Bringing Biocatalysis into the Deuteration Toolbox

<p></p><p>Chemicals labelled with the heavy hydrogen isotope deuterium (²H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed ²H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only ²H₂O (D₂O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed ²H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from ²H₂O solvent to NAD⁺, with H₂ gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.</p><p></p>

Bringing Biocatalysis into the Deuteration Toolbox

<p></p><p>Chemicals labelled with the heavy hydrogen isotope deuterium (²H) have long been used in chemical and biochemical mechanistic studies, spectroscopy, and as analytical tracers. More recently, demonstration of selectively deuterated drug candidates that exhibit advantageous pharmacological traits has spurred innovations in metal-catalysed ²H insertion at targeted sites, but asymmetric deuteration remains a key challenge. Here we demonstrate an easy-to-implement biocatalytic deuteration strategy, achieving high chemo-, enantio- and isotopic selectivity, requiring only ²H₂O (D₂O) and unlabelled dihydrogen under ambient conditions. The vast library of enzymes established for NADH-dependent C=O, C=C, and C=N bond reductions have yet to appear in the toolbox of commonly employed ²H-labelling techniques due to requirements for suitable deuterated reducing equivalents. By facilitating transfer of deuterium atoms from ²H₂O solvent to NAD⁺, with H₂ gas as a clean reductant, we open up biocatalysis for asymmetric reductive deuteration as part of a synthetic pathway or in late stage functionalisation. We demonstrate enantioselective deuteration via ketone and alkene reductions and reductive amination, as well as exquisite chemo-control for deuteration of compounds with multiple unsaturated sites.</p><p></p>

Theoretical Investigations on Laser-Assisted Depletion of Gd152 Isotope From Natural Gadolinium

We have proposed laser-assisted depletion of Gd152 isotope from a natural isotopic mixture of Gd to enhance its functional efficiency as a burnable poison. Theoretical investigations on laser-assisted depletion of Gd152 isotope from natural gadolinium have been carried out for two-color resonant three-color photoionization pathways using density matrix formalism. Calculations have been carried out using a density matrix formalism to optimize conditions for high ionization efficiency without much sacrifice in the isotopic selectivity. Optimum conditions for good isotopic selectivity of Gd152 without significant sacrifice in the ion yield have been identified. Under appropriate conditions, all the 17 photoionization schemes are found to be useful for the laser-assisted separation of Gd152 isotopes which can be used for reactor applications. The effect of source, laser, and atom parameters on isotopic selectivity and ionization efficiency has been investigated. Among the photoionization schemes investigated, one of the photoionization scheme has been investigated in detail. Under optimized conditions, this photoionization scheme has resulted in high ionization efficiency (>50%) and high isotopic selectivity (1.2×104).