Metal complex catalysis in living biological systems

Abstract

This feature article discusses synthetic metal complexes that are capable of catalyzing chemical transformations in living organisms. Photodynamic therapy exemplifies what is probably the most established artificial catalytic process exploited in medicine, namely the photosensitized catalytic generation of cell-damaging singlet oxygen. Different redox catalysts have been designed over the last two decades to target a variety of redox alterations in cancer and other diseases. For example, pentaazamacrocyclic manganese(ii) complexes catalyze the dismutation of superoxide to O(2) and H(2)O(2)in vivo and thus reduce oxidative stress in analogy to the native enzyme superoxide dismutase. Recently, piano-stool ruthenium and iridium complexes were reported to influence cellular redox homeostasis indirectly by catalytic glutathione oxidation and catalytic transfer hydrogenation using the coenzyme NADH, respectively. Over the last few years, significant progress has been made towards the application of non-biological reactions in living systems, ranging from the organoruthenium-catalyzed cleavage of allylcarbamates and a gold-catalyzed intramolecular hydroarylation to palladium-catalyzed Suzuki-Miyaura and Sonogashira cross-couplings within the cytoplasm or on the surface of living cells. The design of bioorthogonal catalyst/substrate pairs, which can passively diffuse into cells, combines the advantages of small molecules with catalysis and promises to provide exciting new tools for future chemical biology studies.

Genetic Optimization of Metalloenzymes: Enhancing Enzymes for Non‐Natural Reactions

“…This represents arare example of abiocompatible precious-metal catalyst. [69] Alternatively,t he chemical reagents (Michael acceptors or oxidants) have been exploited to neutralize inhibitors,t hus enabling the screening of [Cp*Ir(biot-p-L)Cl] in the presence of cell lysates (Figure 12). [12] Affinity tags or chromatography may be exploited for the parallel purification of host proteins.…”

Activation of p53 mediated glycolytic inhibition-oxidative stress-apoptosis pathway in Dalton's lymphoma by a ruthenium (II)-complex containing 4-carboxy N-ethylbenzamide

“…Due to effective biodistribution and multimodal cellular actions, during recent past, ruthenium complexes have drawn much attention as next generation anticancer agents [2]. So far mechanistic aspects of anticancer metal complexes are concerned, DNA, once considered as their main target [3,4], is now evident to be highly unselective [5] and therefore, there is an evolving concept to evaluate whether metal complexes could be able to attenuate certain tumor growth associated biochemical events at cellular level [5e7].…”

The Suzuki–Miyaura Cross-Coupling as a Versatile Tool for Peptide Diversification and Cyclization

“…Popular bioorthogonal reactions examples include the Staudinger ligation, click chemistry, cycloadditions, and transition-metal catalyzed C-C bond formation. Of interest to this work, the potential of palladium-mediated chemistry has even been extended to living cells [176][177][178]. However, in case of transformations on highly complex proteins, containing multiple complexation sites, superstoichiometrical quantities (often palladium >50 eq, boronic acid >500 eq) are required.…”