Intramolecular Cation−π Interactions As the Driving Force To Restrict the Conformation of Certain Nucleosides

Abstract

Despite the well-established importance of intermolecular cation-pi interactions in molecular recognition, intramolecular cation-pi interactions have been less studied. Here we describe how the simultaneous presence of an aromatic ring at the 5'-position of an inosine derivative and a positively charged imidazolium ring in the purine base drive the conformation of the nucleoside toward a very major conformer in solution that is stabilized by an intramolecular cation-pi interaction. Therefore, the cation-pi interaction between imidazolium ions and aromatic rings can also be proposed in the design of small molecules where this type of interaction is desirable. The imidazolium ion can be obtained by a simple acidification of the pH of the media. So a simple change in pH can shift the conformational equilibrium from a random to a restricted conformation stabilized by an intramolecular cation-pi interaction. Thus the here described nucleosides can be considered as a new class of pH-dependent conformationally switchable molecules.

Cation−π Interaction: Its Role and Relevance in Chemistry, Biology, and Material Science

“…However they opine that this π type bonding is energetically feasible, only in the absence of perturbing forces. Studies investigating the simultaneous presence of an aromatic ring at the 5′-position of an inosine derivative and a positively charged imidazolium ring in a purine base reveal how an intramolecular cation−π interaction drives the conformation of the nucleoside toward a very major conformer in solution …”

Synthetic Polyamines to Regulate mRNA Translation through the Preservative Binding of Eukaryotic Initiation Factor 4E to the Cap Structure

“…Although detailed insights into the molecular mechanisms have yet to be clarified, it may be worth discussing the possible interaction of the cap structure with the positively charged repeats in the side chain of polyamines. We here notice that the m 7 G group in the cap structure is protonated at cytoplasmic pH and is the only positively charged group in an mRNA strand. − Then, it may be reasonable to assume that this positive charge would generate electrostatic repulsion against the positively charged repeat in the side chains of N-substituted polyaspartamides. The cap structure locates at the 5′ end of mRNA and presumably has flexibility high enough to expose itself to the exterior, so as to minimize electrostatic repulsion against protonated amino groups in complexed polyamines.…”

Transforming Tea Catechins into Potent Anticancer Compound: Analysis of Three Boronated-PEG Delivery System

“…The three solutions are also made up of at least one benzene ring and also have intermolecular interactions through pi stacking. These intermolecular interactions are the driving force for each solution's self-assembly process in nanoparticle synthesis [19]. Each solution is also conjugated with polyethylene glycol-boronic acid (PEG-Br) to bind to the hydroxyl groups and form the shell of the nanoparticle (Figure 5B).…”