Metallomicellar hydrolytic catalysts containing ligand surfactants derived from alkyl pyridin-2-yl ketoxime

Article abstract of DOI:10.1135/cccc19971342

N-Hexyl-(2a), N-octyl-(2b), N-decyl-(2c) and N-dodecyl-N-[2-(hydroxyimino)-2-(pyridin-2-yl)-ethyl]dimethylammonium (2d) nitrates were synthesized as water-soluble cationic ligand surfactants. Three types of micellar catalytic systems employing salts 2 were prepared: homomicellar water solutions of salts 2, comicellar solutions of salts 2 wilh an inert cationic tenside hexadecyltrimethylammonium bromide (CTAB) and comicellar systems consisting of complexes of ligand surfactants 2 with transition metal ions (Co(II), Ni(II), Cu(II) and Zn(II)) and CTAB. Hydrolytic efficiency of all micellar and metallomicellar systems was tested by measuring the kinetics of the model substrate cleavage under pseudo-firsl-order reaction conditions. Of the above-mentioned catalysts, comicellar systems of salts 2 comicellized with CTAB were most efficient. In all cases, with the exception of Zn(II), coordination of a metal ion decreased the hydrolytic efficiency of salts 2.

Full text of DOI:10.1135/cccc19971342

1342
Cibulka, Dvorak, Hampl, Liska:
METALLOMICELLAR HYDROLYTIC CATALYSTS CONTAINING LIGAND
SURFACTANTS DERIVED FROM ALKYL PYRIDIN-2-YL KETOXIME
1
2,
3
Radek CIBULKA , David DVORAK, Frantisek HAMPL * and Frantisek LISKA
Department of Organic Chemistry, Prague Institute of Chemical Technology, 166 28 Prague 6,
Czech Republic; e-mail: 1 cibulkar@vscht.cz, 2 hamplf@vscht.cz, 3 liskaf@vscht.cz
Received April 1, 1997
Accepted May 2, 1997
Dedicated to Professor Jaromir Plesek on the occasion of his 70th birthday.
N-Hexyl- (2a), N-octyl- (2b), N-decyl- (2c) and N-dodecyl-N-[2-(hydroxyimino)-2-(pyridin-2-yl)-
ethyl]dimethylammonium (2d) nitrates were synthesized as water-soluble cationic ligand surfactants.
Three types of micellar catalytic systems employing salts 2 were prepared: homomicellar water solu-
tions of salts 2, comicellar solutions of salts 2 with an inert cationic tenside hexadecyltrimethylam-
monium bromide (CTAB) and comicellar systems consisting of complexes of ligand surfactants 2
with transition metal ions (Co(II), Ni(II), Cu(II) and Zn(II)) and CTAB. Hydrolytic efficiency of all
micellar and metallomicellar systems was tested by measuring the kinetics of the model substrate
cleavage under pseudo-first-order reaction conditions. Of the above-mentioned catalysts, comicellar
systems of salts 2 comicellized with CTAB were most efficient. In all cases, with the exception of
Zn(II), coordination of a metal ion decreased the hydrolytic efficiency of salts 2.
Key words: Ester hydrolysis; Ligand surfactant; Micellar catalysis; Pyridine derivatives.
Catalytic effect of micellar systems on hydrolytic reactions has been studied for several
decades1. So far, a great number of different types of functional tensides have been
designed and studied as hydrolytic catalysts, many of them exhibiting impressive effi-
ciency2. Among them, amphiphilic transition metal ion complexes possessing hydro-
phobic alkyl chain in molecule have been of considerable interest during the last decade3.
These compounds can be considered as “metallotensides” with a cationic metal ion polar
head group. Several “metallomicelles” formed either by aggregation of “metalloten-
sides” (ref.3c) or by their co-aggregation with an inert cationic tenside, such as cetyltri-
methylammonium bromide (CTAB), have been reported to mimic the function of
hydrolytic metalloenzymes, e.g. carboxypeptidase A (ref.4) and alkaline phosphatases5.
They bring together the lipophilic substrate with the nucleophilic function of the cata-
* The author to whom correspondence should be addressed.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Metallomicellar Hydrolytic Catalysts
1343
lyst activated by its coordination to the metal ion. Activation of the electrophilic center
by the metal ion has been also suggested3a,3c,3f
.
In our previous communication6 we described powerful hydrolytic metallocatalysts
containing Ni(II) complexes of lipophilic alkyl pyridin-2-yl ketoximes 1 comicellized
with CTAB. These catalysts efficiently cleaved alkanoates in the span of several pH
units, starting from pH 4 up to pH 9. However, solubility of ligands 1 in micellar
solutions of CTAB was poor, thus limiting the efficiency of the prepared catalysts. This
led us to modify the structure of alkyl pyridin-2-yl ketoximes 1 by introducing a solubi-
lizing quaternary ammonium group into the side alkyl chain. In the present communication
we describe the synthesis of alkyl(dimethyl)[2-(hydroxyimino)-2-(pyridin-2-yl)ethyl]-
ammonium salts 2.
