Light scattering on micellar solutions of N,N′-butyl- n-alkyl-1,4-diazabicyclo-[2,2,2]-octane derivatives of 3′-O-acylthymidine-5′-phosphates

Abstract

Zwitterionic N,N′-butyl- n-alkyl-1,4-diazabicyclo-[2,2,2]-octane derivatives of 3′-O-acylthymidine-5′-phosphates (DNOCl 2) are known to inhibit the growth of resistant neoplasm, and are superior to antineoplastic purine and pyrimidine bases, and nucleoside analogs. We studied both the intensity and the autocorrelation function of light scattered by these zwitterionic micelles for n = 4, 5 and 6. The biologically active surfactants have a high critical micellar concentration (CMC) (0.20–0.25 M), and the aggregates have low aggregation numbers which depend on pH, and on salt and temperature to a lesser degree. The dynamic behavior of the monomers of these zwitterionic surfactants is strongly dependent on surfactant concentration. The dynamics of the DNOCl 2 solutions are influenced by the monomer diffusion owing to the high CMC. Close to the CMC, premicellization exists at least for DNOCl 2, n = 6, and no significant effect on the dynamic properties of the solution is observed, although a sharp crossover on the scattered intensity is seen. From the scattered intensity measured above the CMC, and at large volume fractions, the aggregation numbers ( N agg) including sizes of the micellar aggregates were determined. The sizes remain constant with R H = 12.8Å ( n = 4), and vary between 15 Å ( n = 5) and 20 Å ( n = 6). Above the CMC classical hard-sphere behavior is observed from the volume fraction dependence. DNOCl 2 micelles with n = 6 have a strong attractive potential and must be considered for analyzing the experimental results. The effective diffusion coefficient decreases from the CMC, passes through a minimum and then varies linearly with increasing micelle concentration. This system of DNOCl 2 ( n = 4–6) reveals a heterogeneous solution: pure electrolyte behavior by the monomers, interactions between monomers and counterions, and micelles, showing hard-sphere behavior. The experimental data for DNOCl 2 micelles are consistent with a model of chemical exchange between monomers and micelles, and for a mixture of monomers and micelles.