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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. January 2006, Volume 5, Number 1, 49-59 |
pH-Dependent Complexation of Methacryloyloxydecyl Dihydrogen Phosphate
(MDP) with Dipalmitoylphosphatidylcholine (DPPC) Liposomes:
DSC and NMR Measurements
Seiichiro Fujisawa, Mariko Ishihara, and Yoshinori Kadoma
Internet Electron. J. Mol. Des. 2006, 5, 49-59
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Abstract:
Chelatable methacrylates with phosphate groups, such as MDP,
have been used as tooth-bonding agents in dentistry. 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.
DPPC/MDP (2:1 molar ratio) liposomes were prepared. Phase
transition temperature (Tm) and enthalpy of DPPC/MDP
liposomes were determined by DSC. 1H-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, partial charges, dipole moments,
hydrophobicities (octanol-water partition coefficient, log P) for
COSMO (water) or non-COSMO (vacuum) were calculated by
the PM3 semiempirical method. 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, 1H-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. 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 log P for un-ionized MDP was an order of magnitude greater
than that for ionized one, suggesting that the strong DPPC-MDP
complexation possibly arises from hydrophobic interactions
between acyl chains of DPPC and un-ionized MDP. The PM3
calculation for HOMO and/or LUMO energy in COSMO
suggested that the HOMO for DPPC probably interacts
preferentially with the LUMO for un-ionized MDP. Charges-dipole,
dipole-dipole interactions are probably of restricted
importance for a minor driving force for DPPC-MDP
interactions. The PM3 calculations contributed to interpretation
of the NMR aspects of the interaction between MDP and
liposomes.
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