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F-Alkylated surfactants derived from tertiary amines: synthesis, biocompatibility and physicochemical properties
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B32 F-Alkylated surfactants derived from tertiary amines: synthesis, biocompatibility and physicochemical properties J. B. Nivet, M. Le Blanc and J. G. Riess Unit.3 de Chimie Moticulaire assoctie au CNRS, Universitt! de Nice-Sophia Fact&S d-es Sciences, 06108 Nice C&ex 2 (France)
Antipolis,
Fluorocarbon emulsions are being investigated as injectable gas carriers for in-vivo oxygen administration. New efficient as well as biocompatible surfactants are needed to improve control of the characteristics of such emulsions. These new surfactants need increased affinity for fluorocarbons; hence, to bear an F-alkylated tail. Therefore, we have synthesized several new series of pure, well deIined F-alkylated surfactants (zwitterionic 1, cationic 2 and nonionic 3) derived from perfluoroalkylated tertiary amines in 52 to 96% yield. R R&HZ)n-N:; RF-(CH~)$-(CH&,j-COO- Y Br(CH2),,,CCX3E1 r: 1
RX,
1 H202/CH3COOH )
RF-(CH&-P(I+-RXR
'
RF-(CH$,,-k-0 A
'
3
Their biocompatibility (effect on cell cultures, i.v. toxicity, hemolytic activity) and their physicochemical properties were compared to those of their hydrocarbon analogues. The F-alkylated surfactants were found to be less toxic than their hydrocarbon analogues in the zwitterionic series 1, where the F-alkyl derivatives were also found to be ca. lo3 times less hemolytic. This no longer holds for the cationic compounds 2 where the hemolytic activity appears to be comparable in the hydrocarbon or in the fluorocarbon series. The physicochemical evaluation of the new surfactants includes surface and water/fluorocarbon inter-facial tension measurements, calculations of CMC’s and areas of the polar heads at the airtwater interface (a,,). Within the zwitterionic series, the solubility in water is strongly dependent upon the distance between the charges in the polar head. The CMC’s are lowered and the interfacial properties improved by the presence of the F-alkyl chain. Furthermore, replacing a hydrocarbon fragment by a fluorinated one in the chain appears to decrease a,, for the zwitterionic and nonionic amphiphiles 1 and 3 while it has little or no effect on a, for the cationic compound 2. In the latter case dipole-dipole repulsions appear to be predominant.
B32 F-Alkylated surfactants derived from tertiary amines: synthesis, biocompatibility and physicochemical properties J. B. Nivet, M. Le Blanc and J. G. Riess Unit.3 de Chimie Moticulaire assoctie au CNRS, Universitt! de Nice-Sophia Fact&S d-es Sciences, 06108 Nice C&ex 2 (France)
Antipolis,
Fluorocarbon emulsions are being investigated as injectable gas carriers for in-vivo oxygen administration. New efficient as well as biocompatible surfactants are needed to improve control of the characteristics of such emulsions. These new surfactants need increased affinity for fluorocarbons; hence, to bear an F-alkylated tail. Therefore, we have synthesized several new series of pure, well deIined F-alkylated surfactants (zwitterionic 1, cationic 2 and nonionic 3) derived from perfluoroalkylated tertiary amines in 52 to 96% yield. R R&HZ)n-N:; RF-(CH~)$-(CH&,j-COO- Y Br(CH2),,,CCX3E1 r: 1
RX,
1 H202/CH3COOH )
RF-(CH&-P(I+-RXR
'
RF-(CH$,,-k-0 A
'
3
Their biocompatibility (effect on cell cultures, i.v. toxicity, hemolytic activity) and their physicochemical properties were compared to those of their hydrocarbon analogues. The F-alkylated surfactants were found to be less toxic than their hydrocarbon analogues in the zwitterionic series 1, where the F-alkyl derivatives were also found to be ca. lo3 times less hemolytic. This no longer holds for the cationic compounds 2 where the hemolytic activity appears to be comparable in the hydrocarbon or in the fluorocarbon series. The physicochemical evaluation of the new surfactants includes surface and water/fluorocarbon inter-facial tension measurements, calculations of CMC’s and areas of the polar heads at the airtwater interface (a,,). Within the zwitterionic series, the solubility in water is strongly dependent upon the distance between the charges in the polar head. The CMC’s are lowered and the interfacial properties improved by the presence of the F-alkyl chain. Furthermore, replacing a hydrocarbon fragment by a fluorinated one in the chain appears to decrease a,, for the zwitterionic and nonionic amphiphiles 1 and 3 while it has little or no effect on a, for the cationic compound 2. In the latter case dipole-dipole repulsions appear to be predominant.