Molecular Design of Multinuckear Metal -Ion-Centers for the Efficient Non-enzymatic Hydrolyses of Nucleic Acidsand Peptides by Acid-Base Co-catalysis

研究了在中性水溶液中高效水解RNA的两种催化剂的详细溶液结构；（Zn (II)）_2-L1 (1) （L1=N， N, N^1， N-四（2-吡啶基甲基）- 1,3 -二氨基-2-丙醇）和（Zn (II)）_2-L2 (2) (L2=N， N, N^1， N-四（2-吡啶基甲基）- 1,3 -二（氨基）苯。L1和L2的不同之处在于连接两个双（2-吡啶基甲基）胺单元的连接体部分的结构。两种配合物对RNA的水解速率常数表现出截然不同的pH谱，这可归因于它们的溶液结构非常不同。由于只有配合物2才具有酸碱共催化作用，因此设计了与配合物2结构相似但两个锌（II）处于不等效环境中的新型双核锌（II）配合物。（Zn (II)）_2-L3 （L3=N-（2-氨基乙基）-N, N^1， N-三（2-吡啶基甲基）- 1,3 -双（氨基甲基）苯）和（Zn (II)）_2-L4 （L4=N-（2-羟基乙基）-N, N^1， N-三（2-吡啶基甲基）- 1,3 -双（氨基甲基）苯）。研究发现，在这些分子设计的基础上，可以调节配位水分子的酸度，从而调节锌（II）配合物作为rna酶的催化性能。另一方面，在温和的条件下，由于丝氨酸残基中的内部羟基与金属离子（锌（II）、镉（II）、铜（II）或它们的配合物）的协同作用，肽水解被发现非常有效地促进。研究了溶剂和金属离子种类对反应的影响。通过选择合适的溶剂，可以实现肽的高度序列特异性水解。

Detailed solution structures of two catalysis, which we have find to hydrolyze RNA very efficiently under neutral aqueous solution, were examined ; (Zn (II))_2-L1 (1) (L1=N, N, N^1, N-tetrakis (2-pyridylmethyl) -1, 3-diamino-2-propanol and (Zn (II))_2-L2 (2) (L2=N, N, N^1, N-tetrakis (2-pyridylmenthyl) -1, 3-bis (aminomethl) benzene. L1 and L2 differ only in the structure of the linker moiety, which connects two bis (2-pyridylmethyl) amine units. The rate constants for the RNA hydrolysis by two complexes showed quite different pH profiles from rach other, which can be attributed to their very different solution structures. Because acid-base co-catalysis is strongly suggested only for the complex 2, new dinuclear zinc (II) complexes, having similar structures to the complex 2 but the two zinc (II) is in the unequivalent environment, were disigned. (Zn (II))_2-L3 (L3=N- (2-aminoethyl)-N, N^1, N-tris (2-pyridylmethlyl) -1, 3-bis (aminomethyl) benzene) and (Zn (II))_2-L4 (L4=N- (2-hydroxylethyl) -N, N^1, N-tris (2-pyridylmethyl)-1, 3-bis (aminomethyl) benzene). It was found that, on the basis of these molecular design, acidity of coordinated water molecules could be regukated, and, therefore, the catalytic properties of zinc (II) complexes as RNases could also be regulated. On the other hand, peptide hydrolyses under mild conditions were found to be promoted very efficiently, by the cooperationof an internal hydroxy group in the serine residue and a metal ion (zinc (II), cadmium (II), copper (II) or their complexes). The effect of the solvent and the kind of the metal ion on the reaction were studied. Highly sequence-specific hydrolysis of peptide was found to be achieved by choosing an appropriate solvent.