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MIDA boronates are hydrolysed fast and slow by two different mechanisms.

ABSTRACT: MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, which has hindered efforts to address the current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base mediated and the other neutral. The former can proceed more than three orders of magnitude faster than the latter, and involves a rate-limiting attack by a hydroxide at a MIDA carbonyl carbon. The alternative 'neutral' hydrolysis does not require an exogenous acid or base and involves rate-limiting B-N bond cleavage by a small water cluster, (H2O)n. The two mechanisms can operate in parallel, and their relative rates are readily quantified by 18O incorporation. Whether hydrolysis is 'fast' or 'slow' is dictated by the pH, the water activity and the mass-transfer rates between phases. These findings stand to enable, in a rational way, an even more effective and widespread utilization of MIDA boronates in synthesis.

SUBMITTER: Gonzalez JA

PROVIDER: S-EPMC5115273 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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MIDA boronates are hydrolysed fast and slow by two different mechanisms.

Gonzalez Jorge A JA Ogba O Maduka OM Morehouse Gregory F GF Rosson Nicholas N Houk Kendall N KN Leach Andrew G AG Cheong Paul H-Y PH Burke Martin D MD Lloyd-Jones Guy C GC

Nature chemistry 20160725 11

MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, which has hindered efforts to address the current limitations of this chemistry. Here we show that there are two distinct mechanisms f ...[more]

PMID: 27768100

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Project description:Experimental and theoretical studies demonstrate that neuronal gamma oscillations crucially depend on interneurons, but current models do not consider the diversity of known interneuron subtypes. Moreover, in CA1 of the hippocampus, experimental evidence indicates the presence of multiple gamma oscillators, two of which may be coordinated by differing interneuron populations. In this article, we show that models of networks with competing interneuron populations with different postsynaptic effects are sufficient to generate, within CA1, distinct oscillatory regimes. We find that strong mutual inhibition between the interneuron populations permits distinct fast and slow gamma states, whereas weak mutual inhibition generates mixed gamma states. We develop idealized firing rate models to illuminate dynamic properties of these competitive gamma networks, and reinforce these concepts with basic spiking models. The models make several explicit predictions about gamma oscillators in CA1. Specifically, interneurons of different subtype phase-lock to different gamma states, and one population of interneurons is silenced and the other active during fast and slow gamma events. Finally, mutual inhibition between interneuron populations is necessary to generate distinct gamma states. Previous experimental studies indicate that fast and slow gamma oscillations reflect different information processing modes, although it is unclear whether these rhythms are intrinsic or imposed. The models outlined demonstrate that basic architectures can locally generate these oscillations, as well as capture other features of fast and slow gamma, including theta-phase preference and spontaneous transitions between gamma states. These models may extend to describe general dynamics in networks with diverse interneuron populations.NEW & NOTEWORTHY The oscillatory coordination of neural signals is crucial to healthy brain function. We have developed an idealized neuronal model that generates distinct fast and slow gamma oscillations, a known feature of the rodent hippocampus. Our work provides a mechanism of this phenomenon, as well as a theoretical framework for future experiments concerning hippocampal gamma. It moreover offers a tractable model of competitive gamma oscillations that is generalizable across the nervous system.

Dataset Information

MIDA boronates are hydrolysed fast and slow by two different mechanisms.

Publications

MIDA boronates are hydrolysed fast and slow by two different mechanisms.

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