Phosphodiester Cleavage Properties of Copper(II) Complexes of 1,4,7-Triazacyclononane Ligands Bearing Single Alkyl Guanidine Pendants

Three new metal-coordinating ligands, L-1 center dot 4HCl [1-(2-guanidinoethyl)-1,4,7-triazacyclononane tetrahydrochloride], L-2 center dot 4HCl [1-(3-guanidinopropyl)-1,4,7-triazacyclononane tetrahydrochloride], and L-3 center dot 4HCl [1-(4-guanidinobutyl)-1,4,7-triazacyclononane tetrahydrochloride], have been prepared via the selective N-functionalization of 1,4,7-triazacyclononane (tacn) with ethylguanidine, propylguanidine, and butylguanidine pendants, respectively. Reaction of L-1 center dot 4HCl with Cu(ClO4)(2)center dot 6H(2)O in basic aqueous solution led to the crystallization of a monohydroxo-bridged binuclear copper(II) complex, [Cu2L21(mu-OH)](ClO4)(3)center dot H2O (Cl), while for L2 and L3, mononuclear complexes of composition [Cu((LH)-H-2)Cl-2]Cl center dot(MeOH)(0.5)(H2O)(0.5) (C2) and [Cu((LH)-H-3)Cl-2]Cl center dot(DMF)(0.5)center dot(H2O)(0.5) (C3) were crystallized from methanol and DMF solutions, respectively. X-ray crystallography revealed that in addition to a tacn ring from L-1 ligand, each copper(II) center in C1 is coordinated to a neutral guanidine pendant. In contrast, the guanidinium pendants in C2 and C3 are protonated and extend away from the Cu(II)-tacn units. Complex C1 features a single mu-hydroxo bridge between the two copper(II) centers, which mediates strong antiferromagnetic coupling between the metal centers. Complexes C2 and C3 cleave two model phosphodiesters, bis(p-nitrophenyl)phosphate (BNPP) and 2-hydroxypropyl-p-nitrophenylphosphate (HPNPP), more rapidly than Cl, which displays similar reactivity to [Cu(tacn)-(OH2)(2)](2+). All three complexes cleave supercoiled plasmid DNA (pBR 322) at significantly faster rates than the corresponding bis(alkylguanidine) complexes and [Cu(tacn)(OH2)(2)](2+). The high DNA cleavage rate for Cl {k(obs) = 1.30 (+/-0.01) X 10(-4) s(-1) vs 1.23 (+/-0.37) X 10(-5) s(-1) for [Cu(tacn)(OH2)(2)](2+) and 1.58 (+/-0.05) X 10(-5) s(-1) for the corresponding bis(ethylguanidine) analogue) indicates that the coordinated guanidine group in Cl may be displaced to allow for substrate binding/activation. Comparison of the phosphate ester cleavage properties of complexes C1-C3 with those of related complexes suggests some degree of cooperativity between the Cu(II) centers and the guanidinium groups.