Synthesis of Camphor-Derived Bis(pyrazolylpyridine) Rhodium(III) Complexes: Structure–Reactivity Relationships and Biological Activity

Abstract

Two novel rhodium­(III) complexes, namely, [RhIII(X)­Cl3] (X = 2 2,6-bis­((4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)­pyridine or 2,6-bis­((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)­pyridine), were synthesized from camphor derivatives of a bis­(pyrazolylpyridine), tridentate nitrogen-donor chelate system, giving [RhIII(H2L*)­Cl3] (1a) and [RhIII(Me2L*)­Cl3] (1b). A rhodium­(III) terpyridine (terpy) ligand complex, [RhIII(terpy)­Cl3] (1c), was also synthesized. By single-crystal X-ray analysis, 1b crystallizes in an orthorhombic P212121 system, with two molecules in the asymmetric unit. Tridentate coordination by the N,N,N-donor localizes the central nitrogen atom close to the rhodium­(III) center. Compounds 1a and 1b were reactive toward l-methionine (l-Met), guanosine-5′-monophosphate (5′-GMP), and glutathione (GSH), with an order of reactivity of 5′-GMP > GSH > l-Met. The order of reactivity of the RhIII complexes was: 1b> 1a > 1c. The RhIII complexes showed affinity for calf thymus DNA and bovine serum albumin by UV–vis and emission spectral studies. Furthermore, 1b showed significant in vitro cytotoxicity against human epithelial colorectal carcinoma cells. Since the RhIII complexes have similar coordination modes, stability differences were evaluated by density functional theory (DFT) calculations (B3LYP­(CPCM)/LANL2DZp). With (H2L*) and (terpy) as model ligands, DFT calculations suggest that both tridentate ligand systems have similar stability. In addition, molecular docking suggests that all test compounds have affinity for the minor groove of DNA, while 1b and 1c have potential for DNA intercalation.

Bis-pyrazolylpyridine Complexes of Some Transition Metal Ions: Structure-Activity Relationships and Biological Activity

“…[16] The binding affinity of complexes shown in Figure 1 to CT-DNA and BSA was studied using by different experimental methods. [33][34][35][36] The published results showed that the studied Pd(II) and Pt(II) complexes (1-4) have a very high binding affinity toward DNA molecule ( Table 2). Pt(II) complexes exhibited much higher binding affinity than Pd(II) complexes.…”

“…The kinetic and mechanism of the substitution reactions of studied complexes (Figure 1) with important biological ligands such as thiourea (tu), L-methionine (L-met), L-cysteine (L-cys), glutathione (GSH) and guanosine-5'-monophosphate (5'-GMP) were studied. [33][34][35][36] Some obtained results are given in the Table 1.…”

“…0.41 ± 0.01 0.24 ± 0.02 [35] [Rh(Me 2 L*)Cl 3 ] (9) 5.6 ± 0.1 0.38 ± 0.01 [36] [Rh(terpy)Cl 3 ] (10) 0.40 ± 0.01 0.034 ± 0.001 [36] are more reactive compared to analogue platinum complexes (10 3 -10 5 times), that was expected. [13] In addition, complexes with H 2 L tBu inert ligand (1 and 3) showed slightly higher reactivity than those with Me 2 L tBu (2 and 4), indicating the steric influence of chelating ligands on the reactivity of complexes.…”

“…Similar observations were reported by Bogojeski et al for the kinetic reactivity of Rh(III) pincer complexes with bis-pyrazolylpyridine ligands and for Rh(III)-terpy complexes. [35,36] In addition, we have chosen to study the same type of complexes with Rh(III) as metal ion, since in recent years complexes of Rh, Os and Ir have been intensively examed in relation to possible anti-tumor activity. According to the obtained data (Table 1), studied Rh(III) complexes are reactive toward all of the tested nucleophiles, with order of reactivity 5′-GMP > GSH > L-met.…”

“…According to the obtained data (Table 1), studied Rh(III) complexes are reactive toward all of the tested nucleophiles, with order of reactivity 5′-GMP > GSH > L-met. [35,36] Since Rh(III), unlike Pt, Pd and Au complexes, are borderline hard-soft acids it was expected that they have the highest affinity for nitrogen-bonding nucleophiles, 5'-GMP. The lower reactivity of L-met over GSH could be due to the steric effects.…”