SHORT COMMUNICATION DOI:10.1002/ejic.201402395 A Luminescent Ruthenium Azide Complex as a Substrate for Copper-Catalyzed Click Reactions Anne Kroll, [a] Katharina Monczak, [a] Dieter Sorsche, [a] and Sven Rau* [a] Keywords: Ruthenium / Click chemistry / Copper / Azides / Photodynamic therapy A new ligand and its luminescent polypyridyl–Ru II complex were synthesized and characterized. Both provide two azide functionalities in their periphery, which are electronically separated from the π-system of the 2,2'-bipyridine ligands by a methylene group. This azide-functionalized ruthenium complex provides access to the formerly inaccessible sub- strate spectrum of alkynyl-functionalized coupling substrates by using the copper(I)-catalyzed azide–alkyne cycloaddition Introduction Coupling of luminescent molecules to biological targets such as proteins is of increasing importance for detailed analysis of biological processes. [1] An efficient method towards this aim is the copper(I)-catalyzed azide–alkyne cy- cloaddition (CuAAC), which was invented in 2002 by Sharpless and Medal; it is probably one of the most well- known reactions in the wide field of coupling chemistry based on Claisen–Huisgen cycloadditions. [2,3] Products of this click reaction possess a 1,4-disubstituted-1,2,3-triazole bridge that is selectively formed under copper(I) catalysis. Polypyridyl–ruthenium complexes are very interesting chro- mophores owing to their highly relevant photophysical properties such as large Stokes shift, long lifetimes of the luminescent excited state, and their interesting electrochemi- cal properties. [4,5] Furthermore, they may possess thera- peutic potential based on their photochemistry. [6] Very re- cently, it was shown that polypyridyl–Ru II complexes them- selves could be used as substrates in click reactions. [7–9] However, only alkynyl-substituted luminescent ruthenium complexes have been utilized so far because of the instabil- ity of the azide-substituted complexes. [7] Interestingly, the newly formed triazole moiety, the product of the CuAAC, may be used as a complexation site itself. This was recently exploited for the formation of various polypyridyl–metal complexes. [10–14] To develop the applicability of CuAAC [a] The University of Ulm, Institute of Inorganic Chemistry 1, Materials and Catalysis, Albert-Einstein-Allee 11, 89081 Ulm, Germany E-mail: sven.rau@uni-ulm.de http://www.uni-ulm.de/nawi/nawi-anorg1/startseite.html Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/ejic.201402395. Eur. J. Inorg. Chem. 2014, 3462–3466 © 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 3462 (CuAAC). Test CuAAC reactions were performed on the li- gand and directly on the Ru II complex by using phenylacetyl- ene as a model substrate, and relatively high yields of the products were obtained under mild conditions. Transforma- tion of the azide into the triazole had only minor influences on the photophysical properties of the polypyridyl–ruth- enium core. further it is necessary to design azide-containing polypyri- dyl ligands that form stable luminescent polypyridyl–ruth- enium complexes and to establish their suitability as click substrates. To the best of our knowledge, only one report exists in which a ruthenium azide complex, non-lumines- cent [Ru(p-cymene)(4-azido-2,2'-bipyridine)Cl] + , was suc- cessfully linked through CuAAC. [9] Recently published az- ide-functionalized Ir III complexes were converted success- fully in click reactions. The very low extinction coefficients of these compounds below 400 nm limit their applicability as sensors in biological systems. [15] Furthermore, it would be desirable if the photophysical properties of the lumines- cent ruthenium complex would not change significantly af- ter the CuAAC reaction. The results of Baron et al. for click reactions on their alkyne-functionalized complex show that there is a very small difference in the emission maxima for the precursor alkyne complex in comparison to that of the clicked products (up to 13 nm). [7,16] Importantly, one of the “clicked” systems of Chitre et al., in which aromatic azide functionalities were bound to the bipyridine ligand precur- sor, showed no luminescence at all. [8] To the best of our knowledge, there are difficulties in performing click reac- tions on polypyridyl–Ru II complexes that bear azide func- tionalities because of the instability of aromatic azides on 2,2'-bipyridine ligands. [7] Accordingly, all alkynyl-function- alized substrates known to date are not accessible for the introduction of luminescent metal cores with CuAAC. An approach towards solving this problem could be to separate the azide electronically from the π-system of the 2,2'-bipyr- idine ligands by methylene groups in the sterically opti- mized 4,4'-positions. Recent results on the successful click chemistry with the corresponding 5,5' isomer at copper complexes support the assumption that the 4,4' isomer