Tricarbonyl-rhenium complexes of a thiol-functionalized amphoteric poly(amidoamine).
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.
Donghi
Daniela
D
Dipartimento di Chimica Inorganica, Metallorganica e Analitica L. Malatesta, Universita degli Studi di Milano, via Venezian 21, 20133 Milano, Italy.
Maggioni
Daniela
D
D'Alfonso
Giuseppe
G
Amigoni
Federica
F
Ranucci
Elisabetta
E
Ferruti
Paolo
P
Manfredi
Amedea
A
Fenili
Fabio
F
Bisazza
Agnese
A
Cavalli
Roberta
R
D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D009757:Nylons / Q000737:chemistry* / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D011073:Polyamines / Q000737:chemistry* / Q000494:pharmacology; D012211:Rhenium / Q000737:chemistry* / Q000494:pharmacology
D002614:Chelating Agents; D009757:Nylons; D010879:Piperazines; C531249:Poly(amidoamine); D011073:Polyamines; D012211:Rhenium