Two dicopper(II) complexes bridged by N-phenolato-N′-[2-(dimethylamino)ethyl]oxamide (H₃pdmaeox) and end-capped with 2,2′-diamino-4,4′-bithiazole (dabt) and 2,2′-bipyridine (bpy), respectively, namely [Cu₂(pdmaeox)Cl(CH₃OH)(dabt)]·CH₃OH (1) and [Cu₂(pdmaeox)(bpy)(H₂O)]-(pic)·H₂O (2) (where pic⁻ denotes the picrate anion) have been synthesized. Complex 1 was characterized by elemental analysis, molar conductivity measurements, IR and electronic spectral studies, and single-crystal X-ray diffraction. The crystal structure analyses reveal that the dissymmetric unit of complex 1 contains a neutral dicopper(II) complex moiety [Cu₂(pdmaeox)Cl-(CH₃OH)(dabt)], in which the cis-pdmaeox³⁻ ligand bridges two copper(II) ions with the separation of 5.2238(19) Å. Through hydrogen bonding interactions, complex 1 molecules are assembled into 3D supramolecular structures. The structure and DNA-binding activities of complex 2 have been reported in our previous paper. However, its other properties were not studied. In order to gain some insight into the structure–activity relationship, the reactivities towards DNA and protein of the two dicopper(II) complexes are studied both theoretically and experimentally. The DNA docking study suggests that all the two dicopper(II) complexes can interact with DNA through the minor groove, and the binding affinity follows the order of 1 > 2, which is further validated by spectral titration, electrochemical techniques, and viscosity measurements. Bovine serum albumin (BSA) binding activity studies revealed that the two dicopper(II) complexes can strongly quench the intrinsic fluorescence of BSA through a static quenching mechanism with the ratio of the dicopper(II) complex to BSA being 1 : 1, and the most possible binding site is in the proximity of Trp134. The in vitro anticancer activities indicate that the two dicopper(II) complexes are active against the selected tumor cell lines, and the order of in vitro anticancer activities is consistent with the DNA-binding affinities. The influence of structural variation of the terminal ligands in the dicopper(II) complexes on DNA-binding modes and anticancer activities is preliminarily discussed.

The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to γH2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.

A new µ-oxamido-bridged dicopper(II) complex, [Cu₂(pdmaeox)(bpy)(H₂O)](pic) · H₂O [H₃pdmaeox = N-phenolato-N′-[2-(dimethylamino)ethyl]oxamide, Hpic = 2,4,6-trinitrophenol, bpy = 2,2′-bipyridine], has been synthesized and characterized by elemental analyses, molar conductivity measurement, infrared, and electronic spectra studies, and X-ray single-crystal diffraction. The complex crystallizes in the triclinic system, P 1 space group, with crystallographic data: a = 10.7815(2) Å, b = 11.3598(2) Å, c = 14.1389(3) Å, and z = 2. In [Cu₂(pdmaeox)(bpy)(H₂O)]⁺, one copper(II) resides in the inner site with a square-planar coordination geometry and the other is chelated by the two exo-oxygen atoms of the cis-pdmaeox³⁻ ligand in a square-pyramidal environment. The Cu···Cu separation through cis-pdmaeox³⁻ bridge is 5.1834(4) Å. The crystal structure is stabilized by hydrogen bonds and π–π stacking interactions. The interaction of the dicopper(II) complex with herring sperm-DNA (HS-DNA) has been investigated by electronic absorption titration, fluorescence titration, electrochemical titration, and viscosity measurements. The results reveal that the interaction of the dicopper(II) complex with HS-DNA might be electrostatic binding. The effects of bridging ligand on the interaction of the dinuclear complex with HS-DNA were preliminarily investigated.