Plasma Levels of Polyols Erythritol, Mannitol, and Sorbitol and Incident Coronary Heart Disease Among Women.

BACKGROUND AND AIMS: Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD). METHODS: This prospective nested case-control study included 762 incident cases of CHD and 762 controls from the Nurses' Health Study. Plasma concentrations of polyols were measured at baseline (1989-90 or 2000-02). Associations of erythritol with cardiometabolic risk factors were also analyzed in the Women's Lifestyle Validation Study (n=728; blood collected in 2010-12). RESULTS: Higher erythritol levels were related to more adverse cardiometabolic risk factor status. The relative risk (RR) for CHD per 1-SD increment was 1.15 [95% CI: 1.04, 1.28] for erythritol and 1.16 [1.05, 1.28] for mannitol/sorbitol, after adjusting for diet quality, lifestyles, and adiposity. Compared with women in the lowest quartile, those in the highest quartile (Q4) of erythritol had a RR 1.55 [1.13, 2.14] for CHD. The RR in Q4 of erythritol was 1.61 [1.15, 2.24; p=0.006] when hypertension and dyslipidemia were further added to the model; the RR was 1.21 [0.86, 1.70] after adjustment for diabetes. For mannitol/sorbitol, the RR in the Q4 was 1.42 [1.05, 1.91; p=0.022] for CHD in the multivariable-adjusted model including diabetes. CONCLUSIONS: Higher plasma erythritol and mannitol/sorbitol were related to elevated risks of CHD even after adjustment for diet, lifestyles, adiposity, and other risk factors. The unfavorable association of mannitol/sorbitol, but not erythritol, with CHD risk remained significant independently of diabetes/hyperglycemia.

The present study shows unfavorable associations of circulating erythritol and mannitol/sorbitol with long-term coronary heart disease (CHD) risk even after adjustments for overall diet quality, lifestyle factors, and several other traditional CHD risk factors among women at usual risk. In contrast to mannitol/sorbitol, the association between high erythritol levels and increased CHD risk was no longer significant upon additional inclusion of diabetes in the multivariable-adjusted model. Our findings from the two independent study populations of women without prior CHD suggest endogenous and exogenous erythritol levels are related to unfavorable cardiometabolic risk factor status.

Elevated osmol gaps in patients with alcoholic ketoacidosis.

INTRODUCTION: The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. METHODS: This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. RESULTS: Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. DISCUSSION: The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. CONCLUSIONS: In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 26. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

Huangqi Gegen decoction ameliorates alcohol-induced cognitive dysfunction via attenuating oxidative stress and enhancing blood-brain barrier integrity in rats through the Keap1-Nrf2/HO-1 signaling pathway.

Objectives: Chronic alcohol abuse causes cognitive deficits. Huangqi Gegen Decoction (HGD), a traditional Chinese herbal formula comprising Huangqi and Gegen, has been documented for its therapeutic efficacy in the treatment of alcoholic liver injury. However, its potential neuroprotective effects against alcohol-induced brain injury remain unexplored. This study aims to evaluate the neuroprotection of HGD on alcohol-induced cognitive dysfunction and the associated mechanism. Materials and Methods: Wistar rats were orally administered 50% ethanol for 10 weeks, followed by treatment with HGD at doses of 16, 32, or 64 mg/kg/day for an additional 6 weeks. The spatial learning and memory abilities of rats were assessed through the Morris Water Maze experiment. The pathological condition in the hippocampus was assessed using H&E and Nissl staining. Tight junction proteins, oxidative stress, and inflammation cytokines were measured by IF, ELISA, PCR, and western blot. The mRNA and protein expression of Keap1, Nrf-2, HO-1, and NQO-1 were tested by PCR and western blot. Results: Results showed that HGD effectively mitigated cognitive dysfunction and pathological changes in alcohol-induced rats while enhancing the expression of ZO-1, Occludin, and Claudin-5. Furthermore, HGD effectively mitigated oxidative stress by reducing levels of ROS and MDA, while elevating levels of SOD, CAT, and GSH-PX in brain tissue. Moreover, HGD significantly suppressed microglial activation and down-regulated expressions of IL-1ß, IL-6, and TNF-α. Mechanistically, HGD remarkably up-regulated the expression of Nrf-2, HO-1, and NQO-1 while down-regulating Keap1 expression. Conclusion: These findings suggest that HGD may be a promising therapeutic agent for alleviating alcohol-induced cognitive dysfunction.

