Synthesis and characterization of a novel macrocyclic chelator with 3-hydroxy-4-pyrone chelating arms and its complexes with medicinally important metals.
A new macrocyclic chelator, 6,6',6''-(1,4,7-triazonane-1,4,7-triyl)tris(methylene)tris(5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) (H3NOKA), was synthesized from the reaction of 1 equiv of 1,4,7-triazacyclononane (TACN) and 3 equiv of kojic acid (KA) in the presence of excess formaldehyde. The reaction of H 3NOKA with metal salt forms complexes M(NOKA) (M = Ga, In, and Fe) and Cu(HNOKA). H 3NOKA and its complexes, M(NOKA) (M = Ga, In, and Fe) and Cu(HNOKA), have been characterized by IR, UV/vis, ESI-MS, and elemental analysis. Structures of Ga(NOKA), Fe(NOKA), and Cu(HNOKA) were determined by X-ray crystallography. In the solid state, Ga(NOKA) and Fe(NOKA) are isostructural with the distorted octahedral geometry. In contrast, Cu(HNOKA) has the distorted square-pyramidal coordination geometry in which NOKA is pentadentate with three amine-N and two enolate-O atoms bonding to Cu(II) and one of three 3-hydroxy-4-pyrone chelating arms remaining free and protonated. The cyclic voltammogram of Fe(NOKA) exhibits a quasi-reversible redox wave at E(1/2) = -0.53 mV from the Fe(III)(NOKA)/Fe(II)(NOKA)(-) couple, whereas Cu(HNOKA) shows an irreversible one-electron reduction of Cu(II)(HNOKA)/Cu(I)(HNOKA)(-) at E(pc) = -0.87 V. These low redox potentials indicate that Fe(III) in Fe(NOKA) and Cu(II) in Cu(HNOKA) are preferentially stabilized by NOKA. The variable-temperature (1)H NMR spectral data show that Ga(NOKA) is more rigid than that of In(NOKA) in the solution. The results from this study suggest that the C-substituted NOKA derivatives might be useful as bifunctional chelators for (68)Ga-labeling of small biomolecules, while the corresponding N-substituted analogues are probably more suitable for preparation of the (64)Cu-based target-specific radiotracers.
Yang
Chang-Tong
CT
School of Health Sciences, Purdue University, 550 Stadium Mall Drive, West Lafayette, Indiana 47907, USA.
Sreerama
Subramanya G
SG
Hsieh
Wen-Yuan
WY
Liu
Shuang
S
D002614:Chelating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002867:Chromones / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004563:Electrochemistry; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013057:Spectrum Analysis
D002614:Chelating Agents; D002867:Chromones; D047028:Macrocyclic Compounds; D008670:Metals; D004364:Pharmaceutical Preparations; C030415:pyromeconic acid