Gildas Bertho

Glutamine is under scrutiny regarding its metabolic deregulation linked to energetic reprogramming in cancer cells. Many analytical techniques have been used to better understand the impact of the metabolism of amino acids on biological processes, however only a few are suited to work with complex samples. Here, we report the use of a general dissolution dynamic nuclear polarization (D‐DNP) formulation using an unexpensive radical as a multipurpose tool to study glutamine, with insights from enzymatic modelling to complex metabolic networks and fast imaging. First, hyperpolarized [5‐ 13 C] glutamine is used as molecular probe to study the kinetic action of two enzymes: L‐asparaginase that has been used as an anti‐metabolic treatment for cancer, and glutaminase. These results are also compared with those acquired with another hyperpolarized amino acid, [1,4‐ 13 C] asparagine. Second, we explored the use of hyperpolarized (HP) substrates to probe metabolic pathways by monitoring metabolic profiles arising from hyperpolarized glutamine in E. coli extracts. Finally, a highly concentrated sample formulation is proposed for the purpose of fast imaging applications. We think that this approach can be extended to formulate other amino acids as well as other metabolites and provide complementary insights into the analysis of metabolic networks.

Eighteen new N ‐acylhydrazones ( 9a–r ) containing the imidazo[1,2‐ a ]pyridine scaffold were synthesized through a seven steps reaction sequence, ending with a condensation of 2‐(3‐nitro‐ H ‐imidazo[1,2‐ a ]pyridin‐2‐ylthio)acetohydrazide with various benzaldehyde derivatives ( 8a–r ). All synthesized compounds were characterized by 1D NMR ( 1 H and 13 C NMR) and 2D NMR (NOESY) spectroscopic analyses and high‐resolution mass spectrometry (HRMS). The analysis of 1 H NMR data performed at room temperature in deuterated dimethylsulfoxide (DMSO‐ d 6 ) revealed the presence of ( E ) ‐ 2‐(3‐nitro‐ H ‐imidazo[1,2‐ a ]pyridin‐2‐ylthio)‐ N ′‐benzylideneacetohydrazide ( 9a–r ) as a mixture of two conformers, namely, syn‐periplanar E ( sp E ) and anti‐periplanar E ( ap E ). For all N ‐acylhydrazones that were synthesized, the sp E conformer was found to be the major form except in the case of hydrazone derived from o ‐hydroxybenzaldehyde.