Al(III)-NTA-fluoride: a simple model system for Al-F binding with interesting thermodynamics

Area of Science:

• Radiochemistry
• Coordination Chemistry
• Nuclear Medicine

Background:

• Aluminum(III) complexes are crucial as [18F]fluoride carriers for Positron Emission Tomography (PET).
• Limited understanding of thermodynamic and kinetic properties hinders efficient radiolabeling and purity.
• Investigating fluoride binding to coordinatively unsaturated Al(iii) complexes is essential for improving PET imaging agents.

Purpose of the Study:

• To elucidate the fluoride binding mechanisms to aluminum(III) complexes.
• To understand the thermodynamic and kinetic properties of the Al(iii)-nitrilo-triacetic acid-fluoride system.
• To optimize conditions for radiolabeling Al(iii) complexes with [18F]fluoride for PET applications.

Main Methods:

• Investigated the ternary system Al(iii)-H3NTA-F- using Nuclear Magnetic Resonance (NMR) spectroscopy, potentiometry, and X-ray diffraction.
• Utilized theoretical calculations, including energy ordering, 19F NMR chemical shift interpretation, and natural bonding orbital analysis.
• Performed radiolabeling experiments with [18F]fluoride to assess complex yields and affinities.

Main Results:

• The [Al(NTA)] complex binds two water molecules, which can be replaced by fluoride ions.
• Individual species and isomers exhibit distinct 19F NMR signals and varying stability constants.
• Fluoride binding is favored in weakly acidic or neutral solutions; hydroxide species dominate in alkaline conditions, confirmed by low radiolabeling yields.

Conclusions:

• The study provides detailed insights into fluoride binding to Al(iii) complexes, highlighting the influence of pH and complex speciation.
• Understanding the differential properties of binding sites and the competition with hydroxide is critical for developing efficient Al(iii)-based PET radiotracers.
• The findings suggest that careful control of solution conditions is necessary to maximize radiolabeling efficiency and minimize unwanted side reactions.