Syntheses and structures of and catalysis of hydrolysis by Zn(II) complexes of chelating pyridyl...

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Journal of Inorganic Biochemistry 75 ( 1999) 7-18

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Biochemistry

Syntheses and structures of and catalysis of hydrolysis by Zn(I1) complexes of chelating pyridyl donor ligands

Yilma Gultneh *, A. Raza Khan, Die Blake, Sohail Chaudhry, Bijan Ahvazi, Bake B. Marvey, Ray J. Butcher

Department of Chemistry, Howard University, Washington, DC 20059, USA

Received 24 November 1998; received in revised form 8 February 1999; accepted 25 February 1999

Abstract

Zn( 11) complexes of the ligands bis( 2-pyridyl-2-ethyl)amine (bpea), bis( 2-pyridylmethyl)amine (bpa), 2,2’-dipyridylamine (dipyam) and W’-dipyWl (dipy) [Zn2@peaM~-OH)1 (ClOd, (11, FWbpa) VWM (C10d2 (2), [.Wdipyam)J (BF& (3), [ Zn( dipyam) *( DMF) J (Clod) 2 .( 4) and [ Zn( dipy ) 2( H,O) ] ( BFJ 2 ( 5) have been prepared and characterized. The structures of complexes 1 to 4 have been determined by X-ray crystallography. In complexes 1 and 3, Zn( 11) coordinates in slightly distorted tetrahedral geometry and in complexes 2 and 4 in a distorted octahedral geometry. The number and the pK, values of the zinc-coordinated water molecules in solutions in water/DMF mixed solvent were determined by potentiometric titrations against aqueous NaOH solution. The pK, values are 8.35, 9.85, 8.00 and 9.01 for complexes 1,2,3, and 5 respectively. The pK, value for the hydroxo-bridged dimeric complex 1 is about 0.8 pH units greater than the pK, value (7.55) for the analogous complex [Zn,( F-OH) (m-xylbpea)] (ClO,), of the ligand bis(bis(2-pyridyl-2- ethyl) amino)m-xylene (m-xylbpea) in which the two chelating bis( 2-pyridyl-2-ethyl) amine arms are tethered by a m-xylyl group. The lower pK, value in the latter complex is attributed to the entropic advantage gained as the two Zn(l1) ions are held together by the dinucleating ligand. However, in the hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) catalyzed by Zn( 11) complexes, the observed rate constant above pH 8 for complex 1 is significantly higher than that shown by the analogous complex formed by the dinucleating ligand. This difference for the latter complex may be due to the formation of a catalytically less active, possibly a double hydroxy-bridged moiety at lower pH values. The rate constants are observed to increase and pass through a maximum at or around the pK, values of all the zinc complexes reported here. This is consistent with the widely accepted mechanism in many hydrolytic reactions catalyzed by metal complexes in which the metal- coordinated hydroxide is the reactive nucleophile. Second-order rate constants of the order of IO-3-1O-” M-’ s-’ were calculated for the hydrolysis of BNPP at the optimum pH values for the complexes studied here. 0 1999 Elsevier Science Inc. All rights reserved.

Keywords: Zinc(H) complexes; Bis-2-picolylamine; Bis( 2-ethyl-2-pyridyl)amine; Hydrolysis; Phosphodiesters

1. Introduction

Zinc(I1) is found at the active sites of over 200 types of enzymes, most of which catalyze the hydrolysis of esters, including carboxylic and phosphate esters (hydrolases and phosphatases) [ l-51, amides (carboxypeptidases and ami- nopeptidases [ 6,7] ), and the hydration of CO2 (carbonic anhydrase) [S-lo]. One important function of the zinc center in these enzymes appears to be the generation of Zn-coordinated nucleophiles such as OH-, H-, RO- and COO- in addition to coordinating the substrate and rendering it more susceptible to nucleophilic attack [ 1 l-131. While Zn( II) plays a unique role at the active sites of hydrolytic enzymes

* Corresponding author. Fax: + l-202-806-5442; e-mail: ygultneh@ howard.edu

that cannot be reproduced by other transition metal ions with similar or stronger acidity, the reason for it is not well under- stood although both its Lewis acidity as well as its coordination flexibility due to its d” configuration have been invoked.

From crystal structures, the active site coordination envi- ronments of the metal ion are well known for severalenzymes [ 14-161. However, the dynamic structures during the catalytic processes and hence the detailed mechanism are not as easy to determine. Catalyses of the hydrolysis of amides, and carboxylate and phosphate esters by both mono- and multinuclear Zn( II) synthetic complexes [ 17-2 I ] and zinc-containing metalloenzymes [ 22-271 are known. Cooperativity of metal ions at multinuclear active sites is utilized to enhance the catalytic properties of these enzymes [26,27]. In the solid-state structures of the zinc enzymes, alkaline phospha-

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8 Y. Gultneh et al. /Journal of Inorganic Biochemistry 75 (1999) 7-18

tase, carboxypeptidase, carbonic anhydrase, and alcohol dehydrogenase, Zn is four-coordinate with water or hydroxide ion occupying the fourth site [ 28,291.

The low pK, value of coordinated water in enzymes (about I in carbonic anhydrase, and 6 in carboxypeptidase) affords production of the nucleophilic metal-bound hydroxide species at low physiological pH. The acidity of Zn-coordinated water in Zn( II) complexes has been studied as a function of both the ligand type and coordination mode [ 30,3 11. For complexes of open chain and macrocyclic polyamine ligands, pK, values for Zn( II)-coordinated H,O ranging from about 7 to 11 have been reported [32-341, showing the wide variation that is possible as a function of the ligand. Zn(I1) complexes of macrocyclic polyamine ligands with three and four nitrogen donors have been used widely. Four nitrogen donor ligands produce five-coordinate Zn( II) complexes (with water at the fifth site), rather than the four-coordination observed at the enzyme active site and therefore these do not provide good models [ 351. Macrocyclic and open chain chelating [36] ligands containing nitrogen donors mimic the histidyl imidazole donor coordination environment of Zn( II) in enzymes and are therefore especially relevant in modeling these active sites.

