A Pyrrolyl-Based Triazolophane: A Macrocyclic Receptor With CH and NH Donor Groups That Exhibits a Preference for Pyrophosphate Anions

Abstract

A pyrrolyl-based triazolophane, incorporating CH and NH donor groups, acts as a receptor for the pyrophosphate anion in chloroform solution. It shows selectivity for this trianion, followed by HSO 4 -> H 2 PO 4 -> Cl -> Br -(all as the corresponding tetrabutylammonium salts), with NH-anion interactions being more important than CH-anion interactions. In the solid state, the receptor binds the pyrophosphate anion in a clip-like slot via NH and CH hydrogen bonds.Pyrophosphate detection has aroused interest in the scientific community not only because pyrophosphate is the product of ATP hydrolysis under cellular conditions, 1 but also because it could afford a means of effecting real-time DNA sequencing. 2 Pyrophosphate monitoring may also have a role to play in cancer research since this anion is involved in DNA replication catalyzed by DNA polymerase. 3 Pyrophosphate is also of interest as a larger, more highly charged analogue of inorganic phosphate (H 2 PO 4 -/HPO 4 2-), which has physiological relevance in energy storage and signal transduction, in addition to being a structural component in teeth and bones. 4 Not surprisingly, therefore, considerable effort has been devoted recently to the development of synthetic receptors that allow for the recognition, detection, or extraction of pyrophosphate and related species, such as inorganic phosphate. 5 Systems incorporating neutral or cationic NH hydrogen bond donor groups (e.g., pyrrole, indole, ammonium, and guanidinium) or cationic CH hydrogen bond donor motifs (e.g. imidazolium and triazolium) have been particularly effective in this regard. However, to the best of our knowledge, receptors with neutral CH H-bond donors have yet to be exploited for the purpose of pyrophosphate (or phosphate) anion recognition. CH bonds are present in the overwhelming majority (97%) of chemical compounds. 6 Nevertheless, it is only recently that the importance of CH H-bond in biological and artificial anion recognition has come to be appreciated. 7 In recent pioneering work, Flood and co-workers reported the synthesis and anion binding properties of [3 4 ]triazolophanes. These new macrocycles have a diameter of about 3.8 Å, and display a high affinity for the chloride ion. 7(c) On the basis of this and previous theoretical and experimental studies, 8 it was suggested that the strength of neutral, triazole-derived C-H···X -(X -= halide) bonds can approach those of more traditional NH donors, such as pyrrole. We thus considered it of interest to combine both these recognition motifs within the same macrocyclic framework. Here, we report the first such system, namely the calix[2]1,3-bis(pyrro-2-yl)(1,4)-1,2,3-triazolo-phane (1), and show that it acts as a highly effective receptor for the pyrophosphate anion, both in the solid state and in organic media. 9 Our findings, supported by theory, provide support for the conclusion that NH-anion bonding interactions are more important than CH-anion interactions.The synthesis of 1 is shown in Scheme 1. Using "click" chemistry cond...

Anion Responsive TTF-Appended Calix[4]arenes. Synthesis and Study of Two Different Conformers

“…This means cone -1 shows a high affinity for the pyrophosphate anion, a biologically important species for which bona fide receptor systems are rare. 11 …”

Structurally Characterized Cationic Silver(I) and Ruthenium(II) Carbene Complexes of 1,2,3-Triazol-5-ylidenes

“…14 It relies on the “click”-type copper-catalyzed [3+2] cycloaddition of an aryl diazide and with an alkyne-functionalized pyrrole to create the key triazole functionality. 15 A variety of 1,2,3-triazoles bearing a wide range of functional groups at the 1- and 4-positions can be synthesized via the click reaction.…”

Alfred Werner’s expanded legacy: Anion and metal ion coordination in an unsymmetrical, octaamido cryptand

“…This indicates that all the amide sites associate with the anion. These findings suggest that the expanded cryptand host may serve as a selective pyrophosphate receptor [46,47].…”