Exploring the optimal chain length of modification module in disulfide bond bridged paclitaxel prodrug nanoassemblies for breast tumor treatment.

In the prodrug-based self-assembled nanoassemblies, prodrugs usually consist of drug modules, response modules, and modification modules. Modification modules play a critical role in regulating the nano-assembly ability of the prodrugs. Herein, we carried out a "fatty alcoholization" strategy and chose various lengths of aliphatic alcohol chains (AC) as modification modules to construct disulfide bond bridged paclitaxel (PTX) prodrug nanoassemblies. The PTX-AC prodrugs would self-assemble into nanoassemblies (PTX-AC PNs) with higher drug loading, stability, and tumor selectivity than commercial preparations. After comprehensive exploration, we found the chain length (AC12, AC16, AC20, AC24) of modification modules affected the assembly of PTX-AC PNs, further leading to disparate in vivo fate and antitumor efficacy. With the increase of the chain length of the modification modules (from AC12 to AC20), the assembly ability of the nanoassemblies was improved, attributed to the appropriate enhancement of hydrophobic force. When the chain length was further increased to AC24, the excessive hydrophobic force will lead to the aggregation of prodrugs and weaken the assembly ability. Therefore, PTX-AC20 PNs with proper chain length may solve the paradox of efficacy and tolerance in 4 T1 breast tumor owing to their optimal nano-assembly stability and modest redox-sensitivity. In short, this work highlighted the importance of screening optimal modification modules in developing prodrug nanoassemblies.

Interface-rich porous Fe-doped hcp-PtBi/fcc-Pt heterostructured nanoplates enhanced the CC bond cleavage of C3 alcohols electrooxidation.

Efficient CC bond cleavage and the complete oxidation of alcohols are key to improving the efficiency of renewable energy utilization. Herein, we successfully prepare porous Fe-doped hexagonal close-packed (hcp)-PtBi/face-centered cubic (fcc)-Pt heterostructured nanoplates with abundant grain/phase interfaces (h-PtBi/f-Pt@Fe1.7 PNPs) via a simple solvothermal method. The open porous structure, abundant grain/phase interface and stacking fault defects, and the synergistic effect between intermetallic hcp-PtBi and fcc-Pt make h-PtBi/f-Pt@Fe1.7 PNPs an effective electrocatalyst for the glycerol oxidation reaction (GOR) in direct glycerol fuel cells (DGFCs). Notably, the h-PtBi/f-Pt@Fe1.7 PNPs exhibit an excellent mass activity of 7.6 A mgPt-1 for GOR, 4.75-fold higher than that of commercial Pt black in an alkaline medium. Moreover, the h-PtBi/f-Pt@Fe1.7 PNPs achieve higher power density (125.8 mW cm-2) than commercial Pt/C (81.8 mW cm-2) in a single DGFC. The h-PtBi/f-Pt@Fe1.7 PNPs can also effectively catalyze the electrochemical oxidation of 1-propanol (17.1 A mgPt-1), 1,2-propanediol (7.2 A mgPt-1), and 1,3-propanediol (5.2 A mgPt-1). The in-situ Fourier-transform infrared spectra further reveal that the CC bond of glycerol, 1-propanol, 1,2-propanediol, and 1,3-propanediol was dissociated for the complete oxidation by the h-PtBi/f-Pt@Fe1.7 PNPs. This study provides a new class of porous Pt-based heterostructure nanoplates and insight into the intrinsic activity of different C3 alcohols.

A Comparative Study of Microbial Communities, Biogenic Amines, and Volatile Profiles in the Brewing Process of Rice Wines with Hongqu and Xiaoqu as Fermentation Starters.

