Ultrafast Cycloreversion of Thymine-Toluene [2 + 2] Cycloadducts by DNA Photolyase.

DNA photolyases use blue light and fully reduced flavin cofactor to repair UV-induced cyclobutane pyrimidine dimers (CPD) formed between two adjacent thymine bases in DNA. Thymine can form [2 + 2] cyclobutane adducts with its biological isosteres like toluene upon UV irradiation, resulting in chemically different analogues of CPD. Here, we investigated the cycloreversion reactions of two such adducts formed between thymine and toluene, T<>Tol, catalyzed by a class-I CPD photolyase.

Protonation Weakens the Influence of Ribose on Triplet Decay of 2-Thiocytidine.

Long-lived triplet states are critical intermediates of thiobases for their applications in photodynamic therapy and as photoprobes for DNA/RNA-protein interactions, where thiobases are embedded in DNA/RNA and exist as thionucleosides. However, sugar moieties accelerate triplet decay rates, which is a common issue that must be resolved for thionucleosides. Here, we explore whether protonation of 2-thiocytosine (2tCyt) and 2-thiocytidine (2tCyd) under acidic pH can alter their triplet decays.

Multiphoton tandem photoredox catalysis of [Ir(dFCFppy)(dtbbpy)] facilitating radical acylation reactions.

Photoredox catalytic radical acylation reactions, utilizing [Ir(dFCFppy)(dtbbpy)] (IrIII) as the photocatalyst and α-keto acids as the starting substrates, have recently emerged as an attractive strategy for preparing ketone derivatives. While there is consensus on the importance of detailed mechanistic insights to maximize the formation of desired products, efforts focused on uncovering the underlying elementary mechanisms of IrIII photocatalytic radical acylation reactions are still lacking. Herein, using time-resolved spectroscopy, we observed the efficient quenching of the triplet state, IrIII*, electron transfer from α-keto acids, resulting in the generatation of the reduced IrII.

Dual Functionality of 6-Methylthioguanine: Synergistic Effects Enhancing the Photolability of DNA Nucleobases.

A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising applications in photochemotherapy treatment of cancers or pathogens. However, single substitution confers only limited phototoxicity to DNA. Herein, we combine femtosecond and nanosecond time-resolved spectroscopy with high-level calculations to disentangle the excited-state dynamics of 6-methylthioguanine (me6-TG) under variable wavelength UVA excitation (310-330 nm).

Complexed Photosensitizer of Hypericin with G-Quadruplex: Structure-Dependent Behavior.

Despite the increased interest of visible-light-absorbing compound Hypericin (Hyp) in photodiagnosis, photocatalysis, and photodynamic therapy (PDT) applications, a major obstacle still exists; i.e., the photoactivity is diminished due to the facile aggregation of Hyp in aqueous environment that induces excited-state quenching.

Fluorescence Quenching Dynamics of 2-Amino-7-methyl-1,8-naphthyridine in Abasic-Site-Containing DNA Duplexes for Nucleobase Recognition.

Dramatic fluorescence quenching of small heterocyclic ligands trapped in the abasic site (AP) of DNA has been implemented as an unprecedented strategy recognizing single-base mutations in sequence analysis of cancer genes. However, the key mechanisms governing selective nucleobase recognition remain to be disentangled. Herein, we perform fluorescence quenching dynamics studies for 2-amino-7-methyl-1,8-naphthyridine (AMND) in well-designed AP-containing DNA single/double strands.

Can methylated purine bases act as photoionization hotspots?

The direct photoionization of DNA canonical bases under ultraviolet radiation is difficult due to the high ionization potentials. According to previous quantum chemical calculations, methylation can have great influence on the ionization potential. Are methylated nucleobases prone to photoionization and cause DNA damage? As an important epigenetic modification in transcription, expression, and regulation of genes, it is of great biological significance to explore the effect of methylation on base photoionization from the experimental perspective.

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.

TiO as a Nanozyme Mimicking Photolyase to Repair DNA Damage.

Cyclobutane pyrimidine dimer (CPD) is the most abundant DNA photolesion, and it can be repaired by photolyases based on electron-transfer mechanisms. However, photolyase is absent in the human body and lacks stability for applications. Can one develop natural enzyme mimetics utilizing nanoparticles (termed nanozymes) to mimic photolyase in repairing DNA damage? Herein, we observe the successful reversal of thymine dimer T<>T to normal T base by TiO under UVA irradiation.

Low Energy Photoionization of Phosphorothioate DNA-Oligomers and Ensuing Hole Transfer.

Phosphorothioate (PS) modified oligonucleotides (S-DNA) naturally exist in bacteria and archaea genome and are widely used as an antisense strategy in gene therapy. However, the introduction of PS as a redox active site may trigger distinct UV photoreactions. Herein, by time-resolved spectroscopy, we observe that 266 nm excitation of S-DNA d(A) and d(AA) leads to direct photoionization on the PS moiety to form hemi-bonded -P-S∴S-P- radicals, in addition to A base ionization to produce A/A(-H).

Atomic structure of a seed-sized gold nanoprism.

The growth of nanoparticles along one or two directions leads to anisotropic nanoparticles, but the nucleation (i.e., the formation of small seeds of specific shape) has long been elusive.

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.

Effect of single electrons on the excited state dynamics of rod-shaped Au nanoclusters.

The excited state dynamics of small-sized metal nanoclusters are dependent on their crystal structures, while the effect of the charge state remains largely unknown. Here, we report the influence of single electrons on the excited-state dynamics of non-superatom Au clusters by comparing the transient absorption isotropy and anisotropy dynamics of two rod-shaped Au nanoclusters protected by organic ligands. Two decay lifetimes (0.

