Medi-Physics, Inc.

Neutral Re(V) oxo complexes were synthesized by the reaction of ReOBr₄^- with diamino-thiol-thioether ligands RSCMe₂CH₂NH(o-C₆H₄)NHCH₂CMe₂SH.The complexes were characterized by IR, UV/visible, and ¹H and ¹³C NMR spectroscopy and by fast-atom-bombardment mass spectroscopy.The single-crystal x-ray structure determination on two of the complexes, where R = CH₂CH:CH₂ and Pr, showed them to consist of a square pyramidal Re^VON₂S₂ core.ReO[CH₂:CHCH₂SCMe₂CH₂N(o-C₆H₄)NCH₂CMe₂S] crystallizes in the monoclinic space group P2₁/a with α 17.899(3)Å, b 13.910(1), c 15.936(1) Å, β 104.70(1)°, Z = 8, d_c = 1.813 g cm^-3, and μ(Cu Kα) = 139.8 cm^-1.The Pr derivative complex crystallizes in the monoclinic space group P2₁/a with a 18.076(1), b 13.920(1), c 15.994(1) Å, β 105.09(1)°, Z = 8, d_c = 1.797 g cm^-3, and μ(Cu Kα) = 138.0 cm^-1.The combination of the steric and electronic effects of the aromatic ring fused to the backbone of the N-C-C-N ligand and the S-substitution result in deprotonation of both amine nitrogens and coplanarity of the base of the square pyramidal complex.

A novel class of ligands, phenylenediamine-thiol-thioether (PhAT), was synthesized, and their 99mTc complexes were evaluated for potential use as a functional brain imaging agent. The ligands reacted with Na99mTcO4 and SnCl2 to form single, stable, neutral, and lipophilic 99mTc complexes. Several of these complexes showed significant brain uptake and retention in rats. In particular, the S-ethyl, allyl, and propargyl derivatives had high initial brain uptake (0.88, 0.99, and 0.82% dose/g at 5 min, respectively) and good retention (0.71, 0.75, and 0.67% dose/g at 30 min). The structure-activity relationship of alkyl, alkenyl, and alkynyl thioether derivatives is reported.

Application of chemical methods for characterizing the in vivo behavior of iofetamine HCI 123I (IMP) has shed light on the metabolism of iofetamine in animals and humans. A successful technique consists of ethyl acetate extraction of the metabolites from tissue samples acidified with perchloric acid, separation of the mixture by high performance liquid chromatography, and quantitation of the radioactive components with a sensitive scintillation detector. Metabolism of iofetamine HCI 123I proceeds sequentially from the N-isopropyl group on the amphetamine side chain. The first step, dealkylation to the primary amine p-iodoamphetamine (PIA), occurs readily in the brain, lungs, and liver; activity in the brain and lungs consists of only IMP and PIA even 24 hr after administration. The rate-limiting step appears to be deamination to give the transitory intermediate p-iodophenylacetone, which is rapidly degraded to p-iodobenzoic acid and conjugated with glycine in the liver to give the end product of metabolism, p-iodohippuric acid, which is excreted through the kidneys in the urine.