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        Effect of bridgehead substitution on the fluorescence quenching of 2,3-diazabicyclo[2.2.2]oct-2-enes by solvents and antioxidants

        Meyer, Roland,Zhang, Xiangyang,Nau, Werner M. Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.12

        Azoalkanes of the 2,3-diazabicyclo[2.2.2]-oct-2-ene type have been introduced as probes for antioxidants in homogeneous solution as well as in liposomes and micelles. The bimolecular fluorescence quenching of the bridgehead dichloro-substituted 1,4-dichloro-2,3-diazabicyclo[2.2.2]-oct-2-ene (3) was compared with that of the parent compound 2,3-diazabicyclo[2.2.2]-oct-2-ene (1) and the bridgehead-dialkylated compound 4-methyl-1-isopropyl-2,3-diazabicyclo[2.2.2]-oct-2-ene (2). Compound 3 showed a more efficient fluorescence quenching in C-H containing solvents (e.g., in n-hexane: 30 ns for 3 versus 340 ns for 1 and 770 ns for 2), but a less efficient quenching in aqueous solution (e.g., in deaerated $H_2O$: 485 ns for 3 versus 420 ns for 1 and 340 ns for 2), and also by molecular oxygen ($k_q/10^9M^{-1}s^{-1}$ = 0.32 for 3 versus 2.5 for 1 and 1.9 for 2). Towards low-molecular weight antioxidants, compound 3 showed a significantly higher reactivity (e.g., for reduced glutathione: $k_q/10^9M^{-1}s^{-1}$ = 1.8 for 3 versus 0.82 for 1 and 0.39 for 2), at the expense of a lower differentiation between the investigated antioxidants (lower selectivity). The increased reactivity of 3 and lower, as well as qualitatively different, selectivity is attributed to a combination of factors, most importantly the slightly increased excitation energy of 3 and its lower excited-state nucleophilicity. The latter was independently corroborated, besides its longer fluorescence lifetime in aqueous solution, through the trends in quenching rate constants of the azoalkanes 1.3 towards electron-deficient versus electron-rich lactone antioxidants of the benzofuranone type. While common inorganic buffer constituents caused no fluorescence quenching, significant quenching was observed, as a curiosity, for hydrogencarbonate ($k_q/10^6M^{-1}s^{-1}$ = 1.7 for 3 versus 2.4 for 1 and 0.45 for 2), with a fully manifested kinetic deuterium isotope effect ($k_q(H_2O)/k_q(D_2O)$ = 12) for 3.

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        Aged mice show an increased mortality after anesthesia with a standard dose of ketamine/xylazine

        Sandra Schuetze,Anja Manig,Sandra Ribes,Roland Nau 한국실험동물학회 2019 Laboratory Animal Research Vol.35 No.2

        Geriatric animal models are crucial for a better understanding and an improved therapy of age-related diseases. We observed a high mortality of aged mice after anesthesia with a standard dose of ketamine/xylazine, an anesthetic regimen frequently used in laboratory veterinary medicine. C57BL/6-N mice at the age of 2.14 ± 0.23 months (young mice) and 26.31 ± 2.15 months (aged mice) were anesthetized by intraperitoneal injection of 2 mg ketamine and 0.2 mg xylazine. 4 of 26 aged mice (15.4%) but none of 26 young mice died within 15 min after injection of the anesthetics. The weight of aged mice was significantly higher than that of young mice (32.8 ± 5.4 g versus 23.2 ± 3.4 g, p < 0.0001). Thus, aged mice received lower doses of anesthetics in relation to their body weight which are within the lower range of doses recommended in the literature or even beneath. There were no differences between deceased and surviving aged mice concerning their sex, weight and their motor performance prior to anesthesia. Our data clearly show an age-related increase of mortality upon anesthesia with low standard doses of ketamine/ xylazine. Assessment of weight and motor performance did not help to predict vulnerability of aged mice to the anesthetics. Caution is necessary when this common anesthetic regimen is applied in aged mice: lower doses or the use of alternative anesthetics should be considered to avoid unexpected mortality. The present data from our geriatric mouse model strongly corroborate an age-adjusted reduction of anesthetic doses to reduce anesthesia-related mortality in aged individuals.

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