A pair of chiral zinc porphyrin cages with a monomeric reference have been prepared, and differences in photophysical behaviors have been systematically explored.

The pharmaceutically active compound atenolol, a kind of β-blockers, may result in adverse effects both for human health and ecosystems if it is excreted to the surface water resources. To effectively remove atenolol in the environment, both direct and indirect photodegradation, driven by sunlight play an important role. Among indirect photodegradation, singlet oxygen (1O2), as a pivotal reactive species, is likely to determine the fates of atenolol. Nevertheless, the kinetic information on the reaction of atenolol with singlet oxygen has not been well investigated and the reaction rate constant is still ambiguous. Herein, the reaction rate constant of atenolol with singlet oxygen is investigated directly through observing the decay of the 1O2 phosphorescence at 1270 nm. It is determined that the reaction rate constant between atenolol and 1O2 is 7.0×105 (mol/L)−1·s−1 in D2O, 8.0×106 (mol/L)−1·s−1 in acetonitrile, and 8.4×105 (mol/L)−1·s−1 in EtOH, respectively. Furthermore, the solvent effects on the title reaction were also investigated. It is revealed that the solvents with strong polarity and weak hydrogen donating ability are suitable to achieve high rate constant values. These kinetics information on the reaction of atenolol with singlet oxygen may provide fundamental knowledge to the indirect photodegradation of β-blockers.

Artemisinin is an excellent antimalarial drug widely used in clinical medicine. However, due to the limitation of natural source of artemisinin, the chemical synthesis of artemisinin has achieved substantial attention. Dihydroartemisinic acid is a key precursor for the synthesis of artemisinin. The reaction of dihydroartemisinic acid with singlet oxygen to form peroxide is a pivotal step in the photochemical preparation of artemisinin. Nevertheless, the reaction kinetics of dihydroartemisinic acid with singlet oxygen has not been investigated previously. Herein, we report the rate constants of the reaction between dihydroartemisinic acid and singlet oxygen. By directly detecting the luminescence decay kinetics of singlet oxygen at 1270 nm at room temperature, the reaction rate constants of singlet oxygen and dihydroartemisinic acid in different solvents are obtained to be 1.81×105 (mol/L)−1·s−1 in CCl4, 5.69×105 (mol/L)−1·s−1 in CH3CN, and 3.27×106 (mol/L)−1·s−1 in DMSO, respectively. It is found that the reaction rate constants of dihydroartemisinic acid with singlet oxygen increase as polarity of the solvent increases among the three solvents. These results provide fundamental knowledge to optimize experiment conditions of photochemical synthesis of artemisinin for improving the yields of artemisinin.

The investigation on the catalytic properties of porous organic cages is still in an initial stage. Herein, the reaction of cyclohexanediamine with 5,15-di[3’,5’-diformyl(1,1’-biphenyl)]porphyrin affords a porphyrin tubular organic cage, PTC-1(2H). Transient absorption spectroscopy in solution reveals much prolonged triplet lifetime of PTC-1(2H) relative to monomer reference, illustrating the unique photophysical behavior of cagelike photosensitizer. The long triplet lifetime ensures high-efficiency singlet oxygen evolution according to homogeneous photo-bleach experiment, electron spin-resonance spectroscopy, and aerobic photo-oxidation of benzylamine. Furthermore, microporous supramolecular framework of PTC-1(2H) is able to promote the heterogeneous photo-oxidation of various primary amines with conversion efficiency above 99% under visible light irradiation. These results indicate the great application potentials of porous organic cages in heterogeneous phase.

Gold nanoparticles (AuNPs) have unique optical properties because of their characteristic localized surface plasmon resonances (LSPRs). Upon the excitation of LSPR, AuNPs can affect the adjacent organic molecules strongly in both the ground state and the excited state. Previously, only 2-3 fold of the plasmon enhancement effect on triplet state formation was displayed because of the random and uncontrollable formation of AuNP aggregates. Here, we utilize polymer PDDA to assemble AuNPs forming aggregates with strong plasmonic resonance. By means of transient UV-visible absorption spectroscopy, the triplet state of rose bengal enhanced by PDDA-AuNPs is directly monitored and the maximum enhancement is found to be similar to 10 fold. The large enhancement should be mainly resulted from the plasmon effect of AuNP aggregates. Additionally, it is found that the triplet state enhancement effect of PDDA-assembled AuNPs is sensitive to concentration of the polymer and the size of AuNPs. These findings shed light on the applications of AuNPs in triplet-triplet energy transfer, triplet exciton harvesting, and photodynamic therapy.

