Effects of the Bidentate Ligand on the Photophysical Properties, Cellular Uptake, and (Photo)cytotoxicity of Glycoconjugates Based on the [Ru(tpy)(NN)(L)]2+ Scaffold

Lucien N Lameijer; Tobias G Brevé; Vincent H S van Rixel; Sven H C Askes; M A Siegler; Sylvestre Bonnet

doi:10.1002/chem.201705388

Effects of the Bidentate Ligand on the Photophysical Properties, Cellular Uptake, and (Photo)cytotoxicity of Glycoconjugates Based on the [Ru(tpy)(NN)(L)]²⁺ Scaffold

Chemistry. 2018 Feb 21;24(11):2709-2717. doi: 10.1002/chem.201705388. Epub 2018 Jan 30.

Authors

Lucien N Lameijer¹, Tobias G Brevé¹, Vincent H S van Rixel¹, Sven H C Askes¹, M A Siegler², Sylvestre Bonnet¹

Affiliations

¹ Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
² Departement of Chemistry, Johns Hopkins University, Baltimore, Maryland, 21218, USA.

Abstract

Ruthenium polypyridyl complexes have received widespread attention as potential chemotherapeutics in photodynamic therapy (PDT) and in photochemotherapy (PACT). Here, we investigate a series of sixteen ruthenium polypyridyl complexes with general formula [Ru(tpy)(N-N)(L)]^+/2+ (tpy=2,2':6',2''-terpyridine, N-N=bpy (2,2'-bipyridine), phen (1,10-phenanthroline), dpq (pyrazino[2,3-f][1,10]phenanthroline), dppz (dipyrido[3,2-a:2',3'-c]phenazine, dppn (benzo[i]dipyrido[3,2-a:2',3'-c]phenazine), pmip (2-(4-methylphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline), pymi ((E)-N-phenyl-1-(pyridin-2-yl)methanimine), or azpy (2-(phenylazo)pyridine), L=Cl^- or 2-(2-(2-(methylthio)ethoxy)ethoxy)ethyl-β-d-glucopyranoside) and their potential for either PDT or PACT. We demonstrate that although increased lipophilicity is generally related to increased uptake of these complexes, it does not necessarily lead to increased (photo)cytotoxicity. However, the non-toxic complexes are excellent candidates as PACT carriers.

Keywords: cancer; light; photo-activated therapy (PACT); photodynamic therapy (PDT); ruthenium.