We have previously reported a dinuclear Zn( II) complex of a dinucleating ligand m-xylbpea which has two bis( 2-( 2- pyridyl) ethyl) amine (bpea) tridentate arms connected by a m-xylyl group [ 371. Each arm uses its three nitrogen donors in coordinating to two Zn( II) ions. The fourth coordination site is taken by a common hydroxide ion bridging the two zinc ions. In water/DMF (3/5, vol./vol.) solution, a low pK, value of 7.55 for the deprotonation of Zn( II) -coordinated H,O was determined. In dry acetonitrile solution, saturated with and under an atmosphere of CO,, a precipitate formed, which, in its IR spectrum, showed peaks indicating formation of the HCO; complex. The precipitate then re-dissolved and the IR peaks disappeared when the CO2 atmosphere was removed showing that the hydration of CO2 was reversible:

[LZnz(p-OH)13+ (H,O/DMF) +CO,(g)

P WhWCW13+(ppt) L = m-xylbpea

bps bpea

In a continuation of our work with Zn(I1) complexes of these chelating pyridyl donor ligands, we have studied the variation in pK, and catalytic properties with changing nuclearity and chelate ring size of Zn(I1) complexes. We herein report the syntheses, structures, solution acid-base equilibria, and catalytic properties for the hydrolysis of bis(p- nitrophenyl)phosphate over the pH range from 7.5 to 9.5 for the Zn(I1) complexes of the ligands bis( 2-pyridyl-2- ethyl) amine (bpea) , bis( 2-pyridylmethyl) amine (bpa), 2,2’-dipyridylamine (dipyam), and 2,2’-dipyridyl (dipy)

2. Experimental

2.1. Materials

Methanol, Zn( Clod) 2 * 6H,O, 2-picolylamine, 2-picolyl- chloride*HCl, 2,2’-dipyridyl and 2,2’-dipyridylamine, tris (hydroxymethyl) aminomethane (THAM) , bis (p-nitrophenyl)phosphate sodium salt (BNPP), KOH, and NaOH were reagent grade and used as received from Aldrich, The buffer solutions used in the catalysis experiments were 0.10 M aqueous solutions of THAM adjusted to the desired pH by addition of the proper amounts of aqueous solutions of NaOH and also made 0.02 M in NaClO, to maintain constant ionic strength. Reagent grade DMF (Aldrich) was purified by stirring over KOH pellets for a day to remove decomposition products, followed by filtering, refluxing and distilling from CaO at reduced pressure N2 atmosphere. Vinyl pyridine was distilled before use. Acetonitrile was dried by refluxing and distilling from CaH, under nitrogen gas. The ligands bpa [ 381 and bpea [39,40] were made as described in the literature.

‘H NMR spectra were run in deuterated solvents with internal TMS standard on a GE-300 300 MHz spectrometer. IR spectra were run on a Perkin-Elmer FT-IR spectrometer. UV- Vis spectra were taken in 1 cm quartz cuvettes on a Hewlett- Packard model 8452A diode array spectrometer interfaced with a 486/33 S computer programmed to take spectra at intervals of time. Potentiometric titrations of solutions of the metal complexes in water/DMF solutions were done using a Fisher combination electrode and a Fisher model 50 pH meter. Elemental analyses of the complexes were done by MHW Labs, Phoenix, AZ.

2.2. Synthesis of fZn,fbpea),(~-OH)](ClO,}, (1)

To 4.60 g ( 12.35 mmol) of Zn( ClO,), .6H,O in methanol (30 ml) was added 2.60 g ( 11.45 mmol) of the ligand bpea in methanol ( 15 ml). The mixture was left under slow reflux for 24 h. A colorless precipitate formed which was filtered, washed with ether and dried in air yielding 1.94 g (35%) of a colorless powdery solid. Acetonitrile solution of this solid was layered with ether and, on standing for a day, formed colorless crystals which were used for crystallographic structure determination, The ‘H NMR spectrum of the complex is

Y. Gultneh et al. /Journal of Inorganic Biochemistry 75 (1999) 7-18 9

the same as that of the ligand: 6 ppm (CDCl,) : 8.57 (d, 4H) ; 8.0 (m, 4H); 7.50 (m, 8H); 4.8 (s, b, 1H); 3.39 (m, b, 2H); 2.96 (m, b, 6H); 2.50 (s, b, 1H). IR (Nujol): v (cm-‘): 3450 (OH), 1610 (py), 1088 (ClO, ) . Elemental analysis: Calc. for C,,H,3N6Zn,Cl,0,,: C, 37.4; H, 3.67; N, 9.30. Found: C, 37.8; H, 4.01; N, 8.90%.

2.3. Synthesis of [Zn(bpa)(H20)J(C10,), (2)

To a methanol solution (40 ml) of 1.20 g (6.03 mmol) of the ligand bpa was added while stirring a methanol solution (40 ml) of 2.20 g (5.91 mmol) Zn( C1O4)2 .6H20, which was then stirred under low reflux overnight. Ether was added dropwise to precipitate a colorless powdery solid which was washed with ether and dried in air, yielding 1.50 g (45%) of the complex. Crystals for structural determination were obtained from methanol solution layered with ether. ‘H NMR spectrum (CDCl,): S (ppm): 2.38 (s, 1H); 4.2 (s, b, 4H), 3.92 (s, 4H); 7.2-7.7 (m, 6H); 8.6 (d, 2H). IR (neat) spectrum: v (cm-‘): 3304 (broad, H20, NH); 1608 (py), 1080 (ClO,). Elemental analysis: Calc. for C,,H,4N,C1,0,,Zn: C, 28.94; H, 3.02; N, 8.44, Zn, 13.17. Found: C, 29.4; H, 3.35; N, 8.10; Zn, 12.88%.

2.4. Synthesis of [Zn(2,2’-dipyridylamine),](BF,)2 (3)

To a methanol solution ( 10 ml) of 1.35 g (3.65 mmol) of Zn( BF,) 2. 6H20 was added a methanol solution ( 10 ml) of 1.25 g (8.0 mmol) of 2,2’-dipyridylamine, and the mixture was stirred and refluxed overnight. The white precipitate, formed on adding ether to the cooled solution, was filtered, washed with ether and dried in air to yield 1.78 g (84.5%) of the complex. It was redissolved and layered with ether, which on standing yielded colorless crystals suitable for X- ray diffraction crystallography. IR (Nujol) spectrum: 3300 cm-’ (broad, N-H str.), 1641 cm-’ (H,O), 1586 (py) and 1082 cm-’ (ClO,). ‘H NMR (DMSO-de): 6 (ppm): 3.52 (s, 2H), 7.09 (s,4H), 7.51 (s,4H), 7.88 (s,4H), 8.25 (s, 4H). Elemental analysis: Calc. for C,,H,,N,Cl,OaZn: C, 39.6; H, 2.8; N, 13.87; Zn, 11.6. Found: C, 40.3; H, 2.95; N, 14.66; Zn, 11.3%.

2.5. Synthesis of [Zn(2,2’-dipyridylamine)z(DMF)J(C10& (4)

To a methanol solution ( 10 ml) of 1.35 g (3.65 mmol) of Zn( C104)2. 6H,O was added a methanol solution ( 10 ml) of 1.25 g (8.0 mmol) of 2,2’-dipyridylamine, and the mixture stirred and refluxed overnight. On adding ether, after cooling, a colorless precipitate formed which was filtered, washed and dried in air (yield: 1.78 g, 84.5%). The powder was redissolved in DMF/methanol mixture and recrystallized by layering with ether. Colorless crystals were obtained on standing over several days. IR spectrum (Nujol) : 1760 cm-’ (C=O, DMF), 1602 cm-’ (pyr.), 1088 cm-’ (ClO,). Elemental

analysis: Calc. for C2,H32Ns0,,Cl,Zn: C, 41.45; H, 4.25; N, 14.88. Found: C, 41.77; H, 4.36; N, 14.60%.

