Conformations of a non-steroidal anti-inflammatory drug nabumetone in aqueous environments

Citation
M. Valero et al., Conformations of a non-steroidal anti-inflammatory drug nabumetone in aqueous environments, J PHOTOCH A, 132(1-2), 2000, pp. 67-74
Citations number
29
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physical Chemistry/Chemical Physics
Journal title
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
ISSN journal
1010-6030 → ACNP
Volume
132
Issue
1-2
Year of publication
2000
Pages
67 - 74
Database
ISI
SICI code
1010-6030(20000320)132:1-2<67:COANAD>2.0.ZU;2-L
Abstract
Spectroscopic and photophysical properties of a non-steroidal anti-inflamma tory drug, Nabumetone, were studied in dioxane/water mixtures, cyclodextrin s (alpha-CD, beta-CD and HP-beta-CD) and besides that, for comparison, in a wide range of solvents with different polarities, viscosities and hydrogen bonding ability. The fluorescence quantum yields (phi(f)) and lifetimes (tau(f)) in aqueous and in non-aqueous media, present some evidence which points to the existen ce of two preferred conformations in aqueous media: one with global phi(f)= 0.1-0.3 and tau(f)(2)=7 ns, corresponding to the side chain completely exte nded and the other one, with lower global phi(f)=0.02-0.08 and tau(f)(1)=0. 7-2 ns, likely associated with a folded conformation responsible for the fl uorescence quenching of the naphthalene moiety by the butanone chain. The f ormation of one or other conformation is not much affected by the physical properties of the solvent. By contrast, the presence of water creates a ver y favourable environment for the formation of the folded conformation, whic h is essentially the only one in pure water. This behaviour is explained by a water-structure enforced hydrophobic effect and makes this drug a good w ater sensitive probe. Inclusion of the drug in the beta-cyclodextrin emphas ises the existence of two conformations, whereas in alpha-CD only the exten ded one is present, with a much higher phi(f)=0.4 and tau(f)=15.7 ns. Molec ular mechanics (MM) and molecular orbital (MNDO) calculations also support the existence of two possible conformations in Nabumetone. (C) 2000 Elsevie r Science S.A. All rights reserved.