title: Solvation enthalpies as descriptors of structure--in vitro percutaneous permeation relationship of benzoxazinones regioisomers.
abstract: The aim of this work was to correlate the in vitro human skin permeability, expressed as the permeability coefficient (Kp), and some physicochemical parameters of a new series of benzoxazinones. The in vitro human skin permeability of 14 substances, including regioisomers with CH3, OH, OCH3, and Cl groups in different positions on the aromatic ring, was determined. The modified Franz diffusion cell method was used. The Kp values were in the range 0.14-8.24 cm/h, showing a strong dependence on the position and type of substituent. Physicochemical descriptors usually referred in literature, such as log P, molecular weight and volume (MV), hydrogen bond donor (Hd) and acceptor activity (Ha), and molecular refractivity were considered, with the addition of solvation enthalpy (delta deltaHsolv). Delta deltaHsolv is defined as the difference between formation enthalpies in water and octanol. The algorithm with the best correlation between Kp and physicochemical descriptors was calculated, taking into account the differences observed among the regioisomers. The algorithm obtained with delta deltaHsolv had a good correlation (r2 = 0.749, F = 16.43, P = 0.0005), comparable with the equation, proposed by Potts and Guy, based on MV, Hd and Ha (r2 = 0.830, F = 16.3, P = 0.0004).
authors.affiliation: Istituto di Chimica Farmaceutica e Tossicologica, Università degli Studi di Milano, Milan, Italy. paola.minghetti@unimi.it
authors.forename: P
authors.initials: P
authors.lastname: Minghetti
authors.forename: A
authors.initials: A
authors.lastname: Casiraghi
authors.forename: F
authors.initials: F
authors.lastname: Cilurzo
authors.forename: L
authors.initials: L
authors.lastname: Montanari
authors.forename: M V
authors.initials: MV
authors.lastname: Monzani
authors.forename: G
authors.initials: G
authors.lastname: Bertolini
authors.forename: A
authors.initials: A
authors.lastname: Zaliani
mesh_terms: D006801:Humans; D007536:Isomerism; D010539:Permeability; D012867:Skin / Q000378:metabolism*; D012997:Solvents; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D012997:Solvents