Fluorometric Recognition of Nucleotides within a Water‐Soluble Tetrahedral Capsule

Abstract

The design of aqueous probes and binders for complex, biologically relevant anions presents akey challenge in supramolecular chemistry.H erein, at etrahedral assembly with cationic faces and corners is reported that is capable of discriminating between anionic and neutral guests in water. Electrostatic repulsion between subcomponents can be overcome by the addition of an anionic template,o rg enerating ar obust covalent framework by incorporating tris(2-aminoethyl)amine (TREN). The resultant TREN-capped, watersoluble,f luorescent cage binds mono-and poly-phosphoric esters,i ncluding nucleotides.I ts covalent skeleton renders it stable at micromolar concentrations in water,e nabling the fluorometric detection of biologically relevant guests in an aqueous environment. Selective supramolecular encapsulants, such as 1,c ould enable new sensing applications,s uch as recognition of toxins and drugs,u nder biological conditions.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Design and Applications of Water-Soluble Coordination Cages

“…We recently developed a fluorescent tetrahedral assembly equipped with cationic faces that is capable of discriminating between anionic and neutral guests in water, while allowing fluorometric detection at micromolar concentrations in water at neutral pH. 220 …”

“…(b) While neutral molecules and nucleobases were not encapsulated, their anionic congeners, including nucleotides, were bound in fast exchange; affinity constants were measured from NMR titration experiments. 220 …”

Stabilization and Multiple-Responsive Recognition of Natural Base Pairs in Water by a Cationic Cage

“…To address these problems, supramolecular scientists try to study molecular recognition or self-assembly in aqueous environments by using water-soluble hosts such as clips, macrocycles, and cages through host-guest complexation. [9][10][11][12][13][14] For example, Isaacs and coworker 11 mimicked the supra strong binding between avidin and biotin (K a ≈ 10 15 M −1 ) to find a stronger binding pair of cucurbit [7]uril and the diamantane quaternary diammonium ion with an attomolar dissociation constant in water. Others have explored molecular behavior involving recognition, catalysis, and chirality based on host-guest recognition in aqueous systems.…”

Precise Assembly and Supramolecular Catalysis of Tetragonal- and Trigonal-Elongated Octahedral Coordination Containers

“…Varying the symmetry and length of organic linkers is a key factor to achieve the geometric and size modulation of well-defined nanocavity in coordination containers, thereby providing an accessible approach to regulating host-guest chemistry properties to achieve the desired applications such as selective guest recognition and catalytic reactivity. [24][25][26][27] While C 3 -symmetry tripodal ligands are well-known organic linkers for the construction of tetrahedral and octahedral coordination containers, [28][29][30][31][32] the utilization of tritopic ligands with a lower symmetry for the design of coordination containers is much less common, 33,34 presumably due to the stringent geometrical requirements for the assembly of high-symmetry polyhedral structures, even in rarer cases of severely distorted or irregular coordination polyhedral, constructed from mixed linkers of distinct sizes and shapes. Furthermore, symmetric tripodal organic linkers often occupy the faces of tetrahedral or octahedral coordination containers, likely to prevent specific guest molecules from accessing the endo cavity (where the host-guest chemistry is typically most active) and limit molecular recognition capability.…”