Accurate structural and spectroscopic characterization of prebiotic molecules: The neutral and cationic acetyl cyanide and their related species

In an effort to provide an accurate structural and spectroscopic characterization of acetyl cyanide, its two enolic isomers and the corresponding cationic species, state-of-the-art computational methods, and approaches have been employed. The coupled-cluster theory including single and double excitations together with a perturbative treatment of triples has been used as starting point in composite schemes accounting for extrapolation to the complete basis-set limit as well as core-valence correlation effects to determine highly accurate molecular structures, fundamental vibrational frequencies, and rotational parameters. The available experimental data for acetyl cyanide allowed us to assess the reliability of our computations: structural, energetic, and spectroscopic properties have been obtained with an overall accuracy of about, or better than, 0.001 Å, 2 kcal/mol, 1-10 MHz, and 11 cm−1 for bond distances, adiabatic ionization potentials, rotational constants, and fundamental vibrational frequencies, respectively.We are therefore confident that the highly accurate spectroscopic data provided herein can be useful for guiding future experimental investigations and/or astronomical observations

Accurate structural and spectroscopic characterization of prebiotic molecules: The neutral and cationic acetyl cyanide and their related species

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Free energy profiles for two ubiquitous damaging agents: methylation and hydroxylation of guanine in B-DNA

International audienceDNA methylation and hydroxylation are two ubiquitous reactions in DNA damage induction, yet insights are scarce concerning the free energy of activation within B-DNA. We resort to multiscale simulations to investigate the attack of a hydroxyl radical and of the primary diazonium onto a guanine embedded in a solvated dodecamer. Reaction free energy profiles characterize two strongly exergonic processes, yet allow unprecedented quantification of the barrier towards this damage reaction, not higher than 6 kcal mol−1 and sometimes inexistent, and of the exergonicities. In the case of the [G(C8)-OH]˙ intermediate, we challenge the functional dependence of such simulations: recently-proposed functionals, such as M06-2X and LC-BLYP, agree on a ∼4 kcal mol−1 barrier, whereas the hybrid GGA B3LYP functional predicts a barrier-less pathway. In the long term, multiscale approaches can help build up a unified panorama of DNA lesion induction. These results stress the importance of DFT/MM-MD simulations involving new functionals towards the sound modelling of biomolecule damage even in the ground state

Electronic, structural and vibrational induced effects upon ionization of 2-quinolinone

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Single photon ionization of methyl isocyanide and the subsequent unimolecular decomposition of its cation experiment and theory

International audienceMethyl isocyanide, CH3NC, is a key compound in astrochemistry and astrobiology. A combined theoretical and experimental investigation of the single photon ionization of gas phase methyl isocyanide and its fragmentation pathways is presented. Vacuum ultraviolet (VUV) synchrotron radiation based experiments are used to measure the threshold photoelectron photoion coincidence (TPEPICO) spectra between 10.6 and 15.5 eV. This allowed us to experimentally determine the adiabatic ionization energy (AIE) and fragment ion appearance energies (AE) of gas-phase methyl isocyanide. Its AIE has been measured with a precision never achieved before. It is found to be AIEexp = 11.263 ± 0.005 eV. We observe a vibrational progression upon ionization corresponding to the population of vibrational levels of the ground state of the methyl isocyanide cation. In addition, four fragment ion appearance energies (AEs) were measured to be AE (m/z 40) = 12.80 ± 0.05 eV, AE (m/z 39) = 13.70 ± 0.05, AE (m/z 15) = 13.90 ± 0.05 eV, AE (m/z 14) 13.85 ± 0.05 eV, respectively. In order to interpret the experimental data, we performed state-of-the-art computations using the explicitly correlated coupled cluster approach. We also considered the zero-point vibrational energy (ZPVE), core-valence (CV) and scalar relativistic (SR) effects. The results of theoretical calculations of the AIE and AEs are in excellent agreement with the experimental findings allowing for assignment of the fragmentations to the loss of neutral H, H2, CN and HCN upon ionization of CH3NC. The computations show that in addition to the obvious bond breakings, some of the corresponding ionic fragments result from rearrangements - upon photon absorption - either before or after electron ejection

CO-17: Polymorphismes du gène de la t-cadhérine (CDH13), adiponectinémie et indice de stéatose hépatique dans DESIR

