Rhodium(III) Dihalido Complexes: The Effect of Ligand Substitution and Halido Coordination on Increasing Cancer Cell Potency

Abstract

This work presents the synthesis of eight new rhodium­(III) dihalido complexes, [RhX2(L)­(LH)] (where X = Cl or I), which incorporate two bidentate N-(3-halidophenyl)picolinamide ligands. The ligands have different binding modes in the complexes, whereby one is neutral and bound via N,N (LH) coordination, while the other is anionic and bound via N,O (L) coordination. The solid state and solution studies confirm multiple isomers are present when X = Cl; however, after a halide exchange with potassium iodide (X = I) the complexes exist exclusively as single stable trans isomers. NMR studies reveal the Rh­(III) trans diiodido complexes remain stable in aqueous solution with no ligand exchange reported over 96 h. Chemosensitivity data against a range of cancer cell lines show two cytotoxic complexes, where L = N-(3-bromophenyl)­picolinamide ligand. The results have been compared to the analogous Ru­(III) complexes and overall highlight the Rh­(III) trans diiodido complex to be ∼78× more cytotoxic than the analogous Rh­(III) dichlorido complex, unlike the Ru­(III) complexes which are equitoxic against all cell lines. Additionally, the Rh­(III) trans diiodido complex is more selective toward cancerous cells, with selectivity index (SI) values >25-fold higher than cisplatin against colorectal carcinoma.

Bis(N‐picolinamido)cobalt(II) Complexes Display Antifungal Activity toward Candida albicans and Aspergillus fumigatus

“…For the cis complexes, the high intensity peaks from the simulated pattern do appear in the experimental patterns, but some additional intense peaks are also present in the experimental diffraction patterns, which cannot be matched to the corresponding simulated pattern. This could be ascribed to the presence of a mixture of isomers in the bulk powder sample [48,51] . If the observed differences are due to the presence of a mixture of isomers, as this is only observed for cis complexes, this may imply that the trans complex is the thermodynamic product and the cis complex (or mixture) is the kinetic product of the complex synthesis.…”

“…This could be ascribed to the presence of a mixture of isomers in the bulk powder sample. [ 48 , 51 ] If the observed differences are due to the presence of a mixture of isomers, as this is only observed for cis complexes, this may imply that the trans complex is the thermodynamic product and the cis complex (or mixture) is the kinetic product of the complex synthesis. These mixtures of cis isomers, and stability of the trans isomers has already been observed in our group, when N ‐picolinamide ligands are bound to Ru(III) [48] and Rh(III) [51] metal centers.…”

Effect of cysteine thiols on the catalytic and anticancer activity of Ru(ii) sulfonyl-ethylenediamine complexes

“…Studies of the antiproliferative activity of organometallic complexes, especially the Ir, [1][2][3] Os, 4 Rh 5,6 and Ru 7,8 complexes, have been stimulated by the clinical success of platinum anticancer drugs such as cisplatin, carboplatin and oxaliplatin. [9][10][11] The activity of organometallic half-sandwich complexes can be tuned by the choice of the arene, chelating and monodentate ligands.…”

Cell nucleus localization and high anticancer activity of quinoline–benzopyran rhodium(iii) metal complexes as therapeutic and fluorescence imaging agents

“…Undoubtedly, CDDP and its analogs have been considerably successful in cancer chemotherapy, but many CDDP-resistant tumors remain difficult to treat. [1][2][3][4][5][6][7][8] It is necessary to develop new non-Pt-based complexes that can overcome CDDP resistance while causing no side effects. 1,6 The first Rh(III) complex, [Rh 2 (CH 3 COO) 4 (H 2 O) 2 ], was investigated as an anticancer drug against various tumor cells over 40 years ago.…”

“…[1][2][3][4][5][6][7][8] It is necessary to develop new non-Pt-based complexes that can overcome CDDP resistance while causing no side effects. 1,6 The first Rh(III) complex, [Rh 2 (CH 3 COO) 4 (H 2 O) 2 ], was investigated as an anticancer drug against various tumor cells over 40 years ago. 1,7 Various Rh(III) complexes of well-known CDDP analogs have demonstrated contrasting antiproliferative activities, including bidentate N-(3-halidophenyl)picolinamide Rh(III) dihalido complexes 1, 1 ispinesib-derived Rh(III) trans diiodido complex 2, 6a curcuminbisdemethoxycurcumin Rh(III) compounds 3 and 4, 9,10 imidazo [4,5-f ] [1,10]phenanthroline Rh(III) complexes 5 and 6, 11,12 2-(2-pyridyl)benzimidazole half-sandwich Rh(III) complex 7, 13 1-methylimidazole Rh(III) complex 8, 14 1,2,4-triazole Rh(III) complex 9, 15 1,8-naphthalimide derived Rh(III) complex 10, 16 thiabendazole Rh(III) biscyclometallated complex 11, 17 rhodium(I) N-heterocyclic carbene complex 12, 18 hydroxamic acid Rh(III) complex 13, 19 organometallic Rh(III) half-sandwich anticancer complex 14 20 and other analogs 15-20, [21][22][23][24][25][26] which have been found to be active against various cancer types.…”