CH
3
R
N
R
3
N
N
CH
NOH
NOH
R
NO
3
R
octyl
hexyl
1a
1b
1c
2a
dodecyl
tridecyl
octyl
2b
2c
2d
decyl
dodecyl
Quaternary salts 2 can be considered as cationic “ligand surfactants”, i.e. cationic
tensides containing chelating N,N′-donor grouping in their molecule. The quaternary
salts 2 were expected to be soluble both in CTAB and in pure water forming thus
comicellar and homomicellar systems. The hydrolytic efficiency of micellar systems
containing surfactants 2 and their complexes with several transition metal ions (Co(II),
Ni(II), Cu(II) and Zn(II)) was tested in the cleavage of 4-nitrophenyl hexanoate
(PNPH), 4-nitrophenyl diphenyl phosphate (PNPDPP) and 4-nitrophenyl picolinate
(PNPP) as model substrates.
EXPERIMENTAL
Temperature data were uncorrected. 1H NMR spectra were recorded on a Bruker AM 400 spec-
trometer (400 MHz). Chemical shifts are given in ppm relative to tetramethylsilane as internal standard,
coupling constants J in Hz. IR spectra were recorded on a Nicolet 740 FT-IR spectrometer. Bands
are given in cm–1. Elemental analyses were performed on a Perkin–Elmer 240 analyzer. TLC ana-
lyses were carried out on glass plates Kieselgel 60 F254 or on DC Alufolien, Kieselgel 60 F254
(Merck Laboratory Chemicals). Column chromatography was performed on Kieselgel 60 H (Merck
Laboratory Chemicals).
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1344
Cibulka, Dvorak, Hampl, Liska:
Chemicals: Hexyl-, octyl-, decyl- and dodecylamine, formaldehyde and formic acid (purum) were
obtained from Fluka. 2-Acetylpyridine (purum) and hexadecyltrimethylammonium bromide (p.a.)
were purchased by Merck. 2-(Morpholin-1-yl)ethanesulfonic acid (MES), N-(2-hydroxyethyl)pipe-
razine-N′-(2-ethanesulfonic acid) (HEPES), N-(2-hydroxyethyl)piperazine-N′-(3-propanesulfonic acid)
(EPPS), 2-(cyclohexylamino)ethanesulfonic acid (CHES), 3-(cyclohexylamino)-1-propanesulfonic
acid (CAPS), 4-nitrophenyl hexanoate (PNPH), 4-nitrophenyl pyridine-2-carboxylate (PNPP) (all
p.a.) were products of Sigma. Bromine (purum) was obtained from Reachim. 4-Nitrophenyl diphenyl
phosphate (PNPDPP) was synthesized and purified by published method7.
2-(Bromoacetyl)pyridinium Bromide
A solution of bromine (8.5 ml, 0.165 mol) in CCl4 (30 ml) was added dropwise to the refluxing
solution of 2-acetylpyridine (20 g, 0.165 mol) in CCl4 (370 ml). After 2 h the resulting yellow crystals
were filtrered off, washed with acetone and dried in dessicator. Yield 34.8 g (75%), m.p. 203–207 °C
1
(reported8 204–208 °C ). H NMR spectrum (CD3OD): 3.88 m, 2 H (CH2Br); 8.16 ddd, 1 H, J(5,4) = 8.2,
J(5,6) = 5.9, J(5,3) = 1.3 (H-5); 8.30 dt, 1 H, J(3,4) = 8.2, J(3,5) = J(3,6) = 1.0 (H-3); 8.75 td, 1 H,
J(4,5) = J(4,3) = 7.8, J(4,6) = 1.6 (H-4); 8.83 ddd, 1 H, J(6,5) = 5.8, J(6,4) = 1.5, J(6,3) = 0.7 (H-6).
Alkyl(dimethyl)amines 3
Alkyl(dimethyl)amines 3 were prepared by Eschweiler–Clark methylation of corresponding alkyl-
amines with formaldehyde and formic acid9. The obtained products were purified by distillation.
Hexyl(dimethyl)amine (3a)
1
Yield 135.1 g (55%), b.p. 146 °C (reported10 143–144 °C). H NMR spectrum (CDCl3): 0.87 t, 3 H,
J(6′,5′) = 6.9 (CH3); 1.28 m, 6 H ((CH2)3); 1.44 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.3 (CH2CH2N); 2.20 s, 6 H
((CH3)2N); 2.22 t, 2 H, J(2′,1′) = 7.4 (CH2N).
