Tricarbonyl−Rhenium Complexes of a Thiol-Functionalized Amphoteric Poly(amidoamine)
- 16 November 2009
- journal article
- Published by American Chemical Society (ACS) in Biomacromolecules
- Vol. 10 (12) , 3273-3282
Abstract
An amphoteric thiol-functionalized poly(amidoamine) nicknamed ISA23SH(10%) was synthesized. Rhenium complexes 1 and 2, containing 0.5 and 0.8 equiv of rhenium, respectively, were easily obtained by reacting ISA23SH(10%) with [Re(CO)(3)(H(2)O)(3)](CF(3)SO(3)) in aqueous solution at pH 5.5. Both ISA23SH(10%), and its rhenium complexes were soluble in water under physiological conditions. The resultant solutions were stable, even in the presence of cysteine. Rhenium chelation occurred through the S and N atoms of the cysteamine moiety, as demonstrated by (1)H, (13)C, and (15)N NMR spectroscopy. The diffusion coefficients and the hydrodynamic radii of ISA23SH(10%) and complex 1 were determined by pulsed gradient spin echo (PGSE) NMR experiments. The radius of the rhenium complexes 1 and 2 was always slightly larger than that of the parent polymer. TEM analysis showed that both complexes form spherical nanoparticles with narrow size distributions. Consistent results were obtained by dynamic light scattering. The observed sizes were in good agreement with those evaluated by PGSE. Preliminary in vitro and in vivo biological studies have been performed on complexes 1 and 2 as well as on the parent ISA23SH(10%). Neither hemolytic activity of the two rhenium complexes and the parent polymer, up to a concentration of 5 mg/mL, nor cytotoxic effects were observed on Hela cell after 48 h at a concentration of 100 ng/mL. In vivo toxicological tests showed that ISA23SH(10%) is highly biocompatible, with a maximum tolerated dose (MTD) of 500 mg/kg. No toxic side effects were apparent after the intravenous injection in mice of the two rhenium complexes in doses up to 20 mg/kg.Keywords
This publication has 49 references indexed in Scilit:
- Single amino acid chelates (SAAC): a strategy for the design of technetium and rhenium radiopharmaceuticalsChemical Communications, 2008
- Expedient Multi-Step Synthesis of Organometallic Complexes of Tc and Re in High Effective Specific Activity. A New Platform for the Production of Molecular Imaging and Therapy AgentsInorganic Chemistry, 2008
- Strategies for the Development of Novel Tumor Targeting Technetium and Rhenium RadiopharmaceuticalsChimia, 2007
- Synthesis, Physicochemical Properties, and Preliminary Biological Characterizations of a Novel Amphoteric Agmatine-Based Poly(amidoamine) with RGD-Like Repeating UnitsBiomacromolecules, 2006
- Experimental and quantum‐chemical studies of 15N NMR coordination shifts in palladium and platinum chloride complexes with pyridine, 2,2′‐bipyridine and 1,10‐phenanthrolineMagnetic Resonance in Chemistry, 2006
- Re(CO)3 Complexes Synthesized via an Improved Preparation of Aqueous fac-[Re(CO)3(H2O)3]+ as an Aid in Assessing 99mTc Imaging Agents. Structural Characterization and Solution Behavior of Complexes with Thioether-Bearing Amino Acids as Tridentate LigandsInorganic Chemistry, 2005
- Synthesis and reactivity of [NEt 4 ] 2 [ReBr 3 (CO) 3 ]. Formation and structural characterization of the clusters [NEt 4 ][Re 3 (µ 3 -OH)(µ-OH) 3 (CO) 9 ] and [NEt 4 ][Re 2 (µ-OH) 3 (CO) 6 ] by alkaline titrationJ. Chem. Soc., Dalton Trans., 1994
- Associative thickeners: NMR self-diffusion and rheology studies of aqueous solutions of hydrophobically modified poly(oxyethylene) polymersThe Journal of Physical Chemistry, 1993
- Fourier transform pulsed-gradient spin-echo studies of molecular diffusionProgress in Nuclear Magnetic Resonance Spectroscopy, 1987
- Carbonylrhenium Clusters by Photoreaction of Re2(CO)10 with WaterAngewandte Chemie International Edition, 1975