Continuous glucose monitoring among adults with type 2 diabetes receiving noninsulin or basal insulin therapy in primary care.

Rates of type 2 diabetes (T2D) continue to rise in the United States, with many patients failing to achieve glycemic targets. Primary care providers often serve as the sole clinician managing diabetes. Continuous glucose monitors (CGMs) have shown promise in diabetes management, yet their adoption in primary care settings, especially among patients with T2D not using intensive insulin therapy, remains limited.

Conversion of pyridoxal to pyridoxamine with NH and H on nickel generates a protometabolic nitrogen shuttle under serpentinizing conditions.

Serpentinizing hydrothermal vents are likely sites for the origin of metabolism because they produce H as a source of electrons for CO reduction while depositing zero-valent iron, cobalt, and nickel as catalysts for organic reactions. Recent work has shown that solid-state nickel can catalyze the H-dependent reduction of CO to various organic acids and their reductive amination with H and NH to biological amino acids under the conditions of H-producing hydrothermal vents and that amino acid synthesis from NH, H, and 2-oxoacids is facile in the presence of Ni. Such reactions suggest a metallic origin of metabolism during early biochemical evolution because single metals replace the function of over 130 enzymatic reactions at the core of metabolism in microbes that use the acetyl-CoA pathway of CO fixation.

Nonenzymatic Hydration of Phosphoenolpyruvate: General Conditions for Hydration in Protometabolism by Searching Across Pathways.

Numerous reactions within metabolic pathways have been reported to occur nonenzymatically, supporting the hypothesis that life arose upon a primitive nonenzymatic precursor to metabolism. However, most of those studies reproduce individual transformations or segments of pathways without providing a common set of conditions for classes of reactions that span multiple pathways. In this study, we search across pathways for common nonenzymatic conditions for a recurring chemical transformation in metabolism: alkene hydration.

Triflic Acid-Catalyzed Dehydrative Amination of 2-Arylethanols with Weak N-Nucleophiles in Hexafluoroisopropanol.

The catalytic deoxyamination of readily available 2-arylethanols offers an appealing, simple, and straightforward means of accessing β-(hetero)arylethylamines of biological interest. Yet, it currently represents a great challenge to synthetic chemistry. In most cases, the alcohol has to be either pre-activated in situ or converted into a reactive carbonyl intermediate, limiting the substrate scope for some methods.

Pinpointing Conditions for a Metabolic Origin of Life: Underlying Mechanisms and the Role of Coenzymes.

ConspectusFamously found written on the blackboard of physicist Richard Feynman after his death was the phrase, "What I cannot create, I do not understand." From this perspective, recreating the origin of life in the lab is a necessary condition for achieving a deep theoretical understanding of biology. The "metabolism-first" hypothesis is one of the leading frameworks for the origin of life.

Coenzymes in a pre-enzymatic metabolism.

Experiments now support theoretical suggestions that coenzymes mediated key metabolic reactions before the emergence of enzymes. Three coenzymes believed essential to the core metabolism of the last universal common ancestor to extant life (pyridoxal phosphate, adenosine diphosphate, and nicotinamide adenine dinucleotide) were recently found to be active in their corresponding metabolic reactions in the absence of enzymes. These findings suggest an earlier contribution of coenzymes to abiogenesis, ultimately yielding insights into the prebiotic origins of metabolism.

A povarov-type reaction to access tetrahydroquinolines from -benzylhydroxylamines and alkenes in HFIP.

Here, we report the synthesis of tetrahydroquinolines between newly developed -benzylhydroxylamine reagents and alkenes using HFIP as a solvent. This transformation is notably applicable to highly electronically deactivated styrenes and aliphatic alkenes, expanding the range of tetrahydroquinolines attainable.

Measuring Kinetics under Vibrational Strong Coupling: Testing for a Change in the Nucleophilicity of Water and Alcohols.

Vibrational Strong Coupling (VSC) has been reported to change the rate of organic reactions. However, a lack of convenient and reliable methods to measure reaction kinetics under VSC makes it challenging to obtain mechanistic insight into its influence, hindering progress in the field. Here, we use recently developed fixed-width optical cavities to obtain large kinetic datasets under VSC with small errors (±1-5 %) in an operationally simple manner using UV/Vis spectroscopy.

