Synthesis and characterization of water-soluble tin-based metallodendrimers

摘要

Introduction of ionic or nonionic hydrophilic terminal groups into the hydrophobic dendritic backbone Si(CH2CH2Sn)(4) led to a variety of first-generation water-soluble tin-based dendrimers. Functionalization of the hydridotin dendrimer Si(CH2CH2SnH3)(4) (1) via 12-fold hydrostannation reaction of acrylic acid derivatives served as the key step. 1 reacts with methyl acrylate to give Si[CH2CH2Sn(CH2CH2COOCH3)(3)](4) (2), which by means of alkaline hydrolysis was converted into the water-soluble carboxylate-terminated dendrimers Si[CH2CH2Sn(CH2CH2COOM)(3)](4) [M = Na (3), K (4)]. Reduction of 2 afforded the dendritic polyalcohol Si[CH2CH2Sn(CH2CH2CH2OH)(3)](4) (5). A clearly enhanced water solubility due to nonionic surface functionalization of 2 was obtained by its reaction with 2-aminoethanol, formally yielding Si[CH2CH2Sn(CH2CH2CONHCH2CH2OH)(2.5)(CH2CH2COOCH3)(0.5)](4) (6). The hydrostannation. of O-protected N-(2-hydroxyethyl)acrylamides by 1, however, gave the monodisperse derivatives Si[CH2CH2Sn(CH2CH2CONHCH2CH2OR)(3)](4) [R = (CO2Bu)-Bu-t (7), (SiMe2Bu)-Bu-t (8)]; deprotection of 8 with tetra-n-butylammonium fluoride yielded the water-soluble Si[CH2CH2Sn(CH2CH2CONHCH2CH2OH)(3)](4) (9). Also via hydrostannation reaction by 1, the ester-substituted analogue Si[CH2CH2Sn(CH2CH2COOCH2CH2OH)(3)](4) (10), showing a clearly lower hydrolytic stability, and the homologous amide-substituted dendrimer Si[CH2CH2Sn(CH2CH2CONHCH2CH2OCH2CH2OH)(3)](4) (11) were synthesized. The new organotin dendrimers were characterized by elemental analysis, multinuclear NMR spectroscopy (H-1, C-13, Sn-119), and mass spectrometry (MALDI-TOF, ESI). With respect to the potential use of water-soluble tin-based metallodendrimers as X-ray contrast agents, 6 was studied in vivo in mice, roughly estimating its LD50 to 3 mmol Sn/kg body weight. [References: 55]