version date: 1 December 2006 enthalpic and entropic phenomena [9 The hydrophobic character of different amino acids was deeply studied, and the possibility of creating amino acid hydrophobicity scales was pursued by several biochemical researchers with different methods and approaches [10, 11]. A complete understanding of the forces that guide amino acid interactions within proteins could lead to the prediction of protein structure and processes that drive a protein to fold into its native form The octanol/water partition coefficient(log Porw)constitutes a quantitative, and easily accessible, hydrophobicity measurement. P is defined as the ratio of the equilibrium concentration of a substance dissolved in a two-phase system, formed by two immiscible solvents PoN C water As a result, the partition coefficient P is the quotient of two concentrations and is normally calculated in the form of its logarithm to base 10 (log P), because P ranges from 10 to 10 Log p values are widely used in bio-accumulation studies, in drug absorption and toxicity predictions and, recently, even in biological interactions modeling [ 12, 13]. Several endeavours have been carried out to develop rapid and reliable log P estimation methodologies, capable of predicting the partition coefficient values for compounds not experimentally tested The common and standard procedure adopted for experimental log P estimation is the shake- flask method, used to determine the hydrophobicity of compounds ranging from -2 to 4 log P values. Log P>0 characterize hydrophobic substances soluble in the lipid phase, while log P<0 typifies polar compounds soluble in the water phase(Panel 1) <www.iupac.org/publications/cd/medicinalchemistry/>2 enthalpic and entropic phenomena [9]. The hydrophobic character of different amino acids was deeply studied, and the possibility of creating amino acid hydrophobicity scales was pursued by several biochemical researchers with different methods and approaches [10,11]. A complete understanding of the forces that guide amino acid interactions within proteins could lead to the prediction of protein structure and processes that drive a protein to fold into its native form. The octanol/water partition coefficient (log PO/W) constitutes a quantitative, and easily accessible, hydrophobicity measurement. P is defined as the ratio of the equilibrium concentration of a substance dissolved in a two-phase system, formed by two immiscible solvents: PO/W = water octanol c c As a result, the partition coefficient P is the quotient of two concentrations and is normally calculated in the form of its logarithm to base 10 (log P), because P ranges from 10–4 to 108 . Log P values are widely used in bio-accumulation studies, in drug absorption and toxicity predictions and, recently, even in biological interactions modeling [12,13]. Several endeavours have been carried out to develop rapid and reliable log P estimation methodologies, capable of predicting the partition coefficient values for compounds not experimentally tested. The common and standard procedure adopted for experimental log P estimation is the shake￾flask method, used to determine the hydrophobicity of compounds ranging from –2 to 4 log P values. Log P > 0 characterize hydrophobic substances soluble in the lipid phase, while log P < 0 typifies polar compounds soluble in the water phase (Panel 1). <www.iupac.org/publications/cd/medicinal_chemistry/> version date: 1 December 2006