Search

Introduction: Psychotic depression (PD) was associated with higher and quicker response to ECT, it is an outstanding predictor of response, and it has been proposed to be a distinct nosological entity. Objectives: Comparison of patients with psychotic (n=26) and nonpsychotic (n=40) depression. Methods: Retrospective study including 66 depressive patients treated with bilateral ECT. Patients were rated pre-ECT and after their last session using the Clinical Global Impressions Scale (CGI), the CORE system, the Mini-Mental (MEC-35), and the Global Assessment of Function (GAF). Changes in severity were assessed weekly with the Hamilton Depression Rating Scale (HDRS-21). Results: Pre-ECT HDRS scores were higher in PD (34.35±5.04 vs 26.58±4.489; p<0.001) although weekly percentage decrease, post-ECT HDRS scores, and the number of sessions (11.54±3.65 vs 11.45±2.9) were similar. Response rates were higher in PD (92.3% vs 85%), even though the difference was not statistically significant. PD patients were older (67.81±12.25 vs 58.96±12.825; p=0.007), had higher CGI and CORE, and had lower MEC-35 and GAF pre-ECT. They spent more days in the hospital, had lower Thase and Rush staging, needed less anesthetic dose, and required higher stimulus intensity at first ECT session (all p<0.005). However no differences were found in age of illness onset, number of previous episodes, previous ECT, current episode duration, response and remission rates, or the stimulus dose at last ECT session. Conclusions: ECT was highly effective. PD showed older age, greater severity, psychomotor and cognitive disturbances, poorer functionality, and less pharmacological resistance pre-ECT. PD required less anesthetic dose and higher initial stimulus intensity. [ABSTRACT FROM AUTHOR]

The article discusses a study on the effects of various fentanyl anesthetic mixtures on corticoadrenal function of rabbits. The study involves 10 New Zealand White rabbits which were maintained with under conventional conditions and were assigned in four treatment groups including control group with normal saline solution, group ketamine, and group fentanyl. Results reveal the response of respiratory and heart rates and glucocorticoids following the administration of fentanyl mixtures.

