Disruption of unprecedented B-H...M agostic interactions: An alternative approach for labeling bioactive molecules

The agostic B-H...Re bond in complexes [Re{kappa(3)-R(mu H)B(tim(Me))(2)}(CO)(3)] (R= H (1), Ph (2), tim(Me) = 2-mercapto-1-methylimidazolyl) is readily cleaved by t-butylisonitrile or cyclohexylisonitrile leading to the mixed-ligand complexes [Re{kappa(2)-Ph(mu-H)B(tim(Me))(2)}(C equivalent to (NBu)-Bu-t)(CO)(3)] (3) and [Re{kappa(2)-H(mu-H)B(tim(Me))(2)}(C equivalent to N-cyclohexyl)(CO)(3)] (4), respectively. Bearing in mind the so-called [2 + 1] mixed ligand approach for the development of target-pecific radiopharmaceuticals, reactions of 1 with isonitriles carrying the (2-methoxyphenyl)piperazine pharmacophore (part of WAY 100635) were also studied and the complexes [Re{kappa(2)-H(mu-H)B(tim(Me))(2)}(C equivalent to N-R'-WAY)(CO)(3)] (R' = butylene (5), pentylene (6) or hexylene (7)) isolated. The novel mixed Re(I) tricarbonyl complexes (3-7) have been characterized by the usual analytical techniques, which included X-ray diffraction analysis in the cases of 3, 4 and 5. The affinity of the complexes 5-7 toward the 5-HT1A receptors was tested in competitive receptor binding assays and the IC50 values found were in the 21.9-66.5 nM range. Complex 7, with the longest spacer length between the isonitrile function and the pharmacophore, has shown an improved selectivity towards the 5-HT1A subtype of receptors when compared with 5 and 6.