Investigation of the Coordination Interactions of S-(Pyridin-2-ylmethyl)-l-Cysteine Ligands with M(CO)₃⁺ (M = Re, ^99mTc)

Development of new ligands for fac-M(OH2)3(CO)3+ (M = Re, 99mTc) led the investigation with S-(pyridin-2-ylmethyl)-l-cysteine, 1. The ligand 1 has potential to coordinate with the metal through three different tridentate modes: tripodal through cysteine (O,N,S) and two linear involving the S-pyridyl and cysteine (O,S,NPy, N,S,NPy). From the reaction with 1, two species were observed in the 1H NMR, where the primary product was the linear fac-Re(N,S,NPy-1)(CO)3+, 2a, complex. To identify the coordination mode of the minor product, functionalized analogues of 1 were prepared from S-(pyridin-2-ylmethyl)-Boc-l-cysteine-methyl ester, 3, with orthogonal protecting groups on the C terminus (methyl ester) in S-(pyridin-2-ylmethyl)-l-cysteine methyl ester, 4, or N terminus (Boc) in S-(pyridin-2-ylmethyl)-Boc-l-cysteine, 6, that specifically directed the coordination mode of fac-M(H2O)3(CO)3+ to either N,S,NPy or O,S,NPy, respectively. Two diastereomers [fac-Re(CO)3(N,S,NPy-4)]+, 5a and 5b, were observed and independently characterized by X-ray structure analysis and NMR in high yield with 4. Surprisingly, the O,S,NPy Re complex with ligand 6 was not observed and simplified versions, 3-(pyridin-2-ylmethylthio) propanoic acid, 7, and 2-(pyridin-2-ylmethylthio)acetic acid, 8, were investigated. Ligand 7 did not yield the desired linear tridentate O,S,NPy product. However, the shorter ligand 8 formed fac-Re(CO)3(O,S,NPy-8), 9, in high yield. 99mTc labeling studies were conducted and yielded similar results to the rhenium complex and effective (>99%) at 10−5 M ligand concentration.