TY - JOUR
T1 - The role of Zn-OR and Zn-OH nucleophiles and the influence of para-substituents in the reactions of binuclear phosphatase mimetics
AU - Daumann, Lena J.
AU - Dalle, Kristian E.
AU - Schenk, Gerhard
AU - McGeary, Ross P.
AU - Bernhardt, Paul V.
AU - Ollis, David L.
AU - Gahan, Lawrence R.
PY - 2012/2/14
Y1 - 2012/2/14
N2 - Analogues of the ligand 2,2′-(2-hydroxy-5-methyl-1,3-phenylene) bis(methylene)bis((pyridin-2-ylmethyl)azanediyl)diethanol (CH 3H 3L1) are described. Complexation of these analogues, 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (CH 3HL2), 4-bromo-2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino) methyl)phenol (BrHL2), 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino) methyl)-4-nitrophenol (NO 2HL2) and 4-methyl-2,6-bis(((2-phenoxyethyl) (pyridin-2-ylmethyl)amino)methyl)phenol (CH 3HL3) with zinc(ii) acetate afforded [Zn 2(CH 3L2)(CH 3COO) 2](PF 6), [Zn 2(NO 2L2)(CH 3COO) 2](PF 6), [Zn 2(BrL2)(CH 3COO) 2](PF 6) and [Zn 2(CH 3L3)(CH 3COO) 2](PF 6), in addition to [Zn 4(CH 3L2) 2(NO 2C 6H 5OPO 3) 2(H 2O) 2](PF 6) 2 and [Zn 4(BrL2) 2(PO 3F) 2(H 2O) 2](PF 6) 2. The complexes were characterized using 1H and 13C NMR spectroscopy, mass spectrometry, microanalysis, and X-ray crystallography. The complexes contain either a coordinated methyl- (L2 ligands) or phenyl- (L3 ligand) ether, replacing the potentially nucleophilic coordinated alcohol in the previously reported complex [Zn 2(CH 3HL1)(CH 3COO)(H 2O)](PF 6). Functional studies of the zinc complexes with the substrate bis(2,4-dinitrophenyl) phosphate (BDNPP) showed them to be competent catalysts with, for example, [Zn 2(CH 3L2)] +, k cat = 5.70 ± 0.04 × 10 -3 s -1 (K m = 20.8 ± 5.0 mM) and [Zn 2(CH 3L3)] +, k cat = 3.60 ± 0.04 × 10 -3 s -1 (K m = 18.9 ± 3.5 mM). Catalytically relevant pK as of 6.7 and 7.7 were observed for the zinc(ii) complexes of CH 3L2 - and CH 3L3 -, respectively. Electron donating para-substituents enhance the rate of hydrolysis of BDNPP such that k catp-CH 3 > p-Br > p-NO 2. Use of a solvent mixture containing H 2O 18/H 2O 16 in the reaction with BDNPP showed that for [Zn 2(CH 3L2)(CH 3COO) 2](PF 6) and [Zn 2(NO 2L2)(CH 3COO) 2](PF 6), as well as [Zn 2(CH 3HL1)(CH 3COO)(H 2O)](PF 6), the 18O label was incorporated in the product of the hydrolysis suggesting that the nucleophile involved in the hydrolysis reaction was a Zn-OH moiety. The results are discussed with respect to the potential nucleophilic species (coordinated deprotonated alcohol versus coordinated hydroxide).
AB - Analogues of the ligand 2,2′-(2-hydroxy-5-methyl-1,3-phenylene) bis(methylene)bis((pyridin-2-ylmethyl)azanediyl)diethanol (CH 3H 3L1) are described. Complexation of these analogues, 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (CH 3HL2), 4-bromo-2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino) methyl)phenol (BrHL2), 2,6-bis(((2-methoxyethyl)(pyridin-2-ylmethyl)amino) methyl)-4-nitrophenol (NO 2HL2) and 4-methyl-2,6-bis(((2-phenoxyethyl) (pyridin-2-ylmethyl)amino)methyl)phenol (CH 3HL3) with zinc(ii) acetate afforded [Zn 2(CH 3L2)(CH 3COO) 2](PF 6), [Zn 2(NO 2L2)(CH 3COO) 2](PF 6), [Zn 2(BrL2)(CH 3COO) 2](PF 6) and [Zn 2(CH 3L3)(CH 3COO) 2](PF 6), in addition to [Zn 4(CH 3L2) 2(NO 2C 6H 5OPO 3) 2(H 2O) 2](PF 6) 2 and [Zn 4(BrL2) 2(PO 3F) 2(H 2O) 2](PF 6) 2. The complexes were characterized using 1H and 13C NMR spectroscopy, mass spectrometry, microanalysis, and X-ray crystallography. The complexes contain either a coordinated methyl- (L2 ligands) or phenyl- (L3 ligand) ether, replacing the potentially nucleophilic coordinated alcohol in the previously reported complex [Zn 2(CH 3HL1)(CH 3COO)(H 2O)](PF 6). Functional studies of the zinc complexes with the substrate bis(2,4-dinitrophenyl) phosphate (BDNPP) showed them to be competent catalysts with, for example, [Zn 2(CH 3L2)] +, k cat = 5.70 ± 0.04 × 10 -3 s -1 (K m = 20.8 ± 5.0 mM) and [Zn 2(CH 3L3)] +, k cat = 3.60 ± 0.04 × 10 -3 s -1 (K m = 18.9 ± 3.5 mM). Catalytically relevant pK as of 6.7 and 7.7 were observed for the zinc(ii) complexes of CH 3L2 - and CH 3L3 -, respectively. Electron donating para-substituents enhance the rate of hydrolysis of BDNPP such that k catp-CH 3 > p-Br > p-NO 2. Use of a solvent mixture containing H 2O 18/H 2O 16 in the reaction with BDNPP showed that for [Zn 2(CH 3L2)(CH 3COO) 2](PF 6) and [Zn 2(NO 2L2)(CH 3COO) 2](PF 6), as well as [Zn 2(CH 3HL1)(CH 3COO)(H 2O)](PF 6), the 18O label was incorporated in the product of the hydrolysis suggesting that the nucleophile involved in the hydrolysis reaction was a Zn-OH moiety. The results are discussed with respect to the potential nucleophilic species (coordinated deprotonated alcohol versus coordinated hydroxide).
UR - http://www.scopus.com/inward/record.url?scp=84856738150&partnerID=8YFLogxK
U2 - 10.1039/c1dt11187f
DO - 10.1039/c1dt11187f
M3 - Article
SN - 1477-9226
VL - 41
SP - 1695
EP - 1708
JO - Dalton Transactions
JF - Dalton Transactions
IS - 6
ER -