Iron(II)-Catalyzed 1,2-Diamination of Styrenes Installing a Terminal NH Group Alongside Unprotected Amines.

1,2-Diamination of alkenes represents an attractive way to generate differentiated vicinal diamines, which are prevalent motifs in biologically active compounds and catalysts. However, existing methods are usually limited in scope and produce diamines where one or both nitrogens are protected, adding synthetic steps for deprotection and further N-functionalization to reach a desired target. Furthermore, the range of amino groups that can be introduced at the internal position is fairly limited.

Difunctionalization Processes Enabled by Hexafluoroisopropanol.

In the past 5 years, hexafluoroisopropanol (HFIP) has been used as a unique solvent or additive to enable challenging transformations through substrate activation and stabilization of reactive intermediates. In this Review, we aim at describing difunctionalization processes which were unlocked when HFIP was involved. Specifically, we focus on cyclizations and additions to alkenes, alkynes, epoxides, and carbonyls that introduce a wide range of functional groups of interest.

A prebiotic Krebs cycle analog generates amino acids with H and NH over nickel.

Hydrogen (H) has powered microbial metabolism for roughly 4 billion years. The recent discovery that it also fuels geochemical analogs of the most ancient biological carbon fixation pathway sheds light on the origin of metabolism. However, it remains unclear whether H can sustain more complex nonenzymatic reaction networks.

Rapid Access to Densely Functionalized Cyclopentenyl Sulfoximines through a Sc-Catalyzed Aza-Piancatelli Reaction.

Sulfoximines make up a class of compounds of growing interest for crop science and medicinal chemistry, but methods for directly incorporating them into complex molecular scaffolds are lacking. Here we report a scandium-catalyzed variant of the aza-Piancatelli cyclization that can directly incorporate sulfoximines as nucleophiles rather than the classical aniline substrates. Starting from 2-furylcarbinols and sulfoximines, the reaction provides direct access to 4-sulfoximinocyclopentenones, a new scaffold bearing cyclopentenone and sulfoximine motifs, both of interest for bioactive compounds.

A single phosphorylation mechanism in early metabolism - the case of phosphoenolpyruvate.

Phosphorylation is thought to be one of the fundamental reactions for the emergence of metabolism. Nearly all enzymatic phosphorylation reactions in the anabolic core of microbial metabolism act on carboxylates to give acyl phosphates, with a notable exception - the phosphorylation of pyruvate to phosphoenolpyruvate (PEP), which involves an enolate. We wondered whether an ancestral mechanism for the phosphorylation of pyruvate to PEP could also have involved carboxylate phosphorylation rather than the modern enzymatic form.

Metal/ADP Complexes Promote Phosphorylation of Ribonucleotides.

Under enzyme catalysis, adenosine triphosphate (ATP) transfers a phosphoryl group to canonical ribonucleotide diphosphates (NDPs) to form ribonucleotide triphosphates (NTPs), the direct biosynthetic precursors to RNA. However, it remains unclear whether the phosphorylation of NDPs could have occurred in water before enzymes existed and why an adenosine derivative, rather than another canonical NTP, typically performs this function. Here, we show that adenosine diphosphate (ADP) in the presence of Fe or Al promotes phosphoryl transfer from acetyl phosphate to all canonical NDPs to produce their corresponding NTP in water at room temperature and in the absence of enzymes.

Catalytic Synthesis of β-(Hetero)arylethylamines: Modern Strategies and Advances.

β-(Hetero)arylethylamines appear in a myriad of pharmaceuticals due to their broad spectrum of biological properties, making them prime candidates for drug discovery. Conventional methods for their preparation often require engineered substrates that limit the flexibility of the synthetic routes and the diversity of compounds that can be accessed. Consequently, methods that provide rapid and versatile access to those scaffolds remain limited.

Klebsiella, a Clever Survivor Presenting As Pyogenic Liver Abscess Years After Travel.

 is a known cause of pyogenic liver abscess and has an increased prevalence in Southeast Asia. We present two cases of individuals with remote travel history to southeast Asia presenting with fevers, chills, and abdominal pain secondary to pyogenic liver abscess. Neither individual had a comorbid medical condition or history of prior hepato-biliary pathology that would predispose them to bacterial translocation and abscess formation.

Solvent Polarity under Vibrational Strong Coupling.