2.6. Synthesis of [Zn(2,2’-dipyridyl)2(H,0)](BF,), (5)

To 1 .O g (6.4 mmol) of 2,2’-dipyridyl in methanol (25 ml) was added 1.11 g (3.2 mmol) Zn( BF4)* * 6H,O in methanol (25 ml). The mixture was stirred and refluxed for a day. The solution was concentrated to 20 ml and ether added to precipitate a faintly pink solid (yield: 1.68 g, 92%). Crystal- lographic quality crystals were obtained by dissolving the powder in methanol and layering with ether, which on standing over 2 days yielded faintly pink crystals [ 411. ‘H NMR (acetone-d,) : 6 (ppm) : 4.0 (s, H,O) , 7.85 (m, 4H), 8.43 (d, 4H), 8.7-8.9 (m, 8H); IR (Nujol), v (cm-‘): 3614 (OH), 1610 ( py) ,996 (BF,- ) . Elemental analysis: Calc. for C,,H,,N,OB,F,: C, 42.14; H, 2.98; N, 9.83; Zn, 11.47. Found: C, 44.76; H, 3.22; N, 9.43; Zn, 11.30%.

2.7. Potentiometric titrations

Typically, 0.25 mmol of the complex was dissolved in 25 ml of a water/DMF (3/5, vol./vol.) mixture and titrated against 0.10 M standard solution of NaOH in distilled and CO,-free water. Readings of pH of the solution were recorded every 0.10 to 0.20 ml of the NaOH solution added, and plotted using the Sigma Plot program on a computer. The end point was determined, and the number of coordinated water molecules (i.e. mmoles base per mmole of the complex at the end point) and the pK, values for the metal-coordinated water molecules were determined from the titration curves.

2.8. Rates of hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) in water/DMF solutions: catalytic studies as a function of pH

In a 1 cm quartz cuvet, positioned in a thermostat-con- trolled (75°C) sample compartment of the spectrophoto- meter, was added 3.00 ml of buffer solution. The cuvet had a ground glass top with a stopper. With the cuvet stoppered to avoid evaporation of the solvent, the temperature in the cuvet was allowed to equilibrate (about 30 min) followed by addition of 0.15 ml of 50 mM solution of the substrate (BNPP) and 0.15 ml of 8.85 mM solution of the complex in water/DMF (l/l) mixture. The cuvet was stoppered and absorption measurements at 400 nm were taken and stored every 5 min over a 3 h period using Hewlett-Packard general scan and kinetics computer programs. The absorbance values were converted into the concentration of the absorbing p- nitrophenolate ion and the total analyticalp-nitrophenol product calculated using the buffer pH and the K, ofp-nitrophenol (2.47x lo-‘).

2.9. Crystallographic structure determination

A suitable crystal of each complex was mounted in a ran- dom orientation on the end of a glass fiber using 5 min epoxy


cement and transferred to a goniometer head. Preliminary crystal parameters and reflection data were obtained at room temperature and processed by standard methods [ 42,431 (see Table 1) on a Siemens P4S four-circle X-ray diffractometer using a graphite monochromator on the incident beam and Siemens 486-based PC [ 441. Details of the crystal data col- lection and refinement are given in Table 1. The space groups were unambiguously obtained from a statistical examination of the intensities of the collected data set. Corrections for decay, absorption and extinction were applied as noted in Table 1. Data were collected to the limits of availability. All structures were solved by direct methods [45] as imple- mented in the SHELXTLPC system of computer programs. The structures were refined to convergence by full-matrix least-squares methods. All hydrogen atoms were found and their positional parameters refined. Atomic scattering factors used were those from the International Table for X-ray Crys- tallography [ 461.

3. Results and discussion

Nitrogen donor groups, such as pyridine [ 471 and pyrazole [ 481, have pK, values that are close to those found for the histidyl moieties in several enzymes; hence, the common use of these donors in chelating ligands is that they are useful in modeling active sites of zinc enzymes. Tridentate pyridine donor ligands such as bpa and bpea afford the possibility of stable four-coordinate Zn(I1) complexes with Hz0 as the

Table 1 Crystallographic data a for complexes l-4

fourth ligand. The ligands bpa and bpea also provide the possibility of observing chelate ring size effects in complexes of a homologous set of ligands. We have already observed that the dinucleating ligand, m-xylbpea, formed the dinuclear OH--bridged Zn( II). This complex showed a pK, value of 7.55 for the Zn-coordinate H,O, one of the lowest pK, values reported for a synthetic Zn( II) complex [ 371. It also reacted reversibly with CO*, binding it as the HC03- complex. These properties may, at least in part, have to do with the dinucleating property of the ligand which keeps the Zn( II) centers in close proximity and enhances the concerted reaction of the two zinc ions. To test whether the observed low pK, and the reaction with CO1 were attributable to the dinucleating nature of the ligand, we investigated the complex of the mono- nucleating ligand bpea. We also investigated whether there are differences in efficiencies among the Zn( II) complexes of these ligands in catalyzing the hydrolysis of phosphate esters using bis(p-nitrophenyl)phosphate as substrate. The coordinatively saturated complexes ZnLl (L = bpa, bpea) show negligible capacity to catalyze hydrolysis of BNPP. Therefore, the formations of such complexes were success- fully avoided by using 1: 1 (in the case of bpea and bpa) and 1:2 in (dipyridylamine and dipyridyl) ligand-to-metal ratios in the reaction of the syntheses of the complexes.

3.1. Crystallographic structures of the complexes

Table 2 shows a summary of crystallographic data and structure parameters of complexes 1 to 4: [Zn,(bpea),( p,-

Complex 1 2 3 4

Chemical formula W-W13N60,Jn2 C12H&LN301 Jn (GJMWJWn G,H,zCl,NsO,Jn Formula weight 900.71 517.57 581.4 752.87 Crystal system monoclinic triclinic monoclinic monoclinic Space group CL/c . Pi cwc Cl/C

a (A) 22.922( 8) b 6)

8.014(3) 9.285 ( 1) 24.231(5)

c (‘h l&253(6) 8.754( 2) 12.927(2) 11.188(2) 9.744( 3) 15.643(4) 19.625(2) 15.857(3)

a (7 90 86.61( 1) 90 90 P 0 114.79(3) 79.08( 1) 103.39( 1) 128.12(3) YQ 90 67.82( 1) 90 90 V (A? 3701(2) 997.7(5) 2291.6(5) 3403.3 Z 4 2 4 4 the (g cm-7 1.616 1.723 1.685 1.469 P (mm-‘) 1.582 1.560 1.160 0.942 0 range data colt. (“) 2.23-32.50 2.5 l-30.00 4.0-65.0 2.1 I-23.54

