The role of acid-base equilibria in formal hydrogen transfer reactions: tryptophan radical repair by uric acid as a paradigmatic caseElectronic supplementary information (ESI) available: Deprotonation free energies for H3Ur and H2Ur− fractions (Table S1). Information on the reaction involved in the repair of Trp(−H)&z.rad; by H3Ur (site 2 and 3) (Table S2). Proton transfer free energies between uric acid fractions and tryptophanyl radical (Table S3) Activation free energies (ΔG‡, kcal mol−1) bet
The results presented in this work demonstrate the high complexity of chemical reactions involving species with multiple acid-base equilibria. For the case study investigated here, it was necessary to consider two radical species for tryptophan (Trp (−H) &z.rad; and Trp&z.rad; + ) and three...
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| Main Authors | , , |
|---|---|
| Format | Journal Article |
| Language | English |
| Published |
14.06.2017
|
| Online Access | Get full text |
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| Summary: | The results presented in this work demonstrate the high complexity of chemical reactions involving species with multiple acid-base equilibria. For the case study investigated here, it was necessary to consider two radical species for tryptophan (Trp
(−H)
&z.rad; and Trp&z.rad;
+
) and three fractions for uric acid (H
3
Ur, H
2
Ur
−
and HUr
2−
) in order to properly reproduce the experimental results. At pH = 7.4, two main reaction mechanisms were identified: proton-electron sequential transfer (PEST) and sequential proton gain-electron transfer (SPGET). Combined, they account for more than 99% of the overall reaction, despite the fact that they involve minor species,
i.e.
, H
3
Ur and Trp&z.rad;
+
, respectively. The excellent agreement between the calculated overall rate constant and the experimental value seems to support this proposal. In addition, if only the dominant species at pH = 7.4 (H
2
Ur
−
and Trp
(−H)
&z.rad;) were considered, there would be a large discrepancy with the experimental value (about 4 orders of magnitude), which also supports the finding that the key species in this case are not the most abundant ones. The influence of the pH on the kinetics of the investigated reaction was explored. It was found that the maximum repairing ability of uric acid does not occur at physiological pH, but at a more acidic pH (pH = 5.0).
The sequential proton gain electron transfer and proton electron sequential transfer mechanisms play the most important roles in tryptophan repair by uric acid. |
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| Bibliography: | fractions (Table S1). Information on the reaction involved in the repair of Trp kcal mol z.rad; by HUr G H Electronic supplementary information (ESI) available: Deprotonation free energies for H − (Fig. S3). RMS gradient norm along the reaction pathway for repair reaction of Trp and z.rad; and H between uric acid fractions and tryptophanyl radicals (Fig. S1 and S2). Pre-equilibrium reaction and parameters used to kinetic analysis of PEST mechanism between Trp exp 10.1039/c7cp01557g ‡ or k z.rad; by H (site 4) (Fig. S6). Pre-equilibrium reaction and parameters used to kinetic analysis of PEST mechanism between Trp and the H acceptor (N atom of tryptophan) along the reaction pathway for repair reaction of Trp Ur (site 2 and 3) (Table S2). Proton transfer free energies between uric acid fractions and tryptophanyl radical (Table S3) Activation free energies (Δ 1 Ur (site 1, 2 and 3) (Fig. S7-S9). Reactant and product structures. Transition states and complexes structures. The 2 3 Ur and H for different pHs (Table S4) are included. See DOI overall site 3) (Fig. S4). Distance between the H donor (N3 in HUr Ur (site 3) (Fig. S5). Information on the reaction involved in the repair of Trp hyp |
| ISSN: | 1463-9076 1463-9084 |
| DOI: | 10.1039/c7cp01557g |