Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PEGylated, Water-Soluble, Stable Aminyl Radical.

ABSTRACT: We report the synthesis and kinetic study of PEGylated, water-soluble aminyl radical 2. The radical possesses four mPEG-3 groups replacing four methyl groups in the tert-butyl groups at the 3- and 6-positions of 1,3,6,8-tetra-tert-butyl carbazyl (TTBC). This structure is designed to mitigate the rapid decomposition of the radical via intramolecular 1,5-hydrogen atom transfer (1,5-HAT) that was observed in its constitutional isomer 1-H with four mPEG-3 groups in the vicinity of the nitrogen-centered radical (1- and 8-positions of TTBC). In dry, degassed acetone at 295 K, the radical 2 has a half-life, ?1/2 = 49 h (?H‡ = 17.9 ± 0.8 kcal mol-1), which is 3 orders of magnitude longer than that for 1-H, which decays via 1,5-HAT (?1/2 = 48 s, ?H‡ = 10.0 ± 0.3 kcal mol-1). Aminyl radical 2 aggregates at ambient conditions in water and has a half-life, ?1/2 = 2 h.

SUBMITTER: Wang Y

PROVIDER: S-EPMC5560026 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

PEGylated, Water-Soluble, Stable Aminyl Radical.

Wang Ying Y Rajca Suchada S Rajca Andrzej A

The Journal of organic chemistry 20170712 14

We report the synthesis and kinetic study of PEGylated, water-soluble aminyl radical 2. The radical possesses four mPEG-3 groups replacing four methyl groups in the tert-butyl groups at the 3- and 6-positions of 1,3,6,8-tetra-tert-butyl carbazyl (TTBC). This structure is designed to mitigate the rapid decomposition of the radical via intramolecular 1,5-hydrogen atom transfer (1,5-HAT) that was observed in its constitutional isomer 1-H with four mPEG-3 groups in the vicinity of the nitrogen-cente ...[more]

PMID: 28654284

Similar Datasets

Three-coordinate copper(I) amido and aminyl radical complexes.

Project description:A three-coordinate Cu-NR(2) system (R = p-tolyl) supported by the anionic bis(phosphino)borate ligand [Ph(2)B(CH(2)P(t)Bu(2))(2)](-) has been isolated and structurally characterized in both its anionic Cu(I) and neutral (formally) Cu(II) oxidation states. A large rate constant for the self-exchange electron-transfer reaction (k(S) >or= 10(7) M(-1) s(-1)) makes this system a functional model for the type-1 active sites in blue copper proteins. Multiedge X-ray absorption spectroscopy, multifrequency electron paramagnetic resonance, and density functional theory analyses collectively indicate that the oxidized form is best regarded as a Cu(I)-aminyl radical complex rather than a Cu(II)-amido species, with about 70% localization of the unpaired electron on the NR(2) unit. Hydrogen-atom transfer and C-C coupling reactions are presented as examples of chemical reactivity manifested by this unusual electronic structure.

| S-EPMC3110787 | biostudies-literature

Synthesis of a water-soluble 1,3-bis(diphenylene)-2-phenylallyl radical.

Project description:The design and synthesis of a water-soluble 1,3-bis(diphenylene)-2-phenylallyl (BDPA) radical via the conjugate addition of a derivatized fluorene nucelophile is described. The compound is designed for use in dynamic nuclear polarization NMR. Its 9 GHz EPR spectrum in glycerol/water is reported.

| S-EPMC2882179 | biostudies-literature

Mechanism of Reduction of an Aminyl Radical Intermediate in the Radical SAM GTP 3',8-Cyclase MoaA.

