Research & Faculty

Default Header Image

Modular syntheses of H(4)octapa and H(2)dedpa, and yttrium coordination chemistry relevant to Y-86/Y-90 radiopharmaceuticals

TitleModular syntheses of H(4)octapa and H(2)dedpa, and yttrium coordination chemistry relevant to Y-86/Y-90 radiopharmaceuticals
Publication TypeJournal Article
Year of Publication2014
AuthorsPrice, EW, Cawthray, JF, Adam, MJ, Orvig, C
JournalDalton Trans.
Volume43
Pagination7176-7190
ISSN1477-9226
Abstract

The ligands H(2)dedpa, H(4)octapa, p-SCN-Bn-H(2)dedpa, and p-SCN-Bn-H(4)octapa were synthesized using a new protection chemistry approach, with labile tert-butyl esters replacing the previously used methyl esters as protecting groups for picolinic acid moieties. Additionally, the ligands H(2)dedpa and p-SCN-Bn-H(2)dedpa were synthesized using nosyl protection chemistry for the first time. The use of tert-butyl esters allows for deprotection at room temperature in trifluoroacetic acid (TFA), which compares favorably to the harsh conditions of refluxing HCl (6 M) or LiOH that were previously required for methyl ester cleavage. H(4)octapa has recently been shown to be a very promising In-111 and Lu-177 ligand for radiopharmaceutical applications; therefore, coordination chemistry studies with Y3+ are described to assess its potential for use with Y-86/Y-90. The solution chemistry of H(4)octapa with Y3+ is shown to be suitable via solution NMR studies of the {[}Y(octapa)](-) complex and density functional theory (DFT) calculations of the predicted structure, suggesting properties similar to those of the analogous In3+ and Lu3+ complexes. The molecular electrostatic potential (MEP) was mapped onto the molecular surface of the DFT-calculated coordination structures, suggesting very similar and even charge distributions between both the Lu3+ and Y3+ complexes of octapa(4-), and coordinate structures between 8 (ligand only) and 9 (ligand and one H2O). Potentiometric titrations determined H(4)octapa to have a formation constant (log K-ML) with Y3+ of 18.3 +/- 0.1, revealing high thermodynamic stability. This preliminary work suggests that H(4)octapa may be a competent ligand for future Y-86/Y-90 radiopharmaceutical applications.

DOI10.1039/c4dt00239c
Refereed DesignationRefereed