(28range) Final R indices [I> 2o( I) ] Rl = 0.0564 Rl = 0.0407 R1=0.0646 R1=0.0541

wR2=0.1373 wR2=0.1049 wR2 = 0.0865 wR2 = 0.1470 R indices (all data) R1=0.1372 Rl = 0.0542 RI =O.OO R1=0.0791

wR2 = 0.1840 wR2=0.1364 wR2 = 0.00 wR2 = 0.1756

’ Definitions: R(int)=CIF,2-F,2(mean)Il~[F,2]; R(sigma)=C[a(F,)‘]I~[F,*]; Rl=El IF,1 -F,II/CIF,I; wR2= [C]W(F,,~-F~*)~]/ crw(F,z)~ll”*; Goodness-of-fit=S= [~[w(F,,-F~~)~]/(~-~)]“*, where n is the number of reflections and p is the total number of parameters refined. SHELX-94 was used for structure refinement. This program bases the refinement procedure on F2 rather than the more traditional F and uses all data. Use of the suggested weighing scheme results in values for the goodness-of-fit parameter S which are close to 1 .OO rather than low values for Rw. Consequently, Rw values tend to be much higher than R values.

Y. Gultneh et al. /Journal of inorganic Biochemistry 75 (1999) 7-18

Table 2 Selected bond lengths and bond angles in complexes 14

11

Complex 1: [Zn,(bpea)z(p,-OH)] (ClO,), Bond distances (A) Zn-0 1.888( 1) Zn-N2 2.022( 3) Bond angles (“) O-&-N ( 1) 112.94( 12) N( I)-Zn-N(2) 101.41(14) Zn-0-Zn 145.1

Complex2: [Zn(bpa)(H,O),](ClO,), Bond distances (A) Zn-O( 1) 2.064( 2) Zn-N( 1A) 2.080( 2) Bond angles (“) 0( I)-Zn-N( 1B) 101.61(9) N( lB)-Zn-N( 1A) 156.67( 8) N( lB)-Zn-O(2) 99.64(9) O( I)-Zn-N(2) 103.90(9) N( IA)-Zn-N(2) 79.99( 8)

Complex 3: [Zn($ipyam),] (BF,), Bond distances (A) Zn-N( 1) 1.989(3) Zn-N( 1A) 1.989(3) Bond angles (“) N( I)-Zn-N(2) 95.4( 1) N(2)-Zn-N( 1A) 102.8( 1) N( 2)-Zn-N( 2A) 135.7(2)

Complex 4: [Zn($ipyam),(DMF)z] (C104)2 Bond distances (A) Zn-N( 3) 2.099(3) Zn-N( l)#l 2.121(4) Bond angles (“) N(3)-Zn-N(3)#1 99.1(2) N(3)#1-Zn-N(I) 97.28( 14) N(3)#1-Zn-N( l)#l 85.73( 13) N(3)-Zn-0( lD)#l 172.40( 13) N( I)-Zn-0( lD)#l 89.72( 14) N(3)-Zn-0( 1D) 87.47( 14) N( I)-Zn-O( 1D) 86.91(14) O( lD)#l-Zn-0( 1D) 86.2( 2)

Zn-N( 1) Zn-N3

O-Zn-N( 2) N( l)-Zn-N(3)

Zn-O(2) Zn-N( 2)

0( I)-Zn-N( 1A) O( l)-Zn-O(2) N( IA)-Zn-O(2) N( lB)-Zn-N(2) O(2)-Zn-N(2)

Zn-N(2) Zn-N( 2A)

N( I)-Zn-N( 1A) N( I)-Zn-N(2A) N( IA)-Zn-N(2A)

Zn-N(f)#l Zn-O( lD)#l

N(3)-Zn-N( 1) N(3)-Zn-N( l)#l N( l)-Zn-N( 1)#1 N(3)#3-Zn-O(lD)#l N( l)#l-Zn-0( lD)#l N(3)#1-Zn-O(lD) N(l)#l-Zna( ID)

2.012(3) 2.016(3)

114.87( 12) 0-Zn-N(3) 108.81( 14) 117.77( 13) N(3)-Zn-N(2) 100.4(2)

2.080( 2) 2.142(2)

94.28 92.20( 10) 96.66( 9) 79.69( 8)

163.73(9)

1.990(2) 1.990(2)

130.5(2) 102.8( 1) 95.4( 1)

2.099( 3) Zn-N( 1) 2.185(3) Zn-0( 1D)

85.73( 13) 97.28( 14)

175.4(2) 87.48( 14) 86.91( 14)

172.40( 13) 89.72( 14)

2.121(4) 2.185(3)

OWl(CW3 Cl), [zn(bpa>(H20)21(Clo,>, (2>, [zn- (dipyam)J WA (3), and PXdipyamMDMFM- ( C1O4)2 (4). The crystal structure of the ClO,- salt of the complex 5 has been reported previously [ 4 1 ] and the relevant coordination parameters are the same as those of the BF,- salt, complex 5. Table 2 lists selected bond distances and bond angles while Tables 3-6 show atomic coordinates for complexes 14, respectively.

3.2. Structure of [Zn,(bpea)2(p-OH)](C104)J (1)

Fig. 1 shows an ORTEP drawing of the structure of the cation in which two Zn( II) ions, each one chelated by one tridentate bpea ligand molecule, are bridged by a hydroxide ion to give a distorted tetrahedral environment around each Zn(I1) ion. The dinuclear cation has a crystallographic C, axis passing through the bridging hydroxide. While the bpea internal Namine-Zn-Npy angles (101.4 and 100.4”) are significantly less than the tetrahedral angle, the O-Zn-N,, angles ( 108.8 to 112.9”) are close to tetrahedral and the O-

Zn-N,,,,, angles are 114.87”. The largest deviation is the N,,-Zn-N,, angle of 117.7”. The bond distances in genezal including the Zn-p-OH ( 1.887 A) and Zn.. .Zn (3.564 A) and Zn-O-Zn angles ( 141.5”) are close to those in other singly hydroxo-bridged octahedral complexes [ 49-5 11. Both the bond distances and angles in complex 1 are, as expected, greater than those in the dihydroxo-bridgedoctahedralZn( II) complex of the ligand trispicolylamme reported [52] in which the Zn.. .Zn distance is 2.992 A and the Zn-0-Zn is angle 96.5( 2)“. In a comparison of equivalent bond distances and angles, a larger IVpy-Zn-Namine angle0 (132.1”), and longer Zn.. .Zn (3.624 A) and Zn-0 ( 1.91 A) distances are observed in the analogous hydroxo-bridged dinuclear Zn( II) complex of m-xylbpea [37] which is likely to be a conse- quence of the constraint imposed by the m-xylyl bridge con- necting the two bpea donor sets in the latter. The bond distances observed in complex 1 are in the range generally observed for approximately tetrahedral complexes of Zn( II) [ 53-561. The large Zn-OH-Zn angle of 141.5” is close to that observed in the complex of m-xylbpea ( 140.8”) and must

