Antenna Effect in Noble Metal-Free Dye-Sensitized Photocatalytic Systems Enhances CO2 -to-CO Conversion.

Dye-sensitized photocatalytic systems (DSPs) have been extensively investigated for solar-driven hydrogen (H2 ) evolution. However, their application in carbon dioxide (CO2 ) reduction remains limited. Furthermore, current solar-driven CO2 -to-CO DSPs typically employ rhenium complexes as catalysts. In this study, we have developed DSPs that incorporate noble metal-free components, specifically a zinc-porphyrin as photosensitizer (PS) and a cobalt-quaterpyridine as catalyst (CAT). Taking a significant stride forward, we have achieved an antenna effect for the first time in CO2 -to-CO DSPs by introducing a Bodipy as an additional chromophore to enhance light harvesting efficiency. The energy transfer from Bodipy to zinc porphyrin resulted in remarkable stability (turn over number (TON)=759 vs. CAT), and high CO evolution activity (42 mmol g-1 h-1 vs. CAT).

Guanine Radicals Induced in DNA by Low-Energy Photoionization.

Guanine (G) radicals are precursors to DNA oxidative damage, correlated with carcinogenesis and aging. During the past few years, we demonstrated clearly an intriguing effect: G radicals can be generated upon direct absorption of UV radiation with energy significantly lower than the G ionization potential. Using nanosecond transient absorption spectroscopy, we studied the primary species, ejected electrons and guanine radicals, which result from photoionization of various DNA systems in aqueous solution.The DNA propensity to undergo electron detachment at low photon energies greatly depends on its secondary structure. Undetected for monomers or unstacked oligomers, this propensity may be 1 order of magnitude higher for G-quadruplexes than for duplexes. The experimental results suggest nonvertical processes, associated with the relaxation of electronic excited states. Theoretical studies are required to validate the mechanism and determine the factors that come into play. Such a mechanism, which may be operative over a broad excitation wavelength range, explains the occurrence of oxidative damage observed upon UVB and UVA irradiation.Quantification of G radical populations and their time evolution questions some widespread views. It appears that G radicals may be generated with the same probability as pyrimidine dimers, which are considered to be the major lesions induced upon absorption of low-energy UV radiation by DNA. As most radical cations undergo deprotonation, the vast majority of the final reaction products is expected to stem from long-lived deprotonated radicals. Consequently, when G radical cations are involved, the widely used oxidation marker 8-oxodG is not representative of the oxidative damage.Beyond the biological consequences, photogeneration of electron holes in G-quadruplexes may inspire applications in nanoelectronics; although four-stranded structures are currently studied as molecular wires, their behavior as photoconductors has not been explored so far.In the present Account, after highlighting some key experimental issues, we first describe the photoionization process, and then, we focus on radicals. We use as show-cases new results obtained for genomic DNA and Oxytricha G-quadruplexes. Generation and reaction dynamics of G radicals in these systems provide a representative picture of the phenomena reported previously for duplexes and G-quadruplexes, respectively.

Electron Holes in G-Quadruplexes: The Role of Adenine Ending Groups.

The study deals with four-stranded DNA structures (G-Quadruplexes), known to undergo ionization upon direct absorption of low-energy UV photons. Combining quantum chemistry calculations and time-resolved absorption spectroscopy with 266 nm excitation, it focuses on the electron holes generated in tetramolecular systems with adenine groups at the ends. Our computations show that the electron hole is placed in a single guanine site, whose location depends on the position of the adenines at the 3' or 5' ends. This position also affects significantly the electronic absorption spectrum of (G+)● radical cations. Their decay is highly anisotropic, composed of a fast process (<2 µs), followed by a slower one occurring in ~20 µs. On the one hand, they undergo deprotonation to (G-H2)● radicals and, on the other, they give rise to a reaction product absorbing in the 300-500 nm spectral domain.

Guanine Radicals Generated in Telomeric G-Quadruplexes by Direct Absorption of Low-Energy UV Photons: Effect of Potassium Ions.

