Partition coefficient and molecular flexibility: the concept of lipophilicity space.

Details

Serval ID
serval:BIB_AB8B460889A5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Partition coefficient and molecular flexibility: the concept of lipophilicity space.
Journal
Chemistry & Biodiversity
Author(s)
Vistoli G., Pedretti A., Testa B.
ISSN
1612-1880[electronic]
Publication state
Published
Issued date
2009
Volume
6
Number
8
Pages
1152-1169
Language
english
Abstract
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.
Pubmed
Web of science
Create date
08/10/2009 15:29
Last modification date
20/08/2019 16:15
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