期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：14
页码：5503-5507
DOI：10.1073/pnas.0810190106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In this manuscript, the remarkable NMR signal enhancement that can be provided by dynamic nuclear polarization (DNP) was combined with the reactivity of acetic anhydride with amines to perform rapid, high SNR analyses of amino acid mixtures and to hyperpolarize new biomolecules of interest. [1,1-13C] acetic anhydride is an excellent substrate for DNP hyperpolarization because it can be well polarized in only 30 min and has a relatively long T1 relaxation time (33.9 s at 11.7 T and 37 {degrees}C). The secondary hyperpolarization approach developed in this project takes advantage of the preferential reaction of acetic anhydride with amine nucleophiles, which occurs much more rapidly than hydrolysis to produce hyperpolarized N-acetyl adducts. This new approach was used to reproducibly and near-quantitatively (mean yield - 89.8%) resolve a mixture of amino acids Gly, Ser, Val, Leu, and Ala in a single acquisition (3 s) with a signal enhancement of up to 1,400-fold as compared with thermal equilibrium. Secondary hyperpolarization was performed for several small peptides and N-acetylcysteine, a drug administered intravenously to treat acetaminophen overdose. Although, in general the T1 of the N-acetyl adducts decreased with increasing molecular weight of the biomolecules, the T1 values were still on the order of 10 s, and the correlation of T1 with molecular weight was not exact suggesting the potential of secondarily polarizing relatively large biomolecules. This study demonstrates the feasibility of using prepolarized [1,1-13C] acetic anhydride and rapid chemical reactions to provide high SNR NMR spectra of amino acid derivatives and other biomolecules.
