Titre
Partition coefficient and molecular flexibility: the concept of lipophilicity space.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Vistoli, G.
Auteure/Auteur
Pedretti, A.
Auteure/Auteur
Testa, B.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1612-1880[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
6
Numéro
8
Première page
1152
Dernière page/numéro d’article
1169
Langue
anglais
Résumé
The rationale of this study was to investigate molecular flexibility and its influence on physicochemical properties with a view to uncovering additional information on the fuzzy concept of dynamic molecular structure. Indeed, it is now known that computed molecular interaction fields (MIFs) such as molecular electrostatic potentials (MEPs) and lipophilicity potentials (MLPs) are conformation-dependent, as are dipole moments. A database of 125 compounds was used whose conformational space was explored, while conformation-dependent parameters were computed for each non-redundant conformer found in the conformational space of the compounds. These parameters were the virtual log P (log P(MLP), calculated by a MLP approach), the apolar surface area (ASA), polar surface area (PSA), and solvent-accessible surface (SAS). For each compound, the range taken by each parameter (its property space) was divided by the number of rotors taken as an index of flexibility, yielding a parameter termed 'molecular sensitivity'. This parameter was poorly correlated with others (i.e., it contains novel information) and showed the compounds to fall into two broad classes. 'Sensitive' molecules are those whose computed property ranges are markedly sensitive to conformational effects, whereas 'insensitive' (in fact, less sensitive) molecules have property ranges which are comparatively less affected by conformational fluctuations. A pharmacokinetic application is presented.
PID Serval
serval:BIB_AB8B460889A5
PMID
Date de création
2009-10-08T13:29:06.184Z
Date de création dans IRIS
2025-05-20T22:14:10Z