Femtosecond fluorescence upconversion experiments were combined with CASPT2 and time dependent DFT calculations to characterize the excited state dynamics of the mutagenic etheno adduct 1,N 2 -etheno-2'-deoxyguanosine (ϵdG). This endogenously formed lesion is attracting great interest because of its ubiquity in human tissues and its highly mutagenic properties. The ϵdG fluorescence is strongly modified with respect to that of the canonical nucleoside dG, notably by an about 6-fold increase in fluorescence lifetime and quantum yield at neutral pH. In addition, femtosecond fluorescence upconversion experiments reveal the presence of two emission bands with maxima at 335 nm for the shorter-lived and 425 nm for the longer-lived. Quantum mechanical calculations rationalize these findings and provide absorption and fluorescence spectral shapes similar to the experimental ones. Two different bright minima are located on the potential energy surface of the lowest energy singlet excited state. One planar minimum, slightly more stable, is associated with the emission at 335 nm, whereas the other one, with a bent etheno ring, is associated with the red-shifted emission., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Understanding the competing processes that govern far ultraviolet photodissociation (FUV-PD) of biopolymers such as proteins is a challenge. Here, we report a combined experimental and theoretical investigation of FUV-PD of protonated leucine-enkephalin pentapeptide ([YGGFL + H] + ) in the gas-phase. Time-dependent density functional theory (TD-DFT) calculations in combination with experiments and previous results for amino acids and shorter peptides help in rationalizing the evolution of the excited states. The results confirm that fragmentation of [YGGFL + H] + results mainly from vibrationally excited species in the ground electronic state, populated after internal conversion. We also propose fragmentation mechanisms for specific photo-fragments such as tyrosine side chain loss (with an extra hydrogen) or hydrogen loss. In general, we observe the same mechanisms as for smaller peptides or protonated Tyr and Phe, that are not quenched by the presence of other amino acids. Nevertheless, we also found some differences, as for H loss, in part due to the fact that the charge is solvated by the peptide chain and not only by the COOH terminal group., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Study of alternating DNA GC sequences by different time-resolved spectroscopies has provided fundamental information on the interaction between UV light and DNA, a process of great biological importance. Multiple decay paths have been identified, but their interplay is still poorly understood. Here, we characterize the photophysics of GC-DNA by integrating different computational approaches, to study molecular models including up to 6 bases described at a full quantum mechanical level. Quantum dynamical simulations, exploiting a nonadiabatic linear vibronic coupling (LVC) model, coupled with molecular dynamics sampling of the initial structures of a (GC) 5 DNA duplex, provide new insights into the photophysics in the sub-picosecond time-regime. They indicate a substantial population transfer, within 50 fs, from the spectroscopic states towards G → C charge transfer states involving two stacked bases (CT intra ), thus explaining the ultrafast disappearance of fluorescence. This picture is consistent with that provided by quantum mechanical geometry optimizations, using time dependent-density functional theory and a polarizable continuum model, which we use to parametrize the LVC model and to map the main excited state deactivation pathways. For the first time, the infrared and excited state absorption signatures of the various states along these pathways are comprehensively mapped. The computational models suggest that the main deactivation pathways, which, according to experiment, lead to ground state recovery on the 10-50 ps time scale, involve CT intra followed by interstrand proton transfer from the neutral G to C - . Our calculations indicate that CT intra is populated to a larger extent and more rapidly in GC than in CG steps and suggest the likely involvement of monomer-like and interstrand charge transfer decay routes for isolated and less stacked CG steps. These findings underscore the importance of the DNA sequence and thermal fluctuations for the dynamics. They will also aid the interpretation of experimental results on other sequences., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Epigenetic modifications impart important functionality to nucleic acids during gene expression but may increase the risk of photoinduced gene mutations. Thus, it is crucial to understand how these modifications affect the photostability of duplex DNA. In this work, the ultrafast formation (<20 ps) of a delocalized triplet charge transfer (CT) state spreading over two stacked neighboring nucleobases after direct UV excitation is demonstrated in a DNA duplex, d(G 5f C) 9 •d(G 5f C) 9 , made of alternating guanine (G) and 5-formylcytosine ( 5f C) nucleobases. The triplet yield is estimated to be 8 ± 3%, and the lifetime of the triplet CT state is 256 ± 22 ns, indicating that epigenetic modifications dramatically alter the excited state dynamics of duplex DNA and may enhance triplet state-induced photochemistry.

The dynamics of excited electronic states in self-assembled structures formed between silver(I) ions and cytosine-containing DNA strands or monomeric cytosine derivatives were investigated by time-resolved infrared (TRIR) spectroscopy and quantum mechanical calculations. The steady-state and time-resolved spectra depend sensitively on the underlying structures, which change with pH and the nucleobase and silver ion concentrations. At pH ∼ 4 and low dC 20 strand concentration, an intramolecularly folded i-motif is observed, in which protons, and not silver ions, mediate C-C base pairing. However, at the higher strand concentrations used in the TRIR measurements, dC 20 strands associate pairwise to yield duplex structures containing C-Ag + -C base pairs with a high degree of propeller twisting. UV excitation of the silver ion-mediated duplex produces a long-lived excited state, which we assign to a triplet excimer state localized on a pair of stacked cytosines. The computational results indicate that the propeller-twisted motifs induced by metal-ion binding are responsible for the enhanced intersystem crossing that populates the triplet state and not a generic heavy atom effect. Although triplet excimer states have been discussed frequently as intermediates in the formation of cyclobutane pyrimidine dimers, we find neither computational nor experimental evidence for cytosine-cytosine photoproduct formation in the systems studied. These findings provide a rare demonstration of a long-lived triplet excited state that is formed in a significant yield in a DNA duplex, demonstrating that supramolecular structural changes induced by metal ion binding profoundly affect DNA photophysics.

