-We studied the effect of the antihyperglycemic glitazones, ciglitazone, troglitazone, and rosiglitazone, on glutamine metabolism in renal tubule-derived Madin-Darby canine kidney (MDCK) cells. Troglitazone (25 M) enhanced glucose uptake and lactate production by 108 and 92% (both P Ͻ 0.001). Glutamine utilization was not inhibited, but alanine formation decreased and ammonium formation increased (both P Ͻ 0.005). The decrease in net alanine formation occurred with a change in alanine aminotransferase (ALT) reactants, from close to equilibrium to away from equilibrium, consistent with inhibition of ALT activity. A shift of glutamine's amino nitrogen from alanine into ammonium was confirmed by using L-[2-15 N]glutamine and measuring the [ 15 N]alanine and [15 N]ammonium production. The glitazone-induced shift from alanine to ammonium in glutamate metabolism was dose dependent, with troglitazone being twofold more potent than rosiglitazone and ciglitazone. All three glitazones induced a spontaneous cellular acidosis, reflecting impaired acid extrusion in responding to both an exogenous (NH 4 ϩ ) and an endogenous (lactic acid) load. Our findings are consistent with glitazones inducing a spontaneous cellular acidosis associated with a shift in glutamine amino nitrogen metabolism from predominantly anabolic into a catabolic pathway.

An umber of new magnesium and lithium silyl reagents were prepared and shown to be outstanding nucleophiles in reactions with industrially relevant fluoroolefins. These reactions result in an et transformation of either sp 2 or sp 3 CÀFbonds into CÀSi bonds by two modes of nucleophilic attack( S N VorS N 2'). The methods are mild, proceeding with high chemo-and regioselectivity.M echanistic pathways are described that lead to new substitution patterns from HFO-1234yf,H FO-1234ze,a nd HFO-1336mzz, previously inaccessible by transition metal catalyzeddifluorosilylation routes.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

sp C-F Bonds of fluoroalkanes (7 examples; 1°, 2° and 3°) undergo addition to a low-valent Mg-Mg species generating reactive organomagnesium reagents. Further reactions with a series of electrophiles results in a net C-F to C-B, C-Si, C-Sn or C-C bond transformation (11 examples, diversity). The new reactivity has been exploited in an unprecedented one-pot magnesium-mediated coupling of sp C-F and sp C-F bonds. Calculations suggest that the sp C-F bond activation step occurs by frontside nucleophilic attack of the Mg-Mg reagent on the fluoroalkane.

In this Account we describe a series of new reactions that we, and others, have reported that involve the transformation of C–F bonds into C–Mg, C–Al, C–Si, C–Fe and C–Zn bonds. We focus on the use of highly reactive main group nucleophiles and discuss aspects of reaction scope, selectivity and mechanism.1 Introduction1.1 The Fluorocarbon Industry and Sustainability1.2 Production of Fluorocarbons1.3 Properties of Fluorocarbons1.4 Our Work2 Results and Discussion2.1 Low-Valent Main Group Compounds2.1.1 Reactions with Fluoroarenes2.1.2 Reactions with Fluoroalkanes2.1.3 Reactions with Fluoroalkenes2.2 Main Group Nucleophiles (M1–M2)2.2.1 Reactions of M1–M2 Nucleophiles with Fluoroarenes2.2.2 Reactions of M1–M2 Nucleophiles with Fluoroalkanes2.2.3 Reactions of M1–M2 Nucleophiles with Fluoroalkenes3 Summary and Perspective

The rapid, room-temperature defluorosilylation of trifluoromethane, a highly potent greenhouse gas, has been achieved using a simple silyl lithium reagent.

A number of new magnesium and lithium silyl reagents were prepared and shown to be outstanding nucleophiles in reactions with industrially relevant fluoroolefins. These reactions result in a net transformation of either sp 2 or sp 3 C-F bonds into C-Si bonds by two modes of nucleophilic attack (SNV or SN2'). The methods are mild, proceeding with high chemo-and regioselectivity. Mechanistic pathways are described that lead to new substitution patterns from HFO-1234yf, HFO-1234ze and HFO-1336mzz, previously inaccessible by transition metal catalysed defluorosilylation routes.

<p>The rapid, room-temperature defluorosilylation of trifluoromethane, a highly potent greenhouse gas, has been achieved using a simple silyl lithium reagent. An extensive computational mechanistic analysis provides a viable reaction pathway and demonstrates the unexpected electrophilic nature of LiCF₃. The reaction generates a bench stable fluorinated building block that shows promise as an easy-to-use difluoromethylating agent. The difluoromethyl group is an increasingly important bioisostere in active pharmaceutical ingredients, and therefore our methodology creates value from waste. The potential scalability of the process has been demonstrated by achieving the reaction on a gram-scale.</p>

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