TY - JOUR
T1 - Octadentate Zirconium(IV)-Loaded Macrocycles with Varied Stoichiometry Assembled From Hydroxamic Acid Monomers using Metal-Templated Synthesis
AU - Tieu, William
AU - Lifa, Tulip
AU - Katsifis, Andrew
AU - Codd, Rachel
N1 - Funding Information:
The Australian Research Council (DP140100092) is acknowledged for research support to R.C. and A.K. and for salary support to W.T. The University of Sydney is acknowledged for the provision of a postgraduate research award (cofunded) to T.L.
PY - 2017/3/20
Y1 - 2017/3/20
N2 - The reaction between Zr(IV) and the forward endo-hydroxamic acid monomer 4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoic acid (for-PBH) in a 1:4 stoichiometry in the presence of diphenylphosphoryl azide and triethylamine gave the octadentate Zr(IV)-loaded tetrameric hydroxamic acid macrocycle for-[Zr(DFOT1)] ([M + H]+ calc 887.3, obs 887.2). In this metal-templated synthesis (MTS) approach, the coordination preferences of Zr(IV) directed the preorganization of four oxygen-rich bidentate for-PBH ligands about the metal ion prior to ring closure under peptide coupling conditions. The replacement of for-PBH with 5-[(5-aminopentyl) (hydroxy)amino]-5-oxopentanoic acid (for-PPH), which contained an additional methylene group in the dicarboxylic acid region of the monomer, gave the analogous Zr(IV)-loaded macrocycle for-[Zr(PPDFOT1)] ([M + H]+ calc 943.4, obs 943.1). A second, well-resolved peak in the liquid chromatogram from the for-PPH MTS system also characterized as a species with [M + H]+ 943.3, and was identified as the octadentate complex between Zr(IV) and two dimeric tetradentate hydroxamic acid macrocycles for-[Zr(PPDFOT1D)2]. Treatment of for-[Zr(PPDFOT1)] or for-[Zr(PPDFOT1D)2] with EDTA at pH 4.0 gave the respective hydroxamic acid macrocycles as free ligands: octadentate PPDFOT1 or two equivalents of tetradentate PPDFOT1D (homobisucaberin, HBC). At pH values closer to physiological, EDTA treatment of for-[Zr(DFOT1)], for-[Zr(PPDFOT1)], or Zr(IV) complexes with related linear tri- or tetrameric hydroxamic acid ligands showed the macrocycles were more resistant to the release of Zr(IV), which has implications for the design of ligands optimized for the use of Zr(IV)-89 in positron emission tomography (PET) imaging of cancer.
AB - The reaction between Zr(IV) and the forward endo-hydroxamic acid monomer 4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanoic acid (for-PBH) in a 1:4 stoichiometry in the presence of diphenylphosphoryl azide and triethylamine gave the octadentate Zr(IV)-loaded tetrameric hydroxamic acid macrocycle for-[Zr(DFOT1)] ([M + H]+ calc 887.3, obs 887.2). In this metal-templated synthesis (MTS) approach, the coordination preferences of Zr(IV) directed the preorganization of four oxygen-rich bidentate for-PBH ligands about the metal ion prior to ring closure under peptide coupling conditions. The replacement of for-PBH with 5-[(5-aminopentyl) (hydroxy)amino]-5-oxopentanoic acid (for-PPH), which contained an additional methylene group in the dicarboxylic acid region of the monomer, gave the analogous Zr(IV)-loaded macrocycle for-[Zr(PPDFOT1)] ([M + H]+ calc 943.4, obs 943.1). A second, well-resolved peak in the liquid chromatogram from the for-PPH MTS system also characterized as a species with [M + H]+ 943.3, and was identified as the octadentate complex between Zr(IV) and two dimeric tetradentate hydroxamic acid macrocycles for-[Zr(PPDFOT1D)2]. Treatment of for-[Zr(PPDFOT1)] or for-[Zr(PPDFOT1D)2] with EDTA at pH 4.0 gave the respective hydroxamic acid macrocycles as free ligands: octadentate PPDFOT1 or two equivalents of tetradentate PPDFOT1D (homobisucaberin, HBC). At pH values closer to physiological, EDTA treatment of for-[Zr(DFOT1)], for-[Zr(PPDFOT1)], or Zr(IV) complexes with related linear tri- or tetrameric hydroxamic acid ligands showed the macrocycles were more resistant to the release of Zr(IV), which has implications for the design of ligands optimized for the use of Zr(IV)-89 in positron emission tomography (PET) imaging of cancer.
UR - http://www.scopus.com/inward/record.url?scp=85015765015&partnerID=8YFLogxK
U2 - 10.1021/acs.inorgchem.7b00362
DO - 10.1021/acs.inorgchem.7b00362
M3 - Article
C2 - 28245117
AN - SCOPUS:85015765015
SN - 0020-1669
VL - 56
SP - 3719
EP - 3728
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 6
ER -