12 K Gultneh et al. /Journal of Inorganic Biochemistry 75 (1999) 7-18

Table 3 Table 4 Atomic coordinates ( X 104) and equivalent isotropic displacement parameters (2 X 103) for the cation of complex 1

Atomic coordinates ( X 10“) and equivalent isotropic meters (2 X 103) for the cation of complex 2

displacement para-

Ztl 4194( 1) Cl(l) 1548( 1) (x2) 5000 0 5000 O(ll) 1562(3) O(12) 941(2) Wl3) 1750(2) O( 14) 1983(3) O(21) 4509( 3) O(22) 4771(3) N(l) 3456(2) N(2) 3945(2) N(3) 4149( 1) C(1) 3317(3) C(2) 2804( 3) C(3) 2423(2) C(4) 2556(2) C(5) 3072( 2) C(6) 3253(3) C(7) 3315(3) C(8) 3960( 2) C(9) 4524( 2) cc 10) 4410(2) cc111 4455(2) a 12) 4325(2) C(l3) 4153(2) C( 14) 4123(2)

1857( 1) 1290( 1) 509( 1)

1517(2) 863(3)

1550(4) 866( 2)

1861(3) 85(3)

972( 3) 1474( 2) 1520(2) 2948( 2) 1749(3) 1521(3) 986(3) 692(3) 941(2) 613(3)

1137(3) 2128(3) 2644(3) 3197(2) 3937(3) 4428(3) 4177(2) 3444( 2)

6085( 1) 161( 1)

2500 7500

-995(5) - 189(6) 1491(4) 329(7)

2547(7) 1229(7) 6481(4) 3936(4) 5835(3) 7575(6) 7841(7) 6950(7) 5828(6) 5592(5) 4395(7) 3298(6) 2938(5) 3739(5) 4733(4) 4526(5) 5409( 6) 6512(5) 6701(5)

48(l) 57(l) 89(l) 73(l)

139(2) 169(3) 99(l)

152(2) 159(2) 160(2) 57(l) 62(l) 49(l) 79(l) W2) Q’(2) Q(2) 65(l) 910) 83(z) 75(l) 70(l) 55(l) @3(l) 71(l) 65(l) 55(l)

a U(eq) is defined as one-third of the trace of the orthogonalized U,, tensor.

be due to steric interactions of the pyridyl groups around the two Zn( II) ions. The faces of two of the pyridyl rings on the two ZnO ions are parallel to each other and their centroids are 3.754 A apart.

3.3. Structure of [Zn(bpa)(HzO)J(CIO,), (2)

An ORTEP drawing of the structure of the cation is shown in Fig. 2.Zn( II) is in a distorted octahedral geometry result- ing from the three nitrogen donor groups of the chelating ligand bpa and the additional two molecules of water. The sixth site is taken by a reOmotely interacting oxygen of ClO, at a distance of 2.547 A. The distortion arises from the constraint due to the small chelate-bite angle of bpa. The chelate N,,,,, -Zn-N,, angles of bpa are 79.7” while the O( H,O)-Zn-N,, angles are 96.7 and 99.6” showing a slight deviation from a regular square geometry due to the bite angle constraint of the ligand bpa. The zinc ion is displaced by 0.276 A from the average plane of these four donors toward the coordinated water molecule tram to the interacting ClO,, as shown by the angles the oxygen of this water molecule makes at the Zn ion with each of the nitrogens of the ligand and the second water molecule, which are greater than 90”. In this distorted octahedral coordination, the ligand bpa is chelating meridionally with one water molecule coordinated truns to the amine nitrogen (N,,i,,-Zn-OH, angle

Zn Cl(l) CN2) O(l) O(2) O( 1w O(ll) O( 12) O( 13) O( 14) (321) O(22) o(23) o(24) NC 1.4) NC 1B) N(2) C(l.4) C(2A) C(3A) C(4A) C(5A) C(6A) ‘JlB) C(2J3) C(3B) C(4B) C(5J3) C(6J3)

2471( 1) -1724(l)

8414( 1) 4042(3)

314(3) 2267(5)

211(3) -2399(3) -2621(3) - 2078(6)

7072(4) 8233(5) 8156(4)

10170(4) 1513(3) 3580(3) 4129(3)

486(4) 87(d)

764(5) 1812(4) 2162(3) 3210(4) 3458(4) 4204( 5) 5108(4) 5259(4) 4464(3) 4508(4)

1376( 1) 1478( 1)

-1381(l) 2078(3) 1927(3)

-5527(4) 667(3) 318(3)

2014(4) 2850( 5)

-596(3) -301(4)

- 2823(3) - 1867(4)

3629(2) - 1175(2)

725(2) 5093(3) 6556(3) 6514(4) 5021(3) 3586(3) 1908(3)

-2029(3) -3719(4) -4570(3) -3717(3) -2003(3) - 1012(3)

2311(l) 3802( 1)

825( 1) 1280( 1) 1639(2) 252(2)

3484( 2) 4263(2) 3069(2) 4312(3)

297(2) 1503(2) 1193(2) 281(3)

2966( 1) 2165(l) 3300( 1) 2670( 2) 3100(2) 3846( 2) 4154(2) 3697( 2) 4026( 2) 1503(2) 1454(2) 2105(2) 2776( 2) 2791(2) 3537(2)

36(l) 39(l) 45(l) 49(l) 51(l) 78(l) 66(l) 73(l) @3(l)

130(2) 72( 1) 94(l) 72( 1) 96(l) 36(l) 37(l) 36(l) 45(l) 52(l) 54(l) 45(l) 35(l) 41(l) 46(l) 55(l) 55(l) 48(l) 37(l) 43(l)

’ (I( eq) is defined as one-third of the trace of the orthogonalized U,, tensor.

of 163.7”) and the two pyridyl nitrogens coordinated trans to each other (N,,-Zn-N,, angle of 156.7”). In contrast to this, in the octahedral bis-chelate complex cations, PWW212’~ M=Zn(II),Cd(II) andMn(II),bpaisseen to coordinate only facially [ 571. Meridional coordination is exhibited by bpa in Cr( III) [ 581, Cu( II) [59], and Hg( II) and Cd( II) complexes [ 601. As expected both the chelate angles and, to a lesser extent, the bond distances are different in the two Zn(I1) complexes of the ligands bpa and bpea. Compared to the bpea complex 1, the bpa complex 2 has smaller chelate angles (95.4 versus N 100”) and significantly longer Zn-N,,i,c distance (2.142 versus 2.022 Al while the Zn-N,, distances are longer only by about 0.06 A. The differences in bond distances in complexes 1 and 2 are consistent with the generally observed lengthening of bonds in Zn( II) complexes with higher coordination number. The perchlorate ion packs between layers of the complex cation making distant interactions with the Zn( II) center of one layer and also distant hydrogen bonds with the amine nitrogen in the next layer.

