Curcumin as the OO Bidentate Ligand in “2 + 1” Complexes with the [M(CO)₃]⁺ (M = Re, ^99mTc) Tricarbonyl Core for Radiodiagnostic Applications

Abstract

The synthesis and characterization of "2 + 1" complexes of the [M(CO)(3)](+) (M = Re, (99m)Tc) core with the β-diketones acetylacetone (complexes 2, 8) and curcumin (complexes 5, 10 and 6, 11) as bidentate OO ligands, and imidazole or isocyanocyclohexane as monodentate ligands is reported. The complexes were synthesized by reacting the [NEt(4)](2)[Re(CO)(3)Br(3)] precursor with the β-diketone to generate the intermediate aqua complex fac-Re(CO)(3)(OO)(H(2)O) that was isolated and characterized, followed by replacement of the labile water by the monodentate ligand. All complexes were characterized by mass spectrometry, NMR and IR spectroscopies, and elemental analysis. In the case of complex 2, bearing imidazole as the monodentate ligand, X-ray analysis was possible. The chemistry was successfully transferred at (99m)Tc tracer level. The curcumin complexes 5 and 6, as well as their intermediate aqua complex 4, that bear potential for radiopharmaceutical applications due to the wide spectrum of pharmacological activity of curcumin, were successfully tested for selective staining of β-amyloid plaques of Alzheimer's disease. The fact that the complexes maintain the affinity of the mother compound curcumin for β-amyloid plaques prompts for further exploration of their chemistry and biological properties as radioimaging probes.

Synthesis and Characterization of fac‐Re(CO)3‐aspartic‐N‐monoacetic Acid: Structural Analogue of a Potential Renal Tracer, fac‐99mTc(CO)3(ASMA)

“…[3] As a congener of Tc, Re complexes are also commonly employed as structural analogues for 99m Tc radiotracers. [4] Re analogues allow for elucidation of 99m Tc radiopharmaceuticals, which are otherwise difficult to characterize owing to the short half-life of 99m Tc ( t 1/2 = 6 h) and the tracer level conditions (no-carrier-added) of radiopharmaceutical preparations. Methods for the preparation of Re complexes have been developed to mirror standard radiolabeling conditions for various 99m Tc complexes, including routes to 99m Tc V -oxo, [5] 99m Tc III -trioxo, [6] and 99m Tc I -tricarbonyl complexes.…”

Pharmacological and clinical properties of curcumin

“…116 A chemical entity composed of a [M(CO) 3 ] + (M = Re, 99m Tc) core with curcumin bound to it as a bidentate OO ligand was recently synthesized. 117 This complex demonstrated strong binding to β-amyloid plaques, indicating that this chemical entity could be utilized as a radioimaging probe, particularly in cases of Alzheimer's disease. 117 A Chinese study investigated the potential antidepressive action of curcumin utilizing the exogenous corticosterone (CORT) administration-induced model of depression in rats.…”

“…117 This complex demonstrated strong binding to β-amyloid plaques, indicating that this chemical entity could be utilized as a radioimaging probe, particularly in cases of Alzheimer's disease. 117 A Chinese study investigated the potential antidepressive action of curcumin utilizing the exogenous corticosterone (CORT) administration-induced model of depression in rats. 118 Curcumin therapy significantly reversed depressionlike behavior induced by CORT (as evidenced by rat sucrose consumption and performance of the forced swim test), and this appeared to be mechanistically linked to curcuminmediated restoration of brain-derived neurotrophic factor (BDNF).…”

Crystal structure of fac-(acetylacetonato-κ2 O,O′)tricarbonyl(benzyldiphenylphosphine-κP)rhenium(I), C27H24O5PRe

“…The radiometal that has received significant attention is 99m Tc, because it is easily accessible and possesses almost near perfect nuclear properties; (t 1/2 = 6.02 h; γ = 140 keV, 100%). [14][15][16][17][18][19][20][21]. The geometry around the title complex, fac-[Re(Acac)(CO) 3 (PPh 2 Bz)] is typically octahedral and the central rhenium metal is bound to three fac carbonyl ligands, a chelate β-diketonato ligand, acetylacetonato (Acac) through its oxygen atoms and to a monodentate benzyldiphenylphosphine ligand (PPh 2 Bz) through its phosphorus atom.…”

“…In the coordination sphere, the Re1-P1 bond distance of 2.4718(7) Å is the longest and is consistent with those found in similar Re(I)-tricarbonyl complexes. All the bond distances and angles are considered to be within the normal range [11][12][13][14][15][16][17][18][19][20][21][22][23][24].…”