13 research outputs found

    Ion−Molecule Pairs in Leaving-Group-Promoted Solvolytic Elimination Reactions

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    Concerted and stepwise solvolytic elimination and substitution reactions: Stereochemistry and substituent

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    Abstract: Solvolysis of the R,R and R,S isomers 2a-X and 2b-X, respectively, (X ) I, Br, OBs) in 25 vol % acetonitrile in water gives the elimination products 4, 5a, and 5b along with the substitution products 2a-OH, 2b-OH, 2a-NHCOMe, and 2b-NHCOMe. The rates of elimination (k E ) increase with increasing acidity of the -hydrogen of the substrate as expressed by a Brønsted parameter of R ) 0.08 and 0.07 for the iodides and the bromides, respectively. In contrast, the brosylates, which give much smaller fractions of the stable alkenes, exhibit a negatiVe Brønsted parameter for the elimination, R ) -0.10. This shows that the brosylates, in contrast to the halides, do not give elimination exclusively by a solvent-promoted E1cB reaction or an E2 reaction with a large component of hydron transfer in the transition state and indicates a large amount of reaction through carbocation intermediates to give stable alkenes

    The clinical safety, biodistribution and internal radiation dosimetry of [F-18]AH113804 in healthy adult volunteers

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    Background: Quantitative biodistribution, venous blood and excretion data have been obtained following the intravenous bolus injection of AH113804 (F-18) Injection in six healthy volunteers (HVs), four males and two females, up to approximately 5 h post-injection. For each subject, key organs and tissues were delineated and analytical fits were made to the image data as functions of time to yield the normalised cumulated activities. These were input to an internal radiation dosimetry calculation based upon the Medical Internal Radiation Dose (MIRD) schema for the Cristy-Eckerman adult male or female phantom. The absorbed doses per unit administered activity to the 24 MIRD-specified target organs were evaluated for an assumed 3.5-h urinary bladder voiding interval using the Organ Level INternal Dose Assessment/Exponential Modelling (OLINDA/EXM) code. The sex-specific absorbed doses were then averaged, and the effective dose per unit administered activity was calculated. Results: Excluding the remaining tissue category, the three source regions with the highest mean initial F-18 activity uptake were the liver (18.3%), lung (5.1%) and kidney (4.5%) and the highest mean normalised cumulated activities were the urinary bladder contents and voided urine (1.057 MBq h/MBq), liver (0.129 MBq h/MBq) and kidneys (0.065 MBq h/MBq). The three organs/tissues with the highest mean sex-averaged absorbed doses per unit administered activity were the urinary bladder wall (0.351 mGy/MBq), kidneys (0.052 mGy/MBq) and uterus (0. 031 mGy/MBq). Conclusions: AH113804 (F-18) Injection was safe and well tolerated. Although the effective dose, 0.0298 mSv/MBq, is slightly greater than for other common F-18 PET imaging radiopharmaceuticals, the biodistribution and radiation dosimetry profile remain favourable for clinical PET imaging
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