Unpredictable Dynamic Behaviour of Ruthenium Chelate Pyrrole Derivatives

Abstract

Reaction of [Ru(H)₂(CO)(PPh₃)₃] 1 with an equimolar amount of pyrrole-2-carboxylic acid (H₂L₁) leads to the homoleptic chelate derivative k²(O,O)-[RuH(CO)(HL₁)(PPh₃)₂] 2. Prolonged acetonitrile refluxing promotes an unusual k²(O,O)- → k²(N,O)- dynamic chelate conversion, forming a neutral, stable, air- and moisture- insensitive, solvento-species k²(N,O)-[Ru(MeCN)(CO)(L₁)(PPh₃)₂] 3. Analogously, reaction of 1 with the pyrrole-2-carboxyaldehyde (HL₂) affords k²(N,O)-[RuH(CO)(HL₂)(PPh₃)₂] 4, 5, as a couple of functional isomers. Optimized reaction conditions such as temperature and solvent polarity allow the isolation of dominant configurations. Structure 5 is a pyrrolide Ru-carbaldehyde, obtained from cyclization of the pendant CHO function, whereas species 4 can be viewed as an ethanoyl-conjugated Ru-pyrrole. Derivatives 3-5 were characterized by single crystal X-ray diffraction, ESI-Ms, IR, and NMR spectroscopy, indicating distinct features for the Ru-bonded pyrrolyl groups. DFT computational results, coplanarity, bond equalization, and electron delocalization along the fused five-membered rings support aromatic features. In accordance with the antisymbiotic trans-influence, both the isolated isomers 4 and 5 disclose CO ligands opposite to N- or O-anionic groups. The quantitative Mayer bond order evidences a stabilizing backbonding effect. Antibacterial and antifungal trials on Gram-positive (Staphylococcus aureus), Gram-negative (Escherichia coli), and Candida albicans were further carried out.

Keywords: DFT; SCXRD; antibacterial; chelation change; isomerism; ruthenium.

Figure 1

Selected examples of the previously reported Ru(II)-pyrrolyl complexes [21,22,23,24,25].

Figure 2

Example of phosphoamino-ligand that undergoes Ru-N cleavage, whereas upon hydrolysis, the thioacetamide chelate complex promotes exclusive S-coordination [27,30].

Scheme 1

Synthesis of complexes 2 and 3. (i): Refluxing 1,2-DME, 45 min, -H₂, -PPh₃; (ii): refluxing MeCN, 40 h, -H₂. After purification, the overall yield of complex 3 with respect to the starting complex 1 is 41%.

Figure 3

¹H NMR hydride region in CDCl₃ (from −9.0 to −17.5 ppm) of a kinetic mixture, obtained by running the reaction of 1 with H₂L₁ through MW solicitation for 15 min in CPME, with the attributed geometries based on DFT energetic calculations. The latter were run using the def2-QZVPP basis and the M06 functional including CPME solvent effects and are reported in blue. The small upfield-shifted hydride resonances are assigned to heteroleptic k²(N,O)-derivatives, involving N-H pyrrolyl activation with chelation through the CO-carboxy function.

Scheme 2

DFT calculations suggest a stable syn-k²(O,O)-2 species found at lower energies and exhibiting on the same side pyrrole-NH and Ru-H, whose ¹H NMR signals fall at 8.15 and −15.75 ppm, respectively. Finally, the thermodynamically stable isomers are assigned to N-pyrrolyl donor moiety trans-located to the electron-withdrawing CO ligand. The anti heteroleptic complex shows structures at relatively higher energies, and the corresponding signals disappear upon longer time running of kinetic mixtures. In spite of DFT-calculated low energy, the Et₂O-coordinated species, which could be conceivably formed by elution through CH₂Cl₂/Et₂O column chromatography or during numerous crystallization attempts, has never been spectroscopically intercepted. Arrows are used to show the energy of each structure.

Figure 4

The calculated lowest energy configuration 2 (in vacuo, with def2-TZVP basis and the M06L functional) discloses NH-pyrrolyl and Ru-H units mutually on the same side, being further stabilized by intramolecular dipole interactions of Ph-CH/py-NH acid with basic pyCOO/Ru-CO moieties or notably π-π stacking interactions between pyrrole and phenyl planar rings. Dipole bindings were evaluated as effective if they were less than the sum of the Van der Waals radii [33] and are summarized as exemplary in Supplementary Material Table S1.

Scheme 3

The promising mechanism A is proposed for explaining coordinative transformation from k²(O,O)-2 to solvento-k²(N,O)- species 3. The double dagger (‡) symbol is referred to transition states.

Scheme 4

Proposed mechanism B. The double dagger (‡) symbol is referred to transition states.

Figure 5

The proposed mechanisms are identified by differently colored paths (red for A and black for B). However, the blue-colored higher-energy step (4.1 kcal/mol) belongs to a never-observed isomer, showing the unfavorable opened configuration, with opposite H/C(O)O units. The double dagger (‡) symbol is referred to transition states.

Scheme 5

Different syntheses of complexes 4 and 5.

Scheme 6

Proposed isomers of 4 and 5. The most plausible isomer for each species is framed in the scheme.

Figure 6

Comparison between the Ru-H ¹H NMR signals of 4 and 5. Besides the expected coupling with equivalent apical phosphines (²J_HP = 20.7 Hz), the multiplicity of 5 clearly evidences delocalization from trans-directing Ru-H to the coordinated carboxaldehyde ligand (¹H NMR δ = 8.05 ppm, ²J_HP = 20.7, ⁴J_HH = 1.8 Hz).

Scheme 7

Resonant structures of HL₂-Ru.

Figure 7

Single crystal structure of 4 and 5. Experimental (red) and calculated (black) bond lengths are reported above for 4 and only calculated for 5. Mayer Bond Orders are reported in brackets. In 5, a twofold axis passing through O2, O4, Ru, N, and the C2-C2′ bond is present.

Figure 8

X-ray experimental (red) and DFT-calculated (black) bond lengths of 3. Calculated Mayer Bond Orders are reported in brackets.