Upper Rim Guanidinocalix[4]arenes as Artificial Phosphodiesterases

Abstract

Calix[4]arene derivatives, blocked in the cone conformation and functionalized with two to four guanidinium units at the upper rim were synthesized and investigated as catalysts in the cleavage of the RNA model compound 2-hydroxypropyl p-nitrophenyl phosphate. When compared with the behavior of a monofunctional model compound, the catalytic superiority of the calix[4]arene derivatives points to a high level of cooperation between catalytic groups. Combination of acidity measurements with the pH dependence of catalytic rates unequivocally shows that a necessary requisite for effective catalysis is the simultaneous presence, on the same molecular framework, of a neutral guanidine acting as a general base and a protonated guanidine acting as an electrophilic activator. The additional guanidinium (guanidine) group in the diprotonated (monoprotonated) trifunctional calix[4]arene acts as a more or less innocent spectator. This is not the case with the tetrasubstituted calix[4]arene, whose mono-, di-, and triprotonated forms are slightly less effective than the corresponding di- and triguanidinocalix[4]arene derivatives, most likely on account of a steric interference with HPNP caused by overcrowding.

Moulding calixarenes for biomacromolecule targeting

“…When a critical local concentration is reached, the lipophilic groups of the carriers start to attract each to the other bringing to the compaction of the DNA structure. 81 The tetrafunctionalized catalyst 24c, when monodeprotonated at pH 9.8, cleaves ATP into ADP and phosphate, at least three orders of magnitude faster than the background hydrolysis. 74 The polar ethoxyethyl groups at the lower rim not only fix the calixarene in the cone structure and ensure solubility in water, but also avoid self-aggregation phenomena so that such complexes can be reasonably well considered present as monomers in aqueous solution.…”

Reactivity of carbonyl and phosphoryl groups at calixarenes

“…The catalytic activity of guanidinocalix [4]arenes 26-29 was tested in the transesterification (Equation (3)) of the RNA model compound 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) in 80% dimethyl sulfoxide (DMSO), 258C, at pH 9-12, corresponding to neutral to moderately basic solutions (pK w ¼ 18.4 in 80% DMSO, at 258C) (23). …”

Crown Ether Nucleophilic Catalysts (CENCs): Agents for Enhanced Silicon Radiofluorination

“…To our knowledge, there are no reports of CENCs for silicon substitution reactions, although calix[4]arene-based ether catalysts were reported by the Mandolini group to aid the formation of phosphodiesters. 12 In addition, Bakó and coworkers utilized a glucopyranoside-based hydroxyl-containing crown ether to mediate Michael reactions 13 and Darzens condensations. 10b,13d In our work, we aimed to demonstrate that CENCs, based on an 18-crown-6 (18-C-6) scaffold, enhance the fluorination of organosilanes with both KF and cyclotron-produced 18 F-fluoride ion under mild conditions.…”