Redox isomerizations are examples of atom-economical processes 1 in which one site in an organic substrate is oxidized with concomitant reduction of another site. One especially well-studied example is the conversion of allylic alcohols to aldehydes or ketones, 2,3 which involves movement of the alkene double bond 4-7 over two positions (eq 1, n) 2). Far fewer catalysts exist for the movement of a more remote double bond (n > 2). For example, Kirchner et al. reported 8 that, although [CpRu(PR 3)(CH 3 CN) 2 ] + (1a-1c) were improved catalysts for allylic alcohol isomerization relative to CpRu(PR 3) 2 Cl, it failed in the case of 3-buten-1-ol (n) 3) or alkenes devoid of alcohol functionality. The apparent record for alkene isomerization of any kind is over 20 positions on the hydrocarbon CH 3 (CH 2) 19 CHdCH(CH 2) 19 CH 3 by stoichiometric amounts of the reagent Cp 2 Zr(H)(Cl). 9 The apparent record for catalyzed double bond movement is on 9-decene-1-ol (nine positions, n) 9) using Fe 3 (CO) 12. 10,11 However, 30 mol % was required, which means that nearly a mole of metal was used per mole of alkenol.

Commensal microorganisms in the mammalian gut play important roles in host health and physiology, but a central challenge remains in achieving a detailed mechanistic understanding of specific microbial contributions to host biochemistry. New function-based approaches are needed that analyze gut microbial function at the molecular level by coupling detection and measurements of in situ biochemical activity with identification of the responsible microbes and enzymes. We developed a platform employing β-glucuronidase selective activity-based probes to detect, isolate, and identify microbial subpopulations in the gut responsible for this xenobiotic metabolism. We find that metabolic activity of gut microbiota can be plastic and that between individuals and during perturbation, phylogenetically disparate populations can provide β-glucuronidase activity. Our work links biochemical activity with molecular-scale resolution without relying on genomic inference.

Although a multitude of syndromes have been thoroughly described as a result of vitamin deficiencies, over consumption of such substances may also be quite dangerous. Intratubular crystallization of calcium oxalate as a result of hyperoxaluria can cause acute renal failure. This type of renal failure is known as oxalate nephropathy. Hyperoxaluria occurs as a result of inherited enzymatic deficiencies known as primary hyperoxaluria or from exogenous sources known as secondary hyperoxaluria. Extensive literature has reported and explained the mechanism of increased absorption of oxalate in malabsorptive syndromes leading to renal injury. However, other causes of secondary hyperoxaluria may also take place either via direct dietary consumption of oxalate rich products or via other substances which may metabolize into oxalate within the body. Vitamin C is metabolized to oxalate. Oral or parenteral administration of this vitamin has been used in multiple settings such as an alternative treatment of malignancy or as an immune booster. This article presents a clinical case in which ingestion of high amounts of vitamin C lead to oxalate nephropathy. This article further reviews other previously published cases in order to illustrate and highlight the potential renal harm this vitamin poses if consumed in excessive amounts.

Glutathione S-transferases (GSTs) comprise a diverse family of phase II drug metabolizing enzymes whose shared function is the conjugation of reduced glutathione (GSH) to endo- and xenobiotics. Although the conglomerate activity of these enzymes can be measured, the isoform-specific contribution to the metabolism of xenobiotics in complex biological samples has not been possible. We have developed two activity-based probes (ABPs) that characterize active GSTs in mammalian tissues. The GST active site is composed of a GSH binding “G site” and a substrate binding “H site”. Therefore, we developed (1) a GSH-based photoaffinity probe (GSTABP-G) to target the “G site”, and (2) an ABP designed to mimic a substrate molecule and have “H site” activity (GSTABP-H). The GSTABP-G features a photoreactive moiety for UV-induced covalent binding to GSTs and GSH-binding enzymes. The GSTABP-H is a derivative of a known mechanism-based GST inhibitor that binds within the active site and inhibits GST activity. Validation of probe targets and “G” and “H” site specificity was carried out using a series of competition experiments in the liver. Herein, we present robust tools for the characterization of enzyme- and active site-specific GST activity in mammalian model systems.