Rice wine is primarily crafted from grains through saccharification and liquification with the help of Qu. Qu plays an important role in the formation of the flavor quality of rice wine. Hongqu and Xiaoqu represent two prevalent varieties of Qu that are typically utilized in the brewing process of rice wine and play a crucial role in its production. In this study, GC, GC-MS, HPLC, and metagenomic sequencing techniques were used to contrast the microbial flora, biogenic amines, and aroma characteristics developed during the fermentation of rice wines, with Hongqu and Xiaoqu being used as initiating agents for the brewing process. The results show that the content of higher alcohols (including n-propanol, isobutanol, 3-methyl-1-butanol, and phenethyl alcohol) in rice wine brewed with Xiaoqu (XQW) was significantly higher than that in rice wine brewed with Hongqu (HQW). Contrarily, the concentration of biogenic amines in HQW surpassed that of XQW by a notable margin, but tyramine was significantly enriched in XQW and not detected in HQW. In addition, a multivariate statistical analysis revealed distinct disparities in the constitution of volatile components between HQW and XQW. Hexanoic acid, ethyl acetate, isoamyl acetate, ethyl caproate, ethyl decanoate, 2-methoxy-4-vinylphenol, etc., were identified as the characteristic aroma-active compounds in HQW and XQW. A microbiome analysis based on metagenomic sequencing showed that HQW and XQW had different dominant microorganisms in the brewing process. Burkholderia, Klebsiella, Leuconostoc, Monascus, and Aspergillus were identified as the primary microbial genera in the HQW fermentation period, while Pediococcus, Enterobacter, Rhizopus, Ascoidea, and Wickerhamomyces were the main microbial genera in the XQW brewing process. A bioinformatics analysis revealed that the concentrations of microbial genes involved in biogenic amines and esters biosynthesis were significantly higher in HQW than those in XQW, while the content of genes relevant to glycolysis, higher alcohol biosynthesis, and fatty acid metabolism was significantly higher in XQW than in HQW, which are the possible reasons for the difference in flavor quality between the two kinds of rice wine from the perspective of microbial functional genes.

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. The setup is used to test whether VSC changes a fundamental kinetic property of polar reactions, nucleophilicity, for water and alcohols, species commonly used in VSC-modified chemistry. We determined the rate constants for nucleophilic capture with a library of benzhydrilium ions as reference electrophiles with and without strong coupling of the nucleophile's key vibrations. For all investigated combinations of electrophiles and nucleophiles, only minor changes in the observed rate constants of the reactions were observed, independently of the coupled bands. These results indicate that VSC does not substantially alter the nucleophilicity of water and alcohols, suggesting that polar reactions are modified through other, presently unknown mechanisms. Fixed-width cavities allow for convenient and reproducible UV-vis kinetics, facilitating mechanistic studies of VSC-modified chemistry.

Synthetic biology approaches and bioseparations in syngas fermentation.

Fossil fuel use drives greenhouse gas emissions and climate change, highlighting the need for alternatives like biomass-derived syngas. Syngas, mainly H2 and CO, is produced via biomass gasification and offers a solution to environmental challenges. Syngas fermentation through the Wood-Ljungdahl pathway yields valuable chemicals under mild conditions. However, challenges in scaling up persist due to issues like unpredictable syngas composition and microbial fermentation contamination. This review covers advancements in genetic tools and metabolic engineering to expand product range, highlighting crucial enabling technologies that expedite strain development for acetogens and other non-model organisms. This review paper provides an in-depth exploration of syngas fermentation, covering microorganisms, gas composition effects, separation techniques, techno economic analysis, and commercialization efforts.

Development of Root Caries Associated With the Use of Sugar-Free Nicotine Lozenges: A Long-Term Case Report.

The authors present a case concerning an adult male patient who developed multiple sites of root caries adjacent to the area where he habitually held a sugar-free nicotine lozenge that contained mannitol and maltodextrin. The root caries occurred despite the patient's excellent oral hygiene, exemplary dietary habits, and clinically normal salivary flow. Between 1999 and 2008, he had only required two restorations to repair carious lesions. This patient had a 20+-year habit of using smokeless tobacco before switching to a cessation aid nicotine lozenge in May of 2008. A full-mouth series of radiographs taken in November 2009 revealed carious lesions on virtually every posterior tooth. The nicotine lozenge's principal ingredients were mannitol (75.7%) and maltodextrin. According to the United States' current Food and Drug Administration (FDA) guidelines, manufacturers can advertise these lozenges as sugar-free. Thus, it is assumed by the public that these types of products are incapable of "causing a cavity." However, this case report presents evidence suggesting that frequent use of sugar-free nicotine lozenges may be associated with dental caries.

