Para-hydrogenated Glucose Derivatives as Potential ¹³C-Hyperpolarized Probes for Magnetic Resonance Imaging

Abstract

A set of molecules in which a glucose moiety is bound to a hydrogenable synthon has been synthesized and evaluated for hydrogenation reactions and for the corresponding para-hydrogen-induced polarization (PHIP) effects, in order to select suitable candidates for an in vivo magnetic resonance imaging (MRI) method for the assessment of glucose cellular uptake. It has been found that amidic derivatives do not yield any polarization enhancement, probably due to singlet-triplet state mixing along the reaction pathway. In contrast, ester derivatives are hydrogenated in high yield and afford enhanced (1)H and (13)C NMR spectra after para-hydrogenation. The obtained PHIP patterns are discussed and explained on the basis of the calculated spin level populations in the para-hydrogenated products. These molecules may find interesting applications in (13)C MRI as hyperpolarized probes for assessing the activity of glucose transporters in cells.

Total Synthesis of Ellagitannins <i>via</i> Sequential Site-Selective Functionalization of Unprotected D-Glucose

“…[18][19][20] However, the stereoselectivity of these direct glycosylation reactions (α/β=41 : 59-11 : 89) still has room for improvement. We applied their protocol for glycosylation using unprotected D-glucose as a glycosyl donor to the glycosylation reaction of gallic acid derivative 8.…”

How to design 13C para‐hydrogen‐induced polarization experiments for MRI applications

“…The range of molecules that can be hyperpolarized by means of this technique is strongly limited due to the necessity for a hydrogenable moiety to which para-hydrogen must be added. However this problem can be partially solved by means of the derivatization of a biologically relevant molecule with an appropriate group, such that described in the Materials and methods section (22). Furthermore, a new approach to hyperpolarization by means of para-hydrogen has been put forward (23) that does not require the hydrogenation of substrate.…”

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

“…Among them, succinate 14,15 and phospho-lactate 16,17 are the only metabolites for which good hyperpolarization level has been achieved until now. Alternative routes have been proposed to achieve PHIP on biologically relevant molecules by functionalizing the substrates of interest with moieties capable of hydrogenation [18][19][20] . However, the structural modifications introduced by the unsaturated group may significantly alter their biological behaviour with respect to the native substrates.…”