Reactivity and DNA Damage by Independently Generated 2'-Deoxycytidin-4-yl Radical.

Oxidative stress produces a variety of radicals in DNA, including pyrimidine nucleobase radicals. The nitrogen-centered DNA radical 2'-deoxycytidin-4-yl radical (dC·) plays a role in DNA damage mediated by one electron oxidants, such as HOCl and ionizing radiation. However, the reactivity of dC· is not well understood.

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.

One-electron oxidation of TAT-motif triplex DNA and the ensuing Hoogsteen hydrogen-bonding dissociation.

One-electron oxidation of adenine (A) leads initially to the formation of adenine radical cation (A). Subsequent deprotonation of A can provoke deoxyribonucleic acid (DNA) damage, which further causes senescence, cancer formation, and even cell death. However, compared with considerable reports on A reactions in free deoxyadenosine (dA) and duplex DNA, studies in non-B-form DNA that play critical biological roles are rare at present.

Sulfur-centered hemi-bond radicals as active intermediates in S-DNA phosphorothioate oxidation.

Phosphorothioate (PS) modifications naturally appear in bacteria and archaea genome and are widely used as antisense strategy in gene therapy. But the chemical effects of PS introduction as a redox active site into DNA (S-DNA) is still poorly understood. Herein, we perform time-resolved spectroscopy to examine the underlying mechanisms and dynamics of the PS oxidation by potent radicals in free model, in dinucleotide, and in S-oligomer.

Degradation of Cytosine Radical Cations in 2'-Deoxycytidine and in i-Motif DNA: Hydrogen-Bonding Guided Pathways.

Radical cations of nucleobases are key intermediates causing genome mutation, among which cytosine C is of growing importance because the ensuing cytosine oxidation causes GC → AT transversions in DNA replication. Although the chemistry and biology of steady-state C oxidation products have been characterized, time-resolved study of initial degradation pathways of C is still at the preliminary stage. Herein, we choose i-motif, a unique C-quadruplex structure composed of hemiprotonated base pairs C(H):C, to examine C degradation in a DNA surrounding without interference of G bases.

Probing Laser-Induced Heterogeneous Microenvironment Changes in Room-Temperature Ionic Liquids.

Modulating the heterogeneous microenvironment in room-temperature ionic liquids (RTILs) by external stimuli is an important approach for understanding and designing external field-induced chemical reactions in natural and applied systems. Here, we report for the first time the redistribution of oxygen molecules related to microstructure changes in RTILs induced by an external laser field, which is probed simultaneously by the triplet-state dynamics of porphyrin. A remarkably long-lived triplet state of porphyrin is observed with changes of microstructures after irradiation, suggesting that charge-shifted O molecules are induced by the external field and/or rearranged intrinsic ions move from nonpolar domains into the polar domains of RTILs through electrostatic interactions.

Capturing the radical ion-pair intermediate in DNA guanine oxidation.

Although the radical ion pair has been frequently invoked as a key intermediate in DNA oxidative damage reactions and photoinduced electron transfer processes, the unambiguous detection and characterization of this species remain formidable and unresolved due to its extremely unstable nature and low concentration. We use the strategy that, at cryogenic temperatures, the transient species could be sufficiently stabilized to be detectable spectroscopically. By coupling the two techniques (the cryogenic stabilization and the time-resolved laser flash photolysis spectroscopy) together, we are able to capture the ion-pair transient G⋯Cl in the chlorine radical-initiated DNA guanine (G) oxidation reaction, and provide direct evidence to ascertain the intricate type of addition/charge separation mechanism underlying guanine oxidation.

Gadolinium(III) Porpholactones as Efficient and Robust Singlet Oxygen Photosensitizers.

Construction of Gd(III) photosensitizers is important for designing theranostic agents owing to the unique properties arising from seven unpaired f electrons of the Gd(3+) ion. Combining these with the advantages of porpholactones with tunable NIR absorption, we herein report the synthesis of Gd(III) complexes Gd-1-4 (1, porphyrin; 2, porpholactone; 3 and 4, cis- and trans-porphodilactone, respectively) and investigated their function as singlet oxygen ((1) O2 ) photosensitizers. These Gd complexes displayed (1) O2 quantum yields (ΦΔ s) from 0.

Ultrafast Investigation of Intramolecular Charge Transfer and Solvation Dynamics of Tetrahydro[5]-helicene-Based Imide Derivatives.

We report the excited-state intramolecular charge transfer (ICT) characteristics of four tetrahydro[5] helicene-based imide (THHBI) derivatives with various electron-donating substitutes in different polarity of solvents using steady-state, time-resolved transient absorption (TA) spectroscopy. It is found that, the small bathochromic-shift of the absorption spectra but large red shift of the emission spectra for all dyes with increasing solvent polarity indicates the larger dipole moment of the excited state compared to ground state. The results of theoretical calculations exhibit the charge transfer from the terminal donors to helical backbone, which accounts for the degrees of red shift of the emission spectra from different extent of ICT nature.

Direct observation of guanine radical cation deprotonation in G-quadruplex DNA.

Although numerous studies have been devoted to the charge transfer through double-stranded DNA (dsDNA), one of the major problems that hinder their potential applications in molecular electronics is the fast deprotonation of guanine cation (G(+•)) to form a neutral radical that can cause the termination of hole transfer. It is thus of critical importance to explore other DNA structures, among which G-quadruplexes are an emerging topic. By nanosecond laser flash photolysis, we report here the direct observation and findings of the unusual deprotonation behavior (loss of amino proton N2-H instead of imino proton N1-H) and slower (1-2 orders of magnitude) deprotonation rate of G(+•) within G-quadruplexes, compared to the case in the free base dG or dsDNA.