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Liposomes from Polymerizable Glycolipids.

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These high packing densities together with the increased
stability of the monolayers provide a basis for the use of
these polymer systems as model membranes.
(12), (13): The corresponding dialkylamines are added to
acrylonitrile, reduced with LiAlH,[141,and then allowed to
react with methacryloyl chloride.
Received: November 24, 1980 [Z 652a IE]
German version: Angew. Chem 93, 108 (1981)
A -
A-
Fig. 1. a) Surface-pressure-areadiagram of (5) at 2 "C (-----) and 25 "C (--)
and of polymeric (5) at 25 "C (-.-.-). b) Surface-pressure-area diagram of (13)
(--)
and of polymeric (13) (-. - . -), each at 25 "C.p = surface pressure (mN/
m); A =area (nm'/molecule).
Liposomes, i. e. cell models with bimolecular membranes,
were prepared by sonicating aqueous
of the
monomers at ca. 40 "C. On filtration through a 8-pm Millipore-filter, clear or slightly opaque solutions are obtained,
which turn turbid after some days.
The polymerization of these monomer vesicles is carried
out by UV-irradiation of the aqueous solutions. The polyreaction of the butadiene derivatives (3)-(6) in liposomes
can be followed by the decreasing monomer absorption at
265 nm. The polymerization of the acryl derivatives (7)-(9)
was proved by freeze-drying the aqueous solutions followed
by gel-filtration. In contrast to the monomers the polymer
vesicle solutions are stable for weeks.
It could be shown by electron microscopy that the vesicle
structure is preserved during the polymerization. This is consistent with results obtained on polymerizing diacetylene vesicle~[~~].
Compounds (14) and (15) were synthesized in order to
study the influence of chiral membrane components on model reactions. In addition, mixed systems of polymerizable lipid analogues, natural phospholipids, and proteins are under
current investigation. For investigations on cell recognition,
monolayers and polymer liposomes consisting of glycolipids
have been prepared (cf. i6c1).
Procedure
(1): 11-(N-Methacryloy1amino)undecanoic acid"] is esterified with N-methyliminodiethanol in the presence of dicyclohexylcarbodiimide (DCC) and 4-(dimethy1amino)pyndine and quaternized using methyl bromide[*].
(3): 2,4-Octadecadienoicacid['] is esterified with N-methyliminodiethanol adding DCC/4-(dimethylamino)pyridine
[I] J. H. Fendler, Acc. Chem Res. 13. 7 (1980).
121 a) E Sackmann, Ber. Bunsenges. Phys. Chem. 82, 891 (1978); h) D.A. Tyref!. T. D.Heuth, C. M. Colley. B. E. Ryman, Biochim. Biophys. Acta 457.
259 (1976); c) C.-H. Huung. Biochemistry 8. 344 (1969); d) T. Kunifuke. J.
Macromol. Sci. Chern. A / 3 , 587 (1979); e) G. Scherphof. F Roerdmk, D
Hoeksrra, 3. Zborowski, E Wisse in G. Gregoriudix Liposomes in Biological
Systems. Wiley. New York 1980, p. 179.
[3] C. M . Gupra, C. E. Cosfello. H. G. Khorana, Proc. Natl. Acad. Sci. USA 76.
3139 (1979).
[41 a) H:H. Hub, B. Hupfer, H. Ringsdorf, Am Chem. SOC., Org. Coatings
Plastics Chem. Div. Prepr. 42, 2 (1980); cf. Nachr. Chem. Tech. Lab. 28,215
(1980); b) H:H. Hub, B. Hupfer, H. Koch, H. Ringsdorf, Angew. Chem 92.
962 (1980); Angew. Chem. Int. Ed. Engl. 19. 938 (1980).
[5] a) S.L. Regen, B. Czech, A. Sing,J. Am. Chem. SOC.102,6638 (1980); b) D.
S. Johnsron, S. Sanghera, M. Pons, D. Chapman, Biochim. Biophys. Acta
602, 57 (1980); c) D. O'Brien, private communication.
161 a) D.Day, H.-H. Hub, H. Ringsdorf, Isr. J . Chem. 18, 325 (1979): b) D. Day.
H. Ringsdorf, J . Polym. Sci. Lett. 16. 205 (1978); c) H. Bader, H. Ringsdorf.
J . Skura, Angew. Chem. 93, 109 (1981); Angew. Chem. Int. Ed. Engl. 20,
Nr. 1 (1981).
171 H. G. Burr, J. Koldehofl, Makromol. Chem. 177. 683 (1976).
IS] B. Neises, W. Sreglich. Angew. Chem. YO, 556 (1978); Angew. Chem. Int.
Ed. Engl. 17, 522 (1978).
191 H. Ringsdorf, H. Schupp, Am. Chem. SOC.,Org. Coatings Plastics Chem.
Div. Prepr. 42. 379 (1980)
1101 H. Eibl, D.Arnold, H. U. Welmen, 0.Wesrphul, Justus Liebigs Ann. Chem.
709. 226 (1967).
