Effect of beta-cyclodextrin complexation on the photochemical and photosensitizing properties of tolmetin: a steady-state and time-resolved study.
The effects of beta-cyclodextrin complexation on the photochemical and photosensitizing properties of tolmetin have been investigated. Absorption, emission, circular dichroism and NMR measurements were used to characterize the host-guest complex. Nanosecond laser flash photolysis and steady-state photolysis experiments were performed to clarify the photoreactivity of the drug in the macrocycle. The decarboxylation of the drug is markedly reduced upon inclusion and the rate constants of the decay of the transient intermediates involved in tolmetin photodecomposition were slowed down due to their incorporation in the hydrophobic cavity. This also influenced the distribution of the stable photoproducts. A remarkable cyclodextrin-mediated protection against the tolmetin-photoinduced damage on biological substrates was observed. A rationale for these biological effects is provided.
Sortino
S
S
Department of Chemistry, University of Ottawa, Ontario, Canada.
Scaiano
J C
JC
De Guidi
G
G
Monti
S
S
D003505:Cyclodextrins / Q000737:chemistry / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D010777:Photochemistry; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects / Q000528:radiation effects; D014046:Tolmetin / Q000737:chemistry / Q000494:pharmacology*; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D017319:Photosensitizing Agents; D047392:beta-Cyclodextrins; D014046:Tolmetin; C031215:betadex