Oxorhenium(V) and Oxotechnetium(V) Complexes of Cysteine

Abstract

Earlier attempts to obtain technetium complexes with cysteine always resulted in the formation of a product contaminated with polymeric species. A pure product, which could be chemically characterized and adopted for radiopharmaceutical preparation, has now been obtained by using cystine as the precursor of cysteine. This method has been extended to prepare the corresponding rhenium chelate, isolated as the tetraphenylphosphonium salt [Ph(4)P](+)[{ReO(Cys)(2)}(-){HReO(Cys)(2)}].4H(2)O. The X-ray crystal structure of this compound revealed the presence of both neutral and anionic chelated species. In [HReO(Cys)(2)], the cysteine carboxylate moiety is unidentatedly bound to rhenium, while the carboxylic acid of the second cysteine remains as free COOH. The coordination environment around rhenium in the anionic species [ ReO(Cys)(2)(-)] is similar, the only difference being that the uncoordinated carboxylate moiety is present as a COO(-) anion. The thiolate, amine coordination of the ligand with the metal is present in both the chelate units. The compound crystallized in an orthorhombic system with the space group P2(1)2(1)2(1), and having four formula units in each cell. The crystal data are a = 9.700(2) Å, b = 12.836(3) Å, and c = 36.228(3) Å. The rhenium chelate has been structurally correlated with the technetium chelates through comparable spectroscopic and chromatographic data. The technetium-99m analogue of this rhenium chelate exhibited renal tubular transport and renal retention, which makes this radiopharmaceutical useful for evaluation of the clinical status of renal patients.

Oxorhenium(V) Complexes with the Non-Sulfur-Containing Amino Acid Histidine

“…[14][15][16][17][18] The Re-Cl(1) distance (2.351(3) Å) is slightly longer than Re-Cl(2) (2.334(2) Å), probably because Cl(1) participates in hydrogen bonding, but both distances are within the accepted range. 57 The Re-NH 2 bond is ∼0.05 Å longer than the Re-N(Im) bond, in agreement with the literature data for complexes with amino acids (mean Re V -N ) 2.188 Å, σ ) 0.032 Å, 20 data) 15,17,18,58 and imidazoles (mean Re V -N ) 2.124 Å, σ ) 0.016 Å, 35 data). [59][60][61][62][63][64] The angles listed in Table S-5 (Supporting Information) show that the octahedron is severely distorted.…”

“…Less is known about the higher oxidation states. 11,12 Oxorhenium(V)monomerswerepreparedwithcysteine,penicillamine, [13][14][15] and their methyl esters. [16][17][18] Besides the RedO moiety, these compounds contain two ligands, one tridentate-S,N,O and the other bidentate-S,N (Chart 1).…”

Role of protecting groups in the preparation of thiolate complexes of technetium-99 m using cysteine as a model

“…10 99 Tc-chelate of VII exhibited UV -max at 425 nm and IR stretching bands at 942 cm À1 which were comparable to those of 99 Tc-l-cysteinate (lmax 426 nm and IR band 940 cm À1 ) reported earlier. 10 The reverse phase HPLC retention time of 99 Tc and 99m Tc-l-cysteinate prepared from l-cystine as starting ligands were 5.03 and 5.15 respectively, whereas the 99 Tc and 99m Tc chelates prepared from S-thiomethyl-l-cysteine (VII) exhibited retention times of 5.08 and 5.18, respectively on the same reverse phase HPLC system (Figure 2). Tc-lcysteine under comparable experimental conditions.…”

“…However, this problem could be avoided by using the corresponding disulphide (cystine) as monosulphide precursor; use of large excess of the former produced the above chelate in excellent yield. 10 Therefore it may be concluded that the protection of monosulphide by disulphide formation, which is a useful tool in peptide chemistry, may be successfully applied in thiolate chelation with technetium.…”

“…After the establishment of the molecular structure of technetium cysteine 10 it was apparent that disulphide could be the appropriate precursor of monosulphide towards the preparation of desired technetium chelates. On this basis we further selected S-thiophenyl and S-thiomethyl as two other protective groups.…”