Model Solvent Systems for QSAR Part I. Propylene Glycol Dipelargonate (PGDP). A new Standard Solvent for use in Partition Coefficient Determination

Abstract

Data for 216 partition coefficients in propylene glycol dipelargonate (PGDP) are given, along with 80 derived fragment values and a scheme for calculating the p.e. 2 correction from which many more log P values can be derived. PGDP log P and f‐values are contrasted with those of octanol and discussed in terms of the differing balance of proton donor/acceptor properties which these solvents show. It is suggested that PGDP, in conjunction with octanol, can be used as a model solvent probe for membrane binding and transport characteristics in ways that may have special relevance to biological selectivity.

Hydrophobicity Parameter of Diazines IV: A New Hydrogen‐Accepting Parameter of Monosubstituted (Di)azines for the Relationship of Partition Coefficients in Different Solvent Systems

“…t ͑S HA ͒ = 9.51 ͑␣ < 0.001͒; r 2 ͑log P oct , S HA ͒ = 0.366 (5) In the analysis for pyrimidines (III), the data of the 2-, 4-, and 5-substituted compounds in Table 3 were combined. Equations 6 and 7 indicate again the highly significant contribution of the S HA term: …”

“…1,2 Attention has been paid, however, to other partitioning systems to hopefully better simulate biological systems into which bioactive compounds are incorporated. [3][4][5][6][7][8][9] Moreover, the measurement of the P value by the "standard" shake-flask method is sometimes time-consuming and laborious, especially for very hydrophobic and very hydrophilic compounds. In this respect, the retention factor of reversed-phase liquid chromatography, which reflects the partitioning of compounds between stationary and mobile phases, has been expected to mimic the partitioning between two immiscible solvents.…”

Lipophilicity and Its Relationship with Passive Drug Permeation

“…Thus, four types of isotropic solvent systems (amphiprotic, inert, hydrogen-bond donor and hydrogen-bond acceptor), called the 'critical quartet' (e.g., n-octanol/water, alkanes/ water, chloroform/water, and dibutyl ether/water), are necessary in order to cover adequately the range of biophysical properties of membranes (35,36). The 'critical quartet' expresses in partly overlapping and partly complementary ways the recognition forces that account for membrane partitioning and biological selectivity (37,38).…”

Physicochemical Profiling in Drug Research and Development

“…In the past two decades, partition solvents other than octanol have been explored. Leahy et al [49] proposed the "critical quartet" system consisting of octanol/water, chloroform/water, alkane/water and propylene glycol dipelargonate (PGDP)/water for the general modeling of membranes. Later, 1,2-dichloroethane (DCE) and cyclohexane were found useful organic solvents.…”