Bioaktive lumineszierende Übergangsmetallkomplexe für biomedizinische Anwendungen

Abstract

Die zufällige Entdeckung des krebshemmenden Wirkstoffs Cisplatin festigte in den 1960er Jahren die Stellung der medizinischen anorganischen Chemie. In der Folge kam es zu einem weitverbreiteten Einsatz lumineszierender Metallkomplexe in der Sensorik, in der biologischen Bildgebung und in organischen Leuchtdioden. Übergangsmetallkomplexe weisen viele Vorteile auf, aufgrund derer sie als Therapeutika und als Lumineszenzsonden für Biomoleküle geeignet sind. Daher ist die Entwicklung neuer lumineszierender Metallkomplexe wünschenswert, die über verschiedene Bindungsmodi mit DNA wechselwirken oder auf alternative Teile der zellulären Maschinerie, z. B. auf Proteine, abzielen, um effektivere Mittel zur Überwachung von Krankheitsverläufen zur Verfügung zu stellen. Hier präsentieren wir aktuelle Beispiele biologisch aktiver lumineszierender Metallkomplexe, die auf ein spezifisches Biomolekül abzielen und dieses sondieren, und diskutieren das Potenzial dieser Verbindungen zur Erforschung und Behandlung menschlicher Erkrankungen.

A Bis(dipyridophenazine)(2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Complex with Anticancer Action upon Photodeprotection

“…[2] (Organo)metallic complexes can, however, also exert anticancer activity in their inert intact form. [3] The best examples are the substitutionally inert Ru II scaffolds, which have been found to not only act as potent kinase inhibitors, but also as effective cytotoxic compounds. [2c,e, 4] The mechanism of action for cytotoxic Ru II polypyridyl compounds is believed to be a complex function of inherent physicochemical and pharmacological properties.…”

Regioselective Synthesis of Polycyclic and Heptagon‐embedded Aromatic Compounds through a Versatile π‐Extension of Aryl Halides

“…On the one hand, these compounds are of great interest in optoelectronics [17] and molecular therapeutics, [18] and might be useful ligands in Pd-catalyzed sp 3 -C À Hf unctionalizations. Compounds containing N, S, and Oh eteroatoms were prepared efficiently under standard reaction conditions to give moderate-to-excellent yields (2a-2l,S cheme 3).…”

A Bis(dipyridophenazine)(2‐(2‐pyridyl)pyrimidine‐4‐carboxylic acid)ruthenium(II) Complex with Anticancer Action upon Photodeprotection

“…4 The mechanism of action for cytotoxic Ru II polypyridyl compounds is believed to be a complex function of inherent physicochemical and pharmacological properties. As interest in substitutionally inert metal complexes as anti‐cancer drug candidates has only recently regained momentum,3a, 4a,b,d, 5 in most cases only limited information is available on their precise mode of action and metabolic activity. Moreover, a scarcity of structure–activity relationship (SAR) studies focusing on these aspects also implies that biochemical understanding on most of these systems is still premature 4a–c.…”

“…Whilst photochemical control of activity (also referred to as “photocaging/uncaging”) has been widely explored with organic drugs, application of this concept to metal coordination complexes has been surprisingly limited 9. 11 Of note, metal complexes were previously used in combination with light to trigger biological activity 3a. 11, 12 Specific to substitutionally inert Ru II complexes, photoactivation to date has primarily revolved around the studies exploring their capacity to undergo photoinduced ligand exchange/expulsion, DNA binding, DNA cleavage, and cytotoxic effects 3a.…”