3.4. Structure of [Zn(dipyam),](BF,), (3)

Fig. 3 shows the structure of the [ Zn( dipyam) J ‘+ cation in which the Zn(I1) ion is coordinated to the four pyridyl


Table 5 Table 6 Atomic coordinates ( X 10“) and equivalent isotropic displacement parameters (2 X 103) for the cation of complex 3

Atomic coordinates ( X 104) and equivalent isotropic displacement parameters (2 X 103) for the cation of complex 4

Zn F(l) F(2) F(3) F(4) F(5) F(6) F(7) F(8) F(9) F(13) N(l) N(2) N(3) C(1) C(2) C(3) C(4) C(5) C(6) C(7) (28) C(9) cc 10) B

x Y

0 3002( 12) 2003(7)

844(7) 1062(3) 554(26)

1160(8) 3153( 10) 2278(9) 3131(10) 2489( 29)

-947(3) 1719(3) 743(3)

- 2202(4) -3017(4) -2544(5) - 1292(4) -505(3) 1863(3) 3163(4) 4327(4) 4190(4) 2884(4) 1801(4)

6894( 1) 3781(9) 5178(5) 3802(6) 4755( 2) 4268( 22) 3512(7) 3959( 9) 5360( 6) 4103(g) 4983(20) 7539(2) 6314(2) 6778(2) 8107(3) 8491(3) 8312(3) 7749( 3) 7353(3) 6393(3) 6070(3) 5721(3) 5641(4) 5938(3) 4417(3)

Z

2500 1426(7) 591(3) 597(3)

1551(2) 480( 13) 687(4)

1248(5) 821(4)

1519(6) 673( 14)

3207( 1) 3195( 1) 4169( 1) 2979( 2) 3406( 2) 4123(3) 4369(2) 3894(2) 3888(2) 4360( 2) 4114(2) 3390(2) 2960(2) 1062(2)

We@ a

35(l) 61(3) W2) 52(f) 68(l) 48(5) 55(2) 52(2) 55(2) 46(2) 28(5) 34(l) 33(l) 37(l) 47(l) 52(t) 54(l) 46(l) 33(l) 33(l) 44(f) 51(l) 52(f) 43(l) 42(t)

a Equivalent isotropic U defined as one-third of the trace of the orthogonalized U, tensor.

Fig. 1. ORTEP drawing of the crystal structureof [Zn*(bpea),( p-OH) 13+, the cation of complex 1.

x Y Z Weq) a

Zn Cl O(1) (x12) O(13) O( 14) O(22) o(23) o(24) O( ID) N(l) N(2) N(3) N(lD) C(1) (32) C(3) C(4) C(5) C(6) C(7) C(8) C(9) cc 10) C( IDA) C(2DA) C(3DA) C( 1DB) C(2DB) C(3DB)

0 -1505(l)

-903(3) - 1870(21) - 1833(23) - 1680( 13) - 1362( 10) -2100(4) - 1603( 10)

532(2) 842(2)

1685(2) 626(2) 932(3) 718(3)

1215(3) 1911(3) 2060( 3) 1510(2) 1327(2) 1709(3) 1370(3) 658(3) 307(3) 439( 3)

1657(4) 732(7) 985(5)

1605( 15) 379( 17)

701(l) 4590( 2) 5047( 11) 4441(39) 5695(23) 3758(24) 3761(19) 5163(12) 3903( 19) -725(3) 625(3)

1097(3) 1917(3)

-2575(4) 296(5) -2(6) l](6)

369(5) 697(4)

1802(4) 2391(4) 3119(5) 3301(5) 2687(4)

- 1749(7) -2264(12) -3790(7) - 1449(8) -3145(50) -2999(53)

2500 -153(l)

313(8) -1207(14)

-176(41) 248(22)

-680(15) -938(10)

449(17) 2312(3) 4156(3) 3916(3) 2421(3) 2442(4) 4835(4) 5864(4) 6241(4) 5592(4) 4540(4) 3022(3) 2757(4) 1892(5) 1305(4) 1590(4) 2071(6) 3218(13) 2104(10) 2745(10) 3099(37) 1393(20)

48(l) 77(l)

229(6) 335(38) 306(31) 121(13) 248(12) 102(5) 152(9) 59(l) 41(l) WI) 39(l) 8W2) 57(l) 69(2) 73(z) 58(l) 42(l) 39(l) 531) WI) 6X2) 51(l) 63(2)

162(8) 102(4) NV

164(20) 142( 16)

a U(eq) is defined as one-third of the trace of the orthogonalized U, tensor.

nitrogens of the two 2,2’-dipyridylamine ligands. The bond angles around the metal ion show that the coordination geometry is a flattened tetrahedron with two of the non-chelate N- Zn-N angles 130 and 135” intermediate between square pla- nar and tetrahedral angles, while the other two non-chelate N-Zn-N angles ( 102.8”) are reduced from the tetrahedral angle arising from the twisting of the chelate rings to mini-

Fig. 2. ORTEP drawing of the crystal structure of [ Zn( bpa) (H,O),] *+, the cation of complex 2.


Fig. 3. ORTEP drawing of the crystal structure of [Zn(dipyam),]*+, the cation of complex 3.

mize steric crowding. The chelate angles are 95.4”. The analogous Cu( II) of 2,2’-dipyridylamine shows a more flattened tetrahedral geometry with a slightly smaller chelate angle of 94. l”, two of the non-chelate angles increased to 139.9( 2)“, and the other two are further reduced to 99.4” [ 611. This flattening of the tetrahedron allows near co-planarity of the two pyridyl rings within a dipyridylamine ligand. The Zn( II) complex of the related ligand 2,2’-bipyridine crystallizes with one Zn-coordinated water molecule to give an approximate trigonal bipyramidal geometry [41]. The chelate $ngles (95.4”) are larger and the Zn-N bonds ( 1.989-l .990 A) are shorter in the dipyridylamine complex than those in the dipyridyl complex (79.7 and 78.6” and 2.08 to 2.11 A), as expected r411.

3.5, Structure of [Zn(dipyam)2(DMF)2](C10J2 (4)

Fig. 4 shows the structure of the Zn( dipyam) 2( DMF) 2] *+ cation showing a six-coordinate Zn(I1) ion in which two molecules of DMF, coordinating through the amide oxygens,

Fig. 4. ORTEP drawing of the crystal structure of [Zn(dipyam),- (DMF)J’+, the cation of complex 4.

occupy cis positions and the cation has a crystallographic C2 axis of symmetry. One nitrogen of each dipyridylamine is coordinated truns to a DMF oxygen and forms a $ightly shorter Zn-N bond (2.099 A) than the other (2.12 1 A). The consequences of the higher coordination number in this cation, compared to that of complex 3, are that all the Zn-N bond lengths are longer and the dipyridylamine chelate angles (85.73”) are significantly smaller than those observed in the tetracoordinate complex [ Zn( dipyam),] *+ (95.4”). The Zn( II) ion is displaced from the average N30 coordination plane toward the apical dipyridylamine nitrogen and away from the dimethylformamide oxygen as shown by the O-Zn- N and 0-Zn-0 angles which are all less than 90”. When in solution in DMF/water, complex 3 coordinates two molecules of water per Zn( II) while complex 4 replaces its coordinated DMF by Hz0 and both form the same six-coordinate aqua complex [Zn(dipyam)2(H20)2]2+ as shown by the potentiometric titration (see below).

