Orthopalladation of GFP‐Like Fluorophores Through C–H Bond Activation: Scope and Photophysical Properties

Abstract

The luminescence of oxazolones R1‐C6H4CH=CC(O)O‐CN(R2) (1a–1j) and imidazolones R1‐C6H4CH=CC(O)NR3CN(R2) (1k–1q) has been examined. The new GFP‐like imidazolones (GFP = Green Fluorescent Protein) (1k–1q) have been prepared by reaction of the oxazolones with amines H2NR3 and bis(trimethylsilyl)acetamide. The most intense fluorescence was found in push‐pull systems containing simultaneously strong electron‐donating and electron‐withdrawing substituents. The incorporation of the Pd atom into the molecular skeleton of oxazolones and imidazolones notably changes their luminescence. The reaction of oxazolones (1a–1j) and imidazolones (1k–1q) with Pd(OAc)2 (1:1 molar ratio) in carboxylic acids gives the dinuclear [Pd{R1‐C6H3CH=CC(O)OCN(R2)}(µ‐carboxylate)]2 (2a–2j) and [Pd{R1‐C6H3CH=CC(O)NR3CN(R2)}(µ‐carboxylate)]2 (2k–2q) through regioselective C–H bond activation of the ortho position of the respective 4‐arylidene rings. Complexes 2a–2q react with LiCl in MeOH to give the chloride‐bridge derivatives [Pd{R1‐C6H3CH=CC(O)OCN(R2)}(µ‐Cl)]2 (3a–3j) and [Pd{R1‐C6H3CH=CC(O)NR3CN(R2)}(µ‐Cl)]2 (3k–3q), which further react with Tl(acac) (acac = acetylacetonate) to give the mononuclear species [Pd(R1‐C6H3CH=CC(O)OCN(R2)(acac)] (4a–4j) and [Pd{R1‐C6H3CH=CC(O)NR3CN(R2)(acac)}] (4k–4q). Complexes 4o and 4q, having an orthopalladated push‐pull imidazolone, are strongly fluorescent, showing a notable increase of the quantum yield with respect to the free ligands 1o and 1q up of one order of magnitude.

Functionalized 1,3‐Diaminotruxillic Acids by Pd‐Mediated C–H Activation and [2+2]‐Photocycloaddition of 5(4H)‐Oxazolones

“…The orthopalladation of oxazolones containing a methyl group in the 2‐position of the heterocycle ( 1j – 1o in Figure ) was also attempted with the aim of providing a more general scope for the ligands. The reactivity of some of these compounds ( 1n , 1o ) with Pd(OAc) 2 (1:1 molar ratio) has already been reported by us . As described previously, the orthopalladation of 2‐methyl‐4‐arylidene oxazolones 1j – 1o proceeds under less acidic conditions (acetic acid as solvent) than for the 2‐phenyl counterparts, but they are still relatively harsh (1 hour under reflux: 120 °C).…”

“…The oxazolones containing the phenyl ring in the 2‐position ( 1a – 1i ), those containing the methyl group in the 2‐position ( 1j – 1o ), and the oxidation reagent PhICl 2 were prepared by reported procedures. Compounds 2l , 2n and 2o were prepared as described previously . All other reagents were used as received from commercial suppliers.…”

Fluorescent Orthopalladated Complexes of 4-Aryliden-5(4H)-oxazolones from the Kaede Protein: Synthesis and Characterization

“…Despite the outstanding results, other reports on the amplification of the luminescence by locking of oxazolones through ortho -functionalization have not been published. We recently described a contribution in this area in which palladium complexes were employed as an intramolecular lock, as shown in Figure 3 (left) [ 63 ]. The incorporation of the Pd(II) lock into the skeleton of ( Z )-4-arylidene-2-phenyl-5(4 H )-oxazolones and -imidazolones was achieved using C–H activation processes by methods developed by our group [ 64 , 65 , 66 , 67 , 68 ].…”

“…The acetylacetonate ligand was used as an ancillary group to complete the coordination sphere of the Pd center. The results showed that this type of Pd lock was effective and led to increases in the quantum yield (QY) of push–pull imidazolones by up to one order of magnitude [ 63 ]. With the aim of achieving additional tuning of the fluorescence by changing the ancillary ligands bonded to the palladium, several attempts were made to coordinate chelating ligands L^L other than acetylacetonate.…”

Protein-Pd Complexes Conjugates as Artificial Enzymes

“…Palladium complexes have shown a great relevance in different areas, especially in catalytic application in different process such as C-C bond formation, C-H activation, reduction, multicomponent processes, [1,2] but also in biomedical applications [3] and as GFP-like fluorophores. [4,5] Metalloenzymes are natural biological catalysts. They contain a metal nucleus involved in their catalytic activity in many important biological processes.…”