Very Small and Soft Scorpionates:  Water Stable Technetium Tricarbonyl Complexes Combining a Bis-agostic (k³-H, H, S) Binding Motif with Pendant and Integrated Bioactive Molecules

The novel trihydro(mercaptoazolyl)borates Na[H₃B(tim^Me)] (L¹) (tim^Me = 2-mercapto-1-methylimidazolyl), Na[H₃B(tim^Bupip)] (L²) (tim^Bupip = 1-[4-((2-methoxyphenyl)-1-piperazinyl)butyl]-2-mercaptoimidazolyl), and Na[H₃B(bzt)] (L³) (bzt = 2-mercaptobenzothiazolyl) were synthesized by reaction of NaBH₄ with the corresponding azole. Ligands L¹−L³ represent a new class of light and soft scorpionates that stabilizes the [M(CO)₃]⁺ core (M = ⁹⁹Tc, Re) by formation of the complexes fac-[M{κ³-H(μ-H)₂B(tim^Me)}(CO)₃] (M = ⁹⁹Tc (1), Re (2)), fac-[Re{κ³-H(μ-H)₂B(tim^Bupip)}(CO)₃] (3), and fac-[Re{κ³-H(μ-H)₂B(bzt)}(CO)₃] (4), respectively. The soft scorpionates are coordinated to the metal in unique (κ³-H, H‘, S) fashion, as confirmed by X-ray crystallography of 1, 2, and 4. These complexes with bis-agostic hydride coordination are formed in aqueous solution with the two hydrides replacing two coordinating aquo ligands. The agostic hydrogen atoms were located directly, confirming an unprecedented donor atom set combining one sulfur and two hydrogen atoms. Preliminary studies have shown the possibility of preparing some of these complexes at the no carrier added level (^99mTc), under conditions as required in radiopharmaceutical preparation. Due to their lipophilicity, small-size, and easy functionalization with adequate biomolecules, the trihydro(mercaptoazolyl)borate technetium tricarbonyl complexes are suitable for the design of CNS receptor ligand radiopharmaceuticals as exemplified with 3, comprising a pendant serotonergic 5-HT_1A ligand. The integrated design of radiopharmaceuticals involving a bis-agostic scorpionate ligand is demonstrated by the synthesis of 4, with an integrated benzothiazolyl fragment for the recognition of β-amyloid plaques.