Ultrafast Formation of a Delocalized Triplet-Excited State in an Epigenetically Modified DNA Duplex under Direct UV Excitation.

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(G5fC)9•d(G5fC)9, made of alternating guanine (G) and 5-formylcytosine (5fC) 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.

Triplet Excimer Formation in a DNA Duplex with Silver Ion-Mediated Base Pairs.

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 dC20 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, dC20 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 Excited State Dynamics of a Mutagenic Guanosine Etheno Adduct Investigated by Femtosecond Fluorescence Spectroscopy and Quantum Mechanical Calculations.

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,N2-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, slightly less stable, is associated with the emission at 335 nm, whereas the other, with a bent etheno ring, is associated with the red-shifted emission.

Free-Water Imaging in Friedreich Ataxia Using Multi-Compartment Models.

BACKGROUND: The neurological phenotype of Friedreich ataxia (FRDA) is characterized by neurodegeneration and neuroinflammation in the cerebellum and brainstem. Novel neuroimaging approaches quantifying brain free-water using diffusion magnetic resonance imaging (dMRI) are potentially more sensitive to these processes than standard imaging markers. OBJECTIVES: To quantify the extent of free-water and microstructural change in FRDA-relevant brain regions using neurite orientation dispersion and density imaging (NODDI), and bitensor diffusion tensor imaging (btDTI). METHOD: Multi-shell dMRI was acquired from 14 individuals with FRDA and 14 controls. Free-water measures from NODDI (FISO) and btDTI (FW) were compared between groups in the cerebellar cortex, dentate nuclei, cerebellar peduncles, and brainstem. The relative sensitivity of the free-water measures to group differences was compared to microstructural measures of NODDI intracellular volume, free-water corrected fractional anisotropy, and conventional uncorrected fractional anisotropy. RESULTS: In individuals with FRDA, FW was elevated in the cerebellar cortex, peduncles (excluding middle), dentate, and brainstem (P < 0.005). FISO was elevated primarily in the cerebellar lobules (P < 0.001). On average, FW effect sizes were larger than all other markers (mean ηρ 2 = 0.43), although microstructural measures also had very large effects in the superior and inferior cerebellar peduncles and brainstem (ηρ 2 > 0.37). Across all regions and metrics, effect sizes were largest in the superior cerebellar peduncles (ηρ 2 > 0.46). CONCLUSIONS: Multi-compartment diffusion measures of free-water and neurite integrity distinguish FRDA from controls with large effects. Free-water magnitude in the brainstem and cerebellum provided the greatest distinction between groups. This study supports further applications of multi-compartment diffusion modeling, and investigations of free-water as a measure of disease expression and progression in FRDA. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Valorization applications of pineapple and papaya byproducts in food industry.

The recent increase in the harvesting and industrial processing of tropical fruits such as pineapple and papaya is leading to unavoidable amounts of byproducts rich in valuable compounds. Given the significance of the chemical composition of these byproducts, new research avenues are opening up to exploit them in the food industry. In this sense, the revalorization of pineapple and papaya byproducts is an emerging trend that is encouraging the full harnessing of these tropical fruits, offering the opportunity for developing innovative value-added products. Therefore, the main aim of this review is to provide an overview of the state of the art of the current valorization applications of pineapple and papaya byproducts in the field of food industry. For that proposal, comprehensive research of valorization applications developed in the last years has been conducted using scientific databases, databases, digital libraries, and scientific search engines. The latest valorization applications of pineapple and papaya byproducts in the food industry have been systematically revised and gathered with the objective of synthesizing and critically analyzing existing scientific literature in order to contribute to the advancement of knowledge in the field of tropical byproduct revalorization providing a solid foundation for further research and highlighting scientific gaps and new challenges that should be addressed in the future.

Nucleic Acids as a Playground for the Computational Study of the Photophysics and Photochemistry of Multichromophore Assemblies.

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.

Photophysical Characterization of Isoguanine in a Prebiotic-Like Environment.

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 S1 (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.

Clinical features and lipid metabolism genes as potential biomarkers in advanced lung cancer.