3.6, Potentiometric studies of the acid-base properties of complexes l-5

Acidities of metal-coordinated water molecules play a cen- tral role in the mechanism of the catalysis of hydrolytic enzymes by metal complexes as well as enzymes; thus, determination of such acidities by potentiometric titrations have been very useful in elucidating mechanistic details. Because of the low solubility of the metal complexes in water, in the following acid-base titrations of Zn( II) complexes, a mixture of DMF and water has been used. In our experience pH readings of solutions of HC104 and NaOH in water and in water/DMF (3/5, vol./vol.) mixture have not shown sig- nificant differences within the precision of the measurements. Solutions of the complexes [ Zn,( bpea) *( F-OH) ] (Clod) 3, [zn(bpa)(H20>21(Clo,)2, [Zn(dipyam)2(DMFM- (C104)2, [WQyamM (ClW2 and [Zn(dipy),- (H,O) ] ( C1O,)2 in water/DMF (3/5, vol./vol.) were titrated against aqueous standard solution of NaOH ‘. Figs. 5 and 6 show the potentiometric titration curves. Well-defined end points are observed due to the titration of the Zn( II) - coordinated water molecules by a strong base. From the curves, the number of coordinated water molecules per Zn( II) and pK, values were determined. Table 7 summarizes the number of Zn-coordinated water or hydroxide molecules in aqueous solutions and the pK, values of these species. It was found that there were two Zn-coordinated water molecules in the bpa complex 2 in DMF/water, consistent with results found for the solid by crystallography. The complexes of dipyridylamine (3 and 4) and dipyridyl(5) also show two titratable coordinated water molecules per formula unit in water/DMF solution since they take two equivalents of the

I The use of aqueous acid solutions (such as HCIO,) in direct or back titrations was complicated by the titration of the amine and the protonated amine groups of the ligand along with the coordinated water molecules with indistinguishable end points.


12 -

11 -

z

10 -

9-

8-

4

.

.

.’

L’

i a

2 4 8 8

VolumeofO.lM NaOH

10 12

Fig. 5. Titration curve: graph of pH vs. volume of 0.10 M aqueous NaOH solution in the titration of a solution of 0.25 mmol in 25 ml water/DMF (3/5, vol./ vol.) mixture of (a) complex 1 and (b) complex 2.

*.. ,,.....,‘.’ :. a .:’ ___ ,,.... -.*....-

,’ .’ b

10 - .i B b /__... . .." :'

. ..." _... . . . ;.'

8 _ / ,_, /.. .. a

/'-

6 -1 i,

I I I

0 10 20 30 40 50

Volume of NaOH Fig. 6. Titration curve: graph of pH vs. volume of 0.050 M aqueous NaOH solution in the titration of a solution of 0.50 mmol in 25 ml water/DMF (3/ 5, vol./vol.) mixture of (a) complex 3 and (b) complex 5.

strong base in their titrations (Eq. ( 1) ) . Complex 1, on direct titration against aqueous NaOH solution, requires three equivalents of the base per dinuclear formulaunit. This shows that the complex coordinates three molecules of water per dinuclear unit (Eq. (2) ) in aqueous solution *.

’ Although, in the titration of this complex with aqueous NaOH, only one end point is observed for all three coordinated water molecules, a reviewer

2H20

En(dipy~)212c -+ [Zn(dimMH20)212+ (14 2H20

3H,O

4 [ (bpea)Zn( H20) (p-OH) ] + [ (bpea)Zn( H20)*] *+

(2)

However on direct titration of a solution of complex 1 against an aqueous HClO, solution, it requires three equivalents of acid showing that the amine nitrogens titrate along with the bridging hydroxide ion to the same end point.

It appears that five- and six-coordinations are prevalent in aqueous solutions in complexes of this class of chelating ligands. It is noteworthy that, although both the mononucleat- ing ligand, bpea, and the dinucleating ligand, m-xylbpea, form the same type of hydroxo-bridged complexes in the solid state, in the complex of m-xylbpea, where the two bpea donor sets are tethered by the m-xylyl group, the pK, of the coordinated water (7.55) is about 0.8 pH units less than that of 1. This is illustrative of an entropic effect at work, i.e., the

has pointed out the possible formation of a dihydroxo-bridged dinuclear complex after the deprotonation of one of the three coordinated water molecules on this dinuclear unit by analogy to a similar dinuclear cobalt complex reported by Chin et al. [ 751. This is possible since dihyroxo-bridged zinc and other transition metal ion complexes are fairly common.

16

Table 7

Y. Gultneh et al. /Journal of Inorganic Biochemistry 75 (1999) 7-18

Table of pK, values of Zn-coordinated H,O, pH of peak catalytic activity of complexes 1, 2, 3, 5 and the catalysis initial rate factors at peak activity in the catalysis of the hydrolysis of bis(p-nitrophenyl)phosphate in water/DMF mixture (3/5, vol./vol.) by complexes 1,2,3 and 5

Formula of complex pKa ( Zn-OH,) (in H,O/DMF)

[zn,(bpea),(~-OH)l(CIO,), (1) 8.35 8.35 178 [Zn(bpa)(H20)21(C10,), (2) 9.85 8.85 232

[Zn2(m-xylbpea) (P-OH) 1 (ClW, 7.55 8.25 141

lZn(dW&l (ClO& (3) 8.00 9.00 219

[Zn(dipy)2(H20) 1 (CtO& (5) 9.01 8.75 110

pH of peak catalytic activity Rate factors: initital rates (catalyzed/noncatalyzed) at pH of peak catalytic activity

effect of the cooperation of two Zn( II) ions held in conven- ient proximity by a dinucleating ligand with sufficient rigid- ity. For a long time there has been much interest among bio-inorganic chemists in understanding the way in which numerous enzymes use the cooperation of multinuclear active sites in facilitating reactions that are sluggish at mononuclear sites.

