Phosphodiester hydrolysis and specific DNA binding and cleavage promoted by guanidinium-functionalized zinc complexes

Two new Zn(II) complexes containing guanidinium groups, [Zn(L-1)Cl-2](ClO4)(2)center dot H2O center dot CH3OH (1) and [Zn(L-2)Cl-2](ClO4)(2)center dot 0.5H(2)O (2), were synthesized and characterized (L-1 = 5,5'-di[1-guanidyl)methyl]-2,2'-bipyridyl bication and L-2 = 6,6'-di[1-[guanidyl)methyl]-2,2'-bipyridyl bication). Both complexes are able to catalyze bis(p-nitrophenyl) phosphate (BNPP) hydrolysis efficiently. Obtained kinetic data reveal that both 1 and 2 show nearly 300- and 600-fold rate enhancement of BNPP hydrolysis, respectively, compared to their simple analogue without the guanidinium groups [Zn(bpy)Cl-2] (bpy = 2,2'-bipyridy) (3). Enhanced acceleration for cleavage of BNPP could be attributed to cooperative interaction between the Zn(II) ion and the guanidinium groups by electronstatic interaction and H-bonding. Studies on inhibition of sequence-specific endonucleases (Dral and Smal) by complexes show that 1 and 2 are able to recognize nucleotide sequence, -TTT boolean AND AAA-, and highly effectively cleave the plasmid DNA in the presence of hydrogen peroxide, while 3 has no specific binding to the DNA target sequences and only shows low DNA cleavage activity. (C) 2009 Elsevier Inc. All rights reserved.