2024-03-29T14:39:26Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2206782020-12-24T04:50:28Zcom_10261_99com_10261_5col_10261_352
Hydrogen Abstraction from the C15 Position of the Cholesterol Skeleton
Palumbo, Fabrizio
Andreu, Inmaculada
Brunetti, M.
Schmallegger, M.
Gescheidt, G.
Neshchadin, D.
Miranda, M. A.
Generalitat Valenciana
Hydrogen
Hydrocarbons
Free radicals
Aromatic compounds
Polarization
Cholesterol (Ch) is an integral part of cell membrane, where it is prone to oxidation. In humans, oxidation of Ch is commonly linked to various pathologies like Alzheimer's disease, atherosclerosis, and even cancer, which proceed via mechanisms involving enzymatic and free radical pathways. The latter begin with hydrogen abstraction (HA) from Ch by a reactive free radical. It has been established that the most efficient HA from Ch occurs at C7, although HA from C4 by peroxyl radicals has recently been observed. Conversely, HA from Ch positions other than the thermodynamically preferred C7 or C4 has never been reported. We have designed a Ch derivative where a benzophenone moiety is linked to C7 by a covalent bond. This mirrors a specific orientation of Ch within a confined environment. Product analysis and time-resolved spectroscopic studies reveal an unprecedented HA from C15, which is a thermodynamically unfavorable position. This indicates that a specific topology of reactants is crucial for the reactivity of Ch. The relative orientation of the reactants can also be relevant in biological membranes, where Ch, polyunsaturated fatty acids, and numerous oxidizing species are confined in highly restricted and anisotropic environments.
2020-10-02T10:50:01Z
2020-10-02T10:50:01Z
2019-11-01
2020-10-02T10:50:02Z
artículo
Journal of Organic Chemistry 84(23): 15184-15191 (2019)
http://hdl.handle.net/10261/220678
10.1021/acs.joc.9b02181
http://dx.doi.org/10.13039/501100003359
Postprint
http://dx.doi.org/10.1021/acs.joc.9b02181
Sí
openAccess
ACS Publications