Photophysical characterization of atorvastatin (Lipitor®) ortho-hydroxy metabolite: role of hydroxyl group on the drug photochemistry.
The influence of the phenolic hydroxyl group of ortho-hydroxy atorvastatin metabolite (Ato-OH) on the photochemistry of atorvastatin (Ato) has been evaluated by steady and time-resolved experiments. Direct excitation of Ato and Ato-OH led to phenanthrene-like intermediate formation, being ∼30% for Ato-OH less efficient than that for its parent compound in methanol. Both, Ato and Ato-OH are able to quench benzophenone (E(T)∼69 kcal mol(-1)) and xanthone (E(T)∼74 kcal mol(-1)) triplet excited state with rate constants close to diffusion limit control which suggest energy transfer mechanism is taking place. In fact, lower triplet energies ∼63 kcal mol(-1) and π,π* character, were confirmed by DFT calculations for both compounds. Interestingly, only Ato-OH can act as a hydrogen donor towards triplet benzil excited state (E(T)∼ 54 kcal mol(-1)) due to the presence of the phenolic hydroxyl group. Nevertheless, the presence of this group in Ato-OH does not modify to a significant degree the compound reactivity toward singlet oxygen. The importance of triplet energy transfer in biological systems to form Ato and Ato-OH triplet excited state as well as the hydrogen donor capacity of Ato-OH toward triplet excited state are discussed in the present communication.
Alarcón
Emilio
E
Department of Chemistry and Centre for Catalysis Research and Innovation, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5.
González-Béjar
María
M
Gorelsky
Serge
S
Ebensperger
Roberto
R
Lopez-Alarcón
Camilo
C
Netto-Ferreira
José Carlos
JC
Scaiano
Juan C
JC
D000069059:Atorvastatin / Q000031:analogs & derivatives; D004735:Energy Transfer; D006538:Heptanoic Acids / Q000737:chemistry* / Q000378:metabolism; D006859:Hydrogen / Q000737:chemistry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D000432:Methanol / Q000737:chemistry; D055668:Photochemical Processes; D010782:Photolysis; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism; D011789:Quantum Theory; D026082:Singlet Oxygen / Q000737:chemistry; D013816:Thermodynamics
C518963:2-hydroxyatorvastatin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D026082:Singlet Oxygen; D006859:Hydrogen; D000069059:Atorvastatin; D000432:Methanol