التفاصيل البيبلوغرافية
| العنوان: |
Improved Access to Linear Tetrameric Hydroxamic Acids with Potential as Radiochemical Ligands for Zirconium(iv)-89 PET Imaging. |
| المؤلفون: |
Brown, Christopher J. M.1 (AUTHOR), Gotsbacher, Michael P.1 (AUTHOR), Codd, Rachel1 (AUTHOR) rachel.codd@sydney.edu.au |
| المصدر: |
Australian Journal of Chemistry. 2020, Vol. 73 Issue 10, p969-978. 10p. |
| مصطلحات موضوعية: |
*HYDROXAMIC acids, *CARBOXYLIC acids, *LIGANDS (Chemistry), *POSITRON emission tomography, *ZIRCONIUM, *MONOMERS |
| مستخلص: |
Two new linear tetrameric hydroxamic acid ligands (3 and 4) have been prepared as potential radioligands for immunological ZrIV-89 positron emission tomography (PET) imaging. The ligands were prepared by conjugating endo -hydroxamic acid amino carboxylic acid (endo -HXA) monomers 5-[(5-aminopentyl)(hydroxy)amino]-5-oxopentanoic acid (PPH) or 2-(2-((2-(2-aminoethoxy)ethyl)(hydroxy)amino)-2-oxoethoxy)acetic acid (PPH N O C O) to trimeric desferrioxamine B (DFOB). The properties of DFOB-PPH (3) and DFOB-PPH N O C O (4) were compared with the first-in-class ligand DFO* (named DFOB-PBH (2) in the present work) and DFOB (1). In the initial phase of an FeIII : ZrIV competition experiment, 1 preferentially formed FeIII- 1 , with ZrIV- 1 becoming dominant after 48 h. Tetrameric 2 – 4 selected ZrIV above FeIII at all times. The initial rates of formation of ZrIV- 3 and ZrIV- 4 were greater than ZrIV - 2 , which could reflect a better match between the ZrIV ionic radius and the increased volume of the coordination sphere provided by 3 and 4. In the presence of excess EDTA, ZrIV- 4 dissociated more rapidly than ZrIV- 2 and ZrIV- 3 , which indicated that any beneficial increase in water solubility conferred by the presence of ether oxygen atoms in 4 could be offset by a reduction in complex stability. Outer-sphere solvation of the ether oxygen atoms in ZrIV- 4 may increase the entropic contribution to the dissociation of the complex. The rank order of the initial rate of ZrIV complexation in the presence of equimolar FeIII (highest to lowest) 4 > 3 > 2 >>> 1 together with the rate of the dissociation of the ZrIV complex (lowest to highest) 2 ≈ 3 > 4 >>> 1 identifies 3 as a ligand with potential value for immunological ZrIV-89 PET imaging. In a 1 : 1 FeIII : ZrIV competition experiment, hexadentate desferrioxamine B (DFOB) selected FeIII above ZrIV up to 48 h, with ZrIV-DFOB dominant beyond 48 h. Octadentate DFOB-PBH (DFO*), DFOB-PPH or DFOB-PPH N O C O selected ZrIV above FeIII over a 72-h time course. Excess EDTA extracted ZrIV most readily from ether-containing ZrIV-DFOB-PPH N O C O. DFOB-PPH showed favourable ZrIV-loading and trans -chelation properties. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
Academic Search Index |