I l l ] F. R. Pfegfer, C. K . Miuo, 3. A. Weisbach. J . Org Chem. 35, 221 (1970).
[I21 A. F. Rosenthal, J . Chem. SOC.1965, 7345.
[13] L. Gros, Dissertation, Universrtat Mainz. planned for 1981.
[14] Cronin er a/. US-Pat. 4034040 (1977).
[15] A. Scher, Justus Liehigs Ann. Chem. 589. 234 (1954).
Liposomes from Polymerizable Glycolipids'"'
By Hubert Bader, Helmut Ringsdorf;and Josef Skurai"
Polymerizable analogues of cell membrane components,
e. g. phospholipids and lysophospholipids bearing acryl-, butadiene-, and diyne groups"] in the hydrophobic parts of the
molecules have already been synthesized and investigated in
monolayers and liposomes[21.
In this connexion glycolipids are of particular interest,
since they exhibit vital functions and properties in the natural cell membrane such as cell recognition, antigenicity, histocompatibility, and lectin affinity. Especially their properties as lectin receptors make glycolipids useful tools for
studying specific interactions between lectins (sugar recognizing proteins) and saccharide bearing liposome~['~.
We report here on the first glycolipids with the diyne group [ ( l )
and (2)], their behavior in monomolecular films, their poly-
181.
(4): Monomer (3) is allowed to react with methyl bromide
in acetone.
(5) and (6) are synthesized via conventional lipid chemistry methods["].
(7)-(ll), (14), (15): The corresponding 1,2-diglycerineester [(7)]["], 1,2-diglycerine ethers [(S), (9)][i2',dialkylamines
[(lo),(ll)](Fluka, Eastman) or L-aspartic acid dioctadecyl
are allowed to react with methacryloyl
esters [(14), (15)][l3]
chloride or 6-(N-methacryloylamino)hexanoic acid [(15)]
and DCC.
Angew. Chem. lnr. Ed. Engl. 20 (1981) No. I
[*] Prof. Dr. H. Ringsdorf. H. Bader, Dr. J Skura
Institut fur Organische Chemie der Universitat
J.-J.-Becher-Weg 18-20, D-6500 Mainz 1 (Germany)
[**I Polyreactions in Oriented Systems. Part 24.-Part 23: 111.
0 Verlag Chemie, GmbH. 6940 Weinheim. 1981
0570-0833/81/0l01-W91
$
02.50/0
91
merization in monolayers and liposomes, as well as their interactions with the lectin Concanavalin A (Con A).
The glycolipids (1) and (2) (see Procedure) were spread as
monomolecular layers at the gas-water interphase on a Langmuir film balance. Figure 1 shows the corresponding surfacepressure-area isotherms.
somes. When a conA solution in phosphate buffer (pH 7.4) is
injected under a monomolecular film of (1) on the same buffer at a constant surface pressure of 10 mN/m, a considerable expansion of the film can be observed due to strong interaction of the lectin with the monolayer.
Solutions of monomer and polymer liposomes of glycolipid (1) react with Con A solution by agglutination and precipitation within a short period of time. This effect could not
be observed with different polymer liposomes not bearing
saccharide moieties.
Procedure
Fig. 1. Surface pressure-area isotherms of (I) at 20°C (
and 1 "C (.. .).
of (2) at 20°C (--),
and of polymer (I) at 1 " C (-----). p=surface pressure
(in mN/m), A =area (in nm'/molecule).
The glucose derivative (1) was obtained as a colorless solid
(m.p. 73-75 oC)L61when acetobromoglucose and 10,12hexacosadiyne-1-01 in dry ether were allowed to react in the
presence of silver 4-hydroxyvaleriate (Koenigs-Knorr reactionf51), followed by the cleavage of the protective groups
with sodium methoxide.
The lactobionic acid derivative (2) could be synthesized
via its hydrazide, followed by
from lactobiono-1,5-lactone~'~
coupling with 10,12-hexacosadiynoic acid via its mixed anhydride with ethyl chloroformate (m. p. 114°C)[61.
Received: November 26. 1980 [Z 652b I€]
German version: Angew. Chem. 93, 109 (1981)
While (1) is only in a liquid expanded phase at 20°C with
a collapse point of 0.29 nm2/molecule and 43 mN/m, at 1 "C
it shows a liquid expanded phase up to about 0.45 nm2/molecule and 8 mN/m followed by the solid-analogous phase
with a collapse point of 0.31 nm2/molecule and 51 mN/m.
The high area value at the collapse point evidences the large
area occupied by the glucopyranose ring bound directly to
the diyne alcohol.