Challenging established norms: The unanticipated role of alcohols in UV/PDS radical quenching.

UV/peroxydisulfate (UV/PDS) process is known to be highly efficient for degrading micropollutants from water by generating sulfate (SO4•-) and hydroxyl radicals (HO•). Reliable analyses of short-lived SO4•- and HO• are therefore critical for understanding reaction mechanisms and optimizing operating conditions. Currently, alcohols are commonly used as quenchers to distinguish radicals based on the assumption that they exclusively react with target radicals without other influences. However, this study for the first time reveals a series of unexpected effects that challenge this conventional wisdom because: 1) adding alcohols altered the decomposition rates of PDS by replacing the reactions between SO4•- and HO• with PDS by the reactions between secondary reactive species and PDS; and 2) SO4•- preferably reacted with alcohols to generate nonnegligible level of hydrogen peroxide (H2O2) under oxygen-rich conditions, which subsequently led to indirect formation of HO•. Additionally, the formation of H2O2 was substantially impacted by the types of alcohols, dosages, dissolved oxygen, and solution pH. Using probe tests as tools, we found that the actual SO4•- levels after dosing alcohols were only slightly different from assumed/expected levels, whereas the actually HO• levels were 43.7, 3364.9, and 12.5 times higher than assumed/expected conditions for samples dosed with methanol, iso-propanol, and tert-butanol, respectively. These unanticipated effects thus suggest that cautions are needed when using alcohols to qualitative and quantitative determine HO• and SO4•- in UV/PDS process.

Attenuating Nucleophilicity of Titanocene Hydrides beyond Steric Effects en Route to Fatty Alcohols.

Here, we introduce a new class of titanocene catalysts for epoxide hydrosilylation that frustrates their hydridicity and thereby emphasizes their electron transfer reactivity. This unique attenuation of hydridicity is accomplished by introducing Lewis acidic silicon centers to the cyclopentadienyl ligands for an intramolecular coordination of the titanium bound hydride. The superiority of our rationally designed catalysts over classic titanocenes with alkyl substituted cyclopentadienyl ligands is demonstrated in the dramatically improved regioselectivity of the hydrosilylation of monosubstituted epoxides to primary alcohols.

Highly Selective CO2 Electroreduction to Multi-carbon Alcohols via Amine Modified Copper Nanoparticles at Acidic Conditions.

Electroreduction of CO2 into multi-carbon (C2+) products (e.g. C2+ alcohols) offers a promising way for CO2 utilization. Use of strong alkaline electrolytes is favorable to producing C2+ products. However, CO2 can react with hydroxide to form carbonate/bicarbonate, which results in low carbon utilization efficiency and poor stability. Using acidic electrolyte is an efficient way to solve the problems, but it is a challenge to achieve high selectivity of C2+ products. Here we report that the amine modified copper nanoparticles exhibit high selectivity of C2+ products and carbon utilization at acidic condition. The Faradaic efficiency (FE) of C2+ products reach up to 81.8% at acidic media (pH=2) with a total current density of 410 mA cm-2 over n-butylamine modified Cu. Especially the FE of C2+ alcohols is 52.6%, which is higher than those reported for CO2 electroreduction at acidic condition. In addition, the single-pass carbon efficiency towards C2+ production reach up to 60%. Detailed studies demonstrate that the amine molecule on the surface of Cu cannot only enhance the formation, adsorption and coverage of *CO, but also provide a hydrophobic environment, which result in the high selectivity of C2+ alcohols at acidic condition.

Investigating and Engineering an 1,2-Propanediol-Responsive Transcription Factor-Based Biosensor.

