Guanidine is a Zn(2+)-binding ligand at neutral pH in aqueous solution.
We have found the first well-characterized coordination of guanidine with Zn(2+) in a 1:1 complex (ZnL(1)) with cyclen (= 1,4,7,10-tetraazacyclododecane) functionalized with guanidinylethyl group (L(1) = (2-guanidinyl)ethyl-cyclen). The X-ray structure analysis of the 1:1 complex crystallized at pH 7.5 revealed an apical coordination of the pendant guanidinyl group to Zn(2+) ion in ZnL(1). By potentiometrtic pH titration, initial formation of a 1:1 Zn(L(1).H(+)) complex was indicated, where only the cyclen N's bind to Zn(2+) with the complexation constant, log K(s) (K(s) = [Zn(L(1).H(+))]/[Zn(2+)][L(1).H(+)] (M(-1))), being 12.4 +/- 0.1. Facile deprotonation of the guanidinium pendant in the Zn(L(1).H(+)) occurred with a pK(a) value of 5.9 +/- 0.1 at 25 degrees C with I = 0.1 (NaNO(3)) to yield the guanidine-coordinating complex ZnL(1). 4-Nitrophenyl phosphate dianion (NPP(2-)) interacted with ZnL(1) through a new Zn(2+)-phosphate coordination, as indicated by (31)P NMR titration and potentiometric pH titration. An apparent complexation constant for this new species, log K(app)(Zn(L(1).H(+))-NPP), was 4.0 +/- 0.1, which is larger than the log K(app)(ZnL(2)-NPP) value of 3.1 for the 1:1 complex of Zn(2+)-cyclen (ZnL(2)) with NPP at the common pH 5.6. The interaction of ZnL(1) with a phosphate dianion was proven by the X-ray crystal structure analysis of the 1:1 ZnL(1)-PP(2-) complex (PP(2-) is a dianion of phenyl phosphate) obtained from an aqueous solution at pH 6.5. At higher pH, the pendant guanidinium cation is deprotonated to displace the phosphate to yield the Zn(2+)-guanidine bond.
Aoki
Shin
S
Department of Medicinal Chemistry, Faculty of Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8551, Japan.
Iwaida
Kenta
K
Hanamoto
Noriko
N
Shiro
Motoo
M
Kimura
Eiichi
E
D002413:Cations, Divalent; D018360:Crystallography, X-Ray; D019791:Guanidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008024:Ligands; D015394:Molecular Structure; D012996:Solutions; D014867:Water / Q000737:chemistry; D015032:Zinc / Q000737:chemistry*
D002413:Cations, Divalent; D008024:Ligands; D012996:Solutions; D014867:Water; D015032:Zinc; D019791:Guanidine