Project description:The diversity of the reactions catalyzed by radical S-adenosyl-l-methionine (SAM) enzymes is achieved at least in part through the variety of mechanisms to quench their radical intermediates. In the SPASM-twitch family, the largest family of radical SAM enzymes, the radical quenching step is thought to involve an electron transfer to or from an auxiliary 4Fe-4S cluster in or adjacent to the active site. However, experimental demonstration of such functions remains limited. As a representative member of this family, MoaA has one radical SAM cluster ([4Fe-4S]RS) and one auxiliary cluster ([4Fe-4S]AUX), and catalyzes a unique 3',8-cyclization of GTP into 3',8-cyclo-7,8-dihydro-GTP (3',8-cH2GTP) in the molybdenum cofactor (Moco) biosynthesis. Here, we report a mechanistic investigation of the radical quenching step in MoaA, a chemically challenging reduction of 3',8-cyclo-GTP-N7 aminyl radical. We first determined the reduction potentials of [4Fe-4S]RS and [4Fe-4S]AUX as -510 mV and -455 mV, respectively, using a combination of protein film voltammogram (PFV) and electron paramagnetic resonance (EPR) spectroscopy. Subsequent Q-band EPR characterization of 5'-deoxyadenosine C4' radical (5'-dA-C4'•) trapped in the active site revealed isotropic exchange interaction (∼260 MHz) between 5'-dA-C4'• and [4Fe-4S]AUX1+, suggesting that [4Fe-4S]AUX is in the reduced (1+) state during the catalysis. Together with density functional theory (DFT) calculation, we propose that the aminyl radical reduction proceeds through a proton-coupled electron transfer (PCET), where [4Fe-4S]AUX serves as an electron donor and R17 residue acts as a proton donor. These results provide detailed mechanistic insights into the radical quenching step of radical SAM enzyme catalysis.

| S-EPMC8415136 | biostudies-literature

Direct free radical scavenging effects of water-soluble HMG-CoA reductase inhibitors.

Project description:3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, are widely used for preventing cardiovascular and cerebrovascular diseases by controlling blood cholesterol level. Additionally, previous studies revealed the scavenging effects of statins on free radicals. We assessed direct scavenging activities of two water-soluble statins, fluvastatin and pravastatin, on multiple free radicals using electron spin resonance spectrometry with spin trapping method. We estimated reaction rate constants (k fv for fluvastatin, and k pv for pravastatin). Superoxide anion was scavenged by fluvastatin and pravastatin with k fv and k pv of 4.82 M-1s-1 and 49.0 M-1s-1, respectively. Scavenging effects of fluvastatin and pravastatin on hydroxyl radical were comparable; both k fv and k pv were >109 M-1s-1. Fluvastatin also eliminated tert-butyl peroxyl radical with relative k fv of 2.63 to that of CYPMPO, whereas pravastatin did not affect tert-butyl peroxyl radical. Nitric oxide was scavenged by fluvastatin and pravastatin with k fv and k pv of 68.6 M-1s-1 and 701 M-1s-1, respectively. Both fluvastatin and pravastatin had scavenging effects on superoxide anion, hydroxyl radical and nitric oxide radical. On the other hand, tert-butyl peroxyl radical was scavenged only by fluvastatin, suggesting that fluvastatin might have more potential effect than pravastatin to prevent atherosclerosis and ischemia/reperfusion injury via inhibiting oxidation of lipids.

| S-EPMC6348410 | biostudies-literature

Intramolecular Hydrogen Atom Transfer in Aminyl Radical at Room Temperature with Large Kinetic Isotope Effect.

Project description:We report a large kinetic isotope effect at 298 K, kH/kD ? 150, associated with an intramolecular 1,5-hydrogen atom transfer (1,5-HAT) in the decay of a PEGylated carbazyl (aminyl) radical in solution. The experimental observations surprisingly combine the hallmarks of tunneling, including large KIEs and unusual activation parameters, with linear Arrhenius and Eyring plots over an exceptionally wide temperature range of 116 K.

| S-EPMC5528148 | biostudies-literature

Aminyl Radical Generation via Tandem Norrish Type I Photocleavage, ?-Fragmentation: Independent Generation and Reactivity of the 2'-Deoxyadenosin- N6-yl Radical.

Project description:Formal hydrogen atom abstraction from the nitrogen-hydrogen bonds in purine nucleosides produces reactive intermediates that are important in nucleic acid oxidation. Herein we describe an approach for the independent generation of the purine radical resulting from hydrogen atom abstraction from the N6-amine of 2'-deoxyadenosine (dA•). The method involves sequential Norrish Type I photocleavage of a ketone (7b) and ?-fragmentation of the initially formed alkyl radical (8b) to form dA• and acetone. The formation of dA• was followed by laser flash photolysis, which yields a transient with ?max ? 340 nm and a broader weaker absorption centered at ?560 nm. This transient grows in at ?2 × 105 s-1; however, computations and reactivity data suggest that ?-fragmentation occurs much faster, implying the consumption of dA• as it is formed. Continuous photolysis of 7b in the presence of ferrous ion or thiophenol produces good yields of dA, whereas less reactive thiols afford lower yields presumably due to a polarity mismatch. This tandem photochemical, ?-fragmentation method promises to be useful for site-specific production of dA• in nucleic acid oligomers and/or polymers and also for the production of aminyl radicals, in general.

| S-EPMC5494259 | biostudies-literature

Water-Soluble Polypeptides with Elongated, Charged Side Chains Adopt Ultra-Stable Helical Conformations.

