Unsymmetrical dizinc complexes as models for the active sites of phosphohydrolases

Abstract

The unsymmetrical dinucleating ligand 2-(N-isopropyl-N-((2-pyridyl)methyl)aminomethyl)-6-(N-(carboxylmethyl)-N-((2-pyridyl)methyl)aminomethyl)-4-methylphenol (IPCPMP or L) has been synthesized to model the active site environment of dinuclear metallohydrolases. It has been isolated as the hexafluorophosphate salt H(4)IPCPMP(PF(6))(2) x 2 H(2)O (H(4)L), which has been structurally characterized, and has been used to form two different Zn(II) complexes, [{Zn(2)(IPCPMP)(OAc)}(2)][PF(6)](2) (2) and [{Zn(2)(IPCPMP)(Piv)}(2)][PF(6)](2) (3) (OAc = acetate; Piv = pivalate). The crystal structures of and show that they consist of tetranuclear complexes with very similar structures. Infrared spectroscopy and mass spectrometry indicate that the tetranuclear complexes dissociate into dinuclear complexes in solution. Potentiometric studies of the Zn(II):IPCPMP system in aqueous solution reveal that a mononuclear complex is surprisingly stable at low pH, even at a 2:1 Zn(II):L ratio, but a dinuclear complex dominates at high pH and transforms into a dihydroxido complex by a cooperative deprotonation of two, probably terminally coordinated, water molecules. A kinetic investigation indicates that one of these hydroxides is the active nucleophile in the hydrolysis of bis(2,4-dinitrophenyl)phosphate (BDNPP) enhanced by complex 2, and mechanistic proposals are presented for this reaction as well as the previously reported transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) promoted by Zn(II) complexes of IPCPMP.

Spectroscopic and mechanistic studies of dinuclear metallohydrolases and their biomimetic complexes

“…31,90,112 Numerous research groups have reported Zn(II)Zn(II) hydrolase mimics. [14][15][16]18,20,22,90,92,101,[122][123][124][125][126][127] Bringing two Zn(II) ions in 132 The bidentate-bridging binding mode of the diphenyl phosphate was also proposed in solution using 31 P-NMR measurements because of the rather large shifts observed for the phosphate ester signal. 132 The separation of the two zinc centres in the biomimetics has been shown to be important.…”

Crystal structure and catalytic studies of heterodinuclear complex [CuZn(μ-OAc)(μ-OH)(μ-OH2)(bpy)2](ClO4)2

“…S2(a)), respectively of the bridging acetato groups [15]. Comparison of these symmetric (~1447 cm − 1 , ν 4 ) and antisymmetric (~1560 cm −1 , ν 2 ) frequencies of the bridging carboxylates for complex reveals significant difference suggesting their bridging between different metals [16]. A single strong band at 774 cm −1 is observed which is attributed to out-of-plane motion of the hydrogen atoms as expected for two identical groups of four hydrogen atoms each for bipyridine [15,17].…”

Spectroscopic and Mechanistic Studies of Dinuclear Metallohydrolases and Their Biomimetic Complexes

“…Nordlander et al proposed that asymmetric complexes are not only more appropriate functional models for the active site of phosphoesterase enzymes, but also that they exhibit enhanced catalytic rates compared with their symmetric counterparts. 15,19,20 …”

“…31,90,112 Numerous research groups have reported Zn(II)Zn(II) hydrolase mimics. [14][15][16]18,20,22,90,92,101,[122][123][124][125][126][127] Bringing two Zn(II) ions The separation of the two zinc centres in the biomimetics has been shown to be important. Meyer et al correlated the hydrolytic activity of dizinc phosphodiesterase models with their Zn⋯Zn distances.…”