TY - JOUR

T1 - N^N^C-Cyclometalated rhodium(III) complexes with isomeric pyrimidine-based ligands: unveiling the impact of isomerism on structural motifs, luminescence and cytotoxicity

AU - Vorobyeva, Sofia N

AU - Bautina, Sof'ya A

AU - Shekhovtsov, Nikita A

AU - Nikolaenkova, Elena B

AU - Sukhikh, Taisiya S

AU - Golubeva, Yuliya A

AU - Klyushova, Lyubov S

AU - Krivopalov, Viktor P

AU - Rakhmanova, Marianna I

AU - Gourlaouen, Christophe

AU - Bushuev, Mark B

N1 - The research was supported by the Ministry of Science and Higher Education of the Russian Federation (Nikolaev Institute of Inorganic Chemistry SB RAS, projects numbers 121031700315-2 and 121031700321-3; N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry). The authors thank the Ministry of Science and Higher Education of the Russian Federation for the spectral and analytical measurements performed at the Multi-Access Chemical Research Centre SB RAS (Nikolaev Institute of Inorganic Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry). The work was supported by the Foundation for the Advancement of Theoretical Physics and Mathematics "BASIS". The authors thank XRD Facility of NIIC SB RAS and personally thank A. S. Sukhikh and V. N. Yudin for the X-ray diffraction data collection. The investigation of biological properties was performed on the equipment of the Centre for Collective Use "Proteomic Analysis" (FRC FTM) and supported by the Ministry of Science and Higher Education of the Russian Federation (Project No. 122032200236-1). The Siberian Branch of the Russian Academy of Sciences (SB RAS) Siberian Supercomputer Centre is gratefully acknowledged for providing supercomputer facilities. M.B.B. acknowledges the access to the Computational Centre of Novosibirsk State University.

PY - 2024/4/23

Y1 - 2024/4/23

N2 - 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 (HL2,5) and 4-(3,5-dimethyl-1H-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 RhCl3 leads to the sp2 C-H bond activation, resulting in the isolation of two complexes, [RhL2,5(Solv)Cl2]·nEtOH and [RhL2,6(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 [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.

AB - 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 (HL2,5) and 4-(3,5-dimethyl-1H-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 RhCl3 leads to the sp2 C-H bond activation, resulting in the isolation of two complexes, [RhL2,5(Solv)Cl2]·nEtOH and [RhL2,6(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 [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.

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85191819108&origin=inward&txGid=89ad42d5df87e225f96454d1f050f3fe

U2 - 10.1039/d4dt00824c

DO - 10.1039/d4dt00824c

M3 - Article

C2 - 38683023

VL - 53

SP - 8398

EP - 8416

JO - Dalton Transactions

JF - Dalton Transactions

SN - 1477-9226

IS - 19

ER -