The study deals with the primary species, ejected electrons, and guanine radicals, leading to oxidative damage, that is generated in four-stranded DNA structures (guanine quadruplexes) following photo-ionization by low-energy UV radiation. Performed by nanosecond transient absorption spectroscopy with 266 nm excitation, it focusses on quadruplexes formed by folding of GGG(TTAGGG)3 single strands in the presence of K+ ions, TEL21/K+. The quantum yield for one-photon ionization (9.4 × 10-3) was found to be twice as high as that reported previously for TEL21/Na+. The overall population of guanine radicals decayed faster, their half times being, respectively, 1.4 and 6.7 ms. Deprotonation of radical cations extended over four orders of magnitude of time; the faster step, concerning 40% of their population, was completed within 500 ns. A reaction intermediate, issued from radicals, whose absorption spectrum peaked around 390 nm, was detected.

Populations and Dynamics of Guanine Radicals in DNA strands-Direct versus Indirect Generation.

Guanine radicals, known to be involved in the damage of the genetic code and aging, are studied by nanosecond transient absorption spectroscopy. They are generated in single, double and four-stranded structures (G-quadruplexes) by one and two-photon ionization at 266 nm, corresponding to a photon energy lower than the ionization potential of nucleobases. The quantum yield of the one-photon process determined for telomeric G-quadruplexes (TEL25/Na+) is (5.2 ± 0.3) × 10-3, significantly higher than that found for duplexes containing in their structure GGG and GG sequences, (2.1 ± 0.4) × 10-3. The radical population is quantified in respect of the ejected electrons. Deprotonation of radical cations gives rise to (G-H1)• and (G-H2)• radicals for duplexes and G-quadruplexes, respectively. The lifetimes of deprotonated radicals determined for a given secondary structure strongly depend on the base sequence. The multiscale non-exponential dynamics of these radicals are discussed in terms of inhomogeneity of the reaction space and continuous conformational motions. The deviation from classical kinetic models developed for homogeneous reaction conditions could also be one reason for discrepancies between the results obtained by photoionization and indirect oxidation, involving a bi-molecular reaction between an oxidant and the nucleic acid.

Excited-State Symmetry Breaking in Solvent Mixtures.

A large number of multipolar dyes undergo excited-state symmetry breaking (ESSB) in polar media. During this process, electronic excitation, initially distributed evenly over the molecule, localizes, at least partially, on one donor-acceptor branch. To resolve its initial stage, ESSB is investigated with a donor-acceptor-donor dye in binary mixtures of nonpolar and polar solvents using time-resolved infrared absorption spectroscopy. The presence of a few polar molecules around the dye is sufficient to initiate ESSB. Although the extent of asymmetry in a mixture is close to that in a pure solvent of similar polarity, the dynamics are slower and involve translational diffusion. However, preferential solvation in the mixtures leads to a larger local polarity. Furthermore, inhomogeneous broadening of the S1 ← S0 absorption band of the dye is observed in the mixtures, allowing for a photoselection of solutes with different local environments and ESSB dynamics.

Fluorescence of Bimolecular Guanine Quadruplexes: From Femtoseconds to Nanoseconds.

The paper deals with the fluorescence of guanine quadruplexes (G4) formed by association of two DNA strands d(GGGGTTTTGGGG) in the presence of K+ cations, noted as OXY/K+ in reference to the protozoon Oxytricha nova, whose telomere contains TTTTGGGG repeats. They were studied by steady-state and time-resolved techniques, time-correlated single photon counting, and fluorescence upconversion. The maximum of the OXY/K+ fluorescence spectrum is located at 334 nm, and the quantum yield is 5.8 × 10-4. About 75% of the photons are emitted before 100 ps and stem from ππ* states, possibly with a small contribution of charge transfer. Time-resolved fluorescence anisotropy measurements indicate that ultrafast (<330 fs) excitation transfer, due to internal conversion among exciton states, is more efficient in OXY/K+ compared to previously studied G4 structures. This is attributed to the arrangement of the peripheral thymines in two diagonal loops with restricted mobility, facilitating the interaction among them and with guanines. Thymines should also be responsible for a weak intensity excimer/exciplex emission band, peaking at 445 nm. Finally, the longest living fluorescence component (∼2.1 ns) is observed at the blue side of the spectrum. So far, high-energy long-lived emitting states had been reported only for double-stranded structures but not for G4.

Effect of the DNA Polarity on the Relaxation of Its Electronic Excited States.

