Improved synthesis process of optical-magnetic bimodal probe of Gd-4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl-acetic acid complexes.
- Author:
Hui SHENG
1
;
Lei LIANG
2
;
Tong Liang ZHOU
2
;
Yan Xing JIA
2
;
Tong WANG
1
;
Lan YUAN
1
;
Hong Bin HAN
3
Author Information
1. Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijng 100191, China.
2. Department of Medicinal Chemistry, Peking University School of Pharmaceutical Sciences, Beijng 100191, China.
3. Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China.
- Publication Type:Journal Article
- Keywords:
Bimodal imaging;
Bimodal probe;
Chemical synthesis;
Magnetic resonance imaging;
Optical imaging
- MeSH:
Acetic Acid;
Brain;
Magnetic Resonance Imaging;
Magnetic Resonance Spectroscopy;
Molecular Probes
- From:
Journal of Peking University(Health Sciences)
2020;52(5):959-963
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To improve the methods to synthesize and purify of optical-magnetic bimodal molecular probe of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluorescein thioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes.
METHODS:Target compound (7), optical-magnetic bimodal molecular molecular probe, was synthesized by the use of 1, 4, 7, 10-tetraazacyclododecane (1) as starting material via substitution reaction, hydrolysis reaction, coupling reaction and complexation reaction with metal.
RESULTS:The synthetic route of Gd-[4, 7-Bis-carboxymethyl-10-(2-fluoresceinthioureaethyl)-1, 4, 7, 10-tetraaza-cyclododec-1-yl]-acetic acid complexes was improved. The optical-magnetic bimodal molecular probes were synthesized by substitution reaction, hydrolysis reaction, coupling reaction and complex reaction with metal respectively. For the improved route, the total yield could reach 34.6% which was higher than the original route (18.0%). The structures of those compounds were identified by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and mass spectrometry. The improved route could avoid the uncontrollable disadvantage of the substitution reaction, this process could reduce the formation of impurities and made the purification process easier, and in the aspect of purification and separation, the preparative high-performance liquid chromatography with less sample loading and high cost was improved to a column chromatography with many sample loads and being easy to operate. Therefore, the use of column chromatography could be more conducive to mass production of the optical-magnetic bimodal molecular molecular probe.
CONCLUSION:The improved synthetic route improves the controllability of the reaction conditions and makes it easier to purify and separate the compounds. At the same time, the improved synthetic route can increase the total yield significantly. The optical-magnetic bimodal molecular probe can combine the living magnetic resonance imaging with the in vitro optical imaging to realize the dual synchronous detection of magneto-optics, so that the detection results of the living magnetic resonance imaging and the in vitro optical imaging are mutually verified. In other words, this synthetic optical-magnetic bimodal molecular probe will make the experimental results more accurate and reliable. In subsequent biological experimental studies, the optical-magnetic bimodal molecular probe can be applied to related research of brain structure and function, and the probe can be used for the brain-related diseases researches, such as brain tumors. after intravenous administration, and thus the optical-magnetic bimodal molecular probe can play an important role in medical treatment of brain tumors and cerebrovascular diseases.
