Hans-Juergen Pietzsch

Lipophilic technetium complexes. VI. Neutral oxotechnetium(V) complexes with monothiole/tridentate dithiole coordination

Abstract Reaction of tridentate dithiole ligands HSCH 2 CH 2 XCH 2 CH 2 SH (HSXSH, X= O, S) and monothioles RSH (thiophenoles, aliphatic thioles, mercaptoacetic acid ethylester) with Tc(V) gluconate (or other starting materials containing the oxotechnetium(V) core such as tetrachlorooxotechnetate) leads to a series of mononuclear, neutral complexes of the general formula TcO(SXS)(SR). In the absence of the monodentate thioles, dinuclear complexes of the general formula (TcO) 2 (SXS) 3 are formed. Infrared, NMR, and UV-Vis data of the resulting compounds are reported. A concept for designing smallsized, neutral Tc complexes, involving the principle of common reaction of both a tridentate and a monodentate ligand with an appropriate Tc precursor, is proposed.

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT2A receptorbinding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pKa value leads to ionization of the molecule at blood pH, the pKa value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pKa value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pKa cannot be simply explained by the increase in the pKa-governed proportion of the neutral species.

No carrier added preparations of ‘3 + 1’ mixed-ligand 99mTc complexes

Abstract The no carrier added (n.c.a.) preparation of potentially receptor-binding ‘3 + 1’ mixed-ligand technetium complexes has not so far been successfully accomplished. This article deals with our results in the preparation of n.c.a. Tc complexes with tridentate S-S-S or S-N-S ligands and a series of bulky monothiolato ligands. It was found that Tc(V) gluconate or Tc(V) ethylene glycolate are suitable precursors for the complex formation. In a two-step procedure consisting of a reaction of the monothiolato ligand with the precursor and subsequent addition of the tridentate ligand, the desired ‘3 + 1’ mixed-ligand complexes are formed with yields of up to 90%. Low ligand concentrations and pH 9–10 promote the formation of the technetium compounds. A comparison of their analytical properties (TLC, HPLC) and biodistribution data of carrier added and no carrier added technetium complexes show the identity of the investigated compounds.

STUDY ON THE FORMATION OF MIXED LIGAND OXORHENIUM AND OXOTECHNETIUM COMPLEXES (SNS/S COMBINATION)

Theoretically, several complexes can be formed during the reaction between the tridentate aminedithiol ligand EtN(CH 2 CH 2 SH) 2 , L1H 2 , the monodentate thiol p -ClC 6 H 4 SH, L2H, and the Re V OCl 3 (PPh 3 ) 2 . Three main possibilities are: (i) neutral mixed ligand complexes ReOL1L2, the syn isomer, complex 1 and the anti isomer, complex 2 ; (ii) binuclear complex of the tridentate ligand, (ReO) 2 (L1) 3 , complex 3 and (iii) anionic complex of the monothiol [ReO(L2) 4 ] − , complex 4 . When a mixture of L1H 2 /L2H, 1/1 ratio, is applied, the major product of the reaction is the syn isomer 1 . A small amount of the anti isomer 2 is also isolated (yield 3 and 4 are formed under the above reaction conditions. The oxorhenium complexes 3 and 4 have been synthesized by the reaction of L1H 2 or L2H respectively with the precursor ReOCl 3 (PPh 3 ) 2 . The crystal structures of 1 , 3 , and 4 are determined by X-ray crystallography. The corresponding 99m Tc complexes have been prepared by exchange reaction using 99m Tc-glucoheptonate as precursor. Similarly the major reaction product is the syn isomer, complex 1′ , while none of the other complexes are formed during the reaction at tracer level. The above studies demonstrate that simultaneous action of a tridentate SNS ligand and a monodentate thiol in equimolar quantities on Re V OCl 3 (PPh 3 ) 2 or 99m Tc-glucoheptonate leads to a single rhenium or technetium-99m species, the syn MOL1L2.

Technetium complexes with thioether ligands—ii. Synthesis and structural characterization of neutral oxotechnetium(v) complexes with dithioethers. X-ray structure analysis of μ-oxo-bis(5,8-dithiadodecane)dichlorooxotechnetium(v) and (8-hydroxy-3,6-dithiaoctan-1-olato)dichlorooxotechnetium(v)

Abstract Neutral, bidentate thioethers such as 5,8-dithiadodecane, 3,6-dithiaoctane (“S2”) as well as the dithia-diole 1,8-dihydroxy-3,6-dithiaoctane [“S2(OH)2”] react with tetrachlorooxotechnetate (TcOCl4−) in acetone to give binuclear oxo species of the type [TcO(“S2”)Cl2]2O with dithiaalkanes and [TcO(“S2O(OH)”)Cl2] with the dithia-diole, respectively. The complexes have been characterized by elemental analysis and spectroscopic methods. The crystal structures of [TcO(5,8-dithiadodecane)Cl2]2O (1) and [TcO(8-hydroxy-3,6-dithiaoctan-1-olato)Cl2] (3) were determined from X-ray data: 1 consists of two independent [TcO(“S2”)Cl2] units bridged by an oxygen atom. Each technetium atom is centred in a distorted octahedron with the equatorial plane formed by the S2Cl2 donor set. The sulphur and chlorine atoms of the units are in the anti position with respect to the bridging oxygen. The structural analysis of 3 shows that the metal has distorted octahedral coordination, with the equatorial plane formed by the sulphur and chlorine atoms. Furthermore, one terminal oxygen is coordinated in the trans position to the Tc=O3+ core, while the second hydroxy group is non-coordinated.

