Synthesis and Crystal Structure of Na7Cu3O8, Containing a New Type of Oxocuprate(III) Oligoanion

Na₇Cu₃O₈ was prepared through oxidation of a Na₃CuO₂/NaCuO mixture (2:1) in dried oxygen at 450 °C. Single crystals have been grown by annealing of Na₇Cu₃O₈, in the presence of Na₂O₂, at 450 °C for 2000 h in silver crucibles, which were sealed in glass ampoules under dried Ar. According to the X-ray analysis of the crystal structure ( , Z = 1, a = 5.5891(2), b = 6.0945(2), c = 7.8890(3) Å, α = 110.059(2), β = 108.669(2), γ = 90.237(2)°) a new Cu₃O₈^7- oxocuprate anion, consisting of three edge sharing CuO₄ squares, is the prominent structural feature. These anions are aligned parallel to the space diagonal of the unit cell and can be regarded as infinite chains from which every fourth copper atom has been removed. This new representative of an oxocuprate(III) anion gives support to the expectation that the gap between dimeric and infinite edge sharing units of square planar cuprate anions can be closed, in principle.     

Probing the Binding Requirements of Modified Nucleosides with the DNA Nuclease SNM1A

SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. These compounds include ester, carboxylate and hydroxamic acid malonate derivatives which were installed in the 5′-position or 3′-position of thymidine or as a linkage between two nucleosides. Evaluation as inhibitors of recombinant SNM1A showed that nine of the twelve compounds tested had an inhibitory effect at 1 mM concentration. The most potent compound contains a hydroxamic acid malonate group at the 5′-position. Overall, our studies advance the understanding of requirements for nucleoside-derived inhibitors for SNM1A and indicate that groups containing a negatively charged group in close proximity to a metal chelator, such as hydroxamic acid malonates, are promising structures in the design of inhibitors.     

Designing fluorinated cinchona alkaloids for enantioselective catalysis: controlling internal rotation by a fluorine-ammonium ion gauche effect (φ(NCCF))

The C9 position of cinchona alkaloids functions as a molecular hinge, with internal rotations around the C8-C9 (τ(1)) and C9-C4' (τ(2)) bonds giving rise to four low energy conformers (1; anti-closed, anti-open, syn-closed, and syn-open). By substituting the C9 carbinol centre by a configurationally defined fluorine substituent, a fluorine-ammonium ion gauche effect (σ(C-H) → σ(C-F)*; F(δ-)???N(+)) encodes for two out of the four possible conformers (2). This constitutes a partial solution to the long-standing problem of governing internal rotations in cinchonium-based catalysts relying solely on a fluorine conformational effect.     

Fluorinated organocatalysts for the enantioselective epoxidation of enals: molecular preorganisation by the fluorine-iminium ion gauche effect

The fluorine-iminium ion gauche effect is triggered upon union of a secondary β-fluoroamine and an α,β-unsaturated aldehyde, providing a useful strategy for controlling the molecular topology of intermediates that are central to organocatalytic processes. The β-fluoroamine (S)-2-(fluorodiphenylmethyl)pyrrolidine (1) is an effective catalyst for the enantioselective epoxidation of α,β-unsaturated aldehydes. A process of structural editing has revealed that the efficiency of this catalyst is due to the (fluorodiphenyl)methyl group when it is embedded in a β-fluoroiminium motif. Epoxidations of challenging cyclic α,β-disubstituted, β,β-disubstituted and α,β,β-trisubstituted enals catalysed by 1 proceed with excellent levels of enantiocontrol (up to 98?%?ee).