Physics of Radiation Biology
Kedar N. Prasad in Handbook of RADIOBIOLOGY, 2020
Neptunium has a half-life of 2.33 days, whereas plutonium has a half-life of 24,400 years and is a fissionable element. Natural uranium contains 99.3% 238U and only 0.7% 235U. The natural uranium cannot sustain a chain reaction for two reasons: (1) neutrons from the first fission might escape from the sample, and (2) neutrons might get captured by nonfissionable elements such as 238U. In 1942, many physicists believed that a chain reaction would occur in pure 235U and possibly in an ordinary uranium sample in a properly moderated reactor. The criteria for the moderator were that the elements must be of low atomic material to provide an inelastic collision and at the same time have a very low cross section for neutron capture. Deuterium and carbon are commonly used for this purpose.
Working with Gas Laws
Patrick E. McMahon, Rosemary F. McMahon, Bohdan B. Khomtchouk in Survival Guide to General Chemistry, 2019
Example: Deuterium (D) is the isotope hydrogen-2 (1 p+ and 1 n°); MM = 2.008 g/mole. Deuterium was extracted and concentrated for nuclear experiments by taking advantage of the diffusion rate difference between “normal” hydrogen-1 water (H2O) and D2O (“heavy” water). Calculate the ratio of diffusion of H2O to D2O. Step ( 1): Rate diffusion H2O/rate diffusion D2O = {MM (D2O)/MM (H2O)} ½Step ( 2): MM D2O = 20.02 g/mole; MM H2O = 18.02 g/moleStep ( 3): Rate diffusion H2O/rate diffusion D2O = [(20.02 g/more)/(18.02 g/more)] ½= (1.111) ½ = 1.054
Instrumentation
Clive R. Bagshaw in Biomolecular Kinetics, 2017
Quenched-flow methods have also been used in conjunction with mass spectrometry. Mass spectrometry provides a direct measure of chemical transformations and can readily distinguish between a hydrogen-deuterium substitution in a small peptide. Hence, protein folding reactions can be followed by subjecting the protein, during folding, with a D2O pulse and stopping the exchange with an acid quench (Section 5.1). Mass spectrometry is then performed on the fragmented protein to see which peptides have exchanged and, therefore, which parts of the protein were solvent accessible up to the time of the quench [158,592]. Chemical transformations during enzyme catalysis have been followed by directly interfacing a rapid-mixing device with an electrospray mass spectrometer [434,593]. This is particularly useful for intermediates that are not stable in the stopping solutions used in conventional quenched-flow methods. Rapid-mixing devices interfaced to mass spectrometers continue to be developed [594]. Higher time resolutions (~50 μs) have been achieved by fusing microdroplets (13 μm diameter), which contain the reactants just prior to entry into the mass spectrometer [431].
Understanding the structure–property relationship of bispecific monoclonal antibodies with Fc site-specific substitutions
Published in mAbs, 2023
Bo Zhao, Yunlong Zhao, Stephanie Adaniya, Yue Fu, Youmi Moon, Justin Heftel, Shuzhen Chen, Hui Xiao, Ning Li
Labeling was performed on a LEAP PAL3 HDX automation system (Trajan Scientific and Medical, Morrisville, NC). Samples comprising 8 μL of 3 mg/mL mAb were labeled in 72 μL labeling buffer (1× phosphate-buffered saline (PBS) in D2O, pH = 7.4) three times for each indicated labeling time (30, 240, 1,800, and 14,400 s) at 25°C. After labeling, 50 μL of each labeled sample was quenched with 50 μL of quenching buffer (200 mM sodium phosphate, 4 M guanidine hydrochloride and 500 mM TCEP, pH = 2.3, in water) at 1°C. After quenching, 50 μL of the sample was injected into a chromatography system within a cold box connected to a Waters Acquity UPLC instrument (Waters, Milford, MA). The cold box and LC solvent precooler were maintained at 0°C for all experiments. Injected samples were passed over an immobilized pepsin column (2.1 × 30 mm, NovaBioAssays, Woburn, MA) at 100 μL/min for 120 s with mobile phase A (95% H2O, 5% acetonitrile and 0.5% formic acid). The resulting peptic peptides were captured and desalted on a SymmetryShield C8 trap column (3.9 × 20 mm, Waters, Mildford, MA). The digested peptides were separated on an Acquity BEH C18 column (2.1 × 50 mm, 1.7 μm, 130 Å, Waters, Milford, MA) over a 25 min linear gradient of mobile phase B (0.1% formic acid in acetonitrile) from 0.1% to 30.0%. A Thermo Q ExactiveTM Plus mass spectrometer was used to measure the mass of deuterium-labeled peptides.
A patent review of pharmaceutical and therapeutic applications of oxadiazole derivatives for the treatment of chronic diseases (2013–2021)
Published in Expert Opinion on Therapeutic Patents, 2022
Abbas Hassan, Abid Hussain Khan, Faiza Saleem, Haseen Ahmad, Khalid Mohammed Khan
Zhang et al. envisaged the synthesis of the deuterium isotope of ozanimod for the study of oxidized by-products from the drug metabolism and the study of the kinetic isotope effect. They have synthesized a variety of deuterium analogs for a comprehensive pharmacokinetics and metabolism study. They find out in different in vitro and in vivo assays, such as liver microsomal stability assay, in vitro metabolism using human cytochrome P450 enzymes, monoamine oxidase A and B inhibition and oxidative turnover, S1P1-mediated inhibition of cAMP reporter assay, rat pharmacokinetic assays that the likely metabolism of ozanimod in humans is at the hydroxyethyl group, the isopropyl group, the indenyl methylene, and N-methine groups (Figure 47) [108].
Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia
Published in Expert Review of Neurotherapeutics, 2021
Benjamin J. Dorfman, Joohi Jimenez-Shahed
In order to address the pharmacokinetic challenges seen with tetrabenazine, a deuterated form called deutetrabenazine (Austedo®, Teva Pharmaceuticals) was developed. Deuterium is an isotope of hydrogen containing one neutron, in contrast with the most common isotope of hydrogen, protium, which has no neutrons. Deuterium-carbon bonds are stronger than carbon-hydrogen bonds, and thus, substituting deuterium for hydrogen at sites that are targets for enzymatic degradation may delay the rate of metabolism [39–43]. This has the effect of both prolonging a drug’s half-life and providing a more stable plasma concentration [42,43]. As a result, deuterated drugs can be given at lower doses and reach an effective plasma concentration and therapeutic benefit while reaching a lower Cmax, which may lower risks of peak-dose AEs [44].
Related Knowledge Centers
- Atom
- Helium
- Nuclear Magnetic Resonance
- Radioactive Decay
- Tritium
- Hydrogen
- Atomic Nucleus
- Heavy Water
- Microwave Spectroscopy
- Deuterium Nmr