The interaction between light and multichromophoric assemblies (MCAs) is the primary event of many fundamental processes, from photosynthesis to organic photovoltaics, and it triggers dynamical ...processes that share remarkable similarities at the molecular scale: light absorption, energy and charge transfer, internal conversions, emission, and so on. Those events often involve many chromophores and different excited electronic states that are coupled on an ultrafast time scale. This Account aims to discuss some of the chemical physical effects ruling these processes, a fundamental step toward their control, based on our experience on nucleic acids.In the last 15 years, we have, indeed, studied the photophysics and photochemistry of DNA and its components. By combining different quantum mechanical methods, we investigated the molecular processes responsible for the damage of the genetic code or, on the contrary, those preventing it by dissipating the excess energy deposited in the system by UV absorption. Independently of its fundamental biological role, DNA, with its fluctuating closely stacked bases stabilized by weak nonbonding interactions, can be considered a prototypical MCA. Therefore, it allows one to tackle within a single system many of the conceptual and methodological challenges involved in the study of photoinduced processes in MCA.In this Account, by using the outcome of our studies on oligonucleotides as a guideline, we thus highlight the most critical modellistic issues to be faced when studying, either experimentally or computationally, the interaction between UV light and DNA and, at the same time, bring out their general relevance for the study of MCAs.We first discuss the rich photoactivated dynamics of nucleobases (the chromophores), highlighting the main effects modulating the interplay between their excited states and how the latter can affect the photoactivated dynamics of the polynucleotides, either providing effective monomer-like nonradiative decay routes or triggering reactive processes (e.g., triplet generation).We then tackle the reaction paths involving multiple bases, showing that in the DNA duplex the most important ones involve two stacked bases, forming a neutral excimer or a charge transfer (CT) state, which exhibit different spectral signatures and photochemical reactivity. In particular, we analyze the factors affecting the dynamic equilibrium between the excimer and CT, such as the fluctuations of the backbone or the rearrangement of the solvent.Next, we highlight the importance of the effects not directly connected to the chromophores, such as the flexibility of the backbone or the solvent effect. The former, affecting the stacking geometry of the bases, can determine the preference between different deactivation paths. The latter is particularly influential for CT states, making very important an accurate treatment of dynamical solvation effects, involving both the solvent bulk and specific solute-solvent interactions.In the last section, we describe the main methodological challenges related to the study of polynucleotide excited states and stress the benefits derived by the integration of complementary approaches, both computational and experimental. Only exploiting different point of views, in our opinion, it is possible to shed light on the complex phenomena triggered by light absorption in DNA, as in every MCA.
We here study the effect that a lowering of the pH has on the excited state processes of cytidine and a cytidine/cytidine pair in solution, by integrating time‐dependent density functional theory and ...CASSCF/CASPT2 calculations, and including solvent by a mixed discrete/continuum model. Our calculations reproduce the effect of protonation at N3 on the steady‐state infrared and absorption spectra of a protonated cytidine (CH+), and predict that an easily accessible non‐radiative deactivation route exists for the spectroscopic state, explaining its sub‐ps lifetime. Indeed, an extremely small energy barrier separates the minimum of the lowest energy bright state from a crossing region with the ground electronic state, reached by out‐of‐plane motion of the hydrogen substituents of the CC double bond, the so‐called ethylenic conical intersection typical of cytidine and other pyrimidine bases. This deactivation route is operative for the two bases forming an hemiprotonated cytidine base pair, CH·C+, the building blocks of I‐motif secondary structures, whereas interbase processes play a minor role. N3 protonation disfavors instead the nπ* transitions, associated with the long‐living components of cytidine photoactivated dynamics.
Quantum mechanical calculations show that an easily accessible non‐radiative deactivation route to the ground electronic state exists for photoexcited cytidine, protonated at acidic pH, also when hydrogen bonded to a “neutral” cytidine, forming the building blocks of DNA adopting an I‐motif structure.