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 1 potential of CNG 6, but two S 1 minima for CNG 7 and CNG 8, with considerable geometric reorganization between them, in agreement with the experimental findings. Additionally, a higher-lying S 2 minimum close to S 1 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 1 minima provides mechanistic evidence for the TADF phenomena observed. Non-radiative decay of the T 1 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., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Objective: Maresin 1 (MaR1) is a docosahexaenoic acid-derived proresolving lipid mediator with insulin-sensitizing and anti-steatosis properties. Here, we aim to unravel MaR1 actions on brown adipose tissue (BAT) activation and white adipose tissue (WAT) browning., Methods: MaR1 actions were tested in cultured murine brown adipocytes and in human mesenchymal stem cells (hMSC)-derived adipocytes. In vivo effects of MaR1 were tested in diet-induced obese (DIO) mice and lean WT and Il6 knockout (Il6 -/- ) mice., Results: In cultured differentiated murine brown adipocytes, MaR1 reduces the expression of inflammatory genes, while stimulates glucose uptake, fatty acid utilization and oxygen consumption rate, along with the upregulation of mitochondrial mass and genes involved in mitochondrial biogenesis and function and the thermogenic program. In Leucine Rich Repeat Containing G Protein-Coupled Receptor 6 (LGR6)-depleted brown adipocytes using siRNA, the stimulatory effect of MaR1 on thermogenic genes was abrogated. In DIO mice, MaR1 promotes BAT remodeling, characterized by higher expression of genes encoding for master regulators of mitochondrial biogenesis and function and iBAT thermogenic activation, together with increased M2 macrophage markers. In addition, MaR1-treated DIO mice exhibit a better response to cold-induced BAT activation. Moreover, MaR1 induces a beige adipocyte signature in inguinal WAT of DIO mice and in hMSC-derived adipocytes. MaR1 potentiates Il6 expression in brown adipocytes and BAT of cold exposed lean WT mice. Interestingly, the thermogenic properties of MaR1 were abrogated in Il6 -/- mice., Conclusions: These data reveal MaR1 as a novel agent that promotes BAT activation and WAT browning by regulating thermogenic program in adipocytes and M2 polarization of macrophages. Moreover, our data suggest that LGR6 receptor is mediating MaR1 actions on brown adipocytes, and that IL-6 is required for the thermogenic effects of MaR1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved.)

This study analyses the effects of Maresin 1 (MaR1), a docosahexaenoic acid (DHA)-derived specialized proresolving lipid mediator with anti-inflammatory and insulin-sensitizing actions, on the expression of adipokines, including adiponectin, leptin, dipeptidyl peptidase 4 (DPP-4), cardiotrophin-1 (CT-1), and irisin (FNDC5), both in vitro and in in vivo models of obesity. The in vivo effects of MaR1 (50 μg/kg, 10 days, oral gavage) were evaluated in epididymal adipose tissue (eWAT), liver and muscle of diet-induced obese (DIO) mice. Moreover, two models of human differentiated primary adipocytes were incubated with MaR1 (1 and 10 nM, 24 h) or with a combination of tumor necrosis factor-α (TNF-α, 100 ng/mL) and MaR1 (1-200 nM, 24 h) and the expression and secretion of adipokines were measured in both models. MaR1-treated DIO mice exhibited an increased expression of adiponectin and Ct-1 in eWAT, increased expression of Fndc5 and Ct-1 in muscle and a decreased expression of hepatic Dpp-4 . In human differentiated adipocytes, MaR1 increased the expression of ADIPONECTIN , LEPTIN , DPP4 , CT-1 and FNDC5 . Moreover, MaR1 counteracted the downregulation of ADIPONECTIN and the upregulation of DPP-4 and LEPTIN observed in adipocytes treated with TNF-α. Differential effects for TNF-α and MaR1 on the expression of CT-1 and FNDC5 were observed between both models of human adipocytes. In conclusion, MaR1 reverses the expression of specific adipomyokines and hepatokines altered in obese mice in a tissue-dependent manner. Moreover, MaR1 regulates the basal expression of adipokines in human adipocytes and counteracts the alterations of adipokines expression induced by TNF-α in vitro. These actions could contribute to the metabolic benefits of this lipid mediator.

