Long-range heteronuclear J-coupling constants in esters: Implications for 13C metabolic MRI by side-arm parahydrogen-induced polarization

Side-arm parahydrogen induced polarization (PHIP-SAH) presents a cost-effective method for hyperpolarization of C-13 metabolites (e.g. acetate, pyruvate) for metabolic MRI. The timing and efficiency of typical spin order transfer methods including magnetic field cycling and tailored RF pulse sequences crucially depends on the heteronuclear J coupling network between nascent parahydrogen protons and C-13, post-parahydrogenation of the target compound. In this work, heteronuclear (n)J(HC) (1 < n <= 5) couplings of acetate and pyruvate esters pertinent for PHIP-SAH were investigated experimentally using selective HSQMBC-based pulse sequences and numerically using DFT simulations. The CLIP-HSQMBC technique was used to quantify 2/3-bond JHC couplings, and 4/5-bond J(HC) less than or similar to 0.5 Hz were estimated by the sel-HSQMBC-TOCSY approach. Experimental and numerical (DFT-simulated) nJHC couplings were strongly correlated (P < 0.001). Implications for C-13 hyperpolarization by magnetic field cycling, and PH-INEPT and ESOTHERIC type spin order transfer methods for PHIP-SAH were assessed, and the influence of direct nascent parahydrogen proton to C-13 coupling when compared with indirect homonuclear TOCSY-type transfer through intermediate (non-nascent parahydrogen) protons was studied by the density matrix approach. (C) 2018 Elsevier Inc. All rights reserved.