ABSTRACT
The reaction of fac-[NEt(4)](2)[Re(CO)(3)Br(3)] with (S)-(2-(2'-pyridyl)ethyl)cysteamine, L(1), in methanol leads to the formation of the cationic fac-[Re(CO)(3)(NSN)][Br] complex, 1, with coordination of the nitrogen of the pyridine, the sulfur of the thioether, and the nitrogen of the primary amine. When fac-[NEt(4)](2)[Re(CO)(3)Br(3)] reacts with the homocysteine derivative (S)-(2-(2'-pyridyl)ethyl)-d,l-homocysteine, L(2), the neutral fac-Re(CO)(3)(NSO) complex, 2, is produced with coordination of the nitrogen of the primary amine, the sulfur of the thioether, and the oxygen of the carboxylate group, while the pyridine ring remains uncoordinated. The analogous technetium-99m complexes, 1' and 2', were also prepared quantitatively by the reaction of L(1) and L(2) with the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor at 70 degrees C in water. Given that both (S)-(2-(2'-pyridyl)ethyl)cysteamine and homocysteine can be easily N- or S-derivatized by a bioactive molecule of interest, both the NSN or NSO ligand systems could be used to develop target-specific radiopharmaceuticals for diagnosis and therapy.
Subject(s)
Cysteamine/chemistry , Homocysteine/chemistry , Organotechnetium Compounds/chemistry , Rhenium/chemistry , Crystallography, X-Ray , Ligands , Molecular Conformation , Molecular Structure , Radiopharmaceuticals/chemistryABSTRACT
Two novel 99mTc-(SNS/S) complexes: a mono-ester compound carrying an ethyl ester group on the tridentate ligand, 99mTcO[C(2)H(5)OOCCH(2)N(CH(2)CH(2)S)(2)][SC(6)H(4)CH(3)], 3, and a diester compound, carrying a second ethyl ester group on the monodentate ligand, 99mTcO[C(2)H(5)OOCCH(2)N(CH(2)CH(2)S)(2)][SC(6)H(4)COOC(2)H(5)], 4, were synthesized. The corresponding oxorhenium(V) complexes, 1 and 2 were also synthesized. Enzymatic hydrolysis demonstrated that 3 remains intact after 10 min incubation while 4 is totally converted to an unidentified hydrophilic complex. Tissue distribution data in mice revealed that both complexes, 3 and 4, exhibit significant initial brain uptake (1.42 and 1.01% of injected dose at 5 minutes post injection respectively) and fast blood clearance.
Subject(s)
Technetium Compounds/chemical synthesis , Animals , Brain/metabolism , Esters , Mice , Molecular Structure , Structure-Activity Relationship , Technetium Compounds/chemistry , Technetium Compounds/pharmacokinetics , Tissue DistributionABSTRACT
Two oxorhenium and two oxotechnetium [SN(R)S/S] mixed ligand complexes bearing the phenothiazine moiety on the tridentate ligand SN(R)S have been synthesized and characterized. The corresponding complexes at tracer level (99mTc) have also been prepared.