It is intriguing how a mixture of organic molecules survived the prebiotic UV fluxes and evolved into the actual genetic building blocks. Scientists are trying to shed light on this issue by synthesizing nucleic acid monomers and their analogues under prebiotic Era-like conditions and by exploring their excited state dynamics. To further add to this important body of knowledge, this study discloses new insights into the photophysical properties of protonated isoguanine, an isomorph of guanine, using steady-state and femtosecond broadband transient absorption spectroscopies, and quantum mechanical calculations. Protonated isoguanine decays in ultrafast time scales following 292 nm excitation, consistently with the barrierless paths connecting the bright S 1 (ππ*) state with different internal conversion funnels. Complementary calculations for neutral isoguanine predict similar photophysical properties. These results demonstrate that protonated isoguanine can be considered photostable in contrast to protonated guanine, which exhibits 40-fold longer excited state lifetimes., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

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., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Introduction: High-grade serous ovarian cancer (HGSOC) is the second most frequent gynecological malignancy but the most lethal, partially due to the spread of the disease through the peritoneal cavity. Recent evidence has shown that, apart from their role in immune defense through phagocytosis and degranulation, neutrophils are able to participate in cancer progression through the release of neutrophil extracellular traps (NETs) in a process called NETosis. NETs are composed of DNA, histones, calprotectin, myeloperoxidase (MPO) and elastase and the NETosis process has been proposed as a pre-requisite for the establishment of omental metastases in early stages of HGSOC. Nevertheless, its role in advanced stages remains to be elucidated. Therefore, our principal aim is to characterize a NETosis biomarker profile in biofluids from patients with advanced HGSOC and control women., Methods: Specifically, five biomarkers of NETosis (cell-free DNA (cfDNA), nucleosomes, citrullinated histone 3 (citH3), calprotectin and MPO) were quantified in plasma and peritoneal fluid (PF) samples from patients (n=45) and control women (n=40)., Results: Our results showed that HGSOC patients presented a higher concentration of cfDNA, citH3 and calprotectin in plasma and of all five NETosis biomarkers in PF than control women. Moreover, these biomarkers showed a strong ability to differentiate the two clinical groups. Interestingly, neoadjuvant treatment (NT) seemed to reduce NETosis biomarkers mainly systemically (plasma) compared to the tumor environment (PF)., Discussion: In conclusion, NETosis biomarkers are present in the tumor environment of patients with advanced HGSOC, which might contribute to the progression of the disease. Besides, plasma cfDNA and calprotectin could represent minimally invasive surrogate biomarkers for HGSOC. Finally, NT modifies NETosis biomarkers levels mainly at the systemic level., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tomás-Pérez, Oto, Aghababyan, Herranz, Cuadros-Lozano, González-Cantó, Mc Cormack, Arrés, Castaño, Cana, Martínez-Fernández, Santonja, Ramírez, Herreros-Pomares, Cañete-Mota, Llueca, Marí-Alexandre, Medina and Gilabert-Estellés.)

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.

There is significant interest in developing suitable nucleoside analogs exhibiting high fluorescence and triplet yields to investigate the structure, dynamics, and binding properties of nucleic acids and promote selective photosensitized damage to DNA/RNA, respectively. In this study, steady-state, laser flash photolysis, time-resolved IR luminescence, and femtosecond broad-band transient absorption spectroscopies are combined with quantum chemical calculations to elucidate the excited-state dynamics of 2-oxopurine riboside in aqueous solution and to investigate its prospective use as a fluorescent or photosensitizer analog. The Franck-Condon population in the S 1 (ππ*) state decays through a combination of solvent and conformational relaxation to its minimum in 1.9 ps. The population trapped in the 1 ππ* minimum bifurcates to either fluoresce or intersystem cross to the triplet manifold within ca. 5 ns, while another fraction of the population decays nonradiatively to the ground state. It is demonstrated that 2-oxopurine riboside exhibits both high fluorescent (48%) and significant triplet (between 10% and 52%) yields, leading to a yield of singlet oxygen generation of 10%, making this nucleoside analog a dual fluorescent and photosensitizer analog for DNA and RNA research.

