Potential ATPase mimics by polyammonium macrocycles: Criteria for catalytic activity

Polyazacyclophanes Incorporating Two Pyridine Units and a Heteroaromatic Pendant Group as Potential Cleaving Agents of mRNA 5′-cap Structure

“…Hexa-and heptaazamacrocycles [31] and their N-(2-aminoethyl) and N-(2-hydroxyethyl) derivatives [32] have been shown to cleave the triphosphate bridge at physiological pH, although at a low rate compared to the hydrolysis of ATP by O-bisdien. Dinuclear Zn 2 and Cu 2 chelates of the same ligands have exhibited somewhat higher cleaving activity [32]. As a continuation of these studies, we now report the synthesis of novel hexaazacyclophanes incorporating two pyridine units.…”

“…The latter groups may in principle stack with the 7-methylguanine base, which is known to associate quite readily with easily polarizable aromatic molecule [33], serve as a nucleophile attacking either the base or phosphate moiety, or offer an additional donor atom for metal ions. The ability of these compounds to cleave m 7 G(5')pppG(5') (1) either as free ligands or Zn 2 or Cu 2 chelates has been studied.…”

“…Polyazacyclophanes 16a ± d and 17 and their Cu 2 and Zn 2 complexes were tested as catalysts of the cleavage of a 5'-cap model (1). The concentration of the cleaving agent was 5 mm and that of 1 0.1 mm.…”

“…While O-bisdien (1,4,7,13,16,19-hexaaza-10,22-dioxacyclotetraicosane) [15 ± 17] and [21]aneN 7 (1,4,7,10,13,16,19-heptaazacyclohenicosane) [18] [19] have long been known as the most-efficient catalysts of this dephosphorylation reaction, a 21-membered cyclophane containing one meta-substituted benzene ring (2,5,8,11,14,17-hexaaza[18]metacyclophane) has recently been shown to exhibit comparable catalytic activity [14]. In addition, it has been shown that dinuclear Zn 2 complexes of cyclophanes incorporating a bipyridine [20] or phenantroline [21] unit cleave quite readily bis(4-nitrophenyl)phosphate, and they, hence, are potential candidates also as cleaving agents for triphosphate bridges.…”

Aspects of Anion Coordination from Historical Perspectives

“…Studies of ATP cleavage conducted with the series of azacycloalkanes [3k]aneN k (k = 6-12) (36, 67-72) revealed the key role played by the macrocycle size [165]. The 21-membered macrocycle [21]aneN 7 (67) was shown to be the best catalyst at the examined pHs, with the [24]aneN 8 (68) macrocycle providing also very significant rate enhancements.…”