Telomere shortening rates must be regulated to prevent premature replicative senescence. TERRA R‐loops become stabilized at critically short telomeres to promote their elongation through ...homology‐directed repair (HDR), thereby counteracting senescence onset. Using a non‐bias proteomic approach to detect telomere binding factors, we identified Npl3, an RNA‐binding protein previously implicated in multiple RNA biogenesis processes. Using chromatin immunoprecipitation and RNA immunoprecipitation, we demonstrate that Npl3 interacts with TERRA and telomeres. Furthermore, we show that Npl3 associates with telomeres in an R‐loop‐dependent manner, as changes in R‐loop levels, for example, at short telomeres, modulate the recruitment of Npl3 to chromosome ends. Through a series of genetic and biochemical approaches, we reveal that Npl3 binds to TERRA and stabilizes R‐loops at short telomeres, which in turn promotes HDR and prevents premature replicative senescence onset. This may have implications for diseases associated with excessive telomere shortening.
Synopsis
Npl3 interacts with telomeres through TERRA and RNA‐DNA hybrids. By stabilizing RNA‐DNA hybrids at short telomeres Npl3 drives telomere recombination and prevents accelerated senescence.
Npl3 is an RNA binding protein that associates with telomeres.
Npl3 binds telomeres via TERRA and RNA‐DNA hybrids.
R‐loops are stabilized by Npl3 at short telomeres.
Npl3 promotes recombination to prevent premature senescence.
Npl3 interacts with telomeres through TERRA and RNA‐DNA hybrids. By stabilizing RNA‐DNA hybrids at short telomeres Npl3 drives telomere recombination and prevents accelerated senescence.
Bacteria frequently store excess carbon in hydrophobic granules of polyhydroxybutyrate (PHB) that in some growth conditions can occupy most of the cytoplasmic space. Different types of proteins ...associate to the surface of the granules, mainly enzymes involved in the synthesis and utilization of the reserve polymer and a diverse group of proteins known as phasins. Phasins have different functions, among which are regulating the size and number of the granules, modulating the activity of the granule-associated enzymes and helping in the distribution of the granules inside the cell. Caulobacter crescentus is an oligotrophic bacterium that shows several morphological and regulatory traits that allow it to grow in very nutrient-diluted environments. Under these conditions, storage compounds should be particularly relevant for survival. In this work, we show an initial proteomic characterization of the PHB granules and describe a new type of phasin (PhaH) characterized by the presence of an N-terminal hydrophobic helix followed by a helix-hairpin-helix (HhH) domain. The hydrophobic helix is required for maximal PHB accumulation and maintenance during the stationary phase while the HhH domain is involved in determining the size of the PHB granules and their distribution in the cell.
This study focused on the observational and descriptive analysis of yogurt products available in major supermarket chains across Uruguay. A database of 120 yogurts was established using the FLIP-LAC ...program, facilitating the collection, storage, and analysis of packaging information. The findings revealed a diverse range of yogurts based on fat content, with 18% being whole, 49% low-fat, and 33% non-fat. Significantly, 97% of the yogurts contained sugar or alternative sweeteners, aligning with global trends and highlighting the prevalent use of sweetening agents in dairy products. The study underscored the challenges in assessing sugar intake due to the non-mandatory declaration of sugar content in nutritional labeling. Notably, 3% of yogurts did not contain any sweeteners or sugar. Additionally, 10% of the yogurts displayed an excess sugar warning octagon, indicating sugar content exceeding 26 g per serving. The study emphasized the need for enhanced nutritional education and public policies to empower consumers in making informed dietary choices. Despite regulatory efforts, the absence of mandatory sugar declarations on nutritional labels hinders consumers from tracking and managing their sugar intake effectively. The dataset revealed significant differences in sugar content-based categories on fat content, highlighting potential avenues for industry improvement in producing healthier yogurt options.
•Yogurt adapts to the needs and preferences of each consumer.•64% of the yoghurts surveyed contain sugar among the first three ingredients.•Direct relationship between the content of fat and sugar in yogurts.•Direct relationship between energy value and carbohydrate content in yogurts•10% of the surveyed yogurts presented a warning label with excess sugar.
Elucidating the photophysical mechanisms in sulfur-substituted nucleobases (thiobases) is essential for designing prospective drugs for photo- and chemotherapeutic applications. Although it has long ...been established that the phototherapeutic activity of thiobases is intimately linked to efficient intersystem crossing into reactive triplet states, the molecular factors underlying this efficiency are poorly understood. Herein we combine femtosecond transient absorption experiments with quantum chemistry and nonadiabatic dynamics simulations to investigate 2-thiocytosine as a necessary step to unravel the electronic and structural elements that lead to ultrafast and near-unity triplet-state population in thiobases in general. We show that different parts of the potential energy surfaces are stabilized to different extents via thionation, quenching the intrinsic photostability of canonical DNA and RNA nucleobases. These findings satisfactorily explain why thiobases exhibit the fastest intersystem crossing lifetimes measured to date among bio-organic molecules and have near-unity triplet yields, whereas the triplet yields of canonical nucleobases are nearly zero.
