含磁中心的腙类分子开关作为 pH 成像的磁共振成像弛豫增强剂。

Hydrazone Molecular Switches with Paramagnetic Center as F Magnetic Resonance Imaging Relaxation Enhancement Agents for pH Imaging.

机构信息

Department of Chemical Organic Technology and Petrochemistry, Silesian University of Technology, 44-100 Gliwice, Poland.

Institute of Nuclear Physics Polish Academy of Sciences, 31-342 Krakow, Poland.

出版信息

ACS Sens. 2023 May 26;8(5):1971-1979. doi: 10.1021/acssensors.3c00080. Epub 2023 May 17.

Abstract

The design and synthesis of hydrazone-based switches with a CF reporting group for F pH imaging using relaxation rate changes were described. A paramagnetic center was introduced into the hydrazone molecular switch scaffold by substitution of an ethyl functional group with a paramagnetic complex. The mechanism of activation relies on a gradual increase in and magnetic resonance imaging (MRI) relaxation times as pH decreases due to / isomerization, which results in a change in the distance between fluorine atoms and the paramagnetic center. Among the three possible variants of the ligand, the meta isomer was found to offer the highest potential changes in relaxation rates due to the significant paramagnetic relaxation enhancement (PRE) effect and a stable position of the F signal, allowing for the tracking of a single narrow F resonance for imaging purposes. The selection of the most suitable Gd(III) paramagnetic ion for complexation was conducted by theoretical calculations based on the Bloch-Redfield-Wangsness (BRW) theory, taking into account the electron-nucleus dipole-dipole and Curie interactions only. The results were verified experimentally, confirming the accuracy of theoretical predictions, good solubility, and stability of the agents in water and the reversible transition between E and Z-H isomers. The results demonstrate the potential of this approach for pH imaging using relaxation rate changes instead of chemical shift.

摘要

描述了一种基于腙的开关的设计和合成,该开关带有 CF 报告基团,用于使用弛豫率变化进行 F pH 成像。通过用顺磁配合物取代乙基官能团,将顺磁中心引入腙分子开关支架中。激活机制依赖于由于 / 异构化导致 pH 降低时和磁共振成像(MRI)弛豫时间逐渐增加,这导致氟原子和顺磁中心之间的距离发生变化。在配体的三个可能变体中,发现间位异构体由于显著的顺磁弛豫增强(PRE)效应和 F 信号的稳定位置,提供了最高的弛豫率变化潜力,允许为成像目的跟踪单个狭窄的 F 共振。通过基于 Bloch-Redfield-Wangsness(BRW)理论的理论计算选择最适合络合的 Gd(III)顺磁离子,仅考虑电子-核偶极-偶极和居里相互作用。实验结果证实了理论预测的准确性、试剂在水中的良好溶解性和稳定性以及 E 和 Z-H 异构体之间的可逆转换。结果表明,该方法具有使用弛豫率变化而不是化学位移进行 pH 成像的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8094/10226166/62e5fa3021d4/se3c00080_0002.jpg

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