RhodiumIII complexes

As rhodium(III) coordination complexes have a d6 electronic configuration, they are isoelectronic with Ru(II) and Pt(IV) complexes which are interesting anti-tumor complexes, e.g. (OC-6-43)-[PtCl2(OOCMe)2(CyNH2)(NH3)] (Cy = cyclohexyl) (JM216), an orally active anti-tumor agent. Rhodium(III) complexes generally have an octahedral structure and are inert complexes; nevertheless, many of the Rh(III) coordination complexes tested show considerable anti-tumor and anti-microbial activity. The meridional complex (OC-6-21)-[RhCl3(NH3)3] is remarkably active against sarcoma 180.66,67 The complexes containing dimethyl sulfoxide (OC-6-21)-[RhCl3(Me2SO-S)2(L)] (L = NH3, imidazole) show a cytostatic activity against A2780, A2780/cp8, LoVo and Calu cells similar to that of cisplatin.68 In contrast, the anionic complexes (OC-6-11)-Na[RhCl4(Me2SO-S)2], (OC-6-11)-Na[RhCl4(L)(Me2SO-S)] and (oC-6-11)-LH[RhCl4(L)2] (L = imidazole) are inactive. An anti-neoplastic activity in vivo against rhabdomyosarcoma characterizes a rhodium(III) chloride complex with oxalyl homocysteine thiolactone.69 Administration of the rhodium(III) complex [RhCl2L4]Cl (L = sulfaquinoxaline) to rats treated earlier with thioacetamide (inducing liver tumor) caused a significant restoration of the liver function.70,71

The cytostatic activity of polypyridyl and pyrazole rhodium(III) complexes against HCV29T tumor cells increases in the series [RhCl2(Hpz)4][RhCl4 (Hpz)2] 1 <[RhCl3(tpta)]-H2O 2 <[RhCl3(tpy)] 3 < ¬ęs-[PtCl2(NH3)2]<[Rh(tpy)2(Him)] Cl33H2O 4 (Hpz = pyrazole, Him = imidazole, tpy = 2,2':6',2"-terpyridine, tpta = 2,4,6-tris(2-pyridyl)-1,3,5-triazine) (Figure 20.4).72

The cytostatic activity of the complexes may be a result of their interaction with DNA. The effectiveness of the restraining of DNA migration in the presence of complexes in an 8% native polyacrylamide increased in the order: 1 (20%) < 4 (40%) < 2 (55%) < 3 (90%). This order is consistent with the cytostatic activity of complexes apart from the most active complex 4. It is possible that complex 4 relatively effectively interacts with DNA, but the rate of migration of the interaction product is not very strongly lowered because its structure is considerably different than the structures of DNA adducts with the complexes 1, 2 and 3. Interaction of complex 2 with DNA has been also investigated using DNase I footprinting. Investigations indicated that 2 is the most effective to change the DNase I footprinting of the ATGCGCT fragments of DNA. The obtained results suggest that the cytostatic activity of polypyridyl complexes can result from their interaction with DNA, most likely via formation

Figure 20.4 Chemical structures of [RhCl2(Hpz)4][RhCl4(Hpz)2], [RhCl3(tpy)]- (CH3)2SO, [RhCl3(tpta)]-(CH3)2SO

of a Rh-N coordination bond with guanine or adenine bases. However, intercalation of tpy or tpta ligands between nucleotide bases cannot be excluded.

Rhodium(III) complexes with phenanthrenequinone diimine (phi) and 1,10-phenanthroline and its derivatives specifically bind DNA (Figure 20.5).73 77 The phi ligand intercalates between the DNA base pairs in the major groove site of the DNA and orients the complex with respect to the helix. In these intercalations, the long axis of the phi ligand is parallel to the long axis of the base pair. The complex [Rh(phen)2(phi)]3+ binds to DNA with K > 107M_1 and on photo-excitation, cleaves duplex DNA. These complexes bind DNA selectively in the more accessible major groove sites owing to steric clashes between pyrimidines and the H2 and H9 hydrogens of phenanthroline ligands.

The [Rh(phen)2(phi)]3+ complex cleaves DNA selectively at 5'-pyr-pyr-pur-3' sites, e.g. 5'-CCAG-3', whereas cleavage at 5'-pur-pur-pyr-3' sites is suppressed. Other rhodium(III) complexes containing the phi ligand, with a less sterically demanding coordination sphere, are not selective, e.g. [Rh(bpy)2(phi)2]3+. The phenanthroline complex containing the 5,6-chrysenequinone diimine ligand (chrysi) (Figure 20.5) is too large to intercalate into standard base pair steps. Therefore, this complex can recognize and cleave a single mismatch site within a 2725 base pair sequence of plasmid DNA. Interactions of rhodium(II) complexes [Rh2(OOCR)4] (R = Me, Et, Pr, CF3) and [Rh2{O(NH)CR}4] (r = Me,

CF3) with DNA were investigated using electrochemical methods.78 The analysis of the suppressions of the anodic peak currents for guanine and adenine bases indicate that these complexes interact mainly with adenine.

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