BACKGROUND: Lung cancer is one of the most lethal tumors with a poor survival rate even in those patients receiving new therapies. Metabolism is considered one of the hallmarks in carcinogenesis and lipid metabolism is emerging as a significant contributor to tumor metabolic reprogramming. We previously described a profile of some lipid metabolism related genes with potential prognostic value in advanced lung cancer. AIM: To analyze clinical and pathological characteristics related to a specific metabolic lipid genomic signature from patients with advanced lung cancer and to define differential outcome. METHODS: Ninety samples from NSCLC (non-small cell lung cancer) and 61 from SCLC (small cell lung cancer) patients were obtained. We performed a survival analysis based on lipid metabolic genes expression and clinical characteristics. The primary end point of the study was the correlation between gene expression, clinical characteristics and survival. RESULTS: Clinical variables associated with overall survival (OS) in NSCLC patients were clinical stage, adenocarcinoma histology, Eastern Cooperative Oncology Group (ECOG), number and site of metastasis, plasma albumin levels and first-line treatment with platinum. As for SCLC patients, clinical variables that impacted OS were ECOG, number of metastasis locations, second-line treatment administration and Diabetes Mellitus (DM). None of them was associated with gene expression, indicating that alterations in lipid metabolism are independent molecular variables providing complementary information of lung cancer patient outcome. CONCLUSIONS: Specific clinical features as well as the expression of lipid metabolism-related genes might be potential biomarkers with differential outcomes.

Examination of Cerebellar Grey-Matter Volume in Children with Neurodevelopmental Disorders: a Coordinated Analysis Using the ACAPULCO Algorithm.

Alterations in cerebellar morphology relative to controls have been identified in children with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and developmental coordination disorder (DCD). However, it is not clear if common cerebellar regions are affected in each neurodevelopmental disorder and whether cerebellar morphological changes reflect a generic developmental vulnerability, or disorder-specific characteristic. The present study concatenated anatomical MRI scans from five existing cohorts, resulting in data from 252 children between the age of 7 and 12 years (ASD = 58, ADHD = 86, DCD = 22, Controls = 86). The ACAPULCO processing pipeline for cerebellar segmentation was conducted on T1-weighted images. A voxel-wise approach with general linear model was used to compare grey-matter volume of the 27 cerebellar lobules between each clinical group and controls. Our findings revealed that the ADHD group showed lower grey-matter volume in the left Crus I - part of the executive/non-motor portion of the cerebellum, relative to controls (p = 0.02). This no longer remained significant after controlling for medication status. There were no regions of significant differences in volume of the cerebellar lobules in ASD or DCD compared to controls. Future work will conduct harmonisation of behavioural data (cognitive and motor outcomes) across cohorts, enabling more advanced analyses to identify symptom cluster across neurodevelopmental disorders.

Impaired lung function in multiple sclerosis: a single-center observational study in 371 persons.

INTRODUCTION: Abnormal lung function in people with multiple sclerosis (PwMS) could be considered as the result of muscle weakness or MS-specific structural central nervous system (CNS) abnormalities as a precipitant factor for the worsening of motor impairment or cognitive symptoms. METHODS: This is a cross-sectional observational study in PwMS. Forced spirometry was conducted, and normative metrics of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and the relation FEV1/FVC were calculated. Qualitative and quantitative brain magnetic resonance imaging (MRI) examinations were carried out. RESULTS: A total of 371 PwMS were included in the study. Of those, 196 (53%) had RRMS, 92 (25%) SPMS, and 83 (22%) PPMS. Low FVC and FEV1 was present in 16 (8%), 16 (19%), and 23 (25%) of the patients in the RRMS, PPMS, and SPMS, respectively. PwMS with T2-FLAIR lesions involving the corpus callosum (CC) had a significantly higher frequency of abnormally low FVC and FEV1 (OR 3.62; 95% CI 1.33-9.83; p = 0.012) than patients without lesions in that region. This association remained significant in the RRMS group (OR 10.1; 95% CI 1.3-67.8; p 0.031) when the model excluded PPMS and SPMS. According to our study, for every increase of 1 z score of FVC, we observed an increase of 0.25 cm3 of hippocampal volume (ß 0.25; 95% CI 0.03-0.47; p 0.023) and 0.43 cm3 of left hippocampus volume (ß 0.43; 95% CI 0.16-0.71; p 0.002). CONCLUSIONS: We observed an incremental prevalence of abnormally low pulmonary function tests that parallels a sequence from more early relapsing courses to long-standing progressive courses (RRMS to PPMS or SPMS).