Understanding the primary steps following UV photoexcitation in sulphur-substituted DNA bases (thiobases) is fundamental for developing new phototherapeutic drugs. However, the investigation of the excited-state dynamics in sub-100 fs time scales has been elusive until now due to technical challenges. Here, we track the ultrafast decay mechanisms that lead to the electron trapping in the triplet manifold for 6-thioguanine in an aqueous solution, using broadband transient absorption spectroscopy with a sub-20 fs temporal resolution. We obtain experimental evidence of the fast internal conversion from the S 2 (ππ*) to the S 1 (nπ*) states, which takes place in about 80 fs and demonstrates that the S 1 (nπ*) state acts as a doorway to the triplet population in 522 fs. Our results are supported by MS-CASPT2 calculations, predicting a planar S 2 (ππ*) pseudo-minimum in agreement with the stimulated emission signal observed in the experiment.

Small structural alterations of the purine/pyrimidine core have been related to important photophysical changes, such as the loss of photostability. Similarly to canonical nucleobases, solute-solvent interactions can lead to a change in the excited state lifetimes and/or to the interplay of different states in the photophysics of these modified nucleobases. To shed light on both effects, we here report a complete picture of the absorption spectra and excited state deactivation of deoxyguanosine and its closely related derivative, deoxydeazaguanosine, in water and methanol through the mapping of the excited state potential energy surfaces and molecular dynamics simulations at the TD-DFT level of theory. We show that the N by CH exchange in the imidazole ring of deoxyguanosine translates into a small red-shift of the bright states and slightly faster dynamics. In contrast, changing solvent from water to methanol implies the opposite, i.e., that the deactivation of both systems to the ground state is significantly hindered.

Joint femtosecond fluorescence upconversion experiments and theoretical calculations provide a hitherto unattained degree of characterization and understanding of the mutagenic etheno adduct 3,N4-etheno-2'-deoxycytidine (εdC) excited state relaxation. This endogenously formed lesion is attracting great interest because of its ubiquity in human tissues and its highly mutagenic properties. The εdC fluorescence is modified with respect to that of the canonical base dC, with a 3-fold increased lifetime and quantum yield at neutral pH. This behavior is amplified upon protonation of the etheno ring (εdCH + ). Quantum mechanical calculations show that the lowest energy state ππ*1 is responsible for the fluorescence and that the main nonradiative decay pathway to the ground state goes through an ethene-like conical intersection, involving the out-of-plane motion of the C5 and C6 substituents. This conical intersection is lower in energy than the ππ* state ( ππ*1 ) minimum, but a sizable energy barrier explains the increase of εdC and εdCH + fluorescence lifetimes with respect to that of dC.

Guanine radical cation (G •+ ) is a key intermediate in many oxidative processes occurring in nucleic acids. Here, by combining mixed Quantum Mechanical/Molecular Mechanics calculations and Molecular Dynamics (MD) simulations, we study how the structural behaviour of a tract GGG(TTAGGG) 3 (hereafter Tel21) of the human telomeric sequence, folded in an antiparallel quadruple helix, changes when one of the G bases is ionized to G •+ (Tel21 + ). Once assessed that the electron-hole is localized on a single G, we perform MD simulations of twelve Tel21 + systems, differing in the position of G •+ in the sequence. When G •+ is located in the tetrad adjacent to the diagonal loop, we observe substantial structural rearrangements, which can decrease the electrostatic repulsion with the inner Na + ions and increase the solvent exposed surface of G •+ . Analysis of solvation patterns of G •+ provides new insights on the main reactions of G •+ , i.e. the deprotonation at two different sites and hydration at the C8 atom, the first steps of the processes producing 8oxo-Guanine. We suggest the main structural determinants of the relative reactivity of each position and our conclusions, consistent with the available experimental trends, can help rationalizing the reactivity of other G-quadruplex topologies., (Copyright © 2021. Published by Elsevier B.V.)