Project description:Water-soluble polypeptides adopting ?-helical conformations with unprecedented high helicities were obtained by elongating the charge-containing side chains of the constituent amino acids to allow the terminal charges to be situated distally from the peptide backbone. Poly(?-(4-aminoethylthiopropoxyl)-benzyl-(L)-glutamate) (PAOBLG-AET) with a charge-peptide backbone distance of 17 ?-bonds exhibited a remarkably high helical content (81%) at a degree of polymerization as low as 10. The helical conformations of these short polypeptides were very stable against various harsh, protein-denaturing conditions, such as extreme pH, high temperature, and high salt or urea concentrations.

| S-EPMC3204311 | biostudies-literature

PEGylated nanoceria as radical scavenger with tunable redox chemistry.

Project description:We report the direct synthesis of cerium oxide nanoparticles (CNPs) in polyethylene glycol (PEG) based solutions with efficient radical scavenging properties. Synthesis of CNPs in PEG demonstrated a concentration dependent (of PEG) redox activity characterized by UV-visible spectroscopy. PEGylated CNPs acted as efficient radical scavengers, and superoxide dismutase (SOD) activity of CNPs synthesized in various concentration of PEG did not reduce compared to bare nanoceria. In addition to superoxide, PEGylated nanoceria demonstrated quenching of peroxide radicals as well. It was observed that the reaction with hydrogen peroxide leads to the formation of a charge transfer complex governed by the concentration of PEG. The stability of the charge transfer complex provides the tunable oxidation state of CNPs. The stability of this complex influences the regenerative capacity of the active 3+ oxidation state of CNPs. The cell viability as well as SOD activity of PEGylated CNPs is compared to those of bare CNPs, and the differences are outlined.

| S-EPMC3038119 | biostudies-literature

Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer.

Project description:Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested as model drugs. To determine the level of HGR4113 and HGR4113-d7 in rat plasma, a bioanalytical method using LC-MS/MS was developed. The HGR4113-d7 was intravenously administered to rats that were orally pre-administered HGR4113 at different doses; subsequently, the plasma samples were collected. HGR4113 and HGR4113-d7 were simultaneously determined in the plasma samples, and bioavailability was calculated using plasma drug concentration values. The bioavailability of HGR4113 was 53.3% ± 19.5%, 56.9% ± 14.0%, and 67.8% ± 16.7% after oral dosages of 40, 80, and 160 mg/kg, respectively. By eliminating the differences in clearance between intravenous and oral dosages at different levels, acquired data showed that the current method reduced measurement errors in bioavailability when compared to the conventional approach. The present study suggests a prominent method for evaluating the bioavailability of drugs with poor aqueous solubility in preclinical studies.

| S-EPMC10305361 | biostudies-literature

A Stable Anionic Dithiolene Radical.

Project description:Sulfurization of anionic N-heterocyclic dicarbene, [:C{[N(2,6-Pri2C6H3)]2CHCLi}]n (2), with elemental sulfur (in a 1:2 ratio) in Et2O at low temperature gives 3 by inserting two sulfur atoms into the Li-C (i.e., C2 and C4) bonds in polymeric 2. Further reaction of 3 with 2 equiv of elemental sulfur in THF affords 4• via unexpected C-H bond activation, which represents the first anionic dithiolene radical to be structurally characterized in the solid state. Alternatively, 4• may also be synthesized directly by reaction of 1 with sulfur (in a 1:4 ratio) in THF. Reaction of 4• with GeCl2·dioxane gives an anionic germanium(IV)-bis(dithiolene) complex (5). The nature of the bonding in 4• and 5 was probed by experimental and theoretical methods.

| S-EPMC5551979 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data