Dimethyl(octyl)amine (3b)
Yield 88.6 g (38%), b.p. 97–99 °C/4.7 kPa (reported10 79–80 °C/2.1 kPa). 1H NMR spectrum
(CDCl3): 0.88 t, 3 H, J(8′,7′) = 6.9 (CH3); 1.29 m, 10 H ((CH2)5); 1.45 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.0
(CH2CH2N); 2.21 s, 6 H ((CH3)2N); 2.23 t, 2 H, J(2′,1′) = 7.4 (CH2N).
Decyl(dimethyl)amine (3c)
1
Yield 178.5 g (74%), b.p. 80–83 °C/0.2 kPa (reported10 62 °C/0.1 kPa). H NMR spectrum (CDCl3):
0.88 t, 3 H, J(10′,9′) = 7.0 (CH3); 1.26 m, 14 H ((CH2)7); 1.45 qi, 2 H, J(2′,3′) = J(2′,1′) = 7.2
(CH2CH2N); 2.21 s, 6 H ((CH3)2N); 2.23 t, 2 H, J(2′,1′) = 7.4 (CH2N).
Dodecyl(dimethyl)amine (3d)
Yield 184.9 g (53%), b.p. 108–110 °C/0.1 kPa (reported11 111–114 °C/0.3 kPa). 1H NMR spectrum
(CDCl3): 0.88 t, 3 H, J(12′,11′) = 7.1 (CH3); 1.26 m, 18 H ((CH2)9); 1.45 q, 2 H, J(2′,3′) = J(2′,1′) = 7.3
(CH2CH2N); 2.21 s, 6 H ((CH3)2N); 2.23 t, 2 H, J(2′,1′) = 7.4 (CH2N).
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Metallomicellar Hydrolytic Catalysts
1345
Alkyl(dimethyl)[2-oxo-2-(pyridin-2-yl)ethyl]ammonium Bromides 4. General Procedure
2-(Bromoacetyl)pyridine (5.1 g, 26 mmol) was prepared from its hydrobromide (7 g, 35 mmol) by
reaction with saturated aqueous potassium carbonate (3.5 g, 25 mmol). The liberated base was ex-
tracted into ether (4 × 20 ml) and the solvent was removed by evaporation under reduced pressure.
This procedure was carried out as fast as possible. Freshly prepared crude 2-(bromoacetyl)pyridine
was dissolved in ethanol (50 ml) and alkyl(dimethyl)amine (31 mmol) was added. After 4 days
standing at room temperature the solvent was evaporated and the resulting crude product was recrys-
tallized from ethanol–ether.
Hexyl(dimethyl)[2-oxo-2-(pyridin-2-yl)ethyl]ammonium Bromide (4a)
Yield 3.6 g (56%), m.p. 164–165 °C. For C15H25BrN2O (329.3) calculated: 54.71% C, 7.65% H,
1
8.51% N; found: 55.00% C, 8.04% H, 8.23% N. H NMR spectrum (CDCl3): 0.87 t, 3 H, J(6′,5′) = 7.2
(CH3); 1.30 m, 6 H ((CH2)3); 1.75 m, 2 H (CH2CH2N+); 3.80 s, 6 H ((CH3)2N+); 3.91 t, 2 H, J(2′,1′) = 8.5
(CH2N+); 5.78 s, 2 H (CH2C=O); 7.59 ddd, 1 H, J(5,4) = 7.6, J(5,6) = 4.8, J(5,3) = 1.2 (H-5); 7.91 td,
1 H, J(4,3) = J(4,5) = 7.8, J(4,6) = 1.7 (H-4); 8.04 dt, 1 H, J(3,4) = 7.9, J(3,5) = J(3,6) = 1.0 (H-3);
8.68 ddd, 1 H, J(6,5) = 4.7, J(6,4) = 1.6, J(6,3) = 0.9 (H-6). IR spectrum (KBr): 2 927 (CH3(CH2)n),
1 706 (C=O).
Dimethyl(octyl)[2-oxo-2-(pyridin-2-yl)ethyl]ammonium Bromide (4b)
Yield 3.7 g (41%), m.p. 163.5–164.5 °C. For C17H29BrN2O (357.3) calculated: 57.14% C, 8.18% H,
1
7.84% N; found: 56.85% C, 8.18% H, 7.59% N. H NMR spectrum (CDCl3): 0.87 t, 3 H, J(8′,7′) = 7.0
(CH3); 1.26 m, 10 H ((CH2)5); 1.60 m, 2 H (CH2CH2N+); 3.74 s, 6 H ((CH3)2N+); 3.88 t, 2 H, J(2′,1′) = 8.1
(CH2N+); 5.78 s, 2 H (CH2C=O); 7.60 ddd, 1 H, J(5,4) = 7.6, J(5,6) = 4.7, J(5,3) = 1.2 (H-5); 7.93 td,
1 H, J(4,3) = J(4,5) = 7.8, J(4,6) = 1.7 (H-4); 8.05 dt, 1 H, J(3,4) = 7.9, J(3,5) = J(3,6) = 1.1 (H-3);
8.69 ddd, 1 H, J(6,5) = 4.7, J(6,4) = 1.7, J(6,3) = 0.9 (H-6). IR spectrum (KBr): 2 925 (CH3(CH2)n),
1 708 (C=O).
