Zn(II) Coordination to Polyamine Macrocycles Containing Dipyridine Units. New Insights into the Activity of Dinuclear Zn(II) Complexes in Phosphate Ester Hydrolysis

Abstract

Zn(II) binding by the dipyridine-containing macrocycles L1-L3 has been analyzed by means of potentiometric measurements in aqueous solutions. These ligands contain one (L1, L2) or two (L3) 2,2'-dipyridine units as an integral part of a polyamine macrocyclic framework having different dimensions and numbers of nitrogen donors. Depending on the number of donors, L1-L3 can form stable mono- and/or dinuclear Zn(II) complexes in a wide pH range. Facile deprotonation of Zn(II)-coordinated water molecules gives mono- and dihydroxo-complexes from neutral to alkaline pH values. The ability of these complexes as nucleophilic agents in hydrolytic processes has been tested by using bis(p-nitrophenyl) phosphate (BNPP) as a substrate. In the dinuclear complexes the two metals play a cooperative role in BNPP cleavage. In the case of the L2 dinuclear complex [Zn(2)L2(OH)(2)](2+), the two metals act cooperatively through a hydrolytic process involving a bridging interaction of the substrate with the two Zn(II) ions and a simultaneous nucleophilic attack of a Zn-OH function at phosphorus; in the case of the dizinc complex with the largest macrocycle L3, only the monohydroxo complex [Zn(2)L3(OH)](3+) promotes BNPP hydrolysis. BNPP interacts with a single metal, while the hydroxide anion may operate a nucleophilic attack. Both complexes display high rate enhancements in BNPP cleavage with respect to previously reported dizinc complexes, due to hydrophobic and pi-stacking interactions between the nitrophenyl groups of BNPP and the dipyridine units of the complexes.

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.…”

Zn(II) Coordination by Open-chain Polyamine Ligands Containing Dipyridine Units. Highly Active Dinuclear Zn(II) Complexes in Phosphate Ester Hydrolysis

“…Of note, the hydrolytic activity of the [Zn 2 L2(OH) 2 ] 2+ is only slightly lower than that reported for the dizinc complex with ligand 2 and among the highest observed with binuclear Zn(II) complexes [71]. For instance, the dizinc complexes with ligands not containing aromatic subunits, such as 3-5 in Scheme 1 [46][47][48], display a far lower ability in BNPP hydrolysis.…”

“…BNPP hydrolysis promoted by mono-and dinuclear Zn(II) complexes is generally explained in terms of an "associative" mechanism [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]71], in which the substrate approaches the Zn(II) complex and the oxygens of BNPP start associating with the electrophilic Zn(II) ion. A zincbound hydroxide operates a simultaneous nucleophilic attack to the phosphorus atom.…”

“…A sketch of the proposed hydrolytic mechanism is shown in Scheme 2 (a). a From reference [71]. b from reference [46].…”

“…We have recently reported on mono-and dinuclear Zn(II) complexes with macrocyclic polyamine ligands containing 2,2'-dipyridine, such as 1 and 2 in Scheme 1, able to hydrolyze the phosphate ester bond of activated substrates, such as bis(p-nitrophenyl)phosphate (BNPP) [71]. This study pointed out that the hydrolytic mechanism occurs through interaction of the anionic phosphate moiety with the Zn(II) centers and simultaneous attack of a nucleophilic Zn-OH function to phosphorous.…”