National audienceIntroduction Le Fatty Liver Index (FLI), indice de stéatose hépatique, prédit la survenue du diabète de type 2 à 9 ans dans l'étude D.E.S.I.R. L'adiponectine est une adipocytokine insulino-sensibilisatrice inversement associée à la stéatose hépatique. Nous avons montré que les polymorphismes du gène de la t-cadhérine (CDH13), récepteur des formes actives de l'adiponectine, sont associés au diabète de type 2 et à l'adiponectinémie. Le but de notre étude est d'approfondir les relations entre variations génétiques de CDH13 et le FLI. Patients et Méthodes Quatre polymorphismes de CDH13 (rs11646213, rs12051272, rs3865188, rs4783244) ont été génotypés dans la cohorte issue de la population générale, D.E.S.I.R. Nous avons sélectionné les sujets consommant des doses d'alcool < 30 g/jour pour les hommes et < 20 g/jour pour les femmes (n = 3 650). Les concentrations initiales d'adiponectine ont été dosées chez des sujets devenus hyperglycémiques à 3 ans et des témoins normoglycémiques appariés pour le sexe, l'âge et l'indice de masse corporelle (IMC) (N = 400). Nous avons réparti le FLI en deux classes en fonction du seuil discriminant pour la survenue du diabète de type 2 dans D.E.S.I.R. (< 70 et ≥ 70). Les relations entre polymorphismes et FLI ont été estimées par régression logistique, avec ajustement sur les facteurs confondants (sexe, âge, IMC, consommation d'alcool). Résultats Dans D.E.S.I.R., le FLI est inversement corrélé à la concentration d'adiponectine (p < 0,0001). Les 4 polymorphismes sont associés au FLI. Le risque d'avoir un FLI ≥ 70, à l'entrée et à la fin de l'étude, est diminué chez les porteurs de l'allèle mineur du rs3865188 (début : OR = 0,72 [95 % IC 0,57-0,92] ; fin : OR = 0,75 [0,61-0,92]) et du rs4783244 (début : OR = 0,74 [0,58-0,95] ; fin : OR = 0,77 [0,62-0,94]). Ce risque est augmenté en début d'étude pour les porteurs de l'allèle mineur du rs12051272 (OR = 5,55 [1,19-26,0]) et en fin d'étude pour les porteurs de l'allèle mineur du rs11646213 (OR = 1,22 [1-1,49]). Les résultats restent significatifs après ajustement sur l'HbA1c. Conclusions Les polymorphismes de CDH13, associés au diabète de type 2, sont également associés au FLI dans la population française. Cette association pourrait s'expliquer par des variations d'adiponectinémie et suggérer un lien de causalit

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

International audienceAimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population.MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n = 5212) and people with T2D in the DIABHYCAR study (n = 3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n = 230), and in controls who remained normoglycaemic (n = 226) throughout.ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P = 0.001) and 0.92 (95% CI: 0.87–0.98; P = 0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P = 0.03) and HbA1c (P = 0.006), and lower plasma adiponectin levels (P = 0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P = 0.03), HbA1c (P = 0.02) and Fatty Liver Index (FLI; P ≤ 0.01), and higher plasma adiponectin levels (P = 0.002). Associations with HbA1c, FLI and adiponectin levels persisted after adjusting for BMI.ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin

VUV photoionization and dissociative photoionization of the prebiotic molecule acetyl cyanide: Theory and experiment

International audienceThe present combined theoretical and experimental investigation concerns the single photoionization of gas-phase acetyl cyanide and the fragmentation pathways of the resulting cation. Acetyl cyanide (AC) is inspired from both the chemistry of cyanoacetylene and the Strecker reaction which are thought to be at the origin of medium sized prebiotic molecules in the interstellar medium. AC can be formed by reaction from cyanoacetylene and water but also from acetaldehyde and HCN or the corresponding radicals. In view of the interpretation of vacuum ultraviolet (VUV) experimental data obtained using synchrotron radiation, we explored the ground potential energy surface (PES) of acetyl cyanide and of its cation using standard and recently implemented explicitly correlated methodologies. Our PES covers the regions of tautomerism (between keto and enol forms) and of the lowest fragmentation channels. This allowed us to deduce accurate thermochemical data for this astrobiologically relevant molecule. Unimolecular decomposition of the AC cation turns out to be very complex. The implications for the evolution of prebiotic molecules under VUV irradiation are discussed