Decyl(dimethyl)[2-oxo-2-(pyridin-2-yl)ethyl]ammonium Bromide (4c)
Yield 4.3 g (49%), m.p. 150–151 °C. For C19H33BrN2O (385.4) calculated: 59.22% C, 8.63% H,
7.27% N; found: 58.99% C, 8.78% H, 7.22% N. 1H NMR spectrum (CDCl3): 0.88 t, 3 H, J(10′,9′) = 6.7
(CH3); 1.24 m, 14 H ((CH2)7); 1.61 m, 2 H (CH2CH2N+); 3.76 s, 6 H ((CH3)2N+); 3.88 t, 2 H, J(2′,1′) = 8.6
(CH2N+); 5.78 s, 2 H (CH2C=O); 7.60 ddd, 1 H, J(5,4) = 7.6, J(5,6) = 4.8, J(5,3) = 1.2 (H-5); 7.92 td,
1 H, J(4,3) = J(4,5) = 7.8, J(4,6) = 1.7 (H-4); 8.05 dt, 1 H, J(3,4) = 7.9, J(3,5) = J(3,6) = 1.0 (H-3);
8.69 ddd, 1 H, J(6,5) = 4.7, J(6,4) = 1.6, J(6,3) = 0.9 (H-6). IR spectrum (KBr): 2 924 (CH3(CH2)n),
1 709 (C=O).
Dodecyl(dimethyl)[2-oxo-2-(pyridin-2-yl)ethyl]ammonium Bromide (4d)
Yield 5.0 g (56%), m.p. 140–142 °C. For C21H37BrN2O (413.4) calculated: 61.01% C, 9.02% H,
6.78% N; found: 60.98% C, 9.48% H, 6.42% N. 1H NMR spectrum (CDCl3): 0.88 t, 3 H, J(12′,11′) = 7.06
(CH3); 1.24 m, 18 H ((CH2)9); 1.65 m, 2 H (CH2CH2N+); 3.77 s, 6 H ((CH3)2N+); 3.89 t, 2 H, J(2′,1′) = 8.59
(CH2N+); 5.78 s, 2 H (CH2C=O); 7.60 ddd, 1 H, J(5,4) = 7.61, J(5,6) = 4.75, J(5,3) = 1.22 (H-5);
7.92 td, 1 H, J(4,3) = J(4,5) = 7.77, J(4,6) = 1.69 (H-4); 8.05 dt, 1 H, J(3,4) = 7.86, J(3,5) = J(3,6) = 1.07
(H-3); 8.69 ddd, 1 H, J(6,5) = 4.72, J(6,4) = 1.63, J(6,3) = 0.90 (H-6). IR spectrum (KBr): 2 925
(CH3(CH2)n), 1 708 (C=O).
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Cibulka, Dvorak, Hampl, Liska:
Alkyl(dimethyl)[2-hydroxyimino-2-(pyridin-2-yl)ethyl]ammonium Nitrates 2. General Procedure
Ketone 4 (10 mmol) and hydroxylamine hydrochloride (1.7 g, 20 mmol) were stirred in pyridine (8 ml)
and ethanol (8 ml) at 65 °C for 25 h. Then, the solvents were evaporated under reduced pressure and
the residue purified by column chromatography (chloroform–methanol–acetone–water 15 : 5 : 5 : 1).
The obtained salts were converted to nitrates by anion exchange on Amberlite IRA 400 (OH– form,
solvent ethanol) and neutralization with diluted nitric acid (1 : 1). Pure products were obtained by
repeated crystallization from ethyl acetate.