Power ultrasound treatment of Viognier grapes as a tool to increase the aromatic potential of wines.

BACKGROUND: High-power ultrasound is a novel and non-thermal technique normally used in red vinification to increase the extraction of phenolic compounds. However, few studies have been carried out on its effect on the extraction of aroma compounds and their precursors in white grapes. This study evaluates the effect of high-power ultrasound at winery scale in the maceration of Viognier grapes on the content of varietal volatile compounds (free and glycosidically bound) in musts and wines, in comparison with wines from direct pressing and from short skin maceration. RESULTS: The pre-fermentative ultrasound treatment of the grapes produced an increase in most of the varietal compounds of musts and wines, both in the free fraction and in the bound one, especially in the C6 alcohols, terpenes and norisoprenoids, some of them of sensory relevance, while the effect on esters and lactones was less evident. Ultrasound maceration allowed us to obtain wines of higher aromatic intensity, with a more pronounced varietal character. CONCLUSION: The pre-fermentative ultrasound treatment of Viognier grapes increases the aromatic potential of the wines, as it favors the extraction of free and bound varietal volatile compounds. In addition, it allows the maceration time of the grapes to be reduced compared to conventional pre-fermentation techniques, thus avoiding oxidative processes that could negatively affect the aroma of the wines. © 2022 Society of Chemical Industry.

The technology of high-power ultrasound and its effect on the color and aroma of rosé wines.

BACKGROUND: The application of high-power ultrasound (US) has been studied extensively to obtain value-added red wines using short maceration times. It is a technique of wide interest for the extraction of aromatic compounds and compounds responsible for color, so it could also be an important tool to use in the elaboration process of rosé wines. Thus, this study focused on the effect of the application of US on the phenolic, aromatic, and sensorial profile of rosé wines. For this, three different types of rosé wine were produced: a control with direct pressing after crushing, another wine obtained from a 4 h macerated must, and a wine whose crushed and destemmed grape was sonicated and subsequently pressed. RESULTS: The results showed a higher color intensity and a higher total polyphenol and anthocyanin content in the wine obtained from sonicated grape compared to both control wine and that obtained from grape macerated for 4 h. Ultrasound treatment enhanced the extraction of varietal volatile compounds in must, especially the free faction of terpenes and norisoprenoids. It also gave rise to wines with a higher concentration of C6 alcohols and other compounds such as guaiacol and 4-vinylguaiacol, but led to fewer fatty acids, especially C6, C4 and C8 acids. Sensorially these wines showed intense aromas of red fruits and flowers, while no defects in aroma or astringency were found. CONCLUSIONS: The color and sensory profile of the resulting wines indicate that the US may be an interesting tool for obtaining quality rosé wines, replacing the maceration stage and reducing potential oxidation problems. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Peptide Bond Formation in the Protonated Serine Dimer Following Vacuum UV Photon-Induced Excitation.

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.

Design of a Deployable Helix Antenna at L-Band for a 1-Unit CubeSat: From Theoretical Analysis to Flight Model Results.

The 3Cat-4 mission aims at demonstrating the capabilities of a CubeSat to perform Earth Observation (EO) by integrating a combined GNSS-R and Microwave Radiometer payload into a 1-Unit CubeSat. One of the greatest challenges is the design of an antenna that respects the 1-Unit CubeSat envelope while operating at the different frequency bands: Global Positioning System (GPS) L1 and Galileo E1 band (1575 MHz), GPS L2 band (1227 MHz), and the microwave radiometry band (1400-1427 MHz). Moreover, it requires between 8 and 12 dB of directivity depending on the band whilst providing at least 10 dB of front-to-back lobe ratio in L1 and L2 GPS bands. After a trade-off analysis on the type of antenna that could be used, a helix antenna was found to be the most suitable option to comply with the requirements, since it can be stowed during launch and deployed once in orbit. This article presents the antenna design from a radiation performance point of view starting with a theoretical analysis, then presenting the numerical simulations, the measurements in an Engineering Model (EM), and finally the final design and performance of the Flight Model (FM).

Molecular Identification of the Transient Species Mediating the Deactivation Dynamics of Solvated Guanosine and Deazaguanosine.

