Phosphorylimidazole Derivatives: Potentially Biosignaling Molecules

Abstract

The phosphorylation of imidazole by two activated phosphate diesters and a triester gives phosphorylimidazole derivatives that are stable enough in aqueous solution to be observed and identified by ESI-MS/MS and NMR. Half-lives ranging from hours to days (in the case of the monoethyl ester) show that it is possible to design molecules with variable half-lives with potential to be used for biological intervention experiments as possible inhibitors of biosignaling processes or as haptens for the generation of antibodies.

A tailored biocatalyst achieved by the rational anchoring of imidazole groups on a natural polymer: furnishing a potential artificial nuclease by sustainable materials engineering

“…Although the 13 C NMR spectrum is not quantitative, the intensities of these signals agree with the colorimetric assay: slightly higher intensity for the nonfunctionalized GlcUA moieties. The characteristic pK a for the IMZ group (B7, -NH + ) 16 is observed for GAIMZ, consistent with the functionalization. Additionally, signals for the anchored API were depicted and assigned to the: (i) IMZ ring at d 137.3, d 126.0, and d 120.5 ppm and (ii) secondary carbons at d 44.9, d 42.7, and d 24.9 ppm.…”

The Importance of Methyl Positioning and Tautomeric Equilibria for Imidazole Nucleophilicity

“…To help assess the reaction pathway and to provide comparisons for calculations, thermodynamic parameters were obtained (Table ) through Eyring plots (given in the Supporting Information). The largely negative values of entropies of activation obtained indicate that the reaction mechanism for all cases is in fact most likely a bimolecular nucleophilic displacement pathway …”

“… pH rate profiles for the reactions of xMEI and IMZ with DEDNPP, 0.5 m at 25 °C (left axis). The spontaneous hydrolysis of DEDNPP (right axis) and the IMZ profile are shown for comparisons . The fitting (solid lines) are based on Equation 1.…”

“…It is important to highlight that the mechanistic understanding for dephosphorylation reactions with IMZ derivatives is sometimes limited by the fact that the P−N bond is highly unstable, making intermediates difficult to monitor. Consequently, the combination of experimental and computational studies has allowed new insights into these processes .…”

Rapid cleavage of phosphate triesters by the oxime 2‐(hydroxyimino)‐N‐phenyl‐acetamide

“…The term k 0 represents the first‐order rate constant for the spontaneous water reaction, k OH is the second‐order rate constant for the reaction of hydroxide ion, k Ox1 − is the second‐order rate constant for the reaction of Ox 1 - and χ Ox 1 − is the molar fraction of the reactive anionic species of the oxime, calculated using p K a = 9.35 . Using k 0 = 8.0 ± 0.5 x 10 −6 s −1 (previously reported for the hydrolysis in the absence of nucleophile), it was possible to calculate a value of k Ox1 = 1.48 M −1 s −1 . Comparison of the second‐order rate constant of the reaction of DEDNPP with Ox 1 with that reported for the spontaneous water reaction (corrected by the water molarity) shows that the rate enhancements brought about by the addition of Ox 1 are ca .…”