Catalipids with fluorine label

In 31P-NMR studies the formation of EDC activated phosphate (P*) as well as the phosphorimidazolide formation after reaction with a catalipid is expected to be monitorable (Figure 24). On the other hand, 19F-NMR is expected to allow studying the behaviour of fluorinated catalipids in the reaction mixture by observing the chemical shifts of the fluorine atoms. Thus 19F-NMR measurements should allow one to determine the concentration (cmc), temperature and pH at which the fluorinated amphiphiles form micelles. [39]


Figure 24   Activation of 5'-GMP with EDC and phosphorimidazolide formation with a catalipid


Figure 25   Micelle formation of catalipid-activated 5'-GMP. Potential oligomerization might take place on the surface of micelles.

In such micelles the activated nucleotide phosphates are in close proximity and might react to give oligomeric products which could be detected using mass spectroscopy (Figure 25). Fluorine-containing catalipids are accessible by coupling of ω-fluorinated carboxylic acids to histamine. The required ω-fluorinated carboxylic acids were synthesized starting from the corresponding ω hydroxy compounds. The synthesis of 6-fluorohexanoic acid 22 and 8-fluorooctanoic acid 23 are shown in figure 26 and 27 [40] The ω-fluorinated catalipids MC6FH (24) and MC8FH (25) were obtained after chromatographic work-up and characterized by NMR and MALDI mass spectroscopy (Figure 28).

Figure 26   Synthesis of 6-fluorohexanoic acid 22


Figure 27   Synthesis of 8-fluoroocatanoic acid 23


Figure 28   Synthesis of MC6FH (24) and MC8FH (25)

Experiments towards replication coupled to metabolism and compartmentation as described are in progress.