Inorganic Chemistry p. 1275 - 1287 (2011)
Update date:2022-07-30
Topics:
Chang, Ya-Hui
Chen, Chiao-Yun
Singh, Gyan
Chen, Hsing-Yin
Liu, Gin-Chung
Goan, Yih-Gang
Aime, Silvio
Wang, Yun-Ming
The present study was designed to exploit optimum lipophilicity and high water-exchange rate (kex) on low molecular weight Gd(III) complexs to generate high bound relaxivity (r1b), upon binding to the lipophilic site of human serum albumin (HSA). Two new carbon backbone modified TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid) derivatives, CB-TTDA and Bz-CB-TTDA, were synthesized. The complexes [Gd(CB-TTDA)(H 2O)]2- and [Gd(Bz-CB-TTDA)(H2O)]2- both display high stability constant (log KGdL = 20.28 and 20.09, respectively). Furthermore, CB-TTDA (log K(Gd/Zn) = 4.22) and Bz-CB-TTDA (log K(Gd/Zn) = 4.12) exhibit superior selectivity of Gd(III) against Zn(II) than those of TTDA (log K(Gd/Zn) = 2.93), EPTPA-bz-NO2 (log K(Gd/Zn) = 3.19), and DTPA (log K (Gd/Zn) = 3.76). However, the stability constant values of [Gd(CB-TTDA)(H2O)]2- and [Gd(Bz-CB-TTDA)(H 2O)]2- are lower than that of MS-325. The parameters that affect proton relaxivity have been determined in a combined variable temperature 17O NMR and NMRD study. The water exchange rates are comparable for the two complexes, 232 × 106 s-1 for [Gd(CB-TTDA)(H2O)]2- and 271 × 106 s -1 for [Gd(Bz-CB-TTDA)(H2O)]2-. They are higher than those of [Gd(TTDA)(H2O)]2- (146 × 10 6 s-1), [Gd(DTPA)(H2O)]2- (4.1 × 106 s-1), and MS-325 (6.1 × 106 s-1). Elevated stability and water exchange rate indicate that the presence of cyclobutyl on the carbon backbone imparts rigidity and steric constraint to [Gd(CB-TTDA)(H2O)]2-and [Gd(Bz-CB-TTDA) (H2O)]2-. In addition, the major objective for selecting the cyclobutyl is to tune the lipophilicity of [Gd(Bz-CB-TTDA)(H 2O)]2-. The binding affinity of [Gd(Bz-CB-TTDA)(H 2O)]2- to HSA was evaluated by ultrafiltration study across a membrane with a 30 kDa MW cutoff, and the first three stepwise binding constants were determined by fitting the data to a stoichiometric model. The binding association constants (KA) for [Gd(CB-TTDA)(H 2O)]2- and [Gd(Bz-CB-TTDA)(H2O)]2- are 1.1 × 102 and 1.5 × 103, respectively. Although the KA value for [Gd(Bz-CB-TTDA)(H2O)] 2- is lower than that of MS-325 (KA = 3.0 × 10 4), the r1b value, r1b = 66.7 mM-1 s-1 for [Gd(Bz-CB-TTDA)(H2O)] 2-, is significantly higher than that of MS-325 (r1 b = 47.0 mM-1 s-1). As measured by the Zn(II) transmetalation process, the kinetic stabilities of [Gd(CB-TTDA)(H 2O)]2-, [Gd(Bz-CB-TTDA)(H2O)]2-, and [Gd(DTPA)(H2O)]2- are similar and are significantly higher than that of [Gd(DTPA-BMA)(H2O)]2-. High thermodynamic and kinetic stability and optimized lipophilicity of [Gd(CB-TTDA)(H2O)]2- make it a favorable blood pool contrast agent for MRI.
View MoreShanghai Haoyuan Chemexpress Co., Ltd.
website:https://www.chemexpress.com/
Contact:86-21-58950125
Address:No.3 Building, No.1999, Zhangheng Road, ZhangjiangHighTech Park, Shanghai, P.R.China,201203
Disynthesis Chemical Technology Co. Ltd.
Contact:+86-571-88194596
Address:Dengyun road 380, Gongshu district, Hangzhou city, China
Anhui Sholon New Material Technology Co., Ltd.
website:http://www.sholonchem.com
Contact:+86-550-5261666
Address:4/F Block B, Beijing Chemical Building.No.520 Tianrun Road ,Science & Education Town Wujin District, Changzhou City Jiangsu Province
Anhui Gusheng Import&Export CO.,LTD
Contact:86-551-63662296
Address:Jinzhai Road NO.162 ,hefei, china
Contact:86-607-68073220
Address:1 ave na road jiahua st
Doi:10.1246/bcsj.62.3892
(1989)Doi:10.1039/b815547j
(2008)Doi:10.1021/acs.orglett.8b02023
(2018)Doi:10.1016/j.tetlet.2015.12.025
(2016)Doi:10.1134/S1070428009060189
(2009)Doi:10.1002/anie.201607388
(2016)