The DNA polarity, i.e., the order in which nucleobases are connected together via the phosphodiester backbone, is crucial for several biological processes. But, so far, there has not been experimental evidence regarding its effect on the relaxation of DNA electronic excited states. Here we examine this aspect for two dinucleotides containing adenine and guanine: 5'-dApdG-3' and 5'-dGpdA-3' in water. We used two different femtosecond transient absorption setups: one providing high temporal resolution and broad spectral coverage (330-650 nm) between 30 fs and 50 ps, and the other recording decays at selected wavelengths until 1.2 ns. The transient absorption spectra corresponding to the minima in the potential energy surface of the first excited state were computed by quantum chemistry methods. Our results show that the excited charge transfer state in 5'-dGpdA-3' is formed with a ∼75% higher quantum yield and exhibits slower decay (170 ± 10 ps vs 112 ± 12 ps) compared to 5'-dApdG-3'.

Deprotonation Dynamics of Guanine Radical Cations.

This review is dedicated to guanine radical cations (G+ )· that are precursors to oxidatively generated damage to DNA. (G+ )· are unstable in neutral aqueous solution and tend to lose a proton. The deprotonation process has been studied by time-resolved absorption experiments in which (G+ )· radicals are produced either by an electron abstraction reaction, using an external oxidant, or by low-energy/low-intensity photoionization of DNA. Both the position of the released proton and the dynamics of the process depend on the secondary DNA structure. While deprotonation in duplex DNA leads to (G-H1)· radicals, in guanine quadruplexes the (G-H2)· analogs are observed. Deprotonation in monomeric guanosine proceeds with a time constant of ~60 ns; in genomic DNA, it is completed within 2 µs; and in guanine quadruplexes, it spans from at least 30 ns to over 50 µs. Such a deprotonation dynamics in four-stranded structures, extended over more than three decades of times, is correlated with the anisotropic structure of DNA and the mobility of its hydration shell. In this case, commonly used second-order reaction models are inappropriate for its description.

Equitable access to quality trauma systems in low-income and middle-income countries: assessing gaps and developing priorities in Ghana, Rwanda and South Africa.

Injuries in low-income and middle-income countries are prevalent and their number is expected to increase. Death and disability after injury can be reduced if people reach healthcare facilities in a timely manner. Knowledge of barriers to access to quality injury care is necessary to intervene to improve outcomes. We combined a four-delay framework with WHO Building Blocks and Institution of Medicine Quality Outcomes Frameworks to describe barriers to trauma care in three countries in sub-Saharan Africa: Ghana, South Africa and Rwanda. We used a parallel convergent mixed-methods research design, integrating the results to enable a holistic analysis of the barriers to access to quality injury care. Data were collected using surveys of patient experiences of injury care, interviews and focus group discussions with patients and community leaders, and a survey of policy-makers and healthcare leaders on the governance context for injury care. We identified 121 barriers across all three countries. Of these, 31 (25.6%) were shared across countries. More than half (18/31, 58%) were predominantly related to delay 3 ('Delays to receiving quality care'). The majority of the barriers were captured using just one of the multiple methods, emphasising the need to use multiple methods to identify all barriers. Given there are many barriers to access to quality care for people who have been injured in Rwanda, Ghana and South Africa, but few of these are shared across countries, solutions to overcome these barriers may also be contextually dependent. This suggests the need for rigorous assessments of contexts using multiple data collection methods before developing interventions to improve access to quality care.

The Structural Duality of Nucleobases in Guanine Quadruplexes Controls Their Low-Energy Photoionization.

Guanine quadruplexes are four-stranded DNA/RNA structures composed of a guanine core (vertically stacked guanine tetrads) and peripheral groups (dangling ends and/or loops). Such a dual structural arrangement of the nucleobases favors their photoionization at energies significantly lower than the guanine ionization potential. This effect is important with respect to the oxidative DNA damage and for applications in the field of optoelectronics. Photoionization quantum yields, determined at 266 nm by nanosecond transient absorption spectroscopy, strongly depend on both the type and position of the peripheral nucleobases. The highest value (1.5 × 10-2) is found for the tetramolecular structure (AG4A)4 in which adenines are intermittently stacked on the adjacent guanine tetrads, as determined by nuclear magnetic resonance spectroscopy. Quantum chemistry calculations show that peripheral nucleobases interfere in a key step preceding electron ejection: charge separation, initiated by the population of charge transfer states during the relaxation of electronic excited states.