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.

Ultrafast Excited-State Decay Mechanisms of 6-Thioguanine Followed by Sub-20 fs UV Transient Absorption Spectroscopy.

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 S2(ππ*) to the S1(nπ*) states, which takes place in about 80 fs and demonstrates that the S1(nπ*) state acts as a doorway to the triplet population in 522 fs. Our results are supported by MS-CASPT2 calculations, predicting a planar S2(ππ*) pseudo-minimum in agreement with the stimulated emission signal observed in the experiment.

Adenine Radical Cation Formation by a Ligand-Centered Excited State of an Intercalated Chromium Polypyridyl Complex Leads to Enhanced DNA Photo-oxidation.

Assessment of the DNA photo-oxidation and synthetic photocatalytic activity of chromium polypyridyl complexes is dominated by consideration of their long-lived metal-centered excited states. Here we report the participation of the excited states of [Cr(TMP)2dppz]3+ (1) (TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2',3'-c]phenazine) in DNA photoreactions. The interactions of enantiomers of 1 with natural DNA or with oligodeoxynucleotides with varying AT content (0-100%) have been studied by steady state UV/visible absorption and luminescence spectroscopic methods, and the emission of 1 is found to be quenched in all systems. The time-resolved infrared (TRIR) and visible absorption spectra (TA) of 1 following excitation in the region between 350 to 400 nm reveal the presence of relatively long-lived dppz-centered states which eventually yield the emissive metal-centered state. The dppz-localized states are fully quenched when bound by GC base pairs and partially so in the presence of an AT base-pair system to generate purine radical cations. The sensitized formation of the adenine radical cation species (A•+T) is identified by assigning the TRIR spectra with help of DFT calculations. In natural DNA and oligodeoxynucleotides containing a mixture of AT and GC of base pairs, the observed time-resolved spectra are consistent with eventual photo-oxidation occurring predominantly at guanine through hole migration between base pairs. The combined targeting of purines leads to enhanced photo-oxidation of guanine. These results show that DNA photo-oxidation by the intercalated 1, which locates the dppz in contact with the target purines, is dominated by the LC centered excited state. This work has implications for future phototherapeutics and photocatalysis.

Assessing cerebellar-cortical connectivity using concurrent TMS-EEG: a feasibility study.

Combined single-pulse transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to probe the features of local networks in the cerebral cortex. Here, we investigated whether we can use this approach to explore long-range connections between the cerebellum and cerebral cortex. Ten healthy adults received single-pulse suprathreshold TMS to the cerebellum and an occipital/parietal control site with double-cone and figure-of-eight coils while cerebral activity was recorded. A multisensory electrical control condition was used to simulate the sensation of the double-cone coil at the cerebellar site. Two cleaning pipelines were compared, and the spatiotemporal relationships of the EEG output between conditions were examined at sensor and source levels. Cerebellar stimulation with the double-cone coil resulted in large artifact in the EEG trace. The addition of SOUND filtering to the cleaning pipeline improved the signal such that further analyses could be undertaken. The cortical potentials evoked by the active TMS conditions showed strong relationships with the responses to the multisensory control condition after ∼50 ms. A distinct parietal component at ∼42 ms was found following cerebellar double-cone stimulation. Although evoked potentials differed across all conditions at early latencies, it is unclear as to whether these represented TMS-related network activation of the cerebellarthalamocortical tract, or whether components were dominated by sensory contamination and/or coil-driven artifact. This study highlights the need for caution when interpreting outcomes from cerebellar TMS-EEG studies.NEW & NOTEWORTHY This is the first study to systematically assess the feasibility of obtaining TMS-evoked potentials from cerebellar stimulation with concurrent EEG. An innovative control condition using electrical stimulation was modified to mimic the sensory aspects of cerebellar stimulation with a double-cone coil, and a state-of-the art cleaning pipeline was trialled. The extent of artifact contamination in signals from stimulation of a cerebellar and an occipital/parietal control site using two TMS coil types was highlighted.

Subphthalocyaninato Boron(III) Hydride: Synthesis, Structure and Reactivity.

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.

Solvent-Dependent Stabilization of a Charge Transfer State is the Key to Ultrafast Triplet State Formation in an Epigenetic DNA Nucleoside.

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.