Axial and equatorial cyclohexylacyl and tetrahydropyranyl-2-acyl radicals. An experimental and theoretical study.
Axial and equatorial cyclohexylacyl and tetrahydropyranyl-2-acyl radicals gave distinct EPR spectra thanks to surprisingly large beta-hydrogen atom hyperfine splittings that enabled them to be characterized and monitored. DFT computations indicated that the axial species (X = CH(2)) had a higher barrier to rotation about the (O)C(alpha)-C(beta) bond. The computed difference Delta H degrees for the axial and equatorial radicals (R = H, X = CH(2)) was 0.8 kcal mol(-)(1).
Cycloalkylmethyl radicals. Part 8. A conformational study of dioxa- and dithia-cyclohexylmethyl radicals by EPR spectroscopy
The conformations of some six-membered oxygen- and sulphur-containing heterocyclic rings have been investigated by EPR spectroscopy using the methylenyl group, CH2˙, directly attached to a ring carbon atom as a, ‘spin probe’. For the 2-oxacyclohexylmethyl radical the CH2˙ group has a ‘conformational free energy’ preference for the equatorial position, –ΔG°273= 1.4 kcal mol–1, which is about twice as large as the 0.7 kcal mol–1 found previously for cyclohexylmethyl. The equatorial preference of the CH2˙ group is still greater in (1,3-dioxan-2-yl)methyl radicals; indeed, even with the cis-(5-tert-butyl-1,3-dioxan-2-yl)methyl radical the CH2˙ group was equatorial and the tert-butyl group axial. The CH2˙ group in (1,3-dioxan-5-yl)methyl also exhibits a strong preference for the equatorial position (ΔG° > ca. 1.5 kcal mol–1), but with cis-(2-methyl-1,3-dioxan-5-yl)methyl it is the methyl group which is equatorial and the CH2˙ group axial. These and other axial/equatorial conformational preferences and the rotational conformational preference of the plane of the CH2˙ group with respect to the Cβ–Hβ bond are rationalized in terms of subtle steric factors which involve 1,3-axial/axial interactions, or lack thereof, and the variation in the lengths of C–C, C–O and C–S bonds.
Rotating dialysis cell as in vitro release method for oily parenteral depot solutions.
The purpose of the study was to investigate an in vitro release method based on a rotating dialysis cell for parenteral oil depot formulations using different model conditions and test formulations. The total amount of drug released from the rotating dialysis cell was in accordance with the theoretical values calculated from the partition coefficients. The release rates were shown to depend on the total amount of drug available for the release process and to follow first order kinetics. The rotating dialysis cell has a potential as in vitro release method for characterization of oily depot formulations for parenteral administration.