Technetium complexes with thioether ligands—I. Cationic technetium(III) complexes containing tetradentate thioether/monothiole ligands; X-ray structure analysis of bis(benzenethiolato)(5,8,11,14-tetrathiaoctadecane)technetium(III)hexafluorophosphate

Abstract Cationic technetium(III) complexes containing both tetradentate thioether and monothioles, [Tc(“S4”)(SR)2]PF6 (“S4”: 3,6,9,12-tetrathiatetradecane, 5,8,11,14-tetrathiaoctadecane; SR: monodentate thiolates), were prepared starting from TcO4− and characterized by elemental analysis and spectroscopic methods. Bis(benzenethiolato)(5,8,11,14tetrathiaoctadecane)technetium(III)hexafluorophosphate was characterized by single-crystal X-ray structural analysis (R = 0.084). In the complex the technetium is centred in a heavily distorted octahedron. The benzenethiolate ligands are coordinated in the cis-configuration.

Technetium and rhenium complexes with thioether ligands—IV. Synthesis and structural characterization of binuclear oxorhenium(V) complexes with bidentate thioether coordination☆

Abstract Binuclear oxorhenium(V) complexes, [ReO(“S2”)Cl2]2O, have been prepared by reduction of ReO4− with SnCl2 in strongly acidic solution and in the presence of aliphatic thioethers of the general formula RCH2CH2SCH2CH2SCH2CH2R′ (“S2”; R, R′ = H, Et; R = S—Bu, R′ = Et; R = O—Et, R′ = H; R, R′ = O—Et). Alternatively the compounds can be obtained by ligand exchange reactions starting from [ReOCl4]− in methanolic solution. A representative derived from 5,8-dithiadodecane (R,R′ = Et) has been studied by X-ray diffraction. The complex consists of two independent [ReO(“S2”)Cl2] units bridged by an oxygen atom. Each rhenium atom is centred in a distorted octahedron with the equatorial plane formed by the S2Cl2 donor set. The sulphur and chlorine atoms of the units are in the anti position with respect to the bridging oxygen.

Technetium complexes with thioether ligands. III: Synthesis and structural characterization of cationic nitridotechnetium(V) complexes with thiacrown ethers

Abstract The first representative of a new class of TcN complexes with thiacrown ethers have been prepared by ligand exchange reaction of NBu4[TcNCl4] with 1,4,8,11-tetrathiacyclotetradecane (14S4), 1,5,9,13-tetrathiacyclohexadecane (16S4), 1,5,9,13-tetrathiacyclohexadecane-3,11-diole (16S4-(OH)2) and 1,4,7,10,13,16-hexathiacyclooctadecane (18S6). The crystal structure of [TcNCl(14S4)]TcNCl41) consists of couples of independent cations with the metal in the oxidation state + 5 and hexavalent TcNCl4− anions. In the complex cation the metal is six-coordinated in a rather distorted octahedral geometry, being directly bound to four sulphur atoms from the macrocyclic ligand in the equatorial plane and to the nitrido atom and to one chlorine atom in the axial positions. The strong trans influence of the nitrido ligand causes an extreme lengthening of the TcCl bond distance to 2.718 A. The octahedral molecular structure of [TcNCl(18S6)]TcNCl4 (3) is comparable with that of 1, but only four sulphur atoms of the thiacrown ether form the equatorial plane, two sulphur atoms remain non-coordinated, and the nitrido and Cl− ligands are in axial positions. The most interesting feature in the structure of [TcNCl(16S4-(OH)2)]Cl (5) is the observation of an exceptionally long TcN distance of 1.95 A.

Cleavage of ligand in a Tc/Schiff base system: An unusual reaction

In this paper we report on the reaction of different Schiff bases (derived from the condensation of 2-aminobenzenethiol, H 2 abt, with salicylic aldehyde, diacetyl and acetylacetone) with Tc gluconate of pertechnetate/dithionite in alkaline media, and the preferred formation of [TcO(abt) 2 ] − under these conditions. The mechanism of this unusual reaction is discussed

Lipophilic technetium complexes IX. The reduction of (3-oxapentane-1,5-dithiolato)-(p-carbmethoxybenzenethiolato)oxotechnetium(V) by tertiary phosphines

The present paper describes the reduction of complexes of the type TcO(SXS)(SR) by tertiary phosphines and a new complex with thiol/thioether/phosphine coordination synthesized by facile reduction of (3-oxapentane-1,5-dithiolato)(4-carbmethoxy-benzenethiolato)oxotechnetium(V) with triphenylphosphine as well as by ligand-exchange reaction on TcCl 4 (PPh 3 ) 2