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The Journal of Physical Chemistry. B Aug 2022The ability to exploit carbonyl groups to measure electric fields in enzymes and other complex reactive environments by using the vibrational Stark effect has inspired...
The ability to exploit carbonyl groups to measure electric fields in enzymes and other complex reactive environments by using the vibrational Stark effect has inspired growing interest in how these fields can be measured, tuned, and ultimately designed. Previous studies have concentrated on the role of the solvent in tuning the fields exerted on the solute. Here, we explore instead the role of the solute electronic structure in modifying the local solvent organization and electric field exerted on the solute. By measuring the infrared absorption spectra of amide-containing molecules, as prototypical peptides, and contrasting them with non-amide carbonyls in a wide range of solvents, we show that these solutes experience notable differences in their frequency shifts in polar solvents. Using vibrational Stark spectroscopy and molecular dynamics simulations, we demonstrate that while some of these differences can be rationalized by using the distinct intrinsic Stark tuning rates of the solutes, the larger frequency shifts for amides and dimethylurea primarily result from the larger solvent electric fields experienced by their carbonyl groups. These larger fields arise due to their stronger -π conjugation, which results in larger C═O bond dipole moments that further induce substantial solvent organization. Using electronic structure calculations, we decompose the electric fields into contributions from solvent molecules that are in the first solvation shell and those from the bulk and show that both of these contributions are significant and become larger with enhanced conjugation in solutes. These results show that structural modifications of a solute can be used to tune both the solvent organization and electrostatic environment, indicating the importance of a solute-centric paradigm in modulating and designing the electrostatic environment in condensed-phase chemical processes.
Topics: Amides; Electronics; Solutions; Solvents; Static Electricity
PubMed: 35901512
DOI: 10.1021/acs.jpcb.2c03095 -
Inorganic Chemistry Oct 2018Superoxide dismutases (SODs) utilize a ping-pong mechanism in which a redox-active metal cycles between oxidized and reduced forms that differ by one electron to...
Superoxide dismutases (SODs) utilize a ping-pong mechanism in which a redox-active metal cycles between oxidized and reduced forms that differ by one electron to catalyze the disproportionation of superoxide to dioxygen and hydrogen peroxide. Nickel-dependent SOD (NiSOD) is a unique biological solution for controlling superoxide levels. This enzyme relies on the use of cysteinate ligands to bring the Ni(III/II) redox couple into the range required for catalysis (∼300 mV vs. NHE). The use of cysteine thiolates, which are not found in any other SOD, is a curious choice because of their well-known oxidation by peroxide and dioxygen. The NiSOD active site cysteinate ligands are resistant to oxidation, and prior studies of synthetic and computational models point to the backbone N-donors in the active site (the N-terminal amine and the amide N atom of Cys2) as being involved in stabilizing the cysteines to oxidation. To test the role of the backbone N-donors, we have constructed a variant of NiSOD wherein an alanine residue was added to the N-terminus (Ala0-NiSOD), effectively altering the amine ligand to an amide. X-ray absorption, electronic absorption, and magnetic circular dichroism (MCD) spectroscopic analyses of as-isolated Ala0-NiSOD coupled with density functional theory (DFT) geometry optimized models that were evaluated on the basis of the spectroscopic data within the framework of DFT and time-dependent DFT computations are consistent with a diamagnetic Ni(II) site with two cysteinate, one His1 amide, and one Cys2 amidate ligands. The variant protein is catalytically inactive, has an altered electronic absorption spectrum associated with the nickel site, and is sensitive to oxidation. Mass spectrometric analysis of the protein exposed to air shows the presence of a mixture of oxidation products, the principal ones being a disulfide, a bis-sulfenate, and a bis-sulfinate derived from the active site cysteine ligands. Details of the electronic structure of the Ni(III) site available from the DFT calculations point to subtle changes in the unpaired spin density on the S-donors as being responsible for the altered sensitivity of Ala0-NiSOD to O.
