title: Influence of the side-chain length on the cellular uptake and the cytotoxicity of rhenium triscarbonyl derivatives: a bimodal infrared and luminescence quantitative study.
abstract: Rhenium triscarbonyl complexes fac-[Re(CO)3 (N^N)] with appropriate ancillary N^N ligands are relevant for fluorescent bio-imaging. Recently, we have shown that [Re(CO)3 ] cores can also be efficiently mapped inside cells using their IR signature and that they can thus be used in a bimodal approach. To describe them we have coined the term SCoMPIs for single-core multimodal probes for imaging. In the context of the use of these SCoMPIs in bio-imaging, the questions of their cellular uptake and cytotoxicity are critical. We report here a series of compounds derived from the [Re(CO)3 Cl(pyta)] core (pyta=4-(2-pyridyl)-1,2,3-triazole). The pyta ligand is of interest because it can be easily functionalized. Aliphatic side chains (C4 , C8 , and C12 ) were appended to this core. A correlative study involving IR and luminescence was performed to monitor and quantify their cellular internalization. We studied the relationship between lipophilicity (log P(o/w)), cytotoxicity (IC50 ), and cellular uptake, and we showed that both uptake and cytotoxicity increase with the length of the side chain, with a higher uptake for the C12 derivative. This study stresses the distinction that has to be made between apparent toxicity, determined as an incubation concentration IC50 , and intrinsic toxicity. Indeed, the intrinsic toxicity of a compound can remain hidden if it is not cell permeable. Therefore it must be kept in mind that IC50 values are composite values, reflecting both cellular uptake and intrinsic toxicity.
authors.affiliation: Ecole Normale Supérieure, Département de chimie Sorbonne Universités. UPMC Univ Paris 06, CNRS, Laboratoire des Biomolécules, UMR7203, 24, rue Lhomond, 75005 Paris (France), Fax: (+33) 1-4432-3389.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Clède
authors.forename: François
authors.initials: F
authors.lastname: Lambert
authors.forename: Rénette
authors.initials: R
authors.lastname: Saint-Fort
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Plamont
authors.forename: Hélène
authors.initials: H
authors.lastname: Bertrand
authors.forename: Anne
authors.initials: A
authors.lastname: Vessières
authors.forename: Clotilde
authors.initials: C
authors.lastname: Policar
mesh_terms: D003602:Cytotoxicity, Immunologic; D008024:Ligands; D049449:Luminescence; D012211:Rhenium / Q000737:chemistry*
chemical_list: D008024:Ligands; D012211:Rhenium
keywords: IR spectroscopy; carbonyl ligands; cytotoxicity; fluorescence; imaging agents; luminescence