The intriguing and rich photophysical properties of three curved nanographenes (CNG 6, 7, and 8) are investigated by time-resolved and temperature-dependent photoluminescence (PL) spectroscopy. CNG 7 ...and 8 exhibit dual fluorescence, as well as dual phosphorescence at low temperature in the main PL bands. In addition, hot bands are detected in fluorescence as well as phosphorescence, and, in the narrow temperature range of 100-140 K, thermally activated delayed fluorescence (TADF) with lifetimes on the millisecond time-scale is observed. These findings are rationalized by quantum-chemical simulations, which predict a single minimum of the S
potential of CNG 6, but two S
minima for CNG 7 and CNG 8, with considerable geometric reorganization between them, in agreement with the experimental findings. Additionally, a higher-lying S
minimum close to S
is optimized for the three CNG, from where emission is also possible due to thermal activation and, hence, non-Kasha behavior. The presence of higher-lying dark triplet states close to the S
minima provides mechanistic evidence for the TADF phenomena observed. Non-radiative decay of the T
state appears to be thermally activated with activation energies of roughly 100 meV and leads to disappearance of phosphorescence and TADF at T > 140 K.
A modeling of the transport processes in T-10 tokamak using Astra code for two sets of discharges having ECRH auxiliary heating is presented. Electric potential measurements using HIBP show that ...radial profiles are negative for ohmic heating but become positive for large heating powers. We first obtain
$ T_\alpha $
T
α
and n profiles by adjusting transport coefficients and then try to obtain the radial
$ E_r $
E
r
profiles by assuming three models for it. Results show good agreement for Ohmic and small ECRH power phases but not for large power where
$ E_r \gt 0 $
E
r
>
0
indicating that other processes have to be included.
Possible routes for intra‐cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision‐induced dissociation (in ...correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the 4.6–14 eV range. Moreover, the comparison of photon‐induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by ab initio molecular dynamics and exploration of several excited state potential energy surfaces, unraveling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.
While collision induced dissociation of protonated serine dimers leads only to cluster breakup, clear evidence that irradiation by Vacuum UV (PID) light leads to intra‐cluster bond formation is presented. Furthermore, comparison with the PID of serine dipeptides suggests that peptide bond formation is involved in the process.
The T–T photodimerization paths leading to the formation of cyclobutane pyrimidine dimer (CPD) and 6–4 pyrimidine pyrimidone (64‐PP), the two main DNA photolesions, have been resolved for a T–T step ...in a DNA duplex by two complementary state‐of‐the‐art quantum mechanical approaches: QM(CASPT2//CASSCF)/MM and TD‐DFT/PCM. Based on the analysis of several different representative structures, we define a new‐ensemble of cooperating geometrical and electronic factors (besides the distance between the reacting bonds) ruling T–T photodimerization in DNA. CPD is formed by a barrierless path on an exciton state delocalized over the two bases. Large interbase stacking and shift values, together with a small pseudorotation phase angle for T at the 3′‐end, favor this reaction. The oxetane intermediate, leading to a 64‐PP adduct, is formed on a singlet T→T charge‐transfer state and is favored by a large interbase angle and slide values. A small energy barrier (<0.3 eV) is associated to this path, likely contributing to the smaller quantum yield observed for this process. Eventually, a clear directionality is always shown by the electronic excitation characterizing the singlet photoactive state driving the photodimerization process: an exciton that is more localized on T3 and a 5′‐T→3′‐T charge transfer for CPD and oxetane formation, respectively, thus calling for specific electronic constraints.
CASPT2//CASSCF/MM and TD‐DFT/PCM calculations disentangle the complex structural–electronic–electrostatic factors driving Thy–Thy cyclobutane pyrimidine dimer (CPD) and 6–4‐photoinduced formation in a DNA duplex (see figure).
PDF
