Trends in coordination of rhenium organometallic complexes in the Protein Data Bank

DOI: 10.1107/S2052252522000665

Authors: Alice Brink (University of the Free State; The University of Manchester) , Francois J. F. Jacobs (University of the Free State) , John R. Helliwell (The University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Iucrj , VOL 9 , PAGES 180 - 193

State: Published (Approved)
Published: March 2022
Diamond Proposal Number(s): 8997

Abstract: Radiopharmaceutical development has similar overall characteristics to any biomedical drug development requiring a compound's stability, aqueous solubility and selectivity to a specific disease site. However, organometallic complexes containing 188/186Re or 99mTc involve a d-block transition-metal radioactive isotope and therefore bring additional factors such as metal oxidation states, isotope purity and half life into play. This topical review is focused on the development of radiopharmaceuticals containing the radioisotopes of rhenium and technetium and, therefore, on the occurrence of these organometallic complexes in protein structures in the Worldwide Protein Data Bank (wwPDB). The purpose of incorporating the group 7 transition metals of rhenium/technetium in the protein and the reasons for study by protein crystallography are described, as certain PDB studies were not aimed at drug development. Technetium is used as a medical diagnostic agent and involves the 99mTc isotope which decays to release gamma radiation, thereby employed for its use in gamma imaging. Due to the periodic relationship among group 7 transition metals, the coordination chemistry of rhenium is similar (but not identical) to that of technetium. The types of reactions the potential model radiopharmaceutical would prefer to partake in, and by extension knowing which proteins and biomolecules the compound would react with in vivo, are needed. Crystallography studies, both small molecule and macromolecular, are a key aspect in understanding chemical coordination. Analyses of bonding modes, coordination to particular residues and crystallization conditions are presented. In our Forward look as a concluding summary of this topical review, the question we ask is: what is the best way for this field to progress?

Journal Keywords: organometallic complexes; proteins; rhenium; technetium; radiopharmaceuticals; radioisotopes; transition metals

Subject Areas: Biology and Bio-materials, Chemistry, Medicine


Instruments: I04-1-Macromolecular Crystallography (fixed wavelength)

Added On: 07/03/2022 10:39

Documents:
mf5060.pdf

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)