N^N^C-Cyclometalated rhodium(iii) complexes with isomeric pyrimidine-based ligands: unveiling the impact of isomerism on structural motifs, luminescence and cytotoxicity

Abstract

The impact of isomerism of pyrimidine-based ligands and their rhodium(III) complexes with regard to their structures and properties was investigated. Two isomeric ligands, 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2,5-diphenylpyrimidine (HL^2,5) and 4-(3,5-dimethyl-1H-pyrazol-1-yl)-2,6-diphenylpyrimidine (HL^2,6), were synthesized. The ligands differ by the degree of steric bulk: the molecular structure of HL^2,5 is more distorted due to presence of pyrazolyl and phenyl groups in the neighbouring positions 4 and 5 of the pyrimidine ring. The complexation of HL^2,5 and HL^2,6 with RhCl₃ leads to the sp² C–H bond activation, resulting in the isolation of two complexes, [RhL^2,5(Solv)Cl₂]·nEtOH and [RhL^2,6(Solv)Cl₂]·nEtOH (Solv = H₂O, EtOH), with the deprotonated forms of the pyrazolylpyrimidine molecules which coordinate the Rh³⁺ ion as N^N^C-tridentate ligands. According to DFT modelling, the mechanism of the deprotonation involves (i) the C–H bond breaking in the 2-phenyl group followed by the coordination of the C atom to the Rh atom, (ii) the protonation of coordinated chlorido ligand, (iii) the ejection of the HCl molecule and (iv) the coordination of the H₂O molecule. The ligand isomerism has an impact on emission properties and cytotoxicity of the complexes. Although the excited states of the complexes effectively deactivate through S₀/T₁ and S₀/S₁ crossings associated with the cleavage of the weak H₂O ligands upon excitation, the [RhL^2,5(Solv)Cl₂]·nEtOH complex appeared to be emissive in the solid state, while [RhL^2,6(Solv)Cl₂]·nEtOH is non-emissive at all. The complexes show significant cytotoxic activity against cancerous HepG2 and Hep2 cell lines, with the [RhL^2,6(Solv)Cl₂]·nEtOH complex being more active than its isomer [RhL^2,5(Solv)Cl₂]·nEtOH. On the other hand, noticeable cytotoxicity of the latter against HepG2 is supplemented by its non-toxicity against non-cancerous MRC-5 cells.