Keire, David A. and Jang, Yun Hee and Li, Lin and Dasgupta, Siddharth and Goddard, William A., III and Shively, John E. (2001) Chelators for Radioimmunotherapy: I. NMR and Ab Initio Calculation Studies on 1,4,7,10-Tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-Tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr). Inorganic Chemistry, 40 (17). pp. 4310-4318. ISSN 0020-1669. doi:10.1021/ic0010297. https://resolver.caltech.edu/CaltechAUTHORS:20170424-145553079
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Abstract
This work describes the modification of the chelating agent 1,4,7,10-tetraazacyclododecane-N,N‘,N‘ ‘,N‘ ‘‘-tetraacetic acid (DOTA) to improve the rate of metal loading for radioimmunotherapy applications. Previous ab initio calculations predicted that the compounds 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr) have a ca. 2000-fold improvement in yttrium metal loading rates compared to those of DOTA (Jang, Y. H.; Blanco, M.; Dasgupta, S.; Keire, D. A.; Shively, J. E.; Goddard, W. A., III. J. Am. Chem. Soc. 1999, 121, 6142−6151). In this study, we report the synthesis, purification, 1H-NMR chemical shift assignments, pKa values, metal loading rate measurements, and additional ab initio calculations of these two compounds. The yttrium loading rates of DO3A1Pr are approximately twice those of DOTA, at pH 4.6 and 37 °C. The NMR data indicates that the DO4Pr analogue forms a stable type I complex but does not form a type II complex. The new ab initio calculations performed on DO4Pr and DO3A1Pr indicate that the rate-determining step is the deprotonation of the first macrocycle amine proton, not the second proton as assumed in the previous calculations. The new calculations predict an improvement in the rate of metal loading that more closely matches the experimentally observed change in the rate.
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Additional Information: | © 2001 American Chemical Society. Received 13 September 2000. Published online 19 July 2001. Published in print 1 August 2001. | ||||||||||||
Issue or Number: | 17 | ||||||||||||
DOI: | 10.1021/ic0010297 | ||||||||||||
Record Number: | CaltechAUTHORS:20170424-145553079 | ||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20170424-145553079 | ||||||||||||
Official Citation: | Chelators for Radioimmunotherapy: I. NMR and Ab Initio Calculation Studies on 1,4,7,10-Tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-Tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr) David A. Keire, Yun Hee Jang, Lin Li, Siddarth Dasgupta, William A. Goddard III, and John E. Shively Inorganic Chemistry 2001 40 (17), 4310-4318 DOI: 10.1021/ic0010297 | ||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||
ID Code: | 76871 | ||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||
Deposited By: | Ruth Sustaita | ||||||||||||
Deposited On: | 24 Apr 2017 22:26 | ||||||||||||
Last Modified: | 15 Nov 2021 17:03 |
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