Synthesis of the Sulphonate and Phosphonate Derivatives of Mercaptoacetyltriglycine. X-Ray Crystal Structure of Na2[ReO(Mercaptoacetylglycylglycylaminomethanesulphonate)]·3H2O

摘要

Mercaptoacetyltriglycine forms complexes with 186/188Re and 99mTc radionuclides that are usefulin nuclear medicine because they are substrates of the renal anion transport system. However,the renal clearance of [MO(MAG3)]2-(MAG3 = penta-anionic form of mercaptoacetyltriglycine, M =Re, Tc) complexes are less than ideal. Organic sulphonates are also transported by the renalanion transport system and phosphonates are similar to sulphonates in size and shape. In aneffort to develop new ligands that form Re and Tc complexes and have improved renal clearancescompared to [MO(MAG3)]2- complexes, the sulphonate and phosphonate derivatives ofmercaptoacetyltriglycine were synthesized. The dianion [ReO(MAG2-AMS)]2- (MAG2-AMS =penta-anionic form of mercaptoacetylglycylglycylaminomethanesulphonic acid) was prepared forcharacterization by exchange reaction of ReOCl3(Me2S)(OPPh3) and isolated as the disodiumsalt. The structure of Na2[ReO(MAG2-AMS)]·3H2O (6) was determined by X-ray diffraction. Thecoordination geometry is pseudo square pyramidal, with the nitrogen and sulfur donor atomsforming a square base and the oxo ligand at the apex. The deprotonated sulphonate group has asyn conformation with respect to the oxo ligand. The renal clearances of [99mTcO(MAG2-AMS)]2- and [99mTcO(MAG2-AMP)]3- were similar in rats and suggest that the difference in total charge between the SO3- and PO32- groups is not important to renal clearance. However, their renalclearances were 40-50% less than that of [99mTcO(MAG3)]2- suggesting that the size and shapeof the large tetrahedral SO3- and PO32- groups of [99mTcO(MAG2-AMS)]2- and [99mTcO(MAG2-AMP)]3- inhibit recognition by the renal transport system compared to the small planar CO2- groupof [99mTcO(MAG3)]2-.