APPLICATION AUX ETUDES STRUCTURE-ACTIVITE
II. 3 - Dynamique des complexes ligand/récepteur
II.3. B.6 - Les interactions hydrophobes
L'eau est un solvant qui a la particularité d'avoir ses molécules connectées par un réseau interne de liaisons hydrogènes. L'introduction de molécules présentant des zones hydrophobes, c'est à dire non polaires, entraîne la rupture d'un certain nombre de ces liaisons. Chaque molécule de soluté prise séparément, exposée aux molécules d'eau, contribuerait à une augmentation défavorable de l'énergie libre du système soluté/solvant (facteur entropique). Si les zones non polaires des molécules s'auto-associent, l'effet perturbateur sur le solvant est moins important que les effets combinés pris séparément, l'association des zones non polaires est donc thermodynamiquement plus favorable. Cette association est appelée interaction hydrophobe ou lipophile, et résulte de la
coefficient de partage n-octanol/eau (Log POW), le couple n-octanol/eau ayant été choisi pour ses propriétés de partage proches de celles du milieu biologique153. La lipophilie globale d'une drogue intervient essentiellement lors du franchissement des membranes biologiques rencontrées durant l'acheminement de celle-ci vers son site récepteur. Une drogue diffusera d'autant mieux à travers la bicouche phospholipidique des membranes que son coefficient de partage sera élevé en faveur de la phase non aqueuse, mais un trop fort coefficient gênera son transport dans les milieux aqueux.
L’ensemble de ces forces est en général représenté, par des composantes, dans les champs de forces.
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