Subphthalocyanine (SubPc) chemistry has been limited so far by their high sensitivity toward strong nucleophiles. In particular, the substitution of the axial chlorine atom by a nucleophilic group in the case of less-reactive SubPcs, such as those bearing electron-withdrawing peripheral substituents, presents some limitations and requires harsh conditions. By taking advantage of the electrophilic character of DIBAL-H, it has been possible to prepare for the first time SubPc-hydride derivatives that exhibit high reactivity as hydroboration reagents of aldehydes. This hydride transfer requires using a typical carbonyl activator (trimethylsilyl triflate) and only one equivalent of aldehyde, affording SubPcs with an axial benzyloxy group in good yield. This transformation has proven to be a useful alternative method for the axial functionalisation of dodecafluoroSubPc, a paradigmatic SubPc derivative, by using electrophiles for the first time. Considering the increasing interest in SubPcs as electron-acceptor semiconductors with remarkable absorption in the visible range to replace fullerene in organic photovoltaic (OPV) devices, it is of the utmost importance to develop new synthetic methodologies for their axial functionalisation., (© 2021 The Authors. Published by Wiley-VCH GmbH.)

2'-Deoxy-5-formylcytidine (5fdCyd), a naturally occurring nucleoside found in mammalian DNA and mitochondrial RNA, exhibits important epigenetic functionality in biological processes. Because it efficiently generates triplet excited states, it is an endogenous photosensitizer capable of damaging DNA, but the intersystem crossing (ISC) mechanism responsible for ultrafast triplet state generation is poorly understood. In this study, time-resolved mid-IR spectroscopy and quantum mechanical calculations reveal the distinct ultrafast ISC mechanisms of 5fdCyd in water versus acetonitrile. Our experiment indicates that in water, ISC to triplet states occurs within 1 ps after 285 nm excitation. PCM-TD-DFT computations suggest that this ultrafast ISC is mediated by a singlet state with significant cytosine-to-formyl charge-transfer (CT) character. In contrast, ISC in acetonitrile proceeds via a dark 1 nπ* state with a lifetime of ∼3 ps. CT-induced ISC is not favored in acetonitrile because reaching the minimum of the gateway CT state is hampered by intramolecular hydrogen bonding, which enforces planarity between the aldehyde group and the aromatic group. Our study provides a comprehensive picture of the non-radiative decay of 5fdCyd in solution and new insights into the factors governing ISC in biomolecules. We propose that the intramolecular CT state observed here is a key to the excited-state dynamics of epigenetic nucleosides with modified exocyclic functional groups, paving the way to study their effects in DNA strands., (© 2021 Wiley-VCH GmbH.)

Introduction: Patients with chronic kidney disease (CKD) are at high risk of cardiovascular morbidity and mortality. Subclinical cardiac structural alterations have prognostic value in these patients. The aim was to analyse the prevalence of valvular calcification, the evolution and the relationship with different risk factors., Material and Methods: Part of the sample of the NEFRONA study was randomly selected. Aortic and mitral valve calcification were analysed in echocardiograms performed at the baseline visit and at 24 months., Results: We included 397 patients, the estimated basal glomerular filtrate (eGFR) was 33 ml/min with significant decrease to 30.9 ml/min. There was an increase in the area of carotid and femoral plaque, as well as an increase in patients with aortic and mitral calcification at 24 months. A positive association of mitral calcification at 24 months with age, ankle-brachial index (ABI) and calcium-phosphorus product (CaxP) at baseline visit was observed, without association with eGFR. Aortic calcification at 24 months was positively associated with age, phosphorous and total carotid plaque area at baseline, with no relationship to eGFR., Conclusions: A significant prevalence of valvular calcification was observed in patients with CKD without known cardiovascular disease.Two-year progression was observed independently of the eGFR. Patients with higher risk of mitral valve calcification were those with older age, higher ABI and CaxP product. Patients with a higher risk of aortic calcification were those with older age, higher phosphorous levels and larger area of carotid plaque. Identifying these higher risk patients would help to avoid future cardiovascular events intensifying follow-ups., (Copyright © 2020 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)