A critical concentration for micellar diastereoselectivity

Tetrahedron Lettess,Vol.24,No.26,pp Printed in Great Britain

A CRITICAL

2615-2618,1983

CONCENTRATION

FOR MICELLAR

Robert A. Moss* and Yuan-Ching

The onset of diastereoselectivity

thiocholine

surfactant

is associated

lie above the apparent Stereoselective

P. Chiang

kinetic

micellar

in the esterolyses

with a "critical"

critical

micelle

or vesicular

to enantioselective

substrates,

activated

particularly

been observed,2C

of New Jersey,

of -LL and -DL-Z-Trp-Pro-PNP

surfactant

concentration

by a

which appears

to

concentration.

reagents

have mostly been devoted

have sometimes

DIASTEREOSELECTIVITY

of Chemistry, Rutgers, The State University New Brunswick, New Jersey 08903

Department

Summary.

0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd.

continue

reactions

amino acid esters.

to attract

between

chiral

Although

with few exceptions,2d

Efforts

attention.l#'

nucleophiles

impressive

and chiral

enantioselectivities

little is known about their molecular-

level origins. We studied peptide3f

esters by functional

(&)-Pro-PNP, micellar

the stereoselective

&was

surfactants

cetyltrimethylammonium 16-SH

&(CH3)2CH2CHzSH,

cleavage

of diastereomeric

For example,

such as 16-SH, -la.

(CTA) chloride,

and the kinetic -LL/DL

(vs. 0.28 in CTAC1).3Crdr'

Cl-

R = n-C16H33

(16-SH)

R = g-C12H25

(12-SH)

&,

R = CH3

interactions moieties

our rationale to tripeptide

surfactant

and, based on molecular

COOC~H~-PNO~

(Z-Trp-Pro-PNP)

model

studies,

a mecha-

satisfactorily accounted for the observations, and could be success3f substrates, It was based on specific, favorable 1:l hydrophobic hydrocarbon

in extended

chain with "clefts"

peptide

Here,

we

but show that the onset of diastereoselectivity

concentration

Thiol surfactant

which appears

12-SH

of 16-~~.~

to lie above the critical

(lb) was prepared The thioacetate

defined

conformations. 3a,c

play any role in the diastereoselectivity?

in the synthesis

with

= Br-)

dipeptides,3c

of the surfactant's

the affirmative,

diastereoselecwere observed

was offered.jaJc

of the -LL substrates

surfactant

3 H

2, R = CHZ-(3-indolyl)

(l-SH, counterion

4 other sets of _Z-AA-CL)-Pro-PNP

Although

substrate

I

2,

fully extended

16-SH than by OH- in

CsH3CH2CCONHCHCON

&,

rationale

and tri-

at pH 8, z-(L)-Trp_

-LL diastereoselectivities

R

nistic

dipeptide3a-e

21,000 times more rapidly by 4 x 10T3 M micellar

cleaved

tivity was 5.0 with

micellar

by a reaction precursor

2615

by the Pro, PNP, and R

Did micellization

of the

not only answer

this question

is associated

with a critical

micelle

sequence

concentration

identical

in

(cmc).

to that employed

of 12-SH was characterized

by nmr spec-

2616

troscopy

and elemental

acterized

analysis,

by mar spectroscopy

factant]

profile5

centrations

whereas

12-SH itself

and Ellman's

was determined

of 12-SH between

assay

(mp 131-133'

(93% free SH).

for the cleavage

from CHzC12/EtzO)

A standard

of pnitrophenyl

0.677 x 10m3 and 6.80 x lo-' M.6

rate constant/[sur-

acetate

We observed

was char-

(PNPA) using an apparent

12 concmc of

-1.1 x 10e3 M for 12-SH. Next, we measured by stopped-flow squares

values

mean values results permit

pseudo-first-order

spectroscopy,

rate constants

monitoring

the release

for k were determined in duplicate or triplicate (reproducibility, fS%), and -JI in Figure 1 as a function of [12-SH]. Additionally, in Table I, are kinetic

at 3 surfactant

or nonmicellar Together,

concentrations

thiocholine

bromide,5

the Figure

12-SH is strongly

(selected from the 8 concentrations

of the rate constants

12-SH with -LL or DL-2:

and diastereoselectivities

l-SH

accelerated,

relative

l), which

with micellar

catalytic

"regimes"

12-SH

for reactions

I (2 x 10m3 < [l2-SH] < 5 x 10m3 M), esterolysis to thiocholine

is observed.

