Ruthenium complexes imidazole

Imidazole is characterized mainly by the T) (N) coordination mode, where N is the nitrogen atom of the pyridine type. The rare coordination modes are T) - (jt-) realized in the ruthenium complexes, I-ti (C,N)- in organoruthenium and organoosmium chemistry. Imidazolium salts and stable 1,3-disubsti-tuted imidazol-2-ylidenes give a vast group of mono-, bis-, and tris-carbene complexes characterized by stability and prominent catalytic activity. Benzimidazole follows the same trends. Biimidazoles and bibenzimidazoles are ligands as the neutral molecules, mono- and dianions. A variety of the coordination situations is, therefore, broad, but there are practically no deviations from the expected classical trends for the mono-, di-, and polynuclear A -complexes. 

Further improvements in activity of the ruthenium carbene complexes were achieved by incorporation of methyl groups in 3,4-position of imidazol-2-ylidene moiety. Introduction of sulfur in the trara-position to the N-heterocyclic carbene leads to increased stability of the resulting ruthenium complexes. The synthesis and the first applications of these new rathenium complexes are described herein. 

In contrast to ferrocenes, osmium and ruthenium complexes are capable of forming coordinative bonds with donor centers of GO including histidine imidazoles. There are therefore two ways of bringing coordinated transition metals onto enzyme surfaces, i.e., via natural and artificial donor sites. Artificial centers are commonly made of functionalized pyridines or imidazoles, which must be covalently attached to GO followed by the complexation of an osmium or... 

Scheme 16. The ruthenium complex of the hemin and l-(3-aminopropyl)-imidazole conjugate used for reconstitution of -HRP. From Ref. (201).

Ruthenium and osmium carbene complexes possess metal centers that are formally in the +2 oxidation state, have an electron count of 16 and are penta-coordinated. Ruthenium complexes exhibit a higher catalytic activity when an imidazole carbene ligand is coordinated to the ruthenium metal center (21). 

The preparation of the catalyst starts with the synthesis of 1-mes-ityl-3-(7-octene)-imidazole bromide. This compound is prepared by condensing mesityl imidazole with 8-bromooctene. The resulting salt is deprotonated with (TMS)2NK, where TMS is the tetrameth-ylsilyl radical. This step is performed in tetrahydrofuran at -30°C for 30 min. To this product a solution of the ruthenium complex (PCy3)2Cl2Ru=CHPh is added at 0°C. Bringing the solution slowly to room temperature, after 1 h the ligand displacement was determined to be complete. Afterwards, the reaction mixture is then diluted with n-pentane and heated to reflux for 2 h to induce intramolecular cyclization. 

Ethacrynic acid has been linked to the ruthenium(II)-arene frame via two different approaches. In one approach the acid is connected via an imidazole which coordinates to the ruthenium(II) centre, in place of the pta ligand in RAPTA-type compounds. In the second approach the ethacrynic acid is attached to the arene, via either an amide or ester linker, in such a way that it should be cleaved enzymatically once inside the active site of GST. The ability of the ruthenium complexes to inhibit GST Pl-1 activity was comparable or better than free ethacrynic acid whereas RAPTA-C, employed as a control, exhibited no inhibitory effect on GST Pl-1, even at high concentrations. 

Figure 13.5 Ruthenium complex linked to enzyme substrates (adamantane, ethylbenzene) or ligand (imidazole) [51-53]...

Base-induced cycloaddition of TosMlC 37 to N-sulfonylaldimines 36 affords 4(5)-monosubstituted imidazoles 38 from which the parent imidazoles 39 can be prepared <97T11355>. This type of chemistry has been extended to reaction with arylazosulfones <97T2125>. N-Sulfonyl-2-imidazolines are derived from the ruthenium complex catalyzed reaction between isocyanoacetate and analogs of 36 <97JOC1799>. Cycloaddition of ylide 40 with trifluoroacetonitrile gives trifluoromethyl substituted imidazolines <97TL4359>. 

A family of octahedral ruthenium(III) complexes were developed by Travnicek et al. and investigated in several cell lines and in mice for cytotoxicity and antitumour activity respectively. Whilst the complexes were not found to be cytotoxic in vitro, the in vivo evaluation displayed superior results when compared with NAMI-A, a related imidazole-containing ruthenium complex that has entered clinical trials. 

Among the NHCs used in the preparation of ruthenium complexes so far, the most successful and frequentiy studied complexes were those bearing imidazole-or imidazolin-2-ylidene ligands. As mentioned earlier, studies conducted by Nolan and coworkers on saturated and unsaturated NHCs bearing ruthenium complexes on metathesis activity suggested that a slight variation in the electronic and steric properties can induce a large difference on catalytic activity [33]. 

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