Synthesis and Characterization of fac-[M(CO)₃(P)(OO)] and cis-trans-[M(CO)₂(P)₂(OO)] Complexes (M = Re, ^99mTc) with Acetylacetone and Curcumin as OO Donor Bidentate Ligands

Abstract

The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer's disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

Metal complexes of curcumin – synthetic strategies, structures and medicinal applications

“…[36][37][38] Recently, even technetium complexes containing curcumin have been reported. 39 Moreover, curcumin complexes have been prepared for several lanthanide elements 2,[40][41][42][43] as well as thorium and uranium, with the latter all being uranyl (OQUQO) species. Pioneering work in this area was published in 1997 by Beck and co-workers at the Ludwig-Maximilians-Universität in Munich.…”

“…22,23 Some technetium and rhenium curcumin complexes have recently been reported. 39 It was found that curcumin reacts with the bromide precursors fac-[M(CO) 3 Br 3 ] 2À (M = Tc, Re) through the b-diketonate moiety to generate, under mild synthetic conditions, the aqua complexes fac-M(CO) 3 (H 2 O)(Curc). .…”

Metal complexes designed to bind to amyloid-β for the diagnosis and treatment of Alzheimer's disease

“…18). 104,105 The large trans effect exerted by triphenylphosphine can lead to further substitution and formation of [Re(CO) 2 (PPh 3 ) 2 L 24 ]. The substitution chemistry is similar for 99m Tc.…”

“…When incubated at 60 1C for 20 min, the reaction progresses to form cistrans-[ 99m Tc(CO) 2 (PPh 3 ) 2 L 24 ]. Both fac-[Re(CO) 3 L 24 (PPh 3 )] and cistrans-[Re(CO) 2 (PPh 3 ) 2 L 24 ] bind to Ab plaques in post-mortem human brain tissue 105.…”

Technetium‐99m radiochemistry for pharmaceutical applications

“…As monodentate ligands, phosphines (P), isocyanides (CNR), and aromatic amines have been used. Examples of bidentate ligands are the (N,O) donors such as 2‐picolinic acid (Figure .6); (O,O) donors of the keto‐enol type, like acetylacetone (Figure .7) or 3‐hydroxypyridone; (S,S) donors such as dithiocarbamate (Figure .8); (N,N) donors, like bipyridine; and (P,P) bisphosphine ligands, like 1,2‐bis(hydroxymethylphosphine)ethane . In [ 99m Tc(CO) 3 (P,P)(H 2 O)] complexes, the third position occupied by water is less reactive to substitutions due to the presence of the two strong π‐acidic phosphines.…”