Spectroscopy and Recognition Chemistry of Micelles from Monoalkyl Phosphoryl Nucleosides

Abstract

We describe the properties of aqueous micelles obtained from n-alkyl phosphoryl nucleosides, in particular n-hexadecylphosphoryladenosine (C16-AMP), uridine (C16-UMP), and -cytidine (C16-CMP). These compounds were obtained enzymatically. It is shown that each of these compounds form micelles spontaneously in water with a critical micelle concentration in the range of 20−35 μM and an aggregation number of 69, which indicates that the chemical structure of the bases has no significant influence on the aggregation behavior. UV-absorption and circular dichroic measurements suggest that the nucleoside is in an aqueous environment, as expected from the amphiphilic character of the compounds. UV absorption suggests a moderate self-stacking among the bases for each type of micelle. When we mixed micelles bearing complementary bases with each other (e.g., C16-AMP with C16-CMP), a weak hypochromic effect was observed, which can be taken as an indication of complementary base interaction. However, such electronic perturbation was observed also in noncomplementary bases, e.g., when C16-CMP micelles were mixed with C16-UMP micelles. These micelle data are compared with the corresponding data obtained with liposomes obtained from phosphatidyl nucleosides. All together, these data illustrate a novel type of polymeric nucleoside interaction with which no covalent bonds form among the monomers, and in which the nucleobases are distributed as a supramolecular spherical aggregate.

NMR Study of Micelles Formed by Monoalkylphosphoryl Nucleosides

“…Both the aromatic as well as the aliphatic proton signals can be investigated. The most relevant observation on this 1 H-NMR spectrum is the strong upfield shift of the resonances of the Me group and more generally of the fatty chain as a whole, compared to the spectra obtained in organic solvents as observed already in our preliminary study [2].…”

“…To understand the properties of complementary binding and recognition in a compartmentalized system, our groups have carried out an investigation of phosphatidyl nucleosides obtained from complementary nucleo-bases such as 5'-(1,2-dialkyl-snglycero(3)phospho)adenosine and 5'-(1,2-dialkyl-sn-glycero(3)phospho)uridine [1], which form liposomes, as well as single-chain lipids such as hexadecylphosphoryladenosine, which form micelles in H 2 O [2]. These compounds can be readily synthesized by a biphasic enzymatic reaction originally developed by Shuto et al [3] [4].…”

“…The system forms micelles in D 2 O and, since its CMC is extremely low [2], i.e., in the range of 20 ± 35 mm, the best way to study the demicellization process is to warm the sample, thus inducing melting of the micelles.…”

“…Note, in particular, the large chemical-shift dependence of the Me group (> 0.3 ppm), the CH 2 (11) (> 0.3 ppm), and HÀC(8) (> 0.2 ppm), while the resonances due to HÀC (2) and to the anomeric proton show a very modest temperature dependence (< 0.05 ppm). Thus, different chemical groups are affected by a different local microenvironment.…”

“…Assuming an aggregation number of 70 [2], the presence of an upfield shift would be 70 Â 2 Hz (single average upfield shift), i.e., ca. 140 Hz.…”