Hydrolysis of Thiamin: Evidence for Rate-Limiting Breakdown of the Tricyclic Dihydrothiachromine Intermediate in Neutral Aqueous Solution
✍ Scribed by M.W. Washabaugh; C.C. Yang; A.D. Hollenbach; P. Chen
- Book ID
- 102966022
- Publisher
- Elsevier Science
- Year
- 1993
- Tongue
- English
- Weight
- 988 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0045-2068
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✦ Synopsis
Rate constants in the (\mathrm{pH}) range 3-9 for formation of the enethiolate product upon hydrolysis of (N\left(1^{\prime}\right))-unprotonated ("free") thiamin (1a), (N\left(1^{\prime}\right))-methylthiamin (3), oxythiamine (4), and several 3-substituted-4-methylhiazolium ions in oxygen-containing and amine buffers have been determined by irreversible iodination of the enethiolate at (25^{\circ} \mathrm{C}) and ionic strength 1.0 м in aqueous solution. General acid catalysis of the ring opening of 1a has a Brø⿱sted (\alpha) value of 0.57 and a solvent deuterium isotope effect of (\left(k_{\mathrm{H}, 0} / k_{\mathrm{D}, \mathrm{N}}\right){\mathrm{BI}} .=5.0) for catalysis by acetic acid. The Hammett (\rho{1}) value for catalysis by water or phosphate monoanion of the ring-opening reaction of 3-R-4-methylthiazolium ions is (12 \pm 1) for substituents on the nitrogen atom of the thiazolium ring that cannot function as intramolecular catalysts. There is a 200or 600-fold positive deviation of the rate constant for catalysis by water or phosphate monoanion, respectively, of the ring-opening reaction of la from the corresponding Hammett correlation which is absent when the (N(3))-aminopyrimidinyl substituent is modified to make it unreactive as an intramolecular catalyst in (\mathbf{3}) or (\mathbf{4}). On the basis of an estimated "effective molarity" of (\geq 700 \mathrm{M}) for intramolecular catalysis of the ring-opening reaction by the exocyclic (4^{\prime})-amino group, it is concluded that the N(3)-aminopyrimidinyl substituent of 1a provides significant intramolecular nucleophilic catalysis of nonenzymatic enethiolate formation in neutral aqueous solution. The general acid-catalyzed reaction of (1 \mathbf{a}) is formulated as concerted general acid catalysis of departure of the enethiol from the neutral tricyclic amine addition compound (\left(\mathrm{T}^{\vee}\right)) derived from addition of the (4^{\prime})-amino group to the (\mathrm{C}(2)) position of the thiazolium ion. The water-catalyzed reaction of (\mathbf{1}) is formulated as unassisted expulsion of the enethiolate from (\mathrm{T}^{\mathrm{N}}). 1993 Academic Press. Inc