Abstract 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. The crucial sulphur-centered hemi-bonded intermediates -P–S∴S–P- were observed and found to play critical roles leading to the stable adducts of -P–S–S–P-, which are backbone DNA lesion products. Moreover, the oxidation of the PS moiety in dinucleotides d[GPSG], d[APSA], d[GPSA], d[APSG] and in S-oligomers was monitored in real-time, showing that PS oxidation can compete with adenine but not with guanine. Significantly, hole transfer process from A+• to PS and concomitant -P–S∴S–P- formation was observed, demonstrating the base-to-backbone hole transfer unique to S-DNA, which is different from the normally adopted backbone-to-base hole transfer in native DNA. These findings reveal the distinct backbone lesion pathway brought by the PS modification and also imply an alternative -P–S∴S–P-/-P–S–S–P- pathway accounting for the interesting protective role of PS as an oxidation sacrifice in bacterial genome.

RNA-protein interactions are inevitably existing in many fundamental biological processes of organisms and it is an effective method to investigate the nature of RNA-protein interactions through crosslinking induced by photoactivation. Therefore, it is of great importance to detect the crucial transient intermediates to elucidate the mechanism of photo crosslinking between RNA and proteins, which will shed light on regulating the crosslinking sites as well as the favorable cross-linked amino acids. In this research, we choose the photoactivatable ribonucleotide analog, 4-thiouracil, and the aromatic amino acid, tryptophan, as a model system to study, from which the photo crosslinking is found to be initiated by the electron transfer as the first step. By means of the nanosecond time-resolved laser flash photolysis, the key intermediates of photo-induced electron transfer from tryptophan to the triplet of 4-thiouracil, 4-thiouracil anion radical (4-TU center dot-) and tryptophan cation radical (TrpH(center dot+)) are observed, as well as the deprotonated species of tryptophan neutral radical (Trp(center dot)). By monitoring the 4-TU triplet decay kinetics, the pseudo-first order rate constant of photo-induced electron transfer is determined to be 2.88x10(9) L center dot mol(-1)center dot s(-1) and found to be diffusion-controlled. The pH-effect on the electron transfer and proton transfer have been further examined. In addition, the driving force for electron transfer from tryptophan to 4-TU triplet is estimated using the classic Rehm-Weller empirical equation to be -0.15 eV, which means the photo-induced electron transfer process is favorable thermodynamically. These results demonstrate that photo-induced electron transfer between 4-thiouracil triplet and tryptophan is the key step, which can trigger the following proton transfer and radical coupling processes and lead to the covalent photoadducts. These studies provide a basis for mechanistic understandings of photo crosslinking between RNA and proteins in more complex system.

Gold nanoparticle modifications for TiO2 (Au/TiO2) can extend the absorption wavelength from UV to visible (Vis) and enhance the photocatalytic performance, thus fueling increasing attention as an emerging photocatalysis strategy. To explore the plasmon-enhanced photocatalytic mechanism and directly unveil the intrinsic properties of Au/TiO2, the decay kinetics of photoelectrons upon UV (355 nm) or Vis (532 nm) excitation are monitored by means of nanosecond time-resolved infrared spectroscopy, which is a unique tool offering observations without interference of the holes. Under UV irradiation, the longer lifetime of photoelectrons observed in Au/TiO2 compared to that in bare TiO2 provides unambiguous evidence for the enhanced charge separation by AuNPs. Under Vis irradiation, the long-lived (hundreds of microseconds) electrons produced by injection from here detected for the first time. Moreover, the effects of TiO2 phase composition decay kinetics of long-lived photoelectrons are examined. AuNPs into TiO2 upon plasmon excitation are and the amount of AuNPs loading on the decay kinetics of long-lived photoelectrons are examined.