Transcription factor (TF)-based biosensors have arisen as powerful tools in the advancement of metabolic engineering. However, with the emergence of numerous bioproduction targets, the variety of applicable TF-based biosensors remains severely limited. In this study, we investigated and engineered an 1,2-propanediol (1,2-PD)-responsive transcription activator, PocR, from Salmonella typhimurium to enrich the current biosensor repertoire. Heterologous characterization of PocR in E. coli revealed a significantly limited operational range and dynamic range, primarily attributed to the leaky binding between PocR and its corresponding promoters in the absence of the 1,2-PD inducer. Promiscuity characterization uncovered the minor responsiveness of PocR toward glycerol and 1,2-butanediol (1,2-BD). Using AlphaFold-predicted structure and protein mutagenesis, we preliminarily explored the underlying mechanism of PocR. Based on the investigated mechanism, we engineered a PcoR-F46R/G105D variant with an altered inducer specificity to glycerol, as well as a PocR-ARE (Q107A/S192R/A203E) variant with nearly a 4-fold higher dynamic range (6.7-fold activation) and a 20-fold wider operational range (0-20 mM 1,2-PD). Finally, we successfully converted PocR to a repressor through promoter engineering. Integrating the activation and repression functions established a versatile 1,2-PD-induced bifunctional regulation system based on PocR-ARE. Our work showcases the exploration and exploitation of an underexplored type of transcriptional activator capable of recruiting RNA polymerase. It also expands the biosensor toolbox by providing a 1,2-PD-responsive bifunctional regulator and glycerol-responsive activator.

Regioselective and enantioselective propargylic hydroxylations catalyzed by P450tol monooxygenases.

Regioselective and enantioselective hydroxylation of propargylic C-H bonds are useful reactions but often lack appropriate catalysts. Here a green and efficient asymmetric hydroxylation of primary and secondary C-H bonds at propargylic positions has been established. A series of optically active propargylic alcohols were prepared with high regio- and enantioselectivity (up to 99% ee) under mild reaction conditions by using P450tol, while the C≡C bonds in the molecule remained unreacted. This protocol provides a green and practical method for constructing enantiomerically chiral propargylic alcohols. In addition, we also demonstrated that the biohydroxylation strategy was able to scaled up to 2.25 mmol scale with the production of chiral propargyl alcohol 2a at a yield of 196 mg with 96% ee, which's an important synthetic intermediate of antifungal drug Ravuconazole.

A pH-dependent shift of redox cofactor specificity in a benzyl alcohol dehydrogenase of aromatoleum aromaticum EbN1.

We characterise a reversible bacterial zinc-containing benzyl alcohol dehydrogenase (BaDH) accepting either NAD+ or NADP+ as a redox cofactor. Remarkably, its redox cofactor specificity is pH-dependent with the phosphorylated cofactors favored at lower and the dephospho-forms at higher pH. BaDH also shows different steady-state kinetic behavior with the two cofactor forms. From a structural model, the pH-dependent shift may affect the charge of a histidine in the 2'-phosphate-binding pocket of the redox cofactor binding site. The enzyme is phylogenetically affiliated to a new subbranch of the Zn-containing alcohol dehydrogenases, which share this conserved residue. BaDH appears to have some specificity for its substrate, but also turns over many substituted benzyl alcohol and benzaldehyde variants, as well as compounds containing a conjugated C=C double bond with the aldehyde carbonyl group. However, compounds with an sp3-hybridised C next to the alcohol/aldehyde group are not or only weakly turned over. The enzyme appears to contain a Zn in its catalytic site and a mixture of Zn and Fe in its structural metal-binding site. Moreover, we demonstrate the use of BaDH in an enzyme cascade reaction with an acid-reducing tungsten enzyme to reduce benzoate to benzyl alcohol. KEY POINTS: •Zn-containing BaDH has activity with either NAD + or NADP+ at different pH optima. •BaDH converts a broad range of substrates. •BaDH is used in a cascade reaction for the reduction of benzoate to benzyl alcohol.

HOO• as the Chain Carrier for the Autocatalytic Photooxidation of Benzylic Alcohols.