The glycolipid (2) has a solid phase in the whole temperature range investigated from 20 "C to 40 "C (collapse point
0.18 nm2/moIecule and 63 mN/m). The head-group of (2)
occupies a smaller area than that of (1);the reason for this is
the hydrophilic spacer between galactopyranose and diynoic
acid which permits a deeper penetration of the sugar moiety
into the subphase.
When a monomolecular film of (1) is UV irradiated at
1 " C and a surface pressure higher than 10 mN/m, the typical polymerization of the diyne group takes place. The colorless monomer film turns blue and then redc4].As expected
the polymerized film does not exhibit a liquid expanded
phase any more. The occupied area at the collapse point is
only insignificantly smaller than in the monomer film.
The monomolecular film of (2) also yields a blue polymer
film when irradiated at 20°C and 35 mN/m, but does not
show the color change to red caused by change of the polymer conformation even after 30 min of irradiation. As in the
case of ( I ) , the contraction of the film during the polymerization is very small. When a n aqueous suspension of (1) is sonicated for 15 min at 50°C, a clear colorless solution is obtained, which is polymerized in a quartz cuvette at 0°C by
UV irradiation. As in monolayers, during the polyreaction
the color change via blue to red takes place, as had already
been observed in the case of different liposome forming diacetylene compounds[']. In contrast, no liposomes are formed
by (2) when sonicated for longer periods (up to 30 min) and
at higher temperatures (up to SOOC). Only a crystalline suspension is formed. Its filtrate turns faintly blue o n irradiation. The strong tendency of the hydrazide linkages to form
hydrogen bonds make glycolipid (2) excessively rigid and
poorly dispersible in water, which is also confirmed by the
missing liquid expanded phase in the monolayer.
The interaction of ( 1 ) with the lectin C o n A was investigated in monolayers and with monomer and polymer lipo-
92
0 Verlag Chemie. CmbH, 6940 Weinhelm, I981
CAS Registry numbers:
(I). 76024-88-9; (Z), 76036-52-7: acetobromoglucose. 572-09-8; hexacosa-l0,12diyn-1-01, 75495-26-0; hexacosa-l0,12-diynoic acid, 73510-21-1; lactobionolactone hydrazide, 76024-89-0
111 A Akimoro, K. Dorn. L Gros, H. Ringsdorf; H. Schupp. Angew. Chem. 93,
108 (1981); Angew. Chem. Int. Ed. Engl. 20,W (1981).
121 H:H. Hub, B. Hupfer, H. Koch, H. Ringsdorf, Angew. Chem. 92,962 (1980);
Angew. Chem. Int. Ed. Engl. 19.938 (1980); D.S. Johnston, S. Sanghera. M.
Pons. D. Chapman, Biochim. Biophys. Acta 602, 57 (1980).
131 C A. Orr. R. R. Rando, F. W . Bangerter, J. Biol. Chem. 254, 4721 (1979). R.
Y. Hampton, R. W. Holz, I . J. Goldstein, ibid. 255. 6766 (1980).
141 D. R. Day, H. Ringsdorf, Makromol. Chem. 180, 1059 (1979).
151 G. Wufl. W Kniger, G. Rohle, Chem. Ber. 104. 1387 (1971). G. Wu!fr: C
Rohle, W. Kruger. ibid. 105. 1097 ( I 972).
161 The 1R and NMR spectra are wholly in accord with the assigned structures.
171 T J. Williams, N . R. Plessas. I . J. Goldstein. J . Lonngren, Arch. Biochem.
Biophys. 195. 145 (1979).
Palladium-Catalyzed Reduction of Multiple Bonds
with Mg/CH,OH[**l
By George A . Olah, G. K. Surya Prakash,
Massoud Arvanaghi, and Mark R. Bruce"'
It has long been known that magnesium in methanol (or in
ethyl or isopropyl alcohol) can been used for the reduction of
carbon-heteroatom double bonds"' and N-oxidesI2];more recently, the selective reduction of cx,P-unsaturated nit rile^[^"]
and aryl-substituted ethylenes has also been achieved in this
In all these reactions, however, isolated, nonactivated double or triple bonds were found unaffected by the
reducing system. We now wish to report that addition of catalytic palladium metal on carbon to the Mg/CH30H reagent dramatically enhances its reactivity, thus allowing rapid
I*]
["I
Prof. Dr. G. A. Olah, Dr. G. K. S. Prakash, M. Arvanaghi,
Dr. M.R. Bruce
Hydrocarbon Research Institute and Department of Chemistry
University of Southern California
Los Angeles, California 90007 (USA)
Synthetic Methods and Reactions, Part 94. This work was supported by the
National Science Foundation and the National Institutes of Health -Part
93; G. A . Olah. S. C. Narang, L D Field, C. F. Salem. 3 . Org. Chem. 45,
4792 (1980).
0570-0833/8l/010l-0092
$
02.50/0
Angew. Chem. Inf. Ed. Engl. 20 (1981) No. 1
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