The higher pK, of the Zn-coordinated water in complex 2 (9.85) compared to that of complex 1 (8.35) is partly attributable to the effect of chelate ring size and the coordination geometry on the acidity of the metal ion. The fact that the pK, in the complex 2,2’-dipyridylamine (8.0) with six-membered chelate rings is lower compared to that of the complex of 2,2’-dipyridyl (9.0) with five-membered chelation is also consistent with this. Ab initio Hartree-Fock calculations by Bertini et al. [ 301 on the relationships of coordination number, pK, and nucleophilicity among Zn( II) complexes indi- cate that lower coordination numbers lower the pK, values. This suggests that the difference in the pK, of the complexes of bpa and bpea may be partly the effect of the higher coordination number in bpa complex. This is facilitated by its smaller bite angle compared to that of the bpea analog. A four-coordinate complex, [ Zn( II)L( H,O) ] 2+ (L = the tridentate imidazole analog of bpa) , has been reported [ 621 to show a pK, of 8.3 which is significantly lower than that observed for the five-coordinate complex 2 and closer to that of the four-coordinate complex 1. In a series of analogous macrocyclic polyamine complexes, those which are tridentate and result in four-coordinate Zn( II) complexes show some of the lowest pK, values ( ~7) found in synthetic Zn(I1) complexes [ 631.

3.7. Catalysis of the hydrolysis of bis(p-nitrophenyl)- phosphate by Zn(lI) complexes in DMF/H,O solutions

Studies of the initial rates for hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) in the presence of the Zn(I1) complexes l-5 and as functions of the concentrations of the substrate and the complexes show that the reaction has first- order dependence on the concentration of both the complex and substrate. This is consistent with the acceptedmechanism in which coordination of the phosphate ester to the metal complex is followed by hydrolysis. Figs. 7 and 8 show plots

of the observed pseudo-first order rate constants for the hydrolysis of BNPP in DMF/H,O (l/l) for complexes 1 and 2, and complexes 3 and 5, respectively. At pH values up to 9.5 the rate of hydrolysis of BNPP observed in the presence of these complexes increases by a factor from 100 to 200 times the noncatalyzed rate as seen from the rate ratios in Table 7. In the pH range studied in these experiments the second-order rate constant, kobs, varies from lop2 to lo-’ M- ’ s- ’ which is of the order observed [ 641 in the catalysis of the hydrolysis of BNPP by several Zn(I1) complexes [ 65,661. In general, the rate constant shows sharp increases at or around pH values close to the pK, of the coordinated water molecules in each complex. This is further confirmation for the accepted mechanism in which the metal-coordinated hydroxide is the strong nucleophile.

The anomalous case among this set of complexes is that of the complex of bpa. In this case, kobs reaches a maximum and starts to decline at a pH value significantly less than the observed pK, of the coordinated water (9.85). At high pH values, hydroxide-bridging and/aggregation of complex ions may be responsible for the reduced effectiveness of the catalyst [ 52,65,67]. At all pH values greater than 8, the rate of catalysis by the Zn( II) complex, [ Zn,( F-OH) (m-xyl-

i

8 9 10 11

PH Fig. 7. Plot of observed rate constant vs. buffer pH in the hydrolysis of BNPP catalyzed by (a) [Zn,(bpea),(CL-OH)](ClO~)~ (1) and (b) [Zn(bpa)- (H,O),] (ClO,), (2) in water/DMF (3/5, vol./vol.) solution at 75°C.


J

8 9 IO II

PH Fig. 8. Plot of observed rate constant vs. buffer pH in the hydrolysis of BNPP: (a)Zn,(p-OH)(m-xylbpea)](ClO.,),;(b) [Zn(dipyam)Z](BF,)Z (3); (c) Zn(dipy) (H,O)] (ClO,), (5) and (d) uncatalyzed reaction in water/DMF (3/5, vol./vol.) solution at 75°C.

bpea)] (C1O4)3 (m-xylbpea - a hexadentate Nb donor ligand containing two bpea arms connected via a m-xylene bridge), is far less than that for complex 1, while below pH 8 its rate is only slightly greater. The poor catalytic property of this dinuclear complex, in spite of its low pK,, may be due to the poor nucleophilicity of the Zn-coordinated hydroxide or the effect of hydroxide bridging (possibly double hydroxide bridging) of the Zn(I1) metal ions. Bulky substituents adjacent to the donor atoms have been shown to prevent the formation of such hydroxide bridging in four-coordinate Zn( II) [ 54,55,68-711 and Cu( II) complexes [ 72-741. The maximum amount of the hydrolysis product p-nitrophenol (PNP) has been one mole of PNP per mole of the substrate BNPP when the BNPP:Zn( II) complex molar ratio is 1: 1 and with excess BNPP, which indicates that the p-nitrophenyl- phosphate anion is not further hydrolyzed, i.e., the maximum turnover of the catalyst is unity.

4. Conclusions

We have synthesized Zn( II) complexes of the tridentate ligands bpa, bpea, 2,2’-dipyridylamine, and dipyridyl, in the attempt to study complexes that mimic the structure and function of the active sites of zinc enzymes such as alkaline phos- phatase and carbonic anhydrase. We have determined the structure, pK, of the Zn-coordinated water in H,O/DMF solution, and the catalytic efficiencies for the hydrolysis of BNPP by these zinc complexes at various pH values in water/ DMF solution. We have shown that:

(a) in general the catalytic activities increase roughly in parallel with the concentrations of the nucleophilic Zn-OH species;

(b) there is a large difference in the pK, of the Zn( II) complexes of the ligands bpa and bpea that most likely arises from differences in chelate ring size;

(c) Zn( II) complexes of the two-arm dinucleating ligand, m-xylbpea, and the one-arm ligand, bpea, both crystallize as hydroxide-bridged dinuclear complexes containing nearly tetrahedral Zn( II). However, the pK, of the complex of the dinucleating ligand, m-xylbpea (7.55)) is significantly less than that of the bpea complex, an effect attributable to the dinucleating nature of the ligand;

(d) the Zn (II) complex of m-xylbpea, in spite of its low pK,, is a poorer catalyst for the hydrolysis of BNPP, which may be indicative of differences in nucleophilicities among Zn-OH moieties and the greater tendency of the m-xylbpea complex to form catalytically less active (or inactive) hydroxo- or double hydroxo-bridged complex.

The effectiveness of bulky substituents on pyridine rings in preventing hydroxide bridging of the zinc ions and improv- ing the rate of catalysis is being tested in our laboratory.

5. Supplementary material

Tables of crystal data and refinement parameters (SAl- SA4) (5 pages), anisotropic displacement parameters (SB l- SB4) (4 pages), bond lengths and angles ( SCl-SC4) (5 pages), hydrogen coordinate isotropic displacement parameters (SDl-SD4) (4 pages) and observed and calculated structure factors ( SEl-SE4) (49 pages) for complexes 1 to 4 are available from the author(s) upon request.

Acknowledgements

Y .G. acknowledges funding by the NIH through the MBRS Program of the Graduate School of Arts and Sciences of Howard University to support this work. R.J.B. acknowledges the NIH-MBRS Program for partial support of this research and also DOD-ONR for funds to upgrade the diffractometer.

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Syntheses and structures of and catalysis of hydrolysis by Zn(II) complexes of chelating pyridyl...

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