Hydrolysis of (2-Deoxy-.beta.-D-glucopyranosyl)pyridinium Salts

Abstract

The hydrolysis reactions of three (2-deoxy-/?-D-glucopyranosyl)pyridinium salts exhibit first-order rate constants that are independent of pH in the range of 4.4-10.1 pH units. Derived second-order rate constants for the hydrolysis reactions of (2-deoxy-/J-D-glucopyranosyl)-4'-bromoisoquinolinium bromide (5b) conducted in the presence of nucleophilic monoanions (µ = 2.0) including AcO-, Cl-, Br-, and N3-exhibit a Swain-Scott parameter (s) of 0.03 ± 0.05, indicating that these reactions show no sensitivity to the nature of the anion. However, a substantial quantity of the (2-deoxyglucopyranosyl)pyridinium salt hydrolysis product is formed as a result of a post-ratelimiting reaction involving a nucleophilic anion. Analysis of the product ratios indicates that the first-formed intermediate in the hydrolytic reaction is a solvent-separated ion painmolecule encounter complex. The data allow a calculated estimate of greater than 2.5 x 10-12 s for the lifetime of the glucopyranosyloxocarbenium ion in aqueous solution.

Aspects of Glycosidic Bond Formation in Aqueous Solution: Chemical Bonding and the Role of Water

“…The oxocarbenium is non-solvent equilibrated in light of the apparent necessity of a close approach of the methanol O m before its formation. This was previously found to be the case for many glucopyranoside hydrolysis reactions, [1][2][3] as well as for the theoretical study of glycosyltransferase. [46] double bond to the C 1 ÀO 5 single bond the O 5 site becomes again re-solvated.…”

Poly(ADP‐Ribose)‐Polymerase‐Catalyzed Hydrolysis of NAD+: QM/MM Simulation of the Enzyme Reaction

“…These reactions are on the borderline between D N + A N (S N 1) and A N D N (S N 2) mechanisms (Scheme 2). [32][33][34] A previous semiempirical study of the gas-phase TS of nicotinamide riboside hydrolysis indicated a highly oxacarbenium-ion-like TS structure, which suggests the ability of semiempirical approaches to correctly describe this type of reactive system. [35] In this study, the gas-phase reaction is described by an oxacarbenium-ion-like TS structure with bond distances of C1ÀN (leaving group) and C1ÀO (incoming water group) of 2.13 and 2.45 , respectively (Figure 3 b).…”

“…The overall energy profile of Figure 2 shows an activation energy of 20.66 kcal mol À1 for the NAD + hydrolysis reaction, for which an activation enthalpy of 25.2 kcal mol À1 has been estimated. [33] QM/MM calculations Figure 4 shows the ONIOM2 [31] (AM1/Dreiding)-optimized geometries of the NR-water reactant (Michaelis complex), transition state, and final product of the hydrolysis reaction at the PARP active site. In Figure 5, the energy profile along the reaction coordinate of the PARP-catalyzed NR hydrolysis (B3LYP/6-31 + G(d) single-point calculations on geometry optimized at the QM/MM level) is displayed and shows an activation energy of 7.26 kcal mol…”

“…The reaction is described by a high oxacarbenium-ion-like transition structure [32][33][34] with the distance for C1ÀN (leaving group) and C1ÀO (incoming water molecule) of 2.06 and 2.94 , respectively (Figure 4 b). Going from R (Michaelis complex, Figure 4 a) to TS (Figure 4 b), our calculations show the same trend observed for gas phase, suggesting the partial formation of a double bond between C1 and O4 (p-electron delocalization due to the resulting sp 2 hybridization) and an S N 2 A N D N dissociative mechanism.…”

“…The low activation energy of 7.26 kcal mol À1 for the PARP-catalyzed NAD + hydrolysis reflects once more the relative stability of the oxacarbenium ion complex. [33] Finally, Figure 7 shows a comparison of the energy profiles for the gas-phase and PARP-catalyzed reactions and shows that the presence of the PARP active site lowers the activation energy by 13.4 kcal mol…”