INTERACTION OF 4-TERT-BUTYL-[3-(2-CHLOROETHYL)UREIDO] BENZENE WITH PHOSPHATIDYLCHOLINE BILAYERS - A DIFFERENTIAL SCANNING CALORIMETRY AND INFRARED-SPECTROSCOPY STUDY

We have investigated the interaction between a new antineoplastic drug , 4-tert-butyl-[3-(2-chloroethyl)ureido] benzene (tBCEU), and distearo ylphosphatidylcholine bilayers using differential scanning calorimetry , Fourier transform infrared spectroscopy (FT-IR), and high-pressure i nfrared spectroscopy. The results obtained with the three different te chniques indicate that the drug incorporates in the lipid bilayer. Mor e specifically, the incorporation of the tBCEU results in a decrease i n the phase transition temperature of the lipid and in an increase in the amount of gauche conformers in the liquid-crystalline phase. In th e gel phase, high-pressure FT-IR results indicate that the incorporati on of tBCEU decreases the acyl chain packing. In addition, the results suggest the presence of hydrogen bonding between the lipid carbonyl g roup and a hydrogen bond donor in the tBCEU molecule. A possible candi date for this donor is the NH group adjacent to the phenyl ring. A mod el is proposed for the incorporation of tBCEU in lipid bilayers, with the hydrophobic portion of the drug intercalated between the lipid bil ayers and the hydrophilic region located close to the interfacial regi on of the bilayer. (C) 1996 Academic Press, Inc.