Topics: Amides; Amines; Escherichia coli; Gene Expression Regulation, Enzymologic; Models, Molecular; Nickel; Protein Conformation; Superoxide Dismutase
PubMed: 30281299
DOI: 10.1021/acs.inorgchem.8b01499 -
Nature Aug 2021The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic...
The substitution of an alkyl electrophile by a nucleophile is a foundational reaction in organic chemistry that enables the efficient and convergent synthesis of organic molecules. Although there has been substantial recent progress in exploiting transition-metal catalysis to expand the scope of nucleophilic substitution reactions to include carbon nucleophiles, there has been limited progress in corresponding reactions with nitrogen nucleophiles. For many substitution reactions, the bond construction itself is not the only challenge, as there is a need to control stereochemistry at the same time. Here we describe a method for the enantioconvergent substitution of unactivated racemic alkyl electrophiles by a ubiquitous nitrogen-containing functional group, an amide. Our method uses a photoinduced catalyst system based on copper, an Earth-abundant metal. This process for asymmetric N-alkylation relies on three distinct ligands-a bisphosphine, a phenoxide and a chiral diamine. The ligands assemble in situ to form two distinct catalysts that act cooperatively: a copper/bisphosphine/phenoxide complex that serves as a photocatalyst, and a chiral copper/diamine complex that catalyses enantioselective C-N bond formation. Our study thus expands enantioselective N-substitution by alkyl electrophiles beyond activated electrophiles (those bearing at least one sp- or sp-hybridized substituent on the carbon undergoing substitution) to include unactivated electrophiles.
Topics: Amides; Bromides; Carbon; Catalysis; Copper; Cyclization; Diamines; Ligands; Nitrogen; Phosphines; Photochemistry
PubMed: 34182570
DOI: 10.1038/s41586-021-03730-w -
Molecules (Basel, Switzerland) Jan 2019The addition of amide/sulfonamide bonds to alkynes is not only one of the most important strategies for the direct functionalization of carbon⁻carbon triple bonds, but... (Review)
Review
The addition of amide/sulfonamide bonds to alkynes is not only one of the most important strategies for the direct functionalization of carbon⁻carbon triple bonds, but also a powerful tool for the downstream transformations of amides/sulfonamides. The present review provides a comprehensive summary of amide/sulfonamide bond addition to alkynes, including direct and metal-free aminoacylation, based-promoted aminoacylation, transition-metal-catalyzed aminoacylation, organocatalytic aminoacylation and transition-metal-catalyzed aminosulfonylation of alkynes up to December 2018. The reaction conditions, regio- and stereoselectivities, and mechanisms are discussed and summarized in detail.
Topics: Alkynes; Amides; Carbon; Catalysis; Metals; Molecular Structure; Sulfonamides
PubMed: 30621120
DOI: 10.3390/molecules24010164 -
Scientific Reports Jul 2022Etomidate has been advocated to be used in anesthesia for the elderly and the critically ill patients due to its faint effect on cardiovascular system. But the... (Randomized Controlled Trial)
Randomized Controlled Trial
Etomidate has been advocated to be used in anesthesia for the elderly and the critically ill patients due to its faint effect on cardiovascular system. But the dose-dependent suppression of etomidate on adrenal cortex function leads to the limitation of its clinical application. Clinical research showed that dexmedetomidine could reduce the dose requirements for intravenous or inhalation anesthetics and opioids, and the hemodynamics was more stable during the operation. The objective was to observe the effect of etomidate combined with dexmedetomidine on adrenocortical function in elderly patients. 180 elderly patients scheduled for elective ureteroscopic holmium laser lithotripsy were randomly allocated to PR group anesthetized with propofol-remifentanil, ER group anesthetized with etomidate-remifentanil, and ERD group anesthetized with dexmedetomidine combined with etomidate-remifentanil. Patients in each group whose operation time was less than or equal to 1 h were incorporated into short time surgery group (PR group, ER group and ERD group), and whose surgical procedure time was more than 1 h were incorporated into long time surgery group (PR group, ER group and ERD group). The primary outcome was the serum cortisol and ACTH concentration. The secondary outcomes were the values of SBP, DBP, HR and SpO, the time of surgical procedure, the dosage of etomidate and remifentanil administered during surgery, the time to spontaneous respiration, recovery and extubation, and the duration of stay in the PACU. The Serum cortisol concentration was higher at t in ERD group compared to ER group (P < 0.05). The Serum cortisol concentration at t was higher in ERD group than in ER group (P < 0.05). The Serum ACTH concentration was lower at t in ERD group compared to ER group (P < 0.05). The Serum ACTH concentration at t was lower in ERD group compared to ER group (P < 0.05). The SBP at T and T were higher in ER and ERD group than in PR group (P < 0.05). The DBP in ER and ERD group were higher at T compared to PR group (P < 0.05). The dosage of etomidate was significantly lower in ERD group and ERD group than in ER group and ER group (P < 0.05), respectively. The administration of dexmedetomidine combined with etomidate can attenuate the inhibition of etomidate on adrenocortical function in elderly patients and maintain intraoperative hemodynamic stability.
Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Age Factors; Aged; Anesthetics, Intravenous; Dexmedetomidine; Double-Blind Method; Etomidate; Humans; Hydrocortisone; Propofol; Remifentanil
PubMed: 35853975
DOI: 10.1038/s41598-022-16679-1 -
Anesthesiology Aug 2017We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis.
BACKGROUND
We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis.
METHODS
Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3β-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11β-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD).
RESULTS
At 12 h, lipopolysaccharide induced an overexpression of corticotropin-releasing hormone (32 ± 5 vs. 18 ± 6, P < 0.01), proopiomelanocortin (21 ± 3 vs. 8 ± 0.9, P < 0.0001), P450 side-chain cleavage (32 ± 4 vs. 23 ± 10, P < 0.05), 21-hydroxylase (17 ± 5 vs. 12 ± 2, P < 0.05), and 11β-hydroxylase (11 ± 4 vs. 6 ± 0.5, P = 0.001), and an elevation of corticosterone (642 ± 165 vs. 98.3 ± 63 ng/ml, P < 0.0001). Etomidate and ketamine reduced P450 side-chain cleavage (19 ± 7 and 19 ± 3 vs. 32 ± 4, P < 0.01), 21-hydroxylase (8 ± 0.8 and 8 ± 1 vs. 17 ± 5, P < 0.001), 11β-hydroxylase (4 ± 0.5 and 7 ± 1 vs. 11 ± 4, P < 0.001 and P < 0.05), and corticosterone (413 ± 189 and 260 ± 161 vs. 642 ± 165 ng/ml, P < 0.05 and P < 0.01). Ketamine also inhibited adrenocorticotropin hormone production (2.5 ± 3.6 vs. 36 ± 15 pg/ml, P < 0.05). At 48 h, all four adrenal enzymes were down-regulated by lipopolysaccharide administration with corticosterone levels similar to the control group. Ketamine and etomidate did not modify corticosterone plasma levels.
CONCLUSIONS
Our endotoxemic model induces an initial activation of the hypothalamic-pituitary-adrenal axis, followed by a secondary inhibition of adrenal steroidogenesis processes. Ketamine and etomidate inhibit the enzyme expression and activity of the adrenal gland at the early stage.
Topics: Analgesics; Animals; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Down-Regulation; Endotoxemia; Etomidate; Hypnotics and Sedatives; Hypothalamo-Hypophyseal System; Ketamine; Male; Mice; Mice, Inbred C57BL; Pituitary-Adrenal System; Pro-Opiomelanocortin; Steroid 21-Hydroxylase
PubMed: 28542000
DOI: 10.1097/ALN.0000000000001704 -
Organic Letters Jul 2022A photoinduced, iron(III) chloride-catalyzed C-H activation of -methyl amides and ethers leads to the formation of C-S and C-Se bonds via a ligand-to-metal charge...
