Complementary amphiphilic ribonucleotides confined into nanostructured environments

Abstract

This article focuses on the physico-chemical investigation of the time evolution of self-assembled structures composed by oppositely charged surfactant monomers. The cationic components were represented by the well known cetyl-trimethyl-ammonium-bromide (CTAB) while the anionic monomers consisted of amphiphilic ribonucleotide derivatives, also called nucleo-lipids (NL). The latter were generated in situ by direct reaction between a hydrophobic precursor, dodecyl epoxide (DE), and a pair of complementary ribonucleotide mono-phosphates: adenosine mono-phosphate (AMP) and uridine mono-phosphate (UMP). Analysis of reaction mixtures by liquid chromatography-electrospray ionization-single, tandem and sequential mass spectrometry (LC-ESI-MS, MS/MS and MS(3)) confirmed that the generated NL corresponded to ribonucleotides linked to one, two and even three hydroxy-dodecyl tails on their molecular structures and whose amounts had peculiar time dependences. In the solutions incubated with an equimolar mixture of both types of ribonucleotides, a remarkable positive feedback effect on the reaction products was ascribed to the contemporary presence of AMP and UMP. The variation of aggregate sizes, due to the incorporation process of NL monomers into starting CTAB micelles, was monitored through time-resolved measurements of both dynamic light-scattering (DLS) and electrophoretic mobilities, together with calculated zeta-(zeta)-potential. Finally, a kinetic model based on auto-catalytic mechanisms was outlined to analyze the process of the catanionic vesicles growth observed during the whole reaction time-course. The model was also in good agreement with MS data. The proposed colloidal system may be considered a simplified model whereby to study the potential role of complementary nucleic bases in triggering primitive chemical selections.

Microemulsion Microstructure(s): A Tutorial Review

“…µEs have an extremely large and dynamic interfacial area which can disintegrate and reform in the millisecond scale [ 95 ]. This characteristic structure favors the kinetics of reactions taking place in the nanometer-sized droplets and allows their application as microreactors in several catalytic processes [ 96 , 97 , 98 , 99 ]. In this respect, one of the main characteristics of µEs is the possibility of coexistence of polar and nonpolar solvents.…”

Cytosine to uracil conversion through hydrolytic deamination of cytidine monophosphate hydroxy‐alkylated on the amino group: a liquid chromatography – electrospray ionization – mass spectrometry investigation

“…A systematic investigation on the alkylation of ribonucleotides with 1,2‐dodecyl epoxide (DE) has been then recently undertaken by our research group . The reactivity of DE towards standard ribonucleotides was assumed as a model process, mimicking those potentially occurring on DNA or RNA exposed to long‐chained alkylating agents.…”

“…Moreover, even the OH groups of ribose were found to react, although more slowly, with DE. As a result, a quite complex mixture of mono‐, bi‐ and, after long reaction times, tri‐alkylated ribonucleotides was obtained . The strong potential for structural elucidation provided by tandem (MS 2 ) and sequential (namely MS 3 ) mass spectrometry enabled also the recognition of peculiar effects on reactivity due to the contemporary presence of UMP and AMP in the reaction environment, indicating the existence of an interaction between the complementary bases …”

“…A systematic investigation on the alkylation of ribonucleotides with 1,2-dodecyl epoxide (DE) has been then recently undertaken by our research group. [13][14][15] The reactivity of DE towards standard ribonucleotides was assumed as a model process, mimicking those potentially occurring on DNA or RNA exposed to long-chained alkylating agents. Indeed, a micellar environment provided by cetyl-trimethyl-ammonium-bromide (CTAB), an inert surfactant able to form spherical micelles in aqueous media, was adopted to investigate the role played by a polar/hydrophobic interface in the alkylation mechanism of common nucleotides.…”

“…[14,15] The strong potential for structural elucidation provided by tandem (MS 2 ) and sequential (namely MS 3 ) mass spectrometry enabled also the recognition of peculiar effects on reactivity due to the contemporary presence of UMP and AMP in the reaction environment, indicating the existence of an interaction between the complementary bases. [14,15] In order to verify the existence of a similar behaviour also for the other couple of complementary bases, cytosine and guanine, an extension of the investigation to the reaction of DE with cytidineand guanosine-monophosphate (cytidine monophosphate (CMP) and GMP, respectively) has been undertaken. In the present paper, the unexpected appearance of free UMP in the course of CMP alkylation, proved by a careful interpretation of ESI-MS and MS/MS data, will be discussed.…”