Zn++-complexes as models of metalloenzymes in micellar esterolysis : ligand structure-dependent stoichiometry of the complexes.

Tetrahedron Letters, Vol.32,No.2,pp 193-196. 1991 Printed inGreat Brirain

zn++

0040-4039/91 $3.00+.00 PergnmonRcssplc

:

-COMPLEXES AS MODELS OF METALLOENZYMES IN MICELLAH ESTEROLYSIS LIGAND STRUCTURE-DEPENDENT STOICHIOMETRY OF THE COMPLEXES. V. FAIVRE,

A. BREKBILLA,

D. ROTZARD

and P. LOCHON*

Laboratoire de Chimie-Physique Macromol&culaire associe au CNRS, des Industries Chimiques, 1 rue Grandville, BP 451, 54OCl NANCY,

Ecole Nationale FRANCE

Supkrieure

Abstract Lipophilic their of

2-hydroxymethylbenzimidazoles

esterolytic

cationic

2:l

types

activities

micelles.

were

shown

The

Bivalent have

metallic

been

In a previous

of Zn++

cations In

to

study

the

by

lipophilic position

this

Wmplfxes

as synthetic

paper

medium.

tions)

cation

in which

and

Zn"

ions

stoichiometry

of

were

investigated

picolinate the

active

on the position

of the substituant

associating

imidzzole

analogues

c5) we reported

the heterocycle

for

effects

a

of the

such

including

the

chain

was

for

in the presence 1:1

complexes

or

on the heterocycle

into

a

a

for

i;ydroxyi group ( !,2,3,4).

of the 2_hydroxymethylbenzi-

act cooperatively substrate

the

active

hydrophobic micellar

in the presence in a non-micellar complex.

or electrostatic we

system,

2-hydroxymethylbenzimidazole

on the benzimidazole

and

of metalloenzymes

picolinate

observed (e.g.

complexes

ring

site

activity group

of p-nitrophenyi

microenvironment

of

of a C,O alkyl

the hydroxyl

I:1 stoichiometry

incorporation

an

of the active

the esterolytic

and

the hydrolysis

case

modeis,

the

by

of p-nitrophenyl

concentration.

described

midazole

nature

to be dependent

and on the surfactant

complexed

in the hydrolysis

unit

and

have

In

order

interac-

synthesized

differing

by

the

ring.

;CW+, 5

1-decyl-2-hydroxymethylbenzimidazole

(6)-decyl-2-hydroxymethylbenzimidazole

(II)

(I)

The of The

stoichiometry

of

p-nitrophenyl use

(I) and

of

this

the

active

picolinate surfactaot

(II) in water.

in was

According

complexes the also

was

of

presence nece ssary

an adapted

determined

using

the

hydroiysis

cetyltrimethylammonium

because

version

of the

of the

insolubility

Job's

method

bromide

reaction (CTABr).

of the ligands (61,

the kinetic

measurements were performed by plotting the kobsd valtiesas a r'unctionof the molar fraction

(a) of ligand,

keeping

constant

the sum of ligand

193

and metal

ion concentrations.

194

.-___.

---

CTABr]

3 10 xk

3.0

-4

.

7x10

q

1x10-3M

+

2x10

obsd (’ -I ’

-3

--_

M

M

0.0 0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

IY,: n:olar fraction ~&l&re

1. Depecder,ze

fraction

of

k

!a) of tnc iigand

pii : '1.lb

f!EFES bu,fl‘cr

T = 32”!> ; L

o

and

:"

0

in

the

h:.~drclysi.sof p-nitrcphenyi

obsd (I) and 0.':the surfactant

:0.05

of

COr~centratiord

0.9

1.0

cf :igan,3 (1)

picolinate

on

the molar

concentration.

Nj COntair!i:$ ?jaX$

= total

0.8

(1 =

ti.lJin 1 %

iiga:?d and

Zn++,

(v/v)

;

alcohol-water

= 2 j[ iC'-!+fq,CI

C4o + Lo

L. 0

[Ssteri

=-----; Mo + i_

Sh!;uwSthe

Fig.?

-f

r,f p.n;:rophenol

release

ti,cns. AC

the CTARr

(concentration profile of

plots

= 2.5 x NO-%

Ij

a

compiex

1:

the

overall

activity

113xi.mum, alGjay3 centered

a

ur.der the

strc,r?g increase

tha:

~.f the

substrate Table --phenyl

(:C

First-order

corresponclng was

not

2:l.

si;cus tnat

figure

decrezses

also

rapidly

(Bim).

and

irlaicates

the

kobsd

as

for

the

sur,factafit concentra(cT~&-]

= 7 x

into the xice:iesj,

which

optimal times

(I) and under

inzorpcraLed

raximurn at c1 : 0.67, This

constants,

different

that

the

surfaotant

c*~rve prcfile

-4 pi, 1~)

the curve

stoicbiiometry concentration

presents

a

broad

at cz = 0.6'1.

in a not-mice;lar

Ficolinate

rae

(1) at

to mzx1muni activity,

conditions,

higher)

in

0: = 0.67, the

maximum

2-hydrcxymethylbenziaidaznle-Zn++l:?

7. Ligands

zimidazole

pseudo

= CTAB?

fraction. cf

IKliar

concentraticn

attains

ti-.eactive

Furthermore,

observed

tr,e

tiene,th w?zich Vile ligacd

(fig.