A photoinduced, iron(III) chloride-catalyzed C-H activation of -methyl amides and ethers leads to the formation of C-S and C-Se bonds via a ligand-to-metal charge transfer (LMCT) process. This methodology converts secondary and tertiary amides, sulfonamides, and carbamates into the corresponding amido--acetal derivatives in good yields. Mechanistic work revealed that this transformation proceeds through a hydrogen atom transfer (HAT) involving chlorine radical intermediates.
Topics: Amides; Ethers; Ferric Compounds; Hydrogen; Ligands
PubMed: 35729078
DOI: 10.1021/acs.orglett.2c01505 -
Molecules (Basel, Switzerland) Oct 2016Four new unsaturated aliphatic acid amides, named zanthoamides A-D (-), and eight known ones-tetrahydrobungeanool (), ZP-amide A (), ZP-amide B (), ZP-amide C (),...
Four new unsaturated aliphatic acid amides, named zanthoamides A-D (-), and eight known ones-tetrahydrobungeanool (), ZP-amide A (), ZP-amide B (), ZP-amide C (), ZP-amide D (), ZP-amide E (), bugeanumamide A (), and (2,7,9)--(2-hydroxy-2-methylpropyl)-6,11-dioxo-2,7,9-dodecatrienamide ()-were isolated from the pericarps of . The structures of these compounds were elucidated by extensive use of spectroscopic methods, including HRESIMS, 1D and 2D NMR analyses and comparison with previously reported data. Compound contained a rare C₆ fatty acid unit with an acetal group. Results revealed that compounds , , , and showed inhibitory effects on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages, with ICvalues of 48.7 ± 0.32, 27.1 ± 1.15, 49.8 ± 0.38, and 39.4 ± 0.63 µM, respectively, while the other compounds were inactive (IC > 60 μM). They could contribute to the anti-inflammatory effects of by suppression of NO production.
Topics: Amides; Animals; Anti-Inflammatory Agents; Fatty Acids, Unsaturated; Lipopolysaccharides; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Nitric Oxide; Plant Extracts; RAW 264.7 Cells; Zanthoxylum
PubMed: 27782100
DOI: 10.3390/molecules21101416 -
Molecules (Basel, Switzerland) Dec 2023The lubricating properties of the lubricants were tested under boundary friction conditions; it was found that the surface-active additives had reduced the wear mark and...
The lubricating properties of the lubricants were tested under boundary friction conditions; it was found that the surface-active additives had reduced the wear mark and thus the value of the Goz/40 parameter (limiting load of wear). The introduction of a surfactant containing amide compounds into the oils and greases was highly effective in slowing down the oxidation process. Lubricants containing mono-15 ([3-(,,-dimethylbuthylamine)propyl]hexadecanamide chloride) and 15-4-15 (tetramethylene-bis [3-(,,-dimethylamine)propyl]hexadecanamide) additives were characterised by higher oxidation stability compared to the unmodified lubricants. Both of the analysed substances showed bactericidal properties against and . Tests of antibacterial activity in the lubricants with the addition of mono-15 and 15-4-15 confirmed that these lubricants can be considered bactericidal against Gram-positive and Gram-negative bacteria.
Topics: Lubricants; Anti-Bacterial Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Amides
PubMed: 38202705
DOI: 10.3390/molecules29010122 -
Organic & Biomolecular Chemistry May 2022A solvent-free procedure for the formation of amides without exclusion of air and moisture is described. Using tetramethoxysilane 1, hexamethoxydisilane 2 and...
A solvent-free procedure for the formation of amides without exclusion of air and moisture is described. Using tetramethoxysilane 1, hexamethoxydisilane 2 and dodecamethoxy-neopentasilane 3 as coupling agent carboxylic acids and amines are reacted to form amides in good to excellent yields. The formation of these amides was confirmed by NMR spectroscopy and mass spectrometry. Remarkably, neopentasilane 3 exceeds the performance of the currently used monosilanes as coupling agent in terms of group tolerance and yield.
Topics: Amides; Amines; Carboxylic Acids; Solvents
PubMed: 35441639
DOI: 10.1039/d2ob00589a