To Sandwich Technetium: Highly Functionalized Bis‐Arene Complexes [^99mTc(η⁶‐arene)₂]⁺ Directly from Water and [^99mTcO₄]⁻

Abstract

The labeling of (bio)molecules with metallic radionuclides such as 99mTc demands conjugated, multidentate chelators. However, this is not always necessary since phenyl rings can directly serve as integrated, organometallic ligands. Bis‐arene sandwich complexes are generally prepared by the Fischer–Hafner reaction. In extension of this, we show that [99mTc(η6‐C6R6)2]+‐type complexes are directly accessible from water and [99mTcO4]−, even using arenes incompatible with Fischer–Hafner conditions. To unambiguously confirm the nature of these unprecedented 99mTc complexes, their rhenium homologous have been prepared by substituting naphthalene ligands in [Re(η6‐C10H8)2]+ with the corresponding phenyl groups. The ease with which highly stable [99mTc(η6‐C6R6)2]+ complexes are formed under standard labeling conditions enables a multitude of new potential imaging agents based on commercial pharmaceuticals or lead structures.

[Re(η6‐C6H5‐benzimidazole)2]+ and Derivatives as Dye Mimics; Synthesis, UV Absorption Studies and DFT Calculations

“…Experimental methods, synthetic procedures, analytical data and NMR assignments are described in the Supporting Information for all compounds. In this section only the procedures of the key compounds [4](TFA), [5](TFA), [8](TFA), [10](OTf) and [12](TFA) are given. Complexes [1](OTF), [2](TFA) and [3](TFA) were synthesized according to literature.…”

“…HPLC 2). The product containing fractions were combined and the solvent was evaporated to yield [8](TFA) as an orange solid. Yield: 40.8 mg (0.064 mmol, 49 %).…”

“…[6c,d] The rationale behind is the option of coordinating either of the two elements directly to phenyl groups integrated in pharmaceuticals, without the need of a bifunctional chelator. Whereas the direct synthesis of [ 99m Tc(η 6 -arene) 2 ] + complexes with highly functionalized arenes was recently reported, [8] the preparation of rhenium homologues does not work along this path. Functional modifications have to be introduced after the preparation of the basic [Re(η 6arene) 2 ] + complex.…”

Naphthalene Exchange in [Re(η6‐napht)2]+ with Pharmaceuticals Leads to Highly Functionalized Sandwich Complexes [M(η6‐pharm)2]+ (M=Re/99mTc)

“…Depending on the configuration of the incoming arenes, some interesting stereochemical features become evident. Multisubstituted arenes such as 2,4-dimethylaniline (4), carbazole (10) or melatonin (12) can coordinate from both sides, from Up Figure 1. Ellipsoid displacement plots of complexes [Re(η 6 -4) 2 ] + (5 + , 2,4-dimethylaniline, one isomer), [Re(η 6 -6) 2 ] + (7 + , mequinol), [Re(η 6 -8) 2 ] + (9 + , lidocaine) and [Re(η 6 -6)(η 6 -napht)] + (14 + ).…”

“…In a follow up study, we showed that complexes [ 99m Tc(η 6 -arene) 2 ] + with arene being functionalized phenyls, are accessible in water in one step and directly from [ 99m TcO 4 ] À . [10] This approach offers a general approach to directly labelled pharmaceuticals according to structure D in Scheme 1. It is thus not necessary to introduce additional chelators.…”