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Langmuir 1994,10, 122-125
Effective Neutral Deaggregators Xi-Kui Jiang,* Guo-Zhen Ji, and Jin-Tao Zhang Shanghai Institute of Organic Chemistry, Academia Sinica, 354 Feng-Lin Lu, Shanghai 200032, China Received September 20,1993" Hydrolysis of the aggregated p-nitrophenyl hexadecanoate ((216-Ag) can be appreciably or greatly accelerated by some neutral molecules, hereafter called "deaggregators" or deAgr's, e.g., n-octyl-a-Dglucopyranoside (a-G-81,n-dodecyl-a-D-glucopyranoside(a-G-12),n-dodecyl-8-D-glucopyranoside (8-G12), 13,17-dioxa-15-nonacosanyl-~-maltoside (M-2-12), and 17,21-dioxa-19-heptatriacontanyl-B-maltoside (M-2-16), in the 40:60 (v/v) (4 = 0.40) and 4555 (v/v) (4 = 0.45) dioxane-Hz0 aquiorgano solvent. Experimental data show that the rate enhancement of the C16-Ag is most likely brought about by processes depicted by our simplified "deaggregation" scheme (Scheme l), Le., the deAgr molecules first break into the C16-Ag, then "grab" one (or more) C16 molecule(s)and carry it (them) into the bulk of solvent in which the C16 molecule is released in ita monomeric form. Two double-chained deAgr's (M-2-12 and M-2-16) that incorporatehydrophilicity and lipophilicityin an effectiveand balanced manner possess deaggregating abilities orders of magnitude greater than those of the typical ionic surfactants. The above-mentioned scheme is fully supported by fluorescence spectroscopy with l-(a-naphthyl)-3-oxapentadecane(Np-12) as the fluorescence probe.
Introduction If we call organic molecules which tend to form simple aggregates or coaggregates (Ag's or CoAg's)' "aggregators" (Agr's), then those which tend to break up simple Ag's may be called "deaggregators" (deAgr's). Positively charged surfactants may break up simple Ag's, but only at relatively high concentrations (l0-3-lO-' M),2 presumably by its hydrophilicity, originating from its electric charge, or by micelle formation. Some macromolecular hosts, e.g., sodium carboxymethylamyloseand calixarenes? are known to be able to break up Ag's by formation of host-guest complexes. The aim of the present work is to search for electrically uncharged deAgr's which are structurally simpler than most host molecules and yet much more effective than ionic surfactant molecules. We visualized that such an effective deAgr might mainly operate by a mechanism depicted in a greatly simplified manner by Scheme 1, Le., the deAgr molecule can break up or reduce the size of an Ag or CoAg mainly by two steps, i.e., (1) getting into the Ag (kh)by virtue of the hydrophobic-lipophilic interaction (HLI) between the long hydrocarbon chain(s) of the deAgr and of the Agr molecules in the Ag and (2) "grabbing" one (or two) Agr molecule(s) in the Ag and carrying the latter out of the Ag (k& in the form of a dimeric (or trimeric) species A by virtue of its hydrophilicity. A species, of course, can later release the Agr molecule in its monomeric form to the bulk of the solvent. The A species can also be formed from the dynamic equilibrium between deAgr molecules and monomeric Agr molecules. We presume that the most effective deAgr should possess the best balance among its four rate constants, kh,kin-', kout, and kout-l. Incidentally, confirmation, modification, or disproof of this scheme might provide some insight for designing compounds which might slow down (or even cure) arteriosclerosis in the future. e Abstract published in Advance ACS Abstracts, December 1,
1993. (1) Jiang, X. K. Acc. Chem. Res. 1988,21, 362, and references cited therein. (2) (a) Menger, F. M.; Portnoy, C. E. J. Am. Chem. SOC.1967,89,4698. (b) Menger, F. M.; Venkataram, U. V. J. Am. Chem. SOC.1986,108,2980. (3) (a) Jiang, X. K.; Li, X. Y.; Huang, B. Z. Roc. Indian Acad. Sci. (Chem. Sci.) 1987,98,423. (b) Huang, B. Z.; Li, X. Y.; Jiang, X.K. Acta Chim. Sin. 1989, 47, 1007. (c) Shinkai, S.; Shirahama, Y.; Tsabaki, T.; Manabe, 0. J. Am. Chem. Sac. 1989,111,5477.
0743-7463/94/2410-Ol22$04.50/0
Scheme 1
Agr molecules
in an Ag
deAgr
A
molecule
species
Scheme 2
(,E)
- -(CH2)n.1CH3. n - 12. 16
n-n, R
n-n or n-2-n
CHZO(CHZ)~.~CHJ
n.2-",
R
- .b
n
- 12, 16
AuO(CH~),.~CH~
We report here the deaggregating behavior of several neutral deAgr's, i.e., n-octyl-a-D-glucopyranoside(a-G8), n-dodecyl-a-D-glucopyranoside(a-G-12), n-dodecylP-Dglucopyranoside(&G-12),13,17-dioxa-l9-nonamnsanylP-maltoside (M-2-12), a n d 17,21-dioxa-19-heptatriacontanyl-6-maltoside(M-2-16) (Scheme 2). They are much more effective than the ionic surfactants mentioned previously. Other compounds or additives tested are ethyla-D-glucopyranoside (a-G-21, maltose (M-0), n-dodecylp-maltoside (M-121, n-