d-Orbital Reconstructions Forced by Double Bow-Shaped Deformations and Second Coordination Sphere Effects of Cu(II) Heme Analogs in HER.

Both geometric architecture and electronic configurations of heme proteins contribute to its activity. In this work we designed and synthesized a series of four copper(II) porphyrin complexes (4-, 3-, 2- and 1-Cu) where the molecular conformations are modulated by a pair of stepwise shortened straps on the same porphyrin side (cis-ortho) to give double bow-shaped skeletons. Single crystal structures demonstrate that the straps gradually increase the saddle deformation and the deviation of the metal centers, which is in accordance with two, unusual d-orbital reconstructions of two different ground states, as revealed by 4 K EPR and DFT calculations. In the study of the electrocatalytic hydrogen evolution reaction (HER), 1-Cu, with the shortest straps, showed the most apparent improvement of activity. Second coordination sphere (SCS) effects created by the double bow-shaped architecture and the strong saddle porphyrin core in 1-Cu are found to play key roles in proton trapping during the catalytic process. The work contributes a novel strategy to improve the catalytic performance of heme analogs through ligand geometric modulation.

Fine-Tuning of Electronic Structure of Cobalt(II) Ion in Nonplanar Porphyrins and Tracking of a Cross-Hybrid Stage: Implications for the Distortion of Natural Tetrapyrrole Macrocycles.

The core size of the porphyrin macrocycles was closely related to their stability of the different electron structure in the central metal ion. Cobalt(II) ions can undergo a conversion in electron configurations upon N4 core contraction of 0.05 Šin nonplanar porphyrins, and these ions still maintain low spin forms after and before conversion. The structural fine-tuning can induce the appearance of a cross-hybrid stage [d(x(2)-y(2))sp(2) ↔ d(z(2))sp(2)] based on quadrilateral coordination of the planar core. The results indicate that the configuration conversion plays a key role in electron transfer in redox catalysis involving cobalt complexes. The electronic properties of six monostrapped cobalt(II) porphyrins were investigated by spectral, paramagnetic, and electrochemical methods. The macrocyclic deformations and size parameters of Co-containing model compounds were directly obtained from their crystal structures.

Evaluation of the potential cytotoxicity of metals associated with implanted biomaterials (II).

The effects of metal ions on the cell DNA and RNA synthetic functions and the destruction of cell defensive system caused by metal ions were studied on the investigation of the effects of metal ions on cell alkaline phosphatase (ALP) activity and cell metabolism ability. The poisonous behaviours of metal ions [Cr (VI), Ni, V, Cr (III), Ag, and Al] on living tissue were both quantitatively and qualitatively measured. It was shown that Cr (VI) has a notable action on both cellular DNA and RNA synthetic functions, and following that, were Ni, V. The limitation action of Cr (III) on the synthetic abilities of DNA and RNA increased with the increase of Cr (III) concentration. Different to other five metal ions, the limitation of Al ion on RNA was greater than that on DNA. The limitation of V, Ag ions on DNA was same to that on RNA. Trace Cr (VI), in culture medium resulted in the decreasing of GSH in living tissue. Similar to that, a little higher Ni ion concentration seriously reduced the GSH content in living tissue. It was suggested that Cr (VI), Ni, might destroy and/or disturb the orientation of the microtubulin in cell skeleton. For other four metal ions, together with increasing the concentration in culture medium, the osmotic pressure increased. Consequently, more metal ions entered cell membrane, more GSH were lost in cell.

Cytotoxicity of cantharidin analogues targeting protein phosphatase 2A.

Cantharidin is a natural toxin that possesses potent anti-tumor properties. Its clinical application, however, is limited due to severe side-effects. Its cytotoxicity is believed to be mediated by the inhibition of serine/threonine protein phosphatase 2A. In order to identify new compounds with potential clinical therapeutic use, a series of cantharidin analogues, including those with skeletal modifications at 1-C position (analogues 1-6) and those with anhydride modifications (analogues 7-13), were synthesized, and tested for their inhibitory effects on protein phosphatase 2A and their cytotoxicity to a panel of cancer cell lines. In addition, the mode of inhibition of cantharidin and analogue 13 on protein phosphatase 2A was determined by enzymatic kinetics assay. The data indicated that analogue 13 exhibited potent cytotoxicity to all cancer cell lines, and analogues 9, 11 and 12 showed relatively weak cytotoxicity to one or more cell lines, while other analogues showed little cytotoxicity. Accordingly, analogue 13 exhibited potent inhibitory activity on protein phosphatase 2A, and analogues 9, 11 and 12 showed weak inhibitory activity, while other analogues did not show any inhibitory activity. The findings indicate that the cytotoxicity of synthetic cantharidin analogues is likely to be associated with their protein phosphatase 2A inhibitory activity. The mode of inhibition of cantharidin and analogue 13 on protein phosphatase 2A is identified as noncompetitive inhibition by the Lineweaver-Burk plot.