pH-Dependent Complexation of Methacryloyloxydecyl Dihydrogen Phosphate (MDP) with Dipalmitoylphosphatidylcholine (DPPC) Liposomes: DSC and NMR Measurements

Internet Electronic Conference of Molecular Design 2004, November 23 – December 6 Abstract Motivation. Chelatable methacrylates with phosphate groups, such as MDP, have been used as tooth-bonding agents in dentistry [1, 2]. MDP has shown acceptable pulp response and clinical performance. However, the effect of MDP on biological membranes remains unknown. Liposomes have been employed in model systems at the membrane level to study the interaction of lipid-soluble drugs with biological membranes, and DSC and NMR spectroscopy have been used as powerful, yet relatively rapid and inexpensive, techniques for these studies. In the present study, we investigated the DSC phase-transition properties of DPPC liposomes induced by MDP and the changes in NMR chemical shifts of MDP associated with DPPC liposomes at various pH values. Method. DPPC/MDP (2:1 molar ratio) liposomes were prepared. Phase transition temperature (Tm) and enthalpy of DPPC/MDP liposomes were determined by DSC. H-NMR chemical shifts and coupling constants of DPPC/MDP liposomes were investigated in D2O at pH 2.4 and pH 7.0 at 25, 35 and 50 °C. HOMO, LUMO, and partial charges for COSMO (water) and non-COSMO (vacuum) were calculated by the PM3 semiempirical methods.. Results. The DSC main peak for DPPC/MDP at pH 2.4 was markedly broadened with a considerably decreased enthalpy, whereas a peak with a shoulder at 35 °C appeared at pH 7.0. At pH 2.4, H-NMR signals of MDP associated with DPPC liposomes were not found because of shielding, but those of the phosphodiester groups of DPPC were clearly apparent above or below the Tm. In contrast, at pH 7.0, signals of MDP together with those of DPPC appeared at 35 °C, above the Tm. The appearance of signals of MDP associated with DPPC liposomes was dependent on pH and Tm Conclusions. The DSC and NMR measurements suggest that DPPC-MDP complexation under acidic conditions probably occurs by the formation of hydrogen bonds between un-ionized dihydroxy phosphate groups of MDP and the phosphodiester functions of the DPPC surface. The PM 3 calculations contributed to interpretation of the NMR aspects of the interaction between MDP andliposomes.