Conjugating Biotin to Ruthenium(II) Arene Units via Phosphine Ligand Functionalization

Abstract

Two‐step functionalization of 4‐diphenylphosphino benzoic acid with biotin afforded 2‐(biotinyloxy)ethyl 4‐(diphenylphosphanyl)benzoate (LP), that was subsequently used to synthesize the Ru(II) arene complexes [RuCl2(η6‐p‐cymene)(LP)] (1), [Ru(C2O4)(η6‐p‐cymene)(LP)] (2) and [Ru(curc)(η6‐p‐cymene)(LP)]NO3 ([3]NO3), the latter incorporating curcumin (curcH) as an additional bioactive fragment. [Ru(curc)(η6‐p‐cymene)(PPh3)]NO3 ([4]NO3) was also prepared as a reference compound. Compounds 2 and [3]NO3 exhibited excellent stability in water/DMSO solution while being slowly activated in the cell culture medium over 72 hours. Together with LP, they were therefore assessed for their antiproliferative activity towards a panel of cancer cell lines, with different levels of biotin transporter expression. The apparent affinity of the compounds towards avidin varies, and their antiproliferative activity does not correlate with biotin transporter expression, although it is systematically enhanced when biotin‐free cell culture medium is used.

Polymeric Nanoparticles Containing Ruthenium Complexes for Biomedical Applications: A Mini-Review on Recent Developments

“…They have low therapeutic values because of low target selectivity, high off-target toxicity, and low bioavailability. Such issues can, however, be circumvented by tethering targeting moieties and/or by the use of nanomedicine …”

Research Progress of Metal Anticancer Drugs

“…Six complexes were tested for antitumor activity in vitro, and the results showed that compound 18 had good lipophilic properties, which were conducive to cell absorption, and the strongest anti-tumor activity (human chordoma CH1, IC50 = 29 µmol/L). Fabio’s research group [ 107 ] prepared and characterized a series of arylruthenium (II) complexes ( Figure 10 , 19 and 20 ), which were connected to the metal center by biotin-functionalized triphenylphosphine ligands to synthesize a series of arylruthenium (II) complexes containing biotin fragments. It shows excellent stability in a dimethyl sulfoxide/water mixture.…”

Hetero-Bis-Conjugation of Bioactive Molecules to Half-Sandwich Ruthenium(II) and Iridium(III) Complexes Provides Synergic Effects in Cancer Cell Cytotoxicity

“…In light of these promising results, we decided to coordinate the bis-functionalized bipyridines to Ru­(II) p -cymene and Ir­(III) pentamethylcyclopentadienyl structures, which have been widely investigated for their anticancer potential . Note that double functionalization with two different biofragments is quite rare for these metal scaffolds . Four bioactive carboxylic acids were selected for the present work: ethacrynic acid ( E -CO 2 H ), flurbiprofen ( F -CO 2 H ), biotin ( B -CO 2 H ), and benzylpenicillin ( P -CO 2 H ) (Scheme c).…”