A straightforward access is provided to iron(II) complexes showing exceedingly slow spin-state interconversion by utilizing trigonal-prismatic directing ligands (L(n)) of the extended-tripod type. A detailed analysis of the interrelations between complex structure (X-ray diffraction, density functional theory) and electronic character (SQUID magnetometry, Mössbauer spectroscopy, UV/vis spectroscopy) of the iron(II) center in mononuclear complexes [FeL(n)] reveals spin crossover to occur along a coupled breathing/torsion reaction coordinate, shuttling the complex between the octahedral low-spin state and the trigonal-prismatic high-spin state along Bailar's trigonal twist pathway. We associate both the long spin-state lifetimes in the millisecond domain close to room temperature and the substantial barriers against thermal scrambling (Ea ≈ 33 kJ mol(-1), from Arrhenius analysis) with stereochemical constraints. In particular, the topology of the κ(6)N ligands controls the temporary and structural dynamics during spin crossover.

With the aim of assessing whether Au(iii) compounds with pincer type ligands might be utilized as potential antitumor agents, three new monofunctional Au(iii) complexes of the general formula [Au(N-N'-N)Cl]Cl2, where N-N'-N = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine (H2LtBu, 1), 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine (Me2LtBu, 2) or 2,6-bis((4S,7R)-1,7,8,8-tetramethyl-4,5,6,7-tetrahydro-1H-4,7-methanoindazol-3-yl)pyridine (Me2*L, 3) were synthesized. All complexes were characterized by elemental analysis, spectroscopic techniques (IR, UV-Vis, 1D and 2D NMR) and mass spectrometry (MALDI TOF MS). The chemical behavior of the complexes under physiological conditions was studied by UV-Vis spectroscopy, which showed that all compounds were remarkably stable and that the gold center remained in the 3+ oxidation state. The kinetics and the mechanism of the reaction of complexes 1-3 with guanine derivatives (i.e. guanosine (Guo) and guanosine-5'-monophosphate (5'-GMP)) and calf thymus DNA (CT DNA) were studied by stopped-flow spectroscopy. The three complexes displayed moderately different rate constants in their reactions with Guo, 5'-GMP and CT DNA, which can be explained by the steric hindrance and σ-donicity of the methyl substituent on the bis-pyrazolylpyridine fragment in complexes 2 and 3. The measured enthalpies and entropies of activation (ΔH≠ > 0, ΔS≠ < 0) supported an associative mechanism for the substitution process. The interaction of the newly synthesized complexes 1-3 with CT DNA was investigated by UV-Vis and fluorescence spectroscopy, and also by viscosity measurements, which all indicated that complexes 1-3 bound to CT DNA with moderate binding affinity (Kb = 1.6-5.7 × 103 M-1) and stabilized the duplex of CT DNA. Molecular docking indicated that complexes 1-3 interacted with DNA via intercalation. Complex 1 reduced the cell survival of all the investigated cell lines (A549, A375, and LS-174) with IC50 values being up to 20 μM. We have shown that 1 induced perturbations of the cell cycle and led to apoptosis in human melanoma A375 cells. Complex 1 also affected the level of reactive oxygen species (ROS) in the same cells. However, pre-treatment of A375 cells with NAC (ROS scavenger) reversed the effect of 1 on their survival.

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.

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