Effect of the Hydrophilic/Hydrophobic Pendants on Physicochemical Properties: Applications Based on Cyclotriphosphazene Core

Abstract

This study focused on investigating the effect of hydrophilic and hydrophobic substituents on the physicochemical properties for medical applications. In this study, to understand the effect of hydrophilic and hydrophobic substituents on physicochemical parameters such as lipophilicity and thermosensitivity, a series of cis-tris nongeminal [N3P3(R1-4)(3)(Ra-f)(3)] cyclotriphosphazenes [R1-4=diethylene glycol monomethyl ether (DEGME), triethylene glycol monomethyl ether (TEGME), methoxypolyethylene glycol (mPEG350), methoxypolyethylene glycol-550 (mPEG550); (2-5) respectively; Ra-f=pyrazole, 3,5-dimethylpyrazole, imidazole, 2-methyl imidazole, benzimidazole, 5,6-dimethyl benzimidazole, [2(a-f), 3(a-f), 4(a-f), 5(a-f)] respectively] were synthesized and fully characterized by mass, P-31 and H-1 NMR spectroscopies. Solubility and thermosensitivity based on substituent dependent LCST (lower critical solution temperature) behaviour of all synthesized molecules are investigated. Each compound analysed by HPLC to determine the lipophilicity values (logP(o/w)) between n-octanol and water. A good correlation (r=0.9975 and R-2=0.9948) was observed between the experimentally determined logP(o/w) and estimated milogP values. The results showed that LCST values of the reported compounds were linearly correlated with their lipophilicity values.