (ISC) process of 9H 8-azaadenine (8-AA) in aqueous solution is reported. Broadband transient absorption measurements reveal that the hydrogen atom at N9 position can greatly affect ISC of 8-AA and ISC is more favorable when 8-AA is in its neutral form in aqueous solution. The initial excited ππ* (S2 ) state evolves through ultrafast internal conversion (IC) (4.2 ps) to the lower-lying nπ* state (S1 ), which further stands as a door way state for ISC with a time constant of 160 ps. The triplet state has a lifetime of 6.1 µs. On the other hand, deprotonation at N9 position promotes the IC from the ππ* (S2 ) state to the ground state (S0 ) and the lifetime of the S2 state is determined to be 10 ps. The experimental results are further supported by time-dependent density functional theory (TDDFT) calculations. Singlet oxygen generation yield is measured to be 13.8 % for the neutral 8-AA while the deprotonated one exhibit much lower yield (<2 %), implying that this compound could be a potential pH-sensitized photodynamic therapy agent.