H₄octox: Versatile Bimodal Octadentate Acyclic Chelating Ligand for Medicinal Inorganic Chemistry

Abstract

H 4 octox, a versatile new octadentate acyclic chelating ligand, has been investigated as an alternative to the acyclic DTPA and the macrocyclic DOTA for trivalent metal ions useful in diagnostic medical imaging or therapeutic applications (Y 3+ , In 3+ , La 3+ , Gd 3+ , Lu 3+ ). The synthesis of H 4 octox is straightforward in less steps and thus more economical than those of most previously reported chelators. Complex formation equilibria in the presence of Y 3+ , In 3+ , La 3+ , Gd 3+ , and Lu 3+ revealed fast chelation and high metal-sequestering capacity. Quantitative labeling with 111 In 3+ was achieved within 15 min at room temperature at ligand concentrations as low as 10 −7 M, exactly the properties required for the development of kit-based radiopharmaceuticals. In vitro serum stability studies and in vivo SPECT imaging confirmed excellent complex stability of [ 111 In-(octox)] − . Moreover, it is more lipophilic than most of the multidentate carboxylate-or picolinate-based chelators; it therefore shows more liver clearance and provides a complementary choice in the design of metal-based pharmaceuticals and in the tuning of their pharmacokinetic properties. Finally, H 4 octox showed a large fluorescence enhancement upon complexation with different metals, in particular, with Y 3+ and Lu 3+ , which could be useful for non-radioactive fluorescent stability and cell studies as well as bimodal imaging. Excellent in vitro stability of [Y(octox)] − against transferrin and Fe 3+ was confirmed employing this fluorescence.

Novel Azo-Stilbene and Pyridine-Amine Hybrid Multifunctional Molecules to Target Metal Mediated Neurotoxicity and Amyloid-β Aggregation in Alzheimer’s disease

“…linearly correlated to stability constant of metal complex. [48][49] From the solution speciation, the concentration of unchelated Cu 2+ and Zn 2+ was calculated (Table 4). The pCu values of 9.21 and 10.11 whereas pZn values of 8.47 and 9.20 are obtained respectively for L1 and L2 at pH 7.4…”

Metal ion size profoundly affects H3glyox chelate chemistry

“…24 It is noteworthy that the DFT calculated structures for both [Mn(glyox)(H 2 O)] À and [Mn(dpaa)(H 2 O)] À consist of an additional water molecule coordinated to the metal centre. 32 Cu 2+ prefers ve-fold coordination with H 3 glyox, leading to a distorted square pyramidal geometry (Fig. 2C), in which the donor atoms N1, O1, O2 and O3 dene the basal plane and the S5 and S6.…”

“…Around pH 5, the formation of the [Mn(glyox)] À species can be observed as there is an increase in the absorbance bands at l max ¼ 255 and 370 nm characteristic of quinolinate metal complexes. 16,23,32 The formation of the metal-hydroxo species [Mn(glyox)(OH)] 2À starts aer pH 8 and predominates at basic pH without the presence of free metal in solution (Fig. S9 †).…”

“…For the Lu 3+ -H 3 glyox complexation equilibria, as pH increases from 3.74 to 6.54, there is an increase in absorption spectra at l max ¼ 260 nm with new isosbestic points at l ¼ 252, 338 nm (Fig. S11 † 32 Fig. 4A summarizes the effects of the metal ion size and charge on chelation with H 3 glyox.…”

DFT studies on the structure and stability of tetraaza macrocyclic nickel(II) complexes containing dicarbinolamine ligand moiety

“…[10][11][12][13][14][15] They also find applications as magnetic resonance imaging agents, radioimmuno therapeutic agents, and in color switches. [16][17][18][19][20] The redox potentials of these systems can be altered by making suitable modifications in their structures and some of these are useful in the electrochemical reduction of CO 2 . 21 The macrocyclic hole size in the highly conjugated macrocyclic ligand is smaller than that in the corresponding saturated system.…”