Binuclear Lanthanide Complexes as Catalysts for the Hydrolysis of Bis(p‐nitrophenyl)‐phosphate and Double‐Stranded DNA

Abstract

The catalysis of phosphate ester hydrolysis is of particular interest from two diametric points of view. The formation and cleavage of these ester linkages in nucleic acids are among the most important molecular functions in living systems. At the same time. as chemical warfare agents phosphate esters are the most disastrous inventions of synthetic chemistry; however, it is often forgotten that as insecticides the related aryl phosphates have saved the lives of millions of people. The present communication addresses the hydrolysis of both kinds of esters catalyzed by binuclear metal complexes.Recent work in particular by Bredow,"' Komiyama,[21 Morrow,131 Chin,'41 and their collaborators has shown that highly charged cations, in particular of lanthanides, can greatly accelerate phosphate hydrolysis.[51 Our own efforts are directed primarily towards the development of ligdnds that form sufficiently stable complexes and enhance the catalytic activity of these lanthanide complexes.I6] The presence of several metal ions, both in enzymes as well as in synthetic analogs, is known to enhance rates of hydrolysis substantially. ['] In very recent studies with carefully designed binuclear zinc complexes Chapman and Breslow[81 have demonstrated how the catalytic efficiency depends critically on the distance between the metal centers and the conformation of the spacer. However, the rate of hydrolysis ['] for UpU as a DNA model was enhanced only by a factor of 2, and for his( p-nitropheny1)phosphate (BNPP) the rate enhancement factor was around 12.[81 In other recent reports the application of' binuclear complexes having peroxo ligands, ["] zinc complexes for the hydrolysis of dinucleotides, [' and intramolecular metal complexes" 2 ] for the hydrolysis of phosphonates have been described. With binuclear complexes based on imidazoles, Trogler et al.1131 found a ligand rate factor['] of only 2 for BNPP hydrolysis; in studies with double-stranded DNA binding but no cleavage was observed. We describe here binuclear lanthanide systems that lead to ligand rate factors ['] of up to 72 for the hydrolysis of BNPP and to dramatic enhancements for the cleavage of plasmid DNA.Ligands 1-4 were synthesized according to literature procedures1i41 and treated with twoequivalents of Eu3+ or Pr3+ salts in anhydrous methanol. The complexes with nitrate ions were insoluble in methanol and precipitated immediately from the reaction mixture; the complexes with chloride ions were soluble in methanol and were precipitated by slow addition of acetonitrile. The washed precipitates were generally analytically pure. The elemental analyses and titrations of the complexes with EDTA (the complexes were dissolved in water at pH 2; the pH was then increased to 5.2) indicate that all of the solid complexes contain two metal ions. Unfortunately, the complexes with ligands 1 and 2. containing the more lipophilic benzene rings, were water-soluble only as nitrate salts, which makes comparison to the more reactive chloride salts with 4 difficult. Nitrates are...

Catalytic hydrolysis of DNA by metal ions and complexes

“…While the Eu 3+ ion provided a V max (or k obs ) of 4.210 ±3 min ±1 and K m =3.910 ±5 M ±1 at a concentration of 2.5 mM, addition of intercalating agents, such as naphthylamino-derivatized ionophores, improved the V max to 3.5 10 ±2 min ±1 with K m =5.710 ±4 M ±1 . In a second report, binuclear lanthanide complexes of macrocyclic ligands were found to catalyze DNA hydrolysis with V max of 1.710 ±2 min ±1 , representing an approximately 210 6 -fold rate enhancement over uncatalyzed DNA hydrolysis [33]. In a recent paper, Schneider and co-workers [34] have demonstrated that carboxylic groups can act as cofactors in a series of Eu 3+ -benzo crown ether complexes that mediate hydrolysis of bis(p-nitrophenyl) phosphate.…”

Synthesis, Structure and Hydrolytic Properties of a Family of New Zn Complexes Containing Hexaazamacrocyclic Ligands

“…The macrocyclic ligands 3,6,9,16,19,22-hexaazatricyclo[22.2.2.2 11,14 ]-triaconta-1(27),11 (30),12,14(29),24(28),25-hexaene (H2p), 3,7,11,18, 22,26-hexaazatricyclo[26.2.2.2 13,16 ]tetratriaconta-1(31),13(34), 14,16(33),28(32),29-hexaene (H3p), 3,6,9,16,19,22-hexamethyl-3,6,9,16,19,22-hexaazatricyclo[22.2.2.2 11,14 ]triaconta-1(27),11 (30), 12,14(29),24(28), 6,9,17,20,6,9,17,20,15 ]triaconta-1(29), 11,13,15(30),25,3,7,11,18,22,7,11,18,22,16 ]tetratriaconta-1(31), 13(34),14,16(33), 28(32), 7,11,19,23,7,11,19,23,17 ]tetratriaconta-1(33), 13,15,17(34),29, were prepared according to the published procedures or slight modifications thereof.…”

Synthesis, Characterization and Phosphodiester Bond Cleavage Studies of the Dinuclear, Thioacetatocobalt(II) of 3-methylsulfanylpropionic Acid Complex

“…Several artificial active site models have been reported with molecular centers such as Zn II , Cu II , Co III , Fe III and La III [7][8][9][10]. Facile hydrolysis of phosphodiesters has been observed in the presence of labile metal complexes.…”