Methanolysis of Nitrocefin Catalyzed by One and Two Zn<sup>2+</sup> Ions. A Simplified Model for Class B β-Lactamases
Bibliographic record
Abstract
The methanolysis of nitrocefin (1) was investigated at 25 degrees C in anhydrous methanol as a function of [Zn(2+)] and as a model for the chemistry believed to occur in the active site of Zn(2+)(-)beta-lactamases. In the absence of metal ion, the vs rate constant profile shows a long plateau region having k(obs) = 9 x 10(-5) s(-1) between 7.5 and 12 generated after ionization of the COOH of 1 (kinetic pK(a) of 7.34) followed by attack of CH(3)O(-) with k(CH)3(O) = 1.18 M(-1) s(-1). Strong catalysis of the methanolysis is observed at all pH values between 7.95 and 11.34 in the presence of as little as 0.05-3 mM Zn(2+). Plots of the pseudo-first-order rate constant for methanolysis (k(obs)) as a function of reveal a saturation phenomenon indicative of formation of a 1:Zn(2+) complex, followed by a linear section indicative of the intervention of a second Zn(2+) ion in promoting the methanolysis of the complex. The two processes can be separated since the slope of the linear part of the plots gives the second-order rate constant (k(2)(obs)) for the second Zn process, while the intercept gives the spontaneous rate constant for methanolysis of 1:Zn(2+) (k(cat.)(obs)). A plot of log k(cat.)(obs) vs is bell-shaped, maximizing at 10, with ascending and descending domains both first order in [CH(3)O(-)]. A plot of log k(2) vs gives an ascending domain second order in [CH(3)O(-)], followed by a plateau above 9.5. The data are analyzed in terms of a one-Zn and two-Zn model in which the former involves rate-limiting attack of methoxide on a 1:Zn(2+) complex up to the maximum and a spontaneous reaction of 1:Zn(2+):(CH(3)O(-))(2), while the latter involves bimolecular attack of Zn(2+)(CH(3)O(-))(2) on both 1:Zn(2+) and 1:Zn(2+):(CH(3)O(-))(2). The relevance of these observations is discussed in terms of the currently accepted mechanism for hydrolyses of beta-lactams promoted by the Zn(2+)(-)beta-lactamases.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".