Potassium Ions Enhance Guanine Radical Generation upon Absorption of Low-Energy Photons by G-Quadruplexes and Modify Their Reactivity.

G-Quadruplexes are formed by guanine rich DNA/RNA sequences in the presence of metal ions, which occupy the central cavity of these four-stranded structures. We show that these metal ions have a significant effect on the photogeneration and the reactivity of guanine radicals. Transient absorption experiments on G-quadruplexes formed by association of four TGGGGT strands in the presence of K+ reveal that the quantum yield of one-photon ionization at 266 nm (8.1 × 10-3) is twice as high as that determined in the presence of Na+. Replacement of Na+ with K+ also suppresses one reaction path involving deprotonated radicals, (G-H2)• → (G-H1)• tautomerization. Such behavior shows that the underlying mechanisms are governed by dynamical processes, controlled by the mobility of metal ions, which is higher for Na+ than for K+. These findings may contribute to our understanding of the ultraviolet-induced DNA damage and optimize optoelectronic devices based on four-stranded structures, beyond DNA.

Radicals Generated in Tetramolecular Guanine Quadruplexes by Photoionization: Spectral and Dynamical Features.

G-quadruplexes are four-stranded DNA structures playing a key role in many biological functions and are promising for applications in the field of nanoelectronics. Characterizing the generation and fate of radical cations (electron holes) within these systems is important in relation to the DNA oxidative damage and/or conductivity issues. This study focuses on guanine radicals in G-quadruplexes formed by association of four TGGGGT strands in the presence of Na+ cations, (TG4T)4/Na+. Using nanosecond transient spectroscopy with 266 nm excitation, we quantitatively characterize hydrated ejected electrons and three types of guanine radicals. We show that, at an energy lower by 2.7 eV than the guanine ionization potential, one-photon ionization occurs with quantum yield of (3.5 ± 0.5) × 10-3. Deprotonation of the radical cations is completed within 20 µs, leading to the formation of (G-H2)• radicals, following a strongly nonexponential decay pattern. Within 10 ms, the latter undergoes tautomerization to deprotonated (G-H1)• radicals. The dynamics of the various radicals determined for (TG4T)4/Na+, in connection to those reported previously for telomeric G-quadruplexes TEL21/Na+, is correlated with energetic factors computed by quantum chemical methods. The faster deprotonation of radical cations in (TG4T)4/Na+ compared to TEL21/Na+ explains that irradiation of the former does not generate 8-oxodGuo, which is readily detected by high-performance liquid chromatography/mass spectrometry in the case of TEL21/Na+.

Gold nanoparticles, radiations and the immune system: Current insights into the physical mechanisms and the biological interactions of this new alliance towards cancer therapy.

Considering both cancer's serious impact on public health and the side effects of cancer treatments, strategies towards targeted cancer therapy have lately gained considerable interest. Employment of gold nanoparticles (GNPs), in combination with ionizing and non-ionizing radiations, has been shown to improve the effect of radiation treatment significantly. GNPs, as high-Z particles, possess the ability to absorb ionizing radiation and enhance the deposited dose within the targeted tumors. Furthermore, they can convert non-ionizing radiation into heat, due to plasmon resonance, leading to hyperthermic damage to cancer cells. These observations, also supported by experimental evidence both in vitro and in vivo systems, reveal the capacity of GNPs to act as radiosensitizers for different types of radiation. In addition, they can be chemically modified to selectively target tumors, which renders them suitable for future cancer treatment therapies. Herein, a current review of the latest data on the physical properties of GNPs and their effects on GNP circulation time, biodistribution and clearance, as well as their interactions with plasma proteins and the immune system, is presented. Emphasis is also given with an in depth discussion on the underlying physical and biological mechanisms of radiosensitization. Furthermore, simulation data are provided on the use of GNPs in photothermal therapy upon non-ionizing laser irradiation treatment. Finally, the results obtained from the application of GNPs at clinical trials and pre-clinical experiments in vivo are reported.