Self-Assembled Cagelike Receptor That Binds Biologically Relevant Dicarboxylic Acids via Proton-Coupled Anion Recognition

Abstract

We report here a fully organic, self-assembled dimeric receptor, constructed from acyclic naphthyridyl-polypyrrolic building block. The cage-like dimer is stable in the solid state, in solution, and in gas phase, as inferred from X-ray diffraction, and spectroscopic analyses. This system acts as a receptor for oxalic acid, maleic acid, and malonic acid in the solid state and in THF solution. In contrast, acetic acid, propionic acid, adipic acid and succinic acid, with pKa values > ca. 2.8, were not bound effectively within the cage-like cavity. It is speculated that oxalic acid, maleic acid, and malonic acid serve to protonate the naphthyridine moieties of the host, which then favors binding of the corresponding carboxylate anions via hydrogen-bonding to the pyrrolic NH protons. The present naphthyridine-polypyrrole dimer is stable under acidic conditions, including in the presence of 100 equiv trifluoroacetic acid (TFA), para-toluenesulfonic acid (PTSA), H2SO4, and HCl. However, disassembly may be achieved by exposure to tetrabutylammonium fluoride (TBAF). Washing with water then regenerates the cage. This process of assembly and disassembly could be repeated ≥20 times with little evidence of degradation. The reversible nature of the present system, coupled with its dicarboxylic acid recognition features, leads us to suggest it could have a role to play in effecting the controlled 'capture' and 'release' of biologically relevant dicarboxylic acids.

Solvent-Controlled Self-Assembled Oligopyrrolic Receptor

“…Therefore, a robust form of the supramolecular dimeric cage-like structure was present in CDCl 3 . A similar chemical shift distribution pattern was also seen with receptor 11 , adopting a self-assembled dimeric structure [ 30 ]. The 1 H– 1 H NOESY spectrum ( Figure 4 c) revealed distinct intermolecular spatial interactions between the CH 2 moiety of the terminal OEt groups and the NH of the pyrrole rings in the receptor, suggesting a dimeric structure in CDCl 3 at 298 K. In contrast, in relatively high polar and coordinating solvents (e.g., in both THF- d 8 and DMF- d 7 ), these pyrrolic NH signals shifted significantly (Δδ = 0.85 ppm) upon lowering the temperature, which indicates the considerable solvent coordination of monomeric 10 in these solvents ( Figures S15 and S16 ).…”

“…Herein, we designed and synthesized such a pyridine-based tetrapyrrolic acyclic receptor unit ( 10 ), which self-assembles in the solid phase in two different forms depending on the solvent polarity and the ability to coordinate ( Figure 1 ). Inspired by the successful results obtained from our earlier naphthyridine-based system ( 11 ) that was recently reported [ 30 ], we initially thought that the incorporation of pyridine (p K a = 5.20 in water) into this new receptor skeleton used in the present study may provide a more basic environment than the naphthyridine- based (p K a = 3.39 in water) receptor reported earlier. Similarly to the naphthyridine-based receptor 11 , the presence of sterically crowded ethyl groups at the β -positions of the pyrrole units in our present acyclic receptor system 10 imposes an orthogonal arrangement of terminal pyrrole units relative to the mean plane defined by the three central heterocyclic rings, as inferred from single-crystal X-ray structural analyses.…”

“…The acyclic receptor 10 was synthesized via a multistep process, which is described below in Scheme 1 . Precursor 3 was synthesized using procedures from the literature [ 30 , 31 ]. Compound 5 was synthesized via a Pd(II)-acetate-catalyzed Suzuki–Miyaura cross-coupling reaction using commercially available 2,6-dibromo-pyridine [ 32 ].…”

“…Therefore, capturing and sensing these acids with suitable receptors is an avenue that needs to be explored. Many such synthetic receptors are reported so far in the current literature, and can be used to sense and capture selective organic acids [ 26 , 27 , 28 , 29 , 30 ]. Recently, we have been interested in developing potential oligopyrrolic supramolecular receptors for acid recognition in an organic medium capable of releasing these acid guests upon simple aqueous wash.…”

Solution and Solid State Studies of Urea Derivatives of DITIPIRAM Acting as Powerful Anion Receptors

“…Still, the design and synthesis of receptors capable of strong and selective binding of negatively charged molecules is an essential problem considering the great role that anions play in many biological and chemical processes. Moreover, binding of anions using receptors with precisely selected properties opens the way to many important applications in medicine, pharmacy, catalysis, or transport processes [17][18][19][20][21][22][23][24][25][26][27][28][29]. Despite the high demand for the above-mentioned hosts for anions, numerous studies, and the development of computational techniques, the prediction of the binding properties of artificial hosts is still not a trivial task, sometimes even impossible when the anionic guest is chiral.…”