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. Comprehensive time-resolved spectroscopy were performed to track C•+ dynamics in i-motif and in free base dC. The competing pathways of deprotonation (1.4 × 107 s-1), tautomerization (8.8 × 104 s-1), and hydration (5.3 × 103 s-1) are differentiated, and their rate constants are determined for the first time, underlining the strong reactivity of C•+. Distinct pathway is observed in i-motif compared with dC, showing the prominent features of C•+ hydration forming C(5OH)• and C(6OH)•. By further experiments of pH-dependence, comparison with single strand, and with Ag+ mediated i-motif, the mechanisms of C•+ degradation in i-motif are disclosed. The hydrogen-bonding within C(H)+:C plays a significant role in guiding the reaction flux, by blocking the tautomerization of C(-H)• and reversing the equilibrium from C(-H)• to C•+. The C radicals in i-motif thus retain more cation character, and are mainly subject to hydration leading to lesion products that can induce disruption of i-motif structure and affect its critical roles in gene-regulation.

Exposure of DNA to one-electron oxidants leads initially to the formation of guanine radical cations (G•+), which may degrade by deprotonation or hydration and ultimately cause strand breaks or 8-oxoG lesions. As the structure is dramatically changed by binding of the third strand in the major groove of the target duplex, it makes the triplex an interesting DNA structure to be examined and compared with the duplex on the G•+ degradation pathways. Here, we report for the first time the time-resolved spectroscopy study on the G•+ reaction dynamics in triplex DNA together with the Fourier transform infrared characterization of steady-state products, from which structural effects on the reactivity of G•+ are unraveled. For an antiparallel triplex-containing GGC motif, G•+ mainly suffers from fast deprotonation (9.8 ± 0.2) × 106 s-1, featuring release of both N1-H and N2-H of G in the third strand directly into bulk water. The much faster and distinct deprotonation behavior compared to the duplex should be related to long-resident water spines in the third strand. The G•+ hydration product 8-oxoG is negligible for an antiparallel triplex; instead, the 5-HOO-(G-H) hydroperoxide formed after G•+ deprotonation is identified by its vibrational marker band. In contrast, in a parallel triplex (C+GC), the deprotonation of G•+ occurs slowly (6.0 ± 0.3) × 105 s-1 with the release of N1-H, while G•+ hydration becomes the major pathway with yields of 8-oxoG larger than in the duplex. The increased positive charge brought by the third strand makes the G radical in the parallel triplex sustain more cation character and prone for hydration. These results indicate that non-B DNA (triplex) plays an important role in DNA damage formation and provide mechanistic insights to rationalize why triplex structures might become hot spots for mutagenesis.

Thiobase derivatives have received important investigations due to their wide usage as phototherapeutic agents and their potential carcinogenic side effects as immunosuppressants. The substitution of oxygen atom by the sulfur atom makes the ultraviolet absorption of thiobases redshifted and absorbs UVA light (>300 nm), resulting in unusual high quantum yield of triplet state to generate the singlet oxygen (1O2) through photosensitization. As a type of reactive oxygen species, 1O2 is highly reactive toward thiobases. Herein, we report the measurements of reaction rate constants between different thiobases and 1O2 in different solvents through the direct detection of 1O2 luminescence decay kinetics at 1270 nm. The rate constants of thiouracils with 1O2 are five times smaller than that of thioguanine with 1O2, which suggests that thiopurines are more reactive than thiopyrimidines and thus less suitable to be a photosensitive drug on the application of photodynamic therapy. Additionally, the rate constants of thiobases and 1O2 were found to be obviously influenced by the solvent polarity. With the increase of solvent polarity, the rate constants of thiobases and 1O2 decrease.

Nucleic acids are the most important biomolecules, which function to express, store and transmit genetic information. The major radiation damages to the living things are essentially relative to the physical and chemical reactions of nucleic acids. Therefore, interests in photochemical reaction dynamics of nucleic acids have been intensified in recent years with the development of powerful experimental and computational techniques, boosting a challenging and promising subfield of chemical reaction dynamics interdisciplinary with molecular biology. In this context, we have made great efforts in developing the transient spectroscopic methods, particularly time-resolved infrared, to investigate the excited state and free radical reaction dynamics involved in the photochemical reactions of nucleic acid bases and DNA secondary structures (duplex, quadruplex etc.). By capturing the fast chemical events of these key short-lived transient species and combining quantum chemical calculations, we revealed the reaction mechanisms of [2+2] photocycloaddition, spore photoproduct (SP) photolesion, electron transfer, proton transfer, photosensitization, ROS oxidation, and photocleavage that are closely associated with the crosslink or oxidative DNA damages. The key roles of non-adiabatic surface intersections, excited state electronic structure property, conformation of secondary structure, base-pairing, π-stacking, and hydrogen-bonding in affecting the photochemical reaction pathways are elucidated. Our results provided important chemical insights to understand the DNA damage at the molecular and quantum state specific levels. This review mainly summarizes the recent progress made by our groups and the related work in literatures.