Vibrational strong coupling (VSC) occurs when molecular vibrations hybridize with the modes of an optical cavity, an interaction mediated by vacuum fluctuations. VSC has been shown to influence the rates and selectivity of chemical reactions. However, a clear understanding of the mechanism at play remains elusive.

Metal-Pyridoxal Cooperativity in Nonenzymatic Transamination.

Coenzymes are involved in ≥30% of enzymatic reactions and likely predate enzymes, going back to prebiotic chemistry. However, they are considered poor organocatalysts, and thus their pre-enzymatic function remains unclear. Since metal ions are known to catalyze metabolic reactions in the absence of enzymes, here we explore the influence of metal ions on coenzyme catalysis under conditions relevant to the origin of life (20-75 °C, pH 5-7.

Synthesis of functionalised isochromans: epoxides as aldehyde surrogates in hexafluoroisopropanol.

The oxa-Pictet-Spengler reaction is arguably the most straightforward and modular way to construct the privileged isochroman motif, but its scope is largely limited to benzaldehyde derivatives and to electron-rich β-phenylethanols that lack substitution along the aliphatic chain. Here we describe a variant of this reaction starting from an epoxide, rather than an aldehyde, that greatly expands the scope and rate of the reaction (<1 h, 20 °C). Besides facilitating the initial Meinwald rearrangement, the use of hexafluoroisopropanol (HFIP) as a solvent expands the electrophile scope to include partners equivalent to ketones, aliphatic aldehydes, and phenylacetyl aldehydes, and the nucleophile scope to include modestly electronically deactivated and highly substituted β-phenylethanols.

Ambient temperature CO fixation to pyruvate and subsequently to citramalate over iron and nickel nanoparticles.

The chemical reactions that formed the building blocks of life at origins required catalysts, whereby the nature of those catalysts influenced the type of products that accumulated. Recent investigations have shown that at 100 °C awaruite, a NiFe alloy that naturally occurs in serpentinizing systems, is an efficient catalyst for CO conversion to formate, acetate, and pyruvate. These products are identical with the intermediates and products of the acetyl-CoA pathway, the most ancient CO fixation pathway and the backbone of carbon metabolism in H-dependent autotrophic microbes.

Synthesis of Unprotected β-Arylethylamines by Iron(II)-Catalyzed 1,2-Aminoarylation of Alkenes in Hexafluoroisopropanol.

β-Arylethylamines are prevalent structural motifs in molecules exhibiting biological activity. Here we report a sequential one-pot protocol for the 1,2-aminoarylation of alkenes with hydroxylammonium triflate salts and (hetero)arenes. Unlike existing methods, this reaction provides a direct entry to unprotected β-arylethylamines with remarkable functional group tolerance, allowing key drug-oriented functional groups to be installed in a two-step process.

Quantification of the hydride donor abilities of NADH, NADPH, and BHCN in water.

The nucleophilic reactivities of the hydride donors NADH, NADPH, and BHCN in water were quantified using kinetic measurements with benzhydrylium ions as reference electrophiles. All three hydride donors were found to possess almost identical nucleophilic reactivities, providing a potential explanation for why they are involved in similar transformations in biochemistry and organic synthesis, respectively.

Hydrogen Drives Part of the Reverse Krebs Cycle under Metal or Meteorite Catalysis.

Hydrogen (H ) is a geological source of reducing electrons that is thought to have powered the metabolism of the last universal common ancestor to all extant life, and that is still metabolized by various modern organisms. It has been suggested that H drove a geochemical analogue of some or all of the reverse Krebs cycle at the emergence of the metabolic network, catalyzed by metals, but this has yet to be demonstrated experimentally. Herein, we show that three consecutive steps of the reverse Krebs cycle, converting oxaloacetate into succinate, can be driven without enzymes and in one-pot by H as the reducing agent under mild conditions compatible with biological chemistry.

Quantifying Reductive Amination in Nonenzymatic Amino Acid Synthesis.

Amino acid biosynthesis initiates with the reductive amination of α-ketoglutarate with ammonia to produce glutamate. However, the other α-keto acids derived from the glyoxylate and Krebs cycles are converted into amino acids by transamination, rather than by reductive amination. Why is only one amino acid synthesized by reductive amination and not the others? To explore this question, we quantified the inherent reactivities of keto acids in nonenzymatic reduction and reductive amination by using BH CN as a model nucleophile.