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)·4HCl [1-(2-guanidinoethyl)-1,4,7-triazacyclononane tetrahydrochloride], L(2)·4HCl [1-(3-guanidinopropyl)-1,4,7-triazacyclononane tetrahydrochloride], and L(3)·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)·4HCl with Cu(ClO(4))(2)·6H(2)O in basic aqueous solution led to the crystallization of a monohydroxo-bridged binuclear copper(II) complex, [Cu(2)L(1)(2)(μ-OH)](ClO(4))(3)·H(2)O (C1), while for L(2) and L(3), mononuclear complexes of composition [Cu(L(2)H)Cl(2)]Cl·(MeOH)(0.5)·(H(2)O)(0.5) (C2) and [Cu(L(3)H)Cl(2)]Cl·(DMF)(0.5)·(H(2)O)(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 μ-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 C1, which displays similar reactivity to [Cu(tacn)(OH(2))(2)](2+). All three complexes cleave supercoiled plasmid DNA (pBR 322) at significantly faster rates than the corresponding bis(alkylguanidine) complexes and [Cu(tacn)(OH(2))(2)](2+). The high DNA cleavage rate for C1 {k(obs) = 1.30 (±0.01) × 10(-4) s(-1) vs 1.23 (±0.37) × 10(-5) s(-1) for [Cu(tacn)(OH(2))(2)](2+) and 1.58 (±0.05) × 10(-5) s(-1) for the corresponding bis(ethylguanidine) analogue} indicates that the coordinated guanidine group in C1 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.
School of Chemistry, Monash University, Vic 3800, Australia.
Linda
L
Tjioe
Tanmaya
T
Joshi
Craig M
CM
Forsyth
Boujemaa
B
Moubaraki
Keith S
KS
Murray
Joël
J
Brugger
Bim
B
Graham
Leone
L
Spiccia
D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D053837:DNA Cleavage; D019791:Guanidine / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006860:Hydrogen Bonding; D008024:Ligands; D060328:Magnetic Phenomena; D015394:Molecular Structure; D009596:Nitrophenols / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D010755:Organophosphates / Q000737:chemistry*
D006571:Heterocyclic Compounds; D008024:Ligands; D009596:Nitrophenols; D009942:Organometallic Compounds; D010755:Organophosphates; C075712:1,4,7-triazacyclononane; C002887:bis(4-nitrophenyl)phosphate; D003300:Copper; D019791:Guanidine