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Computer-Assisted Design of Macrocyclic Chelators for Actinium-225 Radiotherapeutics
- Source :
- Inorganic Chemistry. 60:623-632
- Publication Year :
- 2020
- Publisher :
- American Chemical Society (ACS), 2020.
-
Abstract
- Actinium-225 (225Ac) is an excellent candidate for targeted radiotherapeutic applications for treating cancer, because of its 10-day half-life and emission of four high-energy α2+ particles. To harness and direct the energetic potential of actinium, strongly binding chelators that remain stable in vivo during biological targeting must be developed. Unfortunately, controlling chelation for actinium remains challenging. Actinium is the largest +3 cation on the periodic table and has a 6d05f0 electronic configuration, and its chemistry is relatively unexplored. Herein, we present theoretical work focused on improving the understanding of actinium bonding with macrocyclic chelating agents as a function of (1) macrocycle ring size, (2) the number and identity of metal binding functional groups, and (3) the length of the tether linking the metal binding functional group to the macrocyclic backbone. Actinium binding by these chelators is presented within the context of complexation with DOTA4-, the most relevant Ac3+ binding agent for contemporary radiopharmaceutical applications. The results enabled us to develop a new strategy for actinium chelator design. The approach is rooted in our identification that Ac3+-chelation chemistry is dominated by ionic bonding interactions and relies on (1) maximizing electrostatic interactions between the metal binding functional group and the Ac3+ cation and (2) minimizing electronic repulsion between negatively charged actinium binding functional groups. This insight will provide a foundation for future innovation in developing the next generation of multifunctional actinium chelators.
- Subjects :
- Actinium
Macrocyclic Compounds
Static Electricity
Ionic bonding
chemistry.chemical_element
Context (language use)
010402 general chemistry
01 natural sciences
Inorganic Chemistry
chemistry.chemical_compound
Coordination Complexes
Static electricity
Molecule
Chelation
Physical and Theoretical Chemistry
Density Functional Theory
Chelating Agents
Molecular Structure
010405 organic chemistry
Combinatorial chemistry
0104 chemical sciences
chemistry
Functional group
Computer-Aided Design
Density functional theory
Radiopharmaceuticals
Subjects
Details
- ISSN :
- 1520510X and 00201669
- Volume :
- 60
- Database :
- OpenAIRE
- Journal :
- Inorganic Chemistry
- Accession number :
- edsair.doi.dedup.....a65970afb614be3d16c64ee9f89ae200