Hexyl[(2-hydroxyimino)-2-(pyridin-2-yl)ethyl]dimethylammonium Nitrate (2a)
Yield 0.5 g (15%), m.p. 95–96 °C. For C15H26N4O4 (326.4) calculated: 55.20% C, 8.03% H, 17.17% N;
1
found: 55.50% C, 8.29% H, 17.42% N. H NMR spectrum (CDCl3): 0.88 t, 3 H, J(6′,5′) = 6.7 (CH3);
1.32 m, 6 H ((CH2)3); 1.88 m, 2 H (CH2CH2N+); 3.18 s, 6 H ((CH3)2N+); 3.46 t, 2 H, J(2′,1′) = 8.0
(CH2N+); 4.83 s, 2 H (CH2C=NOH); 7.30 dd, 1 H, J(5,4) = 8.0, J(5,6) = 5.0 (H-5); 7.74 t, 1 H,
J(4,5) = J(4,3) = 7.5 (H-4); 8.09 d, 1 H, J(3,4) = 8.1 (H-3); 8.53 d, 1 H, J(6,5) = 4.2 (H-6); 13.59 s,
1 H (OH). IR spectrum (KBr): 2 924 (CH3(CH2)n), 1 618 (C=NOH). pKa = 9.3.
[2-Hydroxyimino-2-(pyridin-2-yl)ethyl]dimethyl(octyl)ammonium Nitrate (2b)
Yield 0.6 g (18%), m.p. 96–98 °C. For C17H30N4O4 (354.5) calculated: 57.61% C, 8.53% H, 15.81% N;
1
found: 57.54% C, 8.89% H, 15.55% N. H NMR spectrum (CDCl3): 0.87 t, 3 H, J(8′,7′) = 6.9 (CH3);
1.26 m, 10 H ((CH2)5); 1.88 m, 2 H (CH2CH2N+); 3.18 s, 6 H ((CH3)2N+); 3.45 t, 2 H, J(2′,1′) = 6.8
(CH2N+); 4.81 s, 2 H (CH2C=NOH); 7.28 ddd, 1 H, J(5,4) = 7.6, J(5,6) = 5.0, J(5,3) = 1.1 (H-5);
7.69 td, 1 H, J(4,5) = J(4,3) = 7.7, J(4,6) = 1.8 (H-4); 8.05 d, 1 H, J(3,4) = 8.1 (H-3); 8.51 ddd, 1 H,
J(6,5) = 4.8, J(6,4) = 1.7, J(6,3) = 1.1 (H-6); 13.50 s, 1 H (OH). IR spectrum (KBr): 2 927
(CH3(CH2)n), 1 618 (C=NOH). pKa = 9.3.
Decyl[2-hydroxyimino-2-(pyridin-2-yl)ethyl]dimethylammonium Nitrate (2c)
Yield 0.5 g (13%), m.p. 82–84 °C. For C19H34N4O4 (385.5) calculated: 59.66% C, 8.96% H, 14.65% N;
found: 59.33% C, 9.08% H, 14.45% N. 1H NMR spectrum (CDCl3): 0.88 t, 3 H, J(10′,9′) = 6.6
(CH3); 1.25 m, 14 H ((CH2)7); 1.88 m, 2 H (CH2CH2N+); 3.18 s, 6 H ((CH3)2N+); 3.46 t, 2 H,
J(2′,1′) = 7.9 (CH2N+); 4.82 s, 2 H (CH2C=NOH); 7.28 d, 1 H, J(5,4) = 7.3 (H-5); 7.70 t, 1 H, J(4,5) =
J(4,3) = 8.0 (H-4); 8.08 d, 1 H, J(3,4) = 8.0 (H-3); 8.52 d, 1 H, J(6,5) = 4.1 (H-6); 13.57 s, 1 H (OH).
IR spectrum (KBr): 2 926 (CH3(CH2)n), 1 621 (C=NOH). pKa = 9.3.
Dodecyl[2-hydroxyimino-2-(pyridin-2-yl)ethyl]dimethylammonium Nitrate (2d)
Yield 0.5 g (11%), m.p. 74–76 °C. For C21H38N4O4 (410.6) calculated: 61.44% C, 9.33% H, 13.65% N;
found: 61.64% C, 9.18% H, 13.42% N. 1H NMR spectrum (CDCl3): 0.88 t, 3 H, J(12′,11′) = 7.0
(CH3); 1.25 m, 18 H ((CH2)9); 1.88 m, 2 H (CH2CH2N+); 3.18 s, 6 H ((CH3)2N+); 3.45 t, 2 H, J(2′,1′) = 8.6
(CH2N+); 4.81 s, 2 H (CH2C=NOH); 7.28 d, 1 H, J(5,4) = 7.5 (H-5); 7.70 t, 1 H, J(4,5) = J(4,3) = 7.7
(H-4); 8.08 d, 1 H, J(3,4) = 8.0 (H-3); 8.52 d, 1 H, J(6,5) = 4.6 (H-6); 13.55 s, 1 H (OH). IR spectrum
(KBr): 2 922 (CH3(CH2)n), 1 618 (C=NOH). pKa = 9.4.
pKa Determination
pKa values were determined spectrophotometrically at two wavelengths (maxima of the =NOH and
=NO– form, respectively). The pH values of oxime solutions were adjusted with 0.05 M buffers
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Metallomicellar Hydrolytic Catalysts
1347
(HEPES, EPPS, CHES, CAPS) ranging from pH 7.2 up to 11.1. The pKa values were obtained by
nonlinear regression analysis of the absorbance vs pH data using software package Enzfitter (Leather-
barrow R. J.: Enzfitter. Elsevier, Amsterdam 1987).
