Catalysis of Diribonucleoside Monophosphate Cleavage by Water Soluble Copper(II) Complexes of Calix[4]arene Based Nitrogen Ligands

Abstract

Calix[4]arenes functionalized at the 1,2-, 1,3-, and 1,2,3-positions of the upper rim with [12]ane-N(3) ligating units were synthesized, and their bi- and trimetallic zinc(II) and copper(II) complexes were investigated as catalysts in the cleavage of phosphodiesters as RNA models. The results of comparative kinetic studies using monometallic controls indicate that the subunits of all of the zinc(II) complexes and of the 1,3-distal bimetallic copper(II) complex 7-Cu(2) act as essentially independent monometallic catalysts. The lack of cooperation between metal ions in the above complexes is in marked contrast with the behavior of the 1,2-vicinal bimetallic copper(II) complex 6-Cu(2), which exhibits high catalytic efficiency and high levels of cooperation between metal ions in the cleavage of HPNP and of diribonucleoside monophosphates NpN'. A third ligated metal ion at the upper rim does not enhance the catalytic efficiency, which excludes the simultaneous cooperation in the catalysis of the three metal ions in 8-Cu(3). Rate accelerations relative to the background brought about by 6-Cu(2) and 8-Cu(3) (1.0 mM catalyst, water solution, pH 7.0, 50 degrees C) are on the order of 10(4)-fold, largely independent of the nucleobase structure, with the exception of the cleavage of diribonucleoside monophosphates in which the nucleobase N is uracil, namely UpU and UpG, for which rate enhancements rise to 10(5)-fold. The rationale for the observed selectivity is discussed in terms of deprotonation of the uracil moiety under the reaction conditions and complexation of the resulting anion with one of the copper(II) centers.

Reactivity of carbonyl and phosphoryl groups at calixarenes

“…In the cleavage of HPNP (water, pH 7, 258C), cooperation between metal centres is significant in the 1,2-vicinal dinuclear complex 37-Cu 2 with a . 10 3 rate enhancement at 0.2 mM catalyst over the reaction carried out in the presence of buffer alone, and 42-fold and 73-fold accelerations over 35-Cu and [12]aneN 3 -Cu, respectively (31). In contrast, the catalytic efficiency of 1,3-distal bimetallic regioisomer 38-Cu 2 is about twice as great as that of monometallic Trimetallic complex 39-Cu 3 cleaves a series of diribonucleoside monophosphates (UpU, UpG, GpU, GpG, ApG, CpG, GpA and CpA) with catalytic rate accelerations in the order of 10 4 -fold in most cases (31).…”

“…10 3 rate enhancement at 0.2 mM catalyst over the reaction carried out in the presence of buffer alone, and 42-fold and 73-fold accelerations over 35-Cu and [12]aneN 3 -Cu, respectively (31). In contrast, the catalytic efficiency of 1,3-distal bimetallic regioisomer 38-Cu 2 is about twice as great as that of monometallic Trimetallic complex 39-Cu 3 cleaves a series of diribonucleoside monophosphates (UpU, UpG, GpU, GpG, ApG, CpG, GpA and CpA) with catalytic rate accelerations in the order of 10 4 -fold in most cases (31). Rate enhancements rise to 10 5 -fold in the cleavage of UpU and UpG and this is believed to be caused by the additional binding site arising from the copper-assisted deprotonation of the uracil moiety at the 5 0 -terminus.…”

Kinematic molecular manufacturing machines

“…The high catalytic efficiency was therefore said to arise from the dynamic binding of the substrate and the "pre-transition state", which was made possible by "rapid, low energy conformational changes of the flexible calix [4]arene backbone". Later work indicated that an eclipsed arrangement of the metals was optimum [66]. As can be seen in Figure 8, the catalyst likely flexes through structures that, first, complement (and facilitate) di-Cu binding by the phosphate and, then, secondly, complement (and faciltate) the transition state for the hydrolysis reaction.…”

Reactivity Control by Calixarenes

“…In the aim at developing metal catalysts which are soluble enough in water to avoid the use of organic cosolvents, the [12]aneN 3 ligating unit seemed appropriate, because its high affi nity for zinc(II) in water (Log K = 8.4 at 25 ° C) ensures extensive binding of the metal ion to the ligand even at submillimolar concentrations. 32 Unfortunately, the zinc(II) complexes of ligands 28 -31 were not soluble enough in water for catalytic studies. Furthermore, catalytic studies carried out in 50% aqueous CH 3 CN (Table 8.3 ) revealed a disappointing lack of synergism between metal ions, which is at variance with the results obtained with the corresponding BAMP complexes.…”