Synthesis and Characterization of Organohydrazino Complexes of Technetium, Rhenium, and Molybdenum with the {M(η¹-H_xNNR)(η²-H_yNNR)} Core and Their Relationship to Radiolabeled Organohydrazine-Derivatized Chemotactic Peptides with Diagnostic Applications

The reduction of perrhenate, molybdate and pertechnetate with 2-hydrazinopyridine dihydrochloride in methanol has led to the preparation of a class of complexes containing the {M(η¹-NNC₅H₄NH_x)(η ²-HNNH_yC₅H₄N)} core, represented by [TcCl₃(NNC₅H₄NH)(HNNC₅H ₄N)] (2), [ReCl₃(NNC₅H₄NH)(HNNC₅H ₄N)] (3), and [MoCl₃(NNC₅H₄NH)(HNNHC₅H ₄N)] (6). The reaction of 3 with NEt₃ results in the formation of [HNEt₃][[ReCl₃(NNC5₅H₄N)(HNNC ₅H₄N)]·H₂O (4) by deprotonation of the pyridine nitrogen site. Similarly, the reduction of perrhenate with 2-hydrazino-2-imidazoline hydrobromide has led to the preparation of the analogous [ReCl₃(NNC₃H₄N₂H)(HNNHC ₃H₄N₂H)] (5). Reaction of 3 with pyridine-2-thiol and pyrimidine-2-thiol yields two structurally characterized derivatives with a modified {Re(η¹-NNC₅H₄N)(η²-HNNC ₅H₄N)} core, [Re(C₅H₄NS)₂(NNC₅H ₄N)(HNNC₅H₄N)] (8) and [Re(C₄H₃N₂S)₂(NNC₅H ₄N)(HNNC₅H₄N)] (9), respectively. Reaction of 6 with pyrimidine-2-thiol led to the isolation of the analogous [Mo(C₄H₃N₂S)₂(NNC₅H ₄N)(HNNHC₅H₄N)] (11) and the seven-coordinate monohydrazine core complex [Mo(C₄H₃N₂S)₃(NNC₅H ₄N)]·CH₂Cl₂ (12). In similar fashion, the reaction of 2 with pyridine-2-thiol yielded a complex structurally analogous to 8, [Tc(C₅H₄NS)₂(NNC₅H ₄N)(HNNC₅H₄N)] (7). Crystal data for 3, C₁₀H₁₀Cl₃N₆Re: triclinic, P1̄, a = 7.527(2) Å, b = 7.599(2) Å, c = 13.118(3) Å, α = 106.55(3)°, β= 90.28(3)°, γ = 93.83(3)°, V = 717.4(4) ų, Z = 2. For 4, C₁₆H₂₇Cl₃N₇ORe: orthorhombic, P2₁2₁2₁, a = 7.503(2) Å, b = 10.3643(2) Å, c = 30.1590(5) Å, V = 2345.20(6) ų, Z = 2. For 5, C₆H₁₂Cl₃N₈Re: monoclinic, P2₁/n, a = 9.093(2) Å, b = 11.105(2) Å, c = 14.295(3) Å, β = 94.71(3)°, V = 1438.6(7) ų, Z = 4. For 6, C₁₀H₁₁Cl₃N₆Mo: monoclinic, P2₁/c, a = 15.366(3) Å, b = 7.804(2) Å, c = 12.378(3) Å, β = 95.92(3)°, V = 1476.4(5) ų, Z = 4. For 7, C₂₀H₁₇N₈S₂Tc: monoclinic, P2₁, a = 8.827(2) Å, b = 9.278(2) Å, c = 13.304(3) Å, β= 98.92(3)°, V = 1076.5(5) ų, Z = 2, 2564 reflections. For 8, C₂₀H₁₇N₈S₂Re: monoclinic, P2₁, a = 8.848(2) Å, b = 9.190(2) Å, c = 13.293(3) Å, β= 98.89(3)°, V = 1067.9(5) ų, Z = 2. For 9, C₁₈H₁₅N₁₀S₂Re: monoclinic, P2₁, a = 8.796(2) Å, b = 9.008(2) Å, c = 13.208(3) Å, β= 97.90(3)°, V = 1036.6(5) ų, Z = 2. For 12, C₁₈H₁₅N₉S₃Cl₂Mo: monoclinic, P2₁/n, a = 10.52900(10) Å, b = 15.1116(3) Å, c = 15.8193(3) Å, β= 108.4790(10)°, V = 2387.23(7) ų, Z = 4. Complexes 2 and 3 serve as models for the binding of Tc(V)-oxo and Re(V)-oxo species to hydrazinonicotinamide (HYNIC)-conjugated chemotactic peptides. Furthermore, since the use of the pyrimidinethiol coligand in the {^99mTc-HYNIC-peptide} radiochemical species results in favorable pharmacokinetics, the thiolate derivatives 8 and 9 provide models for possible modes of interaction of metal-hydrazine cores with coligands in the radiopharmaceutical reagents.