Synthesis and Characterization of fac-Re(CO)3-aspartic-N-monoacetic Acid: Structural Analogue of a Potential Renal Tracer, fac-99mTc(CO)3(ASMA)

• Type of Material: Article
• Authors: Jeff Klenc, Emory University; Malgorzata Lipowska, Emory University; Andrew T Taylor Jr., Emory University; Luigi G. Marzilli, Louisiana State University
• Language: English
• Date: 2012-09
• Publisher: Wiley-VCH Verlag
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/ejic.201200599/abstract
• Title of Journal or Parent Work: European Journal of Inorganic Chemistry
• ISSN: 1434-1948
• Volume: 2012
• Issue: 27
• Start Page: 4334
• End Page: 4341
• Grant/Funding Information: This work was supported by the National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases (Grant No. R37 DK38842).
• Keywords: Imaging agents; Ligand design; Isomer resolution; Aminopolycarboxylate ligands; Rhenium
• Research Categories: Health Sciences, Radiology; Chemistry, Inorganic

Abstract

The reaction of an aminopolycarboxylate ligand, aspartic-N-monoacetic acid (ASMA), with [Re(CO)3(H2O)3]+ was examined. The tridentate coordination of ASMA to this ReI tricarbonyl precursor yielded fac-Re(CO)3(ASMA) as a mixture of diastereomers. The chemistry is analogous to that of the TcI tricarbonyl complex, which yields fac-99mTc(CO)3(ASMA) under similar conditions. The formation, structure, and isomerization of fac-Re(CO)3(ASMA) products were characterized by HPLC, 1H NMR spectroscopy, and X-ray crystallography. The two major fac-Re(CO)3(ASMA) diastereomeric products each have a linear ONO coordination mode with two adjacent five-membered chelate rings, but they differ in the endo or exo orientation of the uncoordinated acetate group, in agreement with expectations based on previous studies. Conditions have been identified for the expedient isomerization of fac-Re(CO)3(ASMA) to a mixture consisting primarily of one major product. Because different isomeric species typically have different pharmacokinetic characteristics, these conditions may provide for the practical isolation of a single 99mTc(CO)3(ASMA) species, thus allowing the isolation of the isomer that has optimal imaging and pharmacokinetic characteristics. This information will aid in the design of future 99mTc radiopharmaceuticals.