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

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-1-pyrazol-1-yl)-2,5-diphenylpyrimidine (HL2,5) and 4-(3,5-dimethyl-1-pyrazol-1-yl)-2,6-diphenylpyrimidine (HL2,6), were synthesized. The ligands differ by the degree of steric bulk: the molecular structure of HL2,5 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 HL2,5 and HL2,6 with RhCl leads to the sp C-H bond activation, resulting in the isolation of two complexes, [RhL2,5(Solv)Cl2]·nEtOH and [RhL2,6(Solv)Cl2]·nEtOH (Solv = HO, EtOH), with the deprotonated forms of the pyrazolylpyrimidine molecules which coordinate the Rh 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 HO 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 S/T and S/S crossings associated with the cleavage of the weak HO ligands upon excitation, the [RhL2,5(Solv)Cl2]·nEtOH complex appeared to be emissive in the solid state, while [RhL2,6(Solv)Cl2]·nEtOH is non-emissive at all. The complexes show significant cytotoxic activity against cancerous HepG2 and Hep2 cell lines, with the [RhL2,6(Solv)Cl2]·nEtOH complex being more active than its isomer [RhL2,5(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.