The oxidation of benzylic alcohols is an important transformation in modern organic synthesis. A plethora of photoredox protocols have been developed to achieve the aerobic oxidation of alcohols into carbonyls. Recently, several groups described that ultraviolet (UV) or purple light can initiate the aerobic oxidation of benzylic alcohols in the absence of an external catalyst, and depicted different mechanisms involving the photoinduction of •O2- as a critical reactive oxygen species (ROS). However, based on comprehensive mechanistic investigations, including control experiments, radical quenching experiments, EPR studies, UV-vis spectroscopy, kinetics studies, and density functional theory calculations (DFT), we elucidate here that HOO•, which is released via the H2O2 elimination of α-hydroxyl peroxyl radicals [ArCR(OH)OO•], serves as the real chain carrier for the autocatalytic photooxidation of benzylic alcohols. The mechanistic ambiguities depicted in the precedent literature are clarified, in terms of the crucial ROS and its evolution, the rate-limiting step, and the primary radical cascade. This work highlights the necessity of stricter mechanistic analyses on UV-driven oxidative reactions that involve aldehydes' (or ketones) generation.

Ceria nanocatalyst-supported oxidative organic transformations of aromatic alcohols andp-nitrotoluene.

Hydrothermally derived nanocubes of CeO2(10 nm) were explored as an efficient heterogeneous catalyst in the partial oxidation of aromatic alcohols to the corresponding aldehydes and aerobic oxidation ofp-nitrotoluene top-nitrobenzoic acid. The CeO2nanocatalyst was characterized by x-ray diffraction, transmission electron microscopy (TEM), energy dispersive spectroscopy, x-ray photoelectron spectroscopy, Brunauer-Emmett-Teller (BET) surface area analysis, Fourier transform infrared spectroscopy, thermal gravimetric analysis and ultraviolet-visible spectroscopy. TEM/high-resolution TEM micrographs reveal a morphology of mostly cubic nanostructures with exposed highly active {100} and {110} facets. The surface area of nanoceria was determined by BET analysis and found to be 33.8 m2g-1. To demonstrate the universality of the catalytic system, the selective oxidation of different substrates of benzylic alcohol and complete oxidation ofp-nitrotoluene was investigated under mild conditions. Absolute selectivity towards their respective aldehydes was found to be 99.50% (benzaldehyde), 90.18% (p-chlorobenzaldehyde), 99.71% (p-nitrobenzaldehyde), 98.10% (p-fluorobenzaldehyde), 94.66% (p-anisaldehyde) and 86.14% (cinnamaldehyde). Moreover, the catalytic oxidative transformation of nitrotoluene results in 100% conversion with 99.29% selectivity towards nitrobenzoic acid.

Imaging Phospholipase D Activity with Clickable Alcohols via Transphosphatidylation.

Phospholipase D (PLD) is an enzyme with many functions, one of which is the synthesis of phosphatidic acid (PA), a molecule with a myriad of effects on various organ systems and processes. These numerous roles make it hard to understand the true action of PA in cellular and bodily processes. Imaging PLD activity is one way to better understand the synthesis of PA and start to elucidate its function. However, many of the current imaging techniques for PLD come with limitations. This chapter presents a thorough methodology of a new imaging technique for PLD activity with clickable alcohols via transphosphatidylation (IMPACT) and Real-Time IMPACT (RT-IMPACT) that takes advantage of clickable chemistry to overcome current limitations. Using strain-promoted azide-alkyne cycloaddition (SPAAC), inverse electron-demand Diels-Alder (IEDDA), and the synthesis of various organic compounds, this chapter will explain a step-by-step procedure of how to perform the IMPACT and RT-IMPACT method(s).

Vinyl 3-(Dimethylamino)propanoate as an Irreversible Acyl Donor Reagent in a Chromatography-free Lipase-Catalyzed Kinetic Resolution of sec-Alcohols.

The reported chemoenzymatic strategy involves the employment of vinyl 3-(dimethylamino)propanoate as an irreversible acyl donor in a chromatography-free lipase-catalyzed kinetic resolution (KR) of racemic sec-alcohols. This biotransformation is achieved in a sequential manner using CAL-B to affect the kinetic resolution, followed by a simple acidic extractive work-up furnishing both KR products with excellent enantioselectivity (E>200; up to 98 % ee). The elaborated method eliminates a single-use silica gel chromatographic separation and significantly reduces organic solvent consumption to foster a more environmentally friendly chemical industry.