(b) Under

lop3 M), esterolytic

rate enhancements

selectivity

sharply over a very narrow

develops

of Figure

observed

(1~). -

and Table reveal three differing

(a) Under Regime

but -no diastereoselectivity

III

of -LL or DL-26 ion at 400 nm. Least-

appear

comparisons

Regime

for the 12-SH cleavage

of pnitrophenoxide

increase

(a factor of -1800 at

Regime

(-5000 at

[SHI = 2.7 x 10s3 M),

II (-5 x 10m3 < [12-SH1 < -5.5 x [SHI = 4.55 x low3 M1 and diastereo-

range of surfactant

(-5.5 x low3 M < [12-SH]), rate constant

of

by

enhancements

concentrations.

reach -35,000,

(kLL/kDL) appears to level off at -5.7. -J,-+ that the rate constant enhancements observed under regime

(c) Under

relative

to

1-SH, and diastereoselectivity We believe kinetic

cmc of l2-SH measured

bilisation

for cleavage

of the more hydrophobic

substrates

is stereoselective

we propose

stereoselective.

At

which

enforces

selectivity.' micellar

association

nomenon.)

However,

model.

of regime

esterolytic

12-SH/LL-2

Appropriate

implies

at

that the abrupt onset

to a second kind of

I are small and loosely packed.

occurs

results

responsible

rate enhancements

packed micelle, for diastereo-

of regime

the cmc.

experiments

I to pre-

would occur at -5 x 10V3 M

is clearly

a micelle-induced

with PNPA and -Z-Ala-Pro-PNP,'

to represent

light scattering

but they are not

to a more densely

interactions3c

diastereoselectivity

in view of the kinetic

The

of these substrates

rate enhancements,

of 12-SH and 2, in which case micellization

5 x low3 M 12-SH too high a concentration micelle

Reactions

to a transition

the non-stereoselective

this interpretation,

I are micellar.

should be lowered upon solu-

for LL-2.7

-5 x 10-a M, transition

the specific

One might attribute

(Even under

12-SH.

[12-SH1

M)

this, however,

that the 12-SH micelles

They bind -LL or DL-2 and induce significant

selectively

LL or DL-2. --

at -5 x 10d3 M 12-SH corresponds

one which

Tentatively,

(-1.1 x 10m3

Accepting

[12-SH1 2 2 x 1O-3 M should be micellar. of diastereoselectivity 12-SH micelle,

of PNPA

Accordingly,

are planned

we prefer

to further

phe-

we consider the two-

test this ex-

planation. Acknowledgments. Society)

We thank the donors of the Petroleum Research Fund (American Chemical

and the U.S. Army Research

Office

for financial

SUppOrt.

2617

20

1s

10

5

0 0

2

4

(see-I), ordinate, vs. 103x[12-SH] (M), abscissa, Figure 1. k of LL-2 (diaonds) or DL-2 (triangles) by 12-SH (lb). -

Table

lo3

I.

[SHI

Cleavage

of -LL or DL-2 by 12-SH or 1-SH

8

6 for the Cleavages

(lb -- or lc).a

Reagent

(!$L)12-SH'$L)l_SS

7.10 7.10

12-SH l-SHb

19.2 0.000546

3.35 0.000689

5.73 0.79

35,200

4.55 4.55

12-SH 1-SH

1.36 0.000270

1.11 0.000361

1.22 0.75

5,040

2.74 2.74

12-SH l-SH

0.487 0.000265

0.472 0.000322

1.03 0.82

1,840

0.00

bufferC

0.000093

0.00022

0.42

a b see ref. 6 for conditions. Rate constants for l-SH cleavages were determined on a Gilford Model 250 spectrophotometer. CValues of k are extrapolated to pure buffer from -Q 3 runs in 20-40% dioxane/buffer; cf., ref. 2c.

