Rhodium-105 tetrathioether complexes: radiochemistry and initial biological evaluation

Area of Science:

• Inorganic Chemistry
• Radiopharmaceutical Chemistry
• Medicinal Chemistry

Background:

• Rhodium(III) complexes are explored for therapeutic applications.
• Tetrathioether ligands offer unique coordination properties.
• Carboxylic acid groups can influence pharmacokinetic profiles.

Purpose of the Study:

• Synthesize and characterize novel rhodium(III) complexes with acyclic tetrathioether ligands bearing carboxylic acid groups.
• Evaluate the stability of these complexes under physiological conditions.
• Assess the in vivo behavior and identify promising candidates for radiopharmaceutical development.

Main Methods:

• Synthesis of three distinct rhodium(III) tetrathioether complexes.
• Characterization using spectroscopic and analytical techniques.
• In vitro stability assays under physiological conditions.
• In vivo studies in normal mice to determine clearance pathways and biodistribution.

Main Results:

• Successful synthesis and characterization of rhodium(III) complexes.
• Demonstrated stability under physiological conditions for promising candidates.
• Renal/urinary system identified as the primary clearance route, correlating with carboxylate groups.
• The cis-[Rh(III)Cl2(2,5,8,11-tetrathiadodecane-1,12-dicarboxylic acid)]+ complex exhibited favorable in vivo characteristics.

Conclusions:

• The synthesized rhodium(III) complexes show potential as therapeutic agents.
• The presence of pendant carboxylate groups facilitates renal clearance.
• The cis-[Rh(III)Cl2(2,5,8,11-tetrathiadodecane-1,12-dicarboxylic acid)]+ complex is a strong candidate for further development as a radiopharmaceutical.