Acetoxymethyl Concept for Intracellular Administration of Carbon Monoxide with Mn(CO)3‐Based PhotoCORMs. Issue 13 (6th February 2018)

• Record Type: Journal Article
• Authors: Mede, Ralf; Hoffmann, Patrick; Neumann, Clara; Görls, Helmar; Schmitt, Michael; Popp, Jürgen; Neugebauer, Ute; Westerhausen, Matthias
• Is Part Of: Chemistry. Volume 24:Issue 13(2018)
• Page Start: 3321
• Page End: 3329
• Publication Date: 2018-02-06
• Subjects: biochemistry -- carbon monoxide -- carbonyl complexes -- esterases -- manganese; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201705686
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Targeted administration of carbon monoxide with CO releasing molecules (CORMs) inside of cells proved to be very challenging. Consequently, there are only very few reports on intracellular uptake of CORMs requiring high extracellular CORM loading because an equilibrium between extra‐ and intracellular concentrations can be assumed. Here we present a strategy for a targeted intracellular administration of manganese(I)‐based CORMs that are altered inside of cells to trap these complexes. Thereafter, carbon monoxide can be liberated by irradiation (photoCORMs). To achieve this innovative task, acetoxymethyl (AM) groups are attached at the periphery of the hydrophobic manganese(I) carbonyl complexes to not influence the CO release behavior. Inside of cells these AM substituents are cleaved by esterases yielding hydrophilic manganese(I) carbonyl compounds which are captured inside of cells. This objective is realized by using the bidentate bases 4‐(acetoxymethoxycarbonyl)phenyl‐bis(3, 5‐dimethylpyrazolyl)methane (1 ) and 4‐(acetoxymethoxy)phenyl‐bis(3, 5‐dimethylpyrazolyl)methane (4 ) at facial (OC)3 MnBr fragments yielding CORM‐AM1 (2 ) and CORM‐AM2 (5 ), respectively. Besides synthesis, crystal structures and spectroscopic properties we present targeted administration and intracellular accumulation of these AM‐containing CORMs. Abstract : The acetoxymethyl (AM) concept facilitates intracellular administration of CO‐releasing molecules (CORMs). Carbonyl complexes with the lipophilic O‐bound acetoxymethyl group penetrate cell membranes, leading to an intracellular enrichment. Inside cells, esterases cleave this AM group and the thus formed hydrophilic functionalities lead to an intracellular trapping of the CORMs.