2618

References

(1) Review:

J. H. Fendler,

"Membrane

Mimetic

and Notes

Chemistry,"

John Wiley

& Sons, New York,

1982,

PP- 309-322. (2) (a) K. Cqino, Y. Kimura, Ohkubo,

I. Tomita,

M. Nango,

N. Matsumoto,

C. G. Griggs, Murakami,

K. Machiya,

and N. Kuroki,

A. Nakano,

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A. Yoshimatsu,

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Tetrahedron

Approaches

group,3a-c

16-SH, cleavage but in OH-/CTACl

tive) intramolecular

2499

Fendler

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although

profiles

Catalysis,"

J. Am. Chem.

pH 8, )J = 0.05

ibid., 23, --

1985

Lett., 22,

(1982);

scissile from

Sot., 102,

(KCl), 25"C,

different

in Micellar

B. S.

(b) R. A. MOSS,

(c) R. A. Moss, Y-S. Lee,

cleavage

carbonyl

(DL-stereoselec-

754 (1980).

[substrate]

CTAHr micelles

and Macromolecular

limits are shifted

ranges

from 1.1-1.4,

x 10e3 M 12-SH diastereoselectivity

"0.75-1.5

= 2.0 x 10m5 M.

are known:

Systems,"

out to -20 x 10d3

rises from -180

(at [12-SH] = 1.5 x 10m3 M) to -600

in USA

3 March

M

1983)

substrates

downward.

J. H.

Academic

Press,

reveal

Similar

From -0.22-0.75

x 10d3 M

and k varies from 3-30. -+12-SH/$SH rapidly rises to -3.1 and remains

12-SH, even as the overall

nearly constant

(Received

Enzyme

(1981).

283 (1981).

with && and E-g-Ala-Trp-Pro-PNP

the concentration

12-SH, -LL/DL diastereoselectivity Between

(i) K.

1975, pp. 32-35.

(8) Hate constant/[l2-SH] phenomena,

alone,

between

"Catalysis

667

(d) R. A. Moss and Y-S. Lee, Tetrahedron and G. 0. Bizzigotti,

and C-W. Huang, buffer,

(1981);

1982, pp. 200 ff;

(1979);

Chem. Lett.,

ibid.,

Sot. Jpn., 54, 576

results mainly to a diketopiperazine. ad

cyclization

0.02 M phosphate

(7) Concentration

2391

(e) Y.

728 (1981);

and N. Kuroki, Lett.,

(c) K.

R. L. Elliott,

(1981);

Sot., 103,

occurs by 16-S- attack on the substrate's or buffer

(5) R. A. Moss, G. 0. Bizzigotti, (6) Conditions:

890

to Understanding

New York,

(f) R. A. Moss, Y-S. Lee, and K. W. Alwis, ibid., 22, (4) In micellar

(b) Y. Ihara,

K. Inoue, and K. Ohkubo,

M. Nango,

J. Am. Chem. Sot., 101,

ibid., 102, 6646

(1982);

(d) J. M. Brown,

and R. Ueoka, Bull. Chem.

Ed., Elsevier,

(e) R. A. Moss, T. Taguchi,

1875

Int. Ed., x, -

Y. Nakagawa,

T. Kunimasa,

(3) (a) R. A. Moss and Y-S. Lee in "Chemical Green,

Chem.

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Y. Ninomiya,

(g) Y. Ihara, N. Kunikiyo,

785 (1981);

Chem. Lett.,

Chem. RapId Commun., 2, 521 (1982);

and H. Ohta, Chem. Cormnun., 739 (1982);

G. Helmchen,

(f) R. Ueoka,

and W. Tagaki, Makromol.

rate constant

enhancement

(at [12-SHI = 17 x 10T3 M).