Kinetic Measurements
Solutions of the reactants were prepared in 0.05 M MES buffer (pH 6.3). No changes in pH were
observed during the kinetic runs. The reactions were followed on a spectrophotometer HP 8452A
(diode array, Hewlett–Packard) equipped with a thermostatted multicell transport cell holder HP
89075C at 25.0 ± 0.1 °C. The reactions were initiated by injection of the 2.0 . 10–3 mol l–1 solution
of the substrate (PNPDPP, PNPH or PNPP) in acetonitrile into the spectrophotometric cell containing
2 ml of the buffered solution of the catalyst. The volume of the added substrate solution was 4 µl
when the concentration of catalyst were below 3 . 10–3 mol l–1 or 20 µl in all other cases, the result-
ing concentrations of the substrate being 4 . 10–6 mol l–1 and 2 . 10–5 mol l–1, respectively. The con-
centration of the 4-nitrophenoxide ion was monitored at 400 nm. The reactions invariably followed
the first-order kinetics up to 90% conversion. The rate constants were obtained by nonlinear re-
gression analysis of the absorbance vs time data using the software package Enzfitter. The fit error
of the rate constant did not exceed 2% in the case of PNPDPP and 5% in the other cases.
RESULTS AND DISCUSSION
Syntheses of the Ligand Surfactants 2
Ketoximes 2 were synthesized starting from 2-acetylpyridine as outlined in Scheme 1.
Its bromination followed by quaternization with alkyl(dimethyl)amines 3 afforded
alkyl(dimethyl)[2-oxo-2-(pyridin-2-yl)ethyl]ammonium bromides 4 in good yields. On
the other hand, transformation of ketones 4 proceeded very slowly and the desired
oximes 2 were obtained in relatively low yields. Similar results were reported by Kuni-
take12 in the synthesis of a structurally related surfactant dodecyl[2-hydroxyimino-2-
phenylethyl]dimethylammonium bromide.
CH
3
R
N
CH
3
3
CH
N
3
CH
3
N
N
Br
N
R
O
O
O
CH
3
Br
4
CH
CH
N
3
3
N
R
N
N
R
3
NOH
NOH
CH
CH
3
NO
3
Cl , Br
2
SCHEME 1
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1348
Cibulka, Dvorak, Hampl, Liska:
Since both bromides and chlorides might occur as counterions in the prepared oximes,
the crude products were subjected to anion exchange as indicated in Scheme 1. Nitrate
was chosen as a counterion for its low coordination ability.
Kinetic Studies
Three model substrates were used for testing the hydrolytic efficiency of micellar and
metallomicellar systems prepared from ligand surfactants 2. 4-Nitrophenyl diphenyl
phosphate (PNPDPP) was employed as a model of toxic organophosphorus com-
pounds3c. 4-Nitrophenyl hexanoate (PNPH) and 4-nitrophenyl pyridine-2-carboxylate
(PNPP) were chosen as representatives of carboxylates, the latter as a substrate possessing
the ability to coordinate itself as a ligand to metal ions in metallocatalysts3a,3d. All the
kinetic experiments were performed under pseudo-first-order conditions, ccat >> csubst
,
with monitoring the appearance of 4-nitrophenoxide ion at 400 nm, at 25 °C in 0.05 M
MES buffer (pH 6.3). These experimental conditions allowed direct comparison of our
results with those reported in previous studies3e,6
.
In the first series of experiments, hydrolytic efficiency of the prepared salts 2 was
tested in comicelles with CTAB (salts 2b–2d) and homomicelles (salt 2d). In all cases,
the comicelles of ligand surfactants 2 with CTAB were much more efficient than analogous
comicellar system of the ligand 1c (ref.6) at the same conditions (Tables I–III). Since
the nucleophile attacking the ester function is oximate anion, the remarkable increase in
hydrolytic activity of salts 2 compared to ligand 1c can be explained by increased
acidity of their hydroxyimino groups. pKa of the ligand 1c was 11.8 (ref.13) while pKa
of salts 2 was close to 9.3 due to the electron-withdrawing effect of the quaternary
nitrogen. The hydrolytic efficiency of salts 2 comicellized in CTAB increased with the
length of the hydrophobic alkyl chain.
