Show-Jen Chiou

Synthetic modeling of zinc thiolates: quantitative assessment of hydrogen bonding in modulating sulfur alkylation rates.

A series of mononuclear zinc thiolate complexes have been prepared and fully characterized. The reactions of the complexes with alkyl halides, leading to zinc halides and the corresponding thioethers, have been examined by kinetic methods. In toluene, the reactions obey a second-order rate law displaying activation parameters consistent with a SN2 attack of the zinc-bound thiolate on the carbon electrophile. Intramolecular hydrogen bonding of an amide N—H to the thiolate sulfur reduces the nucleophilicity and consequently, the rate of alkylation more than 30-fold at 25°C. The H-bonding shows an inverse H/D isotope effect of 0.33 (60°C) ascribed to differential H-bonding for the two isotopomers due to zero point energy differences. These model studies provide quantitative evaluation of H-bonding on reaction rates relevant to zinc thiol-activating proteins.

Dinuclear [{Fe(NO)2}10―{Fe(NO)2}10] Dinitrosyl Iron Complex with Thiolate―CO-Bridged Ligands

Air-sensitive complexes {Fe(NO)(2)}(9)-{Fe(NO)(2)}(9) [Fe(mu-SC(6)H(4)-o-N(CH(3))(2))(NO)(2)](2) (1), {Fe(NO)(2)}(9)-{Fe(NO)(2)}(10) [Fe(mu-SC(6)H(4)-o-N(CH(3))(2))(NO)(2)](2)(-) (2), the anionic {Fe(NO)(2)}(10) [(SC(6)H(4)-o-N(CH(3))(2))Fe(NO)(2)](-) (3), and the anionic {Fe(NO)(2)}(10)-{Fe(NO)(2)}(10) [Fe(NO)(2)(mu-SC(6)H(4)-o-N(CH(3))(2))(mu-CO)Fe(NO)(2)](-) (4) with mixed CO-thiolate-bridged ligands were synthesized. All complexes were characterized by IR, UV-vis, electron paramagnetic resonance, and single-crystal X-ray diffraction. The interconversions among these complexes were demonstrated. The interconversion between complexes 1 and 2 is accomplished by reduction and oxidation. Complex 3 adapts a {Fe(NO)(2)}(10) electronic structure with a N/S ligation mode and serves as a donor reagent of the {Fe(NO)(2)}(10) moiety. {Fe(NO)(2)}(10)-{Fe(NO)(2)}(10) complex 4 possesses the butterfly-like [Fe(mu-S)(mu-C)Fe] core with a shorter Fe...Fe distance of 2.5907(5) A attributed to the shorter Fe-S and Fe-C bond distances.

Effects of curcumin on nitrosyl-iron complex-mediated DNA cleavage and cytotoxicity.

Combination therapy aims to improve the pharmaceutical efficacy of different drugs, thus lowering the dosages used and reducing the side effects. However, interactions between individual drugs may also occur and lead to uncertain consequences. This study demonstrated that curcumin, a natural phenolic compound found in the rhizomes of turmeric, could either inhibit or enhance DNA cleavage caused by the synthetic nitrosyl-iron complex NC10 ([Fe₂(C₂H₅OS)₂(NO)₄]). Without UV irradiation, higher concentrations of curcumin protected DNA from being cleaved by NC10. Conversely, in the presence of lower concentrations of curcumin (< 5 µM), cleaved DNA increased by raising curcumin concentrations. After UV irradiation, the DNA protective effect of curcumin decreased while the enhancing DNA cleavage effect of curcumin remained. UV/visible spectroscopy analysis showed that curcumin is associated with the iron of NC10, suggesting the formation of curcumin-Fe complexes. Furthermore, a cytotoxicity assay revealed that cotreatment of NC10 and curcumin had synergetic effects on the growth inhibition of mouse melanoma B16-F10 cells. To our knowledge, this is the first study of the cotreatment of curcumin with inorganic compounds that showed synergistic cytotoxicity.

Pyrazolyl[(methylthio)methyl]borates: hybrid ligands providing nitrogen and sulfur donors

Two new borate ligands, PhB(CH2SCH3)2(pz)– (1–) and Ph2B(CH2SCH3)(pz)– (2–) (pz = 1-pyrazolyl), have been prepared to provide mixed donor sets, ‘NS2’ and ‘NS’, respectively, to transition metal ions.