The Absence of Quadrupolar Nuclei Facilitates Efficient 13C Hyperpolarization via Reversible Exchange with Parahydrogen
The Absence of Quadrupolar Nuclei Facilitates Efficient 13C Hyperpolarization via Reversible Exchange with Parahydrogen
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DOI：
10.1002/cphc.201700416
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发表时间：
2017-06-20
期刊：
影响因子：
2.9
通讯作者：
Chekmenev, Eduard Y.
中科院分区：
文献类型：
--
作者：
Barskiy, Danila A.;Shchepin, Roman V.;Chekmenev, Eduard Y.
核自旋超极化技术正在彻底改变C-13分子MRI领域。虽然溶解动态核极化（d-DNP）是目前领先的技术，但它通常较慢（需要约1小时）且成本高（约10美元（6））。由于碳在生物化学中的中心地位，迄今为止已经证明了使用C-13 d-DNP生物成像的巨大进展，包括许多临床试验。尽管许多人尝试开发d-DNP的替代品，但竞争方法面临着重大的翻译挑战。在2015年已经报道了使用可逆交换信号放大（SABRE）的N-15、P-31和其他异核的有效超极化，但是将该技术扩展到C-13已被证明是具有挑战性的。在这里，我们提出了有效的超极化的C-13核使用微特斯拉SABRE。多达约6700-在8.45 T下，在几秒内实现核自旋极化的倍数增强，对应于使用50%仲氢时P-13 C约为4.4%（使用更有效的约100%仲氢时P-13 C> 14%将是可行的）。重要的是，通过SABRE实现的C-13极化强烈地不仅取决于自旋-晶格弛豫，而且取决于在结合催化络合物的六配位Ir原子的位点中N-15（I = 1/2）与四极N-14（I = 1）自旋的存在。我们发现，不同的C-13核的测试分子框架-吡啶和乙腈-可以超极化，包括C-13网站高达5个化学键远离可交换的电子。所提出的方法是高度可扩展的，并可应用于数量迅速增长的生物分子可微特斯拉SABRE。
Nuclear spin hyperpolarization techniques are revolutionizing the field of C-13 molecular MRI. While dissolution dynamic nuclear polarization (d-DNP) is currently the leading technique, it is generally slow (requiring approximate to 1 h) and costly (approximate to $USD10(6)). As a consequence of carbon's central place in biochemistry, tremendous progress using C-13 d-DNP bioimaging has been demonstrated to date including a number of clinical trials. Despite numerous attempts to develop alternatives to d-DNP, the competing methods have faced significant translational challenges. Efficient hyperpolarization of N-15, P-31, and other heteronuclei using signal amplification by reversible exchange (SABRE) has been reported in 2015, but extension of this technique to C-13 has proven to be challenging. Here, we present efficient hyperpolarization of C-13 nuclei using micro-Tesla SABRE. Up to ca. 6700-fold enhancement of nuclear spin polarization at 8.45 T is achieved within seconds, corresponding to P-13C approximate to 4.4% using 50% parahydrogen (P-13C > 14% would be feasible using more potent approximate to 100% parahydrogen). Importantly, the C-13 polarization achieved via SABRE strongly depends not only upon spin-lattice relaxation, but also upon the presence of N-15 (I = 1/2) versus quadrupolar N-14 (I = 1) spins in the site binding the hexacoordinate Ir atom of the catalytic complex. We show that different C-13 nuclei in the test molecular frameworks-pyridine and acetonitrile-can be hyperpolarized, including C-13 sites up to five chemical bonds away from the exchangeable hydrides. The presented approach is highly scalable and can be applied to a rapidly growing number of biomolecules amendable to micro-Tesla SABRE.