The dependence of phenol-dienone tautomerism upon the hydrogen bonding characteristics of the solvent: 3,5-dipyrrolidinophenol

Highet, R. J.; Chou, F. Edward

doi:10.1021/ja00452a077

Cited by 12 publications

(4 citation statements)

References 2 publications

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“…The half-life for D 2 O exchange is 7 min for 4HN which exists as a 7:3 mixture of the phenolic to keto forms in acetone (26). Since hydrogen bonding stabilizes the keto forms of m-diphenols (27), it is reasonable that tautomerization of the enone form of 3HN is somewhat slow. Supporting this is that DDBO, which does not tautomerize after dehydration, has a k cat ) 400 s -1 , similar to the value of k 2 on the enzyme.…”

Section: Discussionmentioning

confidence: 99%

Catalytic Mechanism of Scytalone Dehydratase: Site-Directed Mutagenisis, Kinetic Isotope Effects, and Alternate Substrates

et al. 1999

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On the basis of the X-ray crystal structure of scytalone dehydratase complexed with an active center inhibitor [Lundqvist, T., Rice, J., Hodge, C. N., Basarab, G. S., Pierce, J. and Lindqvist, Y. (1994) Structure (London) 2, 937-944], eight active-site residues were mutated to examine their roles in the catalytic mechanism. All but one residue (Lys73, a potential base in an anti elimination mechanism) were found to be important to catalysis or substrate binding. Steady-state kinetic parameters for the mutants support the native roles for the residues (Asn131, Asp31, His85, His110, Ser129, Tyr30, and Tyr50) within a syn elimination mechanism. Relative substrate specificities for the two physiological substrates, scytalone and veremelone, versus a Ser129 mutant help assign the orientation of the substrates within the active site. His85Asn was the most damaging mutation to catalysis consistent with its native roles as a general base and a general acid in a syn elimination. The additive effect of Tyr30Phe and Tyr50Phe mutations in the double mutant is consistent with their roles in protonating the substrate's carbonyl through a water molecule. Studies on a synthetic substrate, which has an anomeric carbon atom which can better stabilize a carbocation than the physiological substrate (vermelone), suggest that His110Asn prefers this substrate over vermelone in order to balance the mutation-imposed weakness in promoting the elimination of hydroxide from substrates. All mutant enzymes bound a potent active-site inhibitor in near 1:1 stoichiometry, thereby supporting their active-site integrity. An X-ray crystal structure of the Tyr50Phe mutant indicated that both active-site waters were retained, likely accounting for its residual catalytic activity. Steady-state kinetic parameters with deuterated scytalone gave kinetic isotope effects of 2.7 on kcat and 4.2 on kcat/Km, suggesting that steps after dehydration partially limit kcat. Pre-steady-state measurements of a single-enzyme turnover with scytalone gave a rate that was 6-fold larger than kcat. kcat/Km with scytalone has a pKa of 7.9 similar to the pKa value for the ionization of the substrate's C6 phenolic hydroxyl, whereas kcat was unaffected by pH, indicating that the anionic form of scytalone does not bind well to enzyme. With an alternate substrate having a pKa above 11, kcat/Km had a pKa of 9.3 likely due to the ionization of Tyr50. The non-enzyme-catalyzed rate of dehydration of scytalone was nearly a billion-fold slower than the enzyme-catalyzed rate at pH 7.0 and 25 degrees C. The non-enzyme-catalyzed rate of dehydration of scytalone had a deuterium kinetic isotope effect of 1.2 at pH 7.0 and 25 degrees C, and scytalone incorporated deuterium from D2O in the C2 position about 70-fold more rapidly than the dehydration rate. Thus, scytalone dehydrates through an E1cb mechanism off the enzyme.

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Section: Discussionmentioning

confidence: 99%

Catalytic Mechanism of Scytalone Dehydratase: Site-Directed Mutagenisis, Kinetic Isotope Effects, and Alternate Substrates

et al. 1999

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“…S14, ESI†). 93,94 This analysis shows that the PG molecules appear mostly in the enol form, as depicted in Tables S1, S2 and Fig. S15, S19, S20 (ESI†).…”

Section: Resultsmentioning

confidence: 85%

Revealing two chemical strategies to tune bright one- and two-photon excited fluorescence of carbon nanodots

Mucha,

Firlej,

Formalik

et al. 2024

J. Mater. Chem. C

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“…The spectra agree with those reported in the literature for DPP. 3 The main peaks in the mass spectrum were at 232 (molecular weight of DPP), 178 (DPP -2 HCN), and 205 (DPP -HCN). exponential change in the absorption with the same rate is observed, i.e.…”

Section: Methodsmentioning

confidence: 97%

The hydrolysis of 1,3,5-tripyrrolidinobenzene

Knoche¹,

Vogel²

1988

J. Chem. Soc., Perkin Trans. 2

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In acidic solutions Ir3,5-tripyrrolidinobenzene (TPB) and methyl-TPB hydrolyse forming 3,5dipyrrolidinophenol (DPP) and methyl-D PP, respectively. The reaction proceeds by two successive protonations on carbon atoms of the aromatic ring followed by hydrolysis. The reaction mechanism is described, and the protonation equilibria of TPB and DPP are determined.o-Complexes are known to be intermediates in electrophilic substitution reactions of benzene and its derivatives, as shown in Scheme 1. In the case of the protonation of 1,3,5-t5 H 11

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The dependence of phenol-dienone tautomerism upon the hydrogen bonding characteristics of the solvent: 3,5-dipyrrolidinophenol

Cited by 12 publications

References 2 publications

Catalytic Mechanism of Scytalone Dehydratase: Site-Directed Mutagenisis, Kinetic Isotope Effects, and Alternate Substrates

Catalytic Mechanism of Scytalone Dehydratase: Site-Directed Mutagenisis, Kinetic Isotope Effects, and Alternate Substrates

Revealing two chemical strategies to tune bright one- and two-photon excited fluorescence of carbon nanodots

The hydrolysis of 1,3,5-tripyrrolidinobenzene

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