Recognition of unusual left-handed Z-DNA by specific binding of small molecules is crucial for understanding biological functions in which this particular structure participates. Recent investigations indicate that zinc cationic porphyrin (ZnTMPyP4) is promising as a probe for recognizing Z-DNA due to its characteristic chiroptical properties upon binding with Z-DNA. However, binding mechanisms of the ZnTMPyP4/Z-DNA complex remain unclear. By employing time-resolved UV-visible absorption spectroscopy in conjunction with induced circular dichroism (ICD), UV-vis, and fluorescence measurements, we examined the binding interactions of ZnTMPyP4 towards B-DNA and Z-DNA. For the ZnTMPyP4/Z-DNA complex, two coexisting binding modes were identified as the electrostatic interaction between pyridyl groups and phosphate backbones, and the major groove binding by zinc(II) coordinating with the exposed guanine N7. The respective contribution of each mode is assessed, allowing a complete scenario of binding modes revealed for the ZnTMPyP4/Z-DNA. These interaction modes are quite different from those (intercalation and partial intercalation modes) for the ZnTMPyP4/B-DNA complex, thereby resulting in explicit differentiation between B-DNA and Z-DNA. Additionally, the binding interactions of planar TMPyP4 to DNA were also investigated as a comparison. It is shown that without available virtual orbitals to coordinate, TMPyP4 binds with Z-DNA solely in the intercalation mode, as with B-DNA, and the intercalation results in a structural transition from Z-DNA to B-ZNA. These results provide mechanistic insights for understanding ZnTMPyP4 as a probe of recognizing Z-DNA and afford a possible strategy for designing new porphyrin derivatives with available virtual orbitals for the discrimination of B-DNA and Z-DNA.

G-rich and C-rich DNA can fold into the tetrastranded helical structures G quadruplex or C quadruplex (i-motif), which are considered to be specific drug targets for cancer therapy. A large number of small molecules (so-called ligands), which can bind and modulate the stability of G quadruplex structures, have been widely examined. Much less is known, however, about the ligand binding interactions with the C quadruplex (i-motif). By combining steady-state measurements (UV/Vis, fluorescence, and induced circular dichroism (ICD)) with time-resolved laser flash photolysis spectroscopy, we have studied the binding interactions of cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21 H,23 H-porphyrin, abbreviated as TMPyP4) with i-motifs (C3 TA2 )3 C3 T and (C4 A4 C4 )2. The intercalation binding mode through π-π stacking of the porphyrin macrocycle and the C:C+ hemiprotonated base pair has been identified for the first time. The coexistent binding modes of intercalation (≈80 %) versus external major-groove binding (≈20 %) have been determined quantitatively, thereby allowing a fuller understanding of the porphyrin-i-motif interactions. The ionic strength was found to play an important role in affecting affects the binding modes, with the progressive increase in the ionic strength resulting in the gradual decrease in the intercalation percentage and an increase in the groove-binding percentage. Furthermore, an extended study of the porphyrin derivative with four bulky side-arm substituents (T4) suggests a complete prohibition of the intercalation mode owing to large steric hindrance, thereby providing a novel groove-binding ligand with site selectivity. These results provide in-depth mechanistic insights to better understand the ligand interactions with i-motifs and guidance for related applications in anticancer drug design.