Increases,

tne vx

; surfactant

medium

rate-cocstants

conditisns

rate

complex

(for c1 = C.51(taole

(II) gicoal

the optimal

[CT&+: for

= 7 x tnis

18

M,

complex,

tswar-d p.nitrophenyl

3ne

observes

compared

to

picolinate

1:. kobsd

as compared

for with

the

nydrolysis

of p-nitro-

that of 2_hydroxymethylben-

195

[ligandl none UAW

(7 x 10%

LTABr

pH

:2 x 10-3N)

z 7.14

HEPES

Bim

1 x 10-4M

(1)

1.34

(0.05

M)

1

10 -4M

x

-4

1x10

(II)

Buffer

[Metal] x

x

III-~PI

1 x lo-41?

containing

NaNG3

(I

0.1)

q

obsd

-4 -1 2.75 x IO s

IC -4N

0.66

F

k

in

2.76

x

10-3s-'

2.y4

x

10-38-l

1 % (v/v) alcohol-water

;

T : 30°C, [Ester] : 2.5 x ltim5M. This

being

basicaily and

complex

sence

of

1:l

is

a bidental can

Very

2:l

be explained the

freedom

concentration

ratio,

such

complex.

that

at high

of complexes

micelles,

in surfactant of the

assume

types

particularly

latter

ment

we

so, two

which

that

the

likely

can

complex

degrees

results

free

with

of

energy

very

overall

entropy,

the

system

the

is

system

by

per micelle, 1:l complex,

activity.

The fact

limited. compiex

In 'his case,

disadvanlages

expressed

units

bidental

dG;e to the are

but less reactive.

of

reactive

of the 2:l

in a diminu Lion

behaviour

of benzimidazole

a not

high

by a favourable

is more stable

this

concentrations

be formed,

the

Che

very

broad

formation that

However, ratio

of

the

in the pre-

an increase

to tine benefit

the spatial formation k obsd

arrange-

of vs

the

2: 1

(13) curve

profile. The chain

most on

unexpected the

result

heterocyclic

comes nitrogen

from

the

ligand

In tnis

atom.

(II) case,

which at

is

low

substitued

surfactant

by

an

alkyl

concentrations,

plot.3 Cflg.2) rresent a brc~d profile accompanied k ‘J3 (:.iga,;.cmolar fracticn) obsd by an overall activity comparaole to that obtained for the first model at high surfactant tne

concentrations.

4 3

-1

10 Xkobsd (s

n

9x10

-4 M

[CT-r]

-3

)

o 1x10

a 2x10 X 3x10

M -3

M M

0.5 0.6 0.7 0.8 0.9 ?igiire 2. fraction Conditions

3ependence

of k

(~1 of the ligand identical

in the hydrolysis of ObSd (II) and on tre scrfactbnt

to those nentlonoa

f‘igurel

?-nltrocnenyi ccrcentraticn.

picolinate

on

the

molar

196

For

a

concentration

presenting to

two

rance

two

overall

two

overall

2:l

complex

profile

pletely

a

complexes

becomes

can

(c1)) and

because

concentration

than

that

of

in an overall In this by

a

higher

the alkyl The

(which the

using

the

chain

the

appea-

increase

in

the

of

the

1:l

sites

surfactant

by

(the

1:l

the

the

I:1 complex.

concentrations

2:1

is com-

ligands)

and

group).

benefit When

decreases

curve

and

(which

hydroxyl

to

complex

broad

bidental

disappear

for the

of

that

very

3:l complex

function

complexes

and

the

that

as a

coordinable

activity

at

sharp

increases,

suggest time

active

proportion

resulting,

a

The

of

At the

the surfac-

more

close

to

rapidly 6.1c3 M,

due to the 2:l complex.

formation energy

of

overall

by

profile,

correspond

which

respectively.

concentrations,

same

the

0.67,

curve

for the I:1 complex.

activity

inactive

the

CI =

types

concentration

the

remarkable

of

and

this

a

complex

spatial

rather

than

arrangement

that

of

compatible

I:1

the

with

the

one,

is favoured

incorporation

of

into the micelle.

freezes

the

a higher

mainly

at

involve

the

complex,

of the alkyl the

formation

is governed All

activity

overall

and

2:l

accompanied

surfactant

saturation

not

increased,

2:l

free

position

low

the do

with

is

the

case,

the

is

important

low

a very

c( q0.5

at

I:1 and

the

surfactant At

concentration,

1:l and 2:l complexes, tant

*ore

as

quantities,

of

which

of

observed

concentration

is, however,

in small

CTABr

centered

preponderant.

complexes

2.1r3H

maxima

decreases

vs

inactive

monodental

10s3M,

this

form

we

= 2 x

stoichiometry at

which

activity

(kobsd

complexes

the

with

activity,

The

CTABr

distinct

very

complexes of

of

of

chain

molecular

complexes

by the enthalpic

experiments

hydrophobic

were

on the benzimidazole conformation

of

different

or the entropic

carried

alkyioxy

picolinic

out

through types,

hydrophobic

depending

on

a

hydrophilic

their

can free

cause energy

temperature.

ester.

Further

it: the

are in progress

in micelles

interactlons) whether

factor at the studied

with

esters,

ring and the concentration

kinetic

studies,

laboratory.

References

1.

T. EIKI, S. KAWADA,

2.

K. OGINO,

3.

R.S. BROWN,

N.J. CURTIS

and J. HUGUET,

4.

R.S. BROWN,

W. ZAMKANEI

and J.L. CCCEO,

5.

A. BREMBILLA

6.

D.S. SIGMAN

K. SHINDO,

K. MATSUSHIMA,

T. HINAMI,

and P. LOCHON,

1990)

W. TAGAKI

J. Chim.

and C.T. JORGENSEN,

(Received in France 17 September

M. MCRI and W. TAGAKI,

Chem. Lett.,

and T. EIKI, Bull.

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Phys.-Chim.

J. Am. Chem.

Sot.,

2,

(1980)

Chem. Sot. Jpn, s,

6953-9

5222-t) (1984)

Eiol., B,

1724-30

1101-06

(1981)

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Pnys.

997-1000

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(1972)

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