Dinuclear Copper(II) Complexes with {Cu₂(μ-hydroxo)bis(μ-carboxylato)}⁺ Cores and Their Reactions with Sugar Phosphate Esters: A Substrate Binding Model of Fructose-1,6-bisphosphatase

Reactions of CuX2.nH2O with the biscarboxylate ligand XDK (H2XDK = m-xylenediamine bis(Kemp's triacid imide)) in the presence of N-donor auxiliary ligands yielded a series of dicopper(II) complexes, [Cu2(mu-OH)(XDK)(L)2]X (L = N,N,N',N'-tetramethylethylenediamine (tetmen), X = NO3 (1a), Cl (1b); L = N,N,N'-trimethylethylenediamine (tmen), X = NO3 (2a), Cl (2b); L =2,2'-bipyridine (bpy), X = NO3 (3); L = 1,10-phenanthroline (phen), X = NO3 (4); L = 4,4'-dimethyl-2,2'-bipyridine (Me2bpy), X = NO3 (5); L = 4-methyl-1,10-phenanthroline (Mephen), X = NO3 (6)). Complexes 1-6 were characterized by X-ray crystallography (Cu...Cu = 3.1624(6)-3.2910(4) A), and the electrochemical and magnetic properties were also examined. Complexes 3 and 4 readily reacted with diphenyl phosphoric acid (HDPP) or bis(4-nitrophenyl) phosphoric acid (HBNPP) to give [Cu2(mu-phosphate)(XDK)(L)2]NO3 (L = bpy, phosphate = DPP (11); L = phen, phosphate = DPP (12), BNPP (13)), where the phsophate diester bridges the two copper ions in a mu-1,3-O,O' bidentate fashion (Cu...Cu = 4.268(3)-4.315(1) A). Complexes 4 and 6 with phen and Mephen have proven to be good precursors to accommodate a series of sugar monophosphate esters (Sugar-P) onto the biscarboxylate-bridged dicopper centers, yielding [Cu2(mu-Sugar-P)(XDK)(L)2] (Sugar-P = alpha-D-Glc-1-P (23a and b), D-Glc-6-P (24a and b), D-Man-6-P (25a), D-Fru-6-P (26a and b); L = phen (a), Mephen (b)) and [Cu2(mu-Gly-n-P)(XDK)(Mephen)2] (Gly-n-P = glycerol n-phosphate; n = 2 (21), 3 (22)), where Glc, Man, and Fru are glucose, mannose, and fructose, respectively. The structure of [Cu2(mu-MNPP)(XDK)(phen)2(CH3OH)] (20) was characterized as a reference compound (H2MNPP = 4-nitrophenyl phosphoric acid). Complexes 4 and 6 also reacted with d-fructose 1,6-bisphosphate (D-Fru-1,6-P2) to afford the tetranuclear copper(II) complexes formulated as [Cu4(mu-D-Fru-1,6-P2)(XDK)2(L)4] (L = phen (27a), Mephen (27b)). The detailed structure of 27a was determined by X-ray crystallography to involve two different tetranuclear complexes with alpha- and beta-anomers of D-Fru-1,6-P2, [Cu4(mu-alpha-D-Fru-1,6-P2)(XDK)2(phen)4] and [Cu4(mu-beta-D-Fru-1,6-P2)(XDK)2(phen)4], in which the D-Fru-1,6-P2 tetravalent anion bridges the two [Cu2(XDK)(phen)2]2+ units through the C1 and C6 phosphate groups in a mu-1,3-O,O' bidentate fashion (Cu...Cu = 4.042(2)-4.100(2) A). Notably, the structure with alpha-D-Fru-1,6-P2 demonstrated the presence of a strong hydrogen bond between the C2 hydroxyl group and the C1 phosphate oxygen atom, which may support the previously proposed catalytic mechanism in the active site of fructose-1,6-bisphosphatase.