The interaction of ligands with G-quadruplexes has attracted considerable attention due to its importance in molecular recognition and anticancer drugs design. Here, we utilize triplet excited state as a sensitive reporter to study the binding interaction of zinc cationic porphyrin (ZnTMPyP4) with three G-quadruplexes, AG3(T2AG3)3, (G4T4G4)2, and (TG4T)4. By monitoring the triplet decay dynamics of ZnTMPyP4 with transient absorption spectroscopy, the coexisted binding modes via π-π stacking of porphyrin macrocycle and the G-quartets are allowed to be identified quantitatively, which involve intercalation (25% and 36%) versus end-stacking (75% and 64%) for AG3(T2AG3)3 and (G4T4G4)2, and end-stacking (23%) versus partial intercalation (77%) for (TG4T)4. It is shown that the steric hindrance of the axial water decreases greatly the percentage of intercalation. Further, a rapid assessment of binding stoichiometry is fulfilled by measuring the triplet decay dynamics under various [G-quadruplex]/[ZnTMPyP4] ratios. The binding stoichiometric ratios of G-quadruplex/ZnTMPyP4 are 1:2 for AG3(T2AG3)3, 1:1 for (G4T4G4)2, and 1:2 for (TG4T)4, which agree well with results obtained by the conventional method of continuous variation analysis. These results reveal a clear scenario of G-quadruplex/ZnTMPyP4 interaction and provide mechanistic insights for the application of anticancer drug designs using G-quadruplex as target.

The key radical ion-pair transient in DNA guanine oxidation is directly observed at low temperature by time-resolved spectroscopy.

5-Iodouracil (5-IU) can be integrated into DNA and acts as a UV sensitive chromophore suitable for probing DNA structure and DNA-protein interactions based on the photochemical reactions of 5-IU. Here, we perform joint studies of time-resolved Fourier transform infrared (TR-FTIR) spectroscopy and ab initio calculations to examine the state-specific photochemical reaction mechanisms of the 5-IU. The fact that uracil (U) is observed in TR-FTIR spectra after 266 nm irradiation of 5-IU in acetonitrile and ascribed to the product of hydrogen abstraction by the uracil-5-yl radical (U·) provides experimental evidence for the C-I bond homolysis of 5-IU. The excited state potential energy curves are calculated with the complete active space second-order perturbation//complete active space self-consistent field method, from which a singlet predissociation mechanism is elucidated. It is shown that the initially populated 1(ππ*) state crosses with the repulsive 1(πσ*) or 1(nIσ*) state, through which 5-IU undergoes dissociation to the fragments of (U·) radical and iodine atom. In addition, the possibility of intersystem crossing (ISC) is evaluated based on the calculated vertical excitation energies. Although a probable ISC from 1(ππ*) state to 3(nOπ*) and then to the lowest triplet 3(ππ*) could occur in principal, there is little possibility for the excited state populations bifurcating to triplet manifold, given that the singlet state predissociation follows repulsive potential and should occur within dozens to hundreds of femtoseconds. Such low population of triplet states means that the contribution of triplet state to photoreactions of 5-IU should be quite minor. These results demonstrate clearly a physical picture of C-I bond homolysis of 5-IU and provide mechanistic illuminations to the interesting applications of 5-IU as photoprobes and in radiotherapy of cancer.

The rich photo-oxidation pathways and products of terrylenediimide (TDI) with singlet oxygen ((1)O2) have been examined by powerful computational approaches. Potential energy profiles and product fluorescence properties are characterized. A variety of new products are unraveled and predicted to emit fluorescence at both visible and near-infrared ranges, which could open the possibility for interesting applications of using TDI as a fluorescence probe for the single-molecule detection of (1)O2 and designing multicolor photoconvertible fluorophores based on (1)O2 oxidation.

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 0.64-0.99 with the order Gd-1<Gd-2<Gd-3<Gd-4. The gradually enhanced (1) O2 sensitization after β-oxazolone moiety replacement was ascribed to the narrowing of the energy gap (ΔE) between the lowest triplet states (T1 ) of the ligand and the energy level of the (1) Δg →(3) Σg transition of (1) O2 . In particular, Gd-4 is capable of excitation in the visible to NIR region (400-700 nm) with a quantum yield near unity. These Gd complexes were first demonstrated as efficient photosensitizers in photocatalysis such as oxidative C-H bond functionalization of secondary or tertiary amines, and the oxygenation of the natural product cholesterol. Finally, after glycosylation, these water-soluble Gd complexes showed potential applications in photodynamic therapy (PDT) in HeLa cells. This work revealed that Gd(III) complexes of "bioinspired" β-modified porpholactones are efficient NIR photosensitizers and form a chemical basis to construct appealing photocatalysts and theranostic agents based on lanthanides.