In our previous paper6 we reported acceleration of the PNPH hydrolysis by a factor
of 20 as a result of fourfold decrease of the cCTAB/c1a molar ratio. This fact demon-
strated that both the substrate and the catalyst were tightly bound in micelles due to the
hydrophobic forces; consequently, high concentrations of the reactants were achieved
in a small micellar volume. On the other hand, the observed rate constant kobs of the
PNPH cleavage in the presence of the comicellar system 2b–CTAB was almost unaf-
fected by a change of the cCTAB/c2b molar ratio, thus revealing that a significant part of
the salt 2a remained in non-aggregated form in bulk water phase without the kinetic
benefit of micellar catalysis. At low concentrations of CTAB, the reactivity of the cata-
lyst was limited by the amount of micelles present in the solution and by the partition
of the salt 2b between micellar and bulk water phase. At high concentrations of CTAB,
salt 2b was diluted in the micellar phase by the inert cationic tenside. As a result, the
kobs vs cCTAB/c2b plot was a flat curve with a maximum at cCTAB/c2b ≈ 20 (Fig. 1).
Comicelles of the more lipophilic salt 2d and CTAB were more reactive at the same
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Metallomocellar Hydrolytic Catalyst
1349
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1350
Cibulka, Dvorak, Hampl, Liska:
conditions and an expected monotonic kobs vs cCTAB/c2d plot was obtained (Fig. 1). The
lower gradient in comparison with ligand 1a indicated higher hydrophilicity of the salt 2d.
In the absence of the comicellizing tenside CTAB, the reactivity of the octyl-
ammonium salt 2b was poor and the kobs vs c plot gave evidence that no aggregates
were formed in the solution (Fig. 2). A rate profile characteristic of a spontaneous
aggregation and micellar catalysis was observed in the case of the most lipophilic
dodecylammonium salt 2d (Fig. 2); the critical micelle concentration (CMC) estimated
from this plot was approximatelly 3 . 10–3 mol l–1. PNPDPP was the only substrate the
cleavage of which we were able to follow in homomicellar solutions of the salt 2d. The
hydrolysis of both PNPH and PNPP under above mentioned conditions (pH 6.3, 25 °C)
was too fast (τ1/2 < 2 s).
Preparation of metallomicellar systems and basic evaluation of their hydrolytic effi-
ciency was carried out as described in previous studies3d,3e. Metal ions were added in
proper amount to comicellar solutions of ligand 2 and CTAB. The formation of com-
plexes was monitored spectrophotometrically by appearance of new bands in UV spec-
tra (Table IV). Interestingly, while Cu(II) complexes were formed immediately after
the addition of Cu(NO3)2 to comicellar solutions of ligand surfactants 2, formation of
Co(II) complexes was completed approximately after 5 s and complexation of Ni(II)
took more than 1 min. The UV/VIS spectra gave no evidence of the formation of Zn(II)
complexes.
Kinetics of complexation in homogeneous and micellar solutions can be different as
was demonstrated by Tondre et al.14 in the case of coordination of Cu(II) and Ni(II) to
6-[(alkylamino)methyl]-2-(hydroxymethyl)pyridines and 7-(4-ethyl-1-methyloctyl)qui-
nolin-8-ol comicellized with CTAB. The authors explained the decrease in the rate of
complex formation by electrostatic repulsion of metal ions by the positive surface
6
6
2
kobs . 103
4
k
. 10
obs
s–1
2
4
2
0
0
20
cCTAB/cox
40
FIG. 1
Plots of pseudo-first-order rate constants
of PNPH cleavage vs cCTAB/cox ratio for
oximes 2b (❍) and 2d (❐) at pH 6.3 (0.05 M
MES buffer) and 25 °C, cox = 4 . 10–4 mol l–1
0
20
40
c
/c
CTAB ox
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Metallomicellar Hydrolytic Catalysts
1351
charge of cationic micelles. We do not expect that the dependence of complexation
velocity on the type of metal ion can be explained by electrostatic repulsions due to the
surface charge of micelles. So far, we have not found any plausible explanation for this
phenomenon.
The results of the preliminary kinetic screening of the hydrolytic efficiency of the
metallomicellar catalysts prepared from ligand surfactants 2 are summarized in Tables I–III.
Relative values kobs/kCTAB showing the rate enhancement of the PNPDPP and PNPH
hydrolysis in the presence of metallomicellar systems compared to the reaction running
in CTAB are given as well (Tables I and II). Since the transition metal ions themselves
TABLE III
Hydrolytic activitya of the ligand 2d and its complexes towards PNPP
2d
1c (ref.6b)
kobs, s–1
Cation
kM, s–1(ref.6b)
kobs, s–1
kobs/kM
kobs/kM
–
–
5.98 . 10–2
3.68 . 10–3
2.67 . 10–2
1.95 . 10–1
6.82 . 10–2
–
38
3.15 . 10–4
3.22 . 10–4
1.12 . 10–2
1.83 . 10–2
1.31 .10–3
–
3.3
29
Co(II)
Ni(II)
Cu(II)
Zn(II)
9.64 . 10–5
3.92 . 10–4
2.63 . 10–2
7.07 . 10–5
68
7.4
970
0.7
19
a
Conditions: [ligand] = [metal] = 4 . 10–4 mol l–1, [CTAB] = 8 . 10–3 mol l–1, 0.05 M MES buffer,
pH 6.3, 25 °C.
