Zong-hui Jiang, P. Chalabi, K. B. Mertes
Sep 1, 1989
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Influential Citations
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Journal
Bioorganic Chemistry
Abstract
Abstract The aminolysis of formyl phosphate by both linear and macrocyclic polyamines at pH 7 and 5°C was examined and found to proceed primarily by C-O cleavege to give the N-formylated amines. In the presence of excess bromide ion (ionic strength 0.3) the reaction was second-order with rate constants ranging from 7.1 to 12 liter m −1 min−1 for the macrocyclic amines 1,4,7,13,16,19-hexaaza-10,22-dioxacyclotetraeicosane ([24]N6O2, 1) and 1,4,7,10,13,16-hexaazacyclooctadecane ([18]N6, 4) and the linear amines 1,4,7,10,13-pentaazatridecane ([L]N5, 5) and 1,4,7,10-tetraazadecane ([L]N4, 6). In the absence of excess bromide ion the reaction was first-order with a rate constant of 0.30 min−1 for 1 and ranged from 0.26 to 0.54 min−1 for the other amines. The addition of a stable substrate analog (phosphonoacetaldehyde) to the reaction significantly decreased the rate of aminolysis. The reaction is proposed to proceed through a supramolecular complex of polyprotonated polyamine and formyl phosphate with a dissociation constant less than 1 × 10−3 m . A similar complex has been proposed for the reaction of acetyl phosphate and 1 which gives P-O, not C-O, cleavage. The rate as a function of pH for the aminolysis of formyl phosphate by 1 is reasonably constant in the mid-pH region and the rate decreases at the extremes of pH 4 and 9. The results of this study more fully characterize the activation of formate in neutral aqueous media by adenosine 5′-triphosphate in the presence of 1, a model for the reaction catalyzed by the enzyme N10-formyltetrahydrofolate synthetase for which formyl phosphate is a proposed intermediate.