4
2
k
. 10
obs
s–1
10
5
kobs . 105
2
0
0
2
4
cox . 102
FIG. 2
0
Plots of pseudo-first-order rate constants
of PNPDPP cleavage vs concentration for
oximes 2b (❍) and 2d (❐) at pH 6.3
(0.05 M MES buffer) and 25 °C.
0
20
40
–1
3
c
. 10 mol l
ox
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

1352
Cibulka, Dvorak, Hampl, Liska:
as Lewis acids accelerate the hydrolysis of PNPP by electrophilic catalysis3a, the cata-
lytic effect of the metallomicellar systems is expressed as kobs/kM where kM stands for
the pseudo-first-order rate constant of the PNPP cleavage in the presence of a metal ion
(Table III). Surprisingly, in all cases with an exception of Zn(II), the presence of metal
ions decreased the reactivity of salts 2 towards the model substrates. The fact that the
hydrolytic efficiency of ligand surfactants 2 was almost unaffected by the presence of
Zn(II) was in accordance with the UV/VIS spectral data giving no evidence of some
complex formation (Table IV).
To our best knowledge, metallomicellar systems based on complexes of salts 2 are
the first known example of deactivation of the nucleophilic function by its coordination
to metal ion.
The generally accepted mechanism of the activation of nucleophilic functions in
hydrolytic metalloenzymes and their models is outlined in Scheme 2. Coordination to a
metal ion increases the acidity of the ligand (in many cases by several orders of magni-
tude15) and consequently the concentration of the nucleophile.
On the other hand, the coordination to a metal ion must decrease the nucleophilicity
of the deprotonated ligand. Apparently, the observed reactivity of the hydrolytic
metallocatalyst is the result of these contradictory effects of the coordination. In the
hitherto published studies3,6 only the activating effect of the metal ions has been mentioned.
This is not surprising since the acidity of the ligands so far investigated has been too
low, with the pKa values ranging approximately from 12 (hydroxyimino group in alkyl
pyridin-2-yl ketoximes13) to 15 (primary or secondary hydroxy group in pyridinyl3d,3e
or imidazolyl3a,3f,3g ligands) and the hydrolytic activity of the micellar and metallo-
micellar systems has been tested mostly under mild conditions close to physiological
pH. Under these conditions, the ligands (regardless whether coordinated or non-coordi-
nated) have been far from the fully deprotonated state in which the differences in the
TABLE IV
UV spectra of the ligands 2 and their complexesa
Cation
λmax, nm
–
270
348
324
328
270
Co(II)
Ni(II)
Cu(II)
Zn(II)
a
Conditions: [ligand] = 1 . 10–4 mol l–1, [metal] = 2 . 10–3 mol l–1, [CTAB] = 8 . 10–3 mol l–1, 0.05 M
MES buffer, pH 6.3.
Collect. Czech. Chem. Commun. (Vol. 62) (1997)

Metallomicellar Hydrolytic Catalysts
1353
nucleophilicity of the free and coordinated ligand could be observed (in micellar and
similar aggregated systems where the reactions proceed mainly at the interface of the
bulk water phase and micellar pseudophase, second order rate constant k2 derived formally
as a quotient of kobs and analytical concentration of the catalyst has no real physical sense).
Contrary to all other ligands so far investigated, the decrease in the nucleophilicity of
the ligand surfactants 2 by their coordination to metal ions was the dominating effect.
This fact can be explained by the relatively high acidity of salts 2 diminishing the
significance of the ligand activation according to Scheme 2.
NuH
D
NuH
D
n+
n+
M
n+
M
-M
2
a
1
pK
pK
n+
a
+H
-H
+H
-H
Nu
Nu
1
a
2
a
M
pK >> pK
D
D
SCHEME 2
Conclusions
Reactivity of the transition metal ion complexes of alkyl(dimethyl)[2-hydroxyimino-2-
(pyridin-2-yl)ethyl]ammonium salts 2 prepared as water soluble ligand surfactants
pointed out that metal ions influenced the efficiency of the hydrolytic metallocatalysts
in two contradictory ways. Until now, solely the activating effect of metal ions due to
the increase of the ligand acidity has been taken into account while the decrease of the
ligand anion nucleophilicity has been ignored. Apparently, the design of new and more
effective metallomicellar hydrolytic catalysts will require optimization of the above
mentioned effects based on the results of detailed investigation of the coordination
processes.
This work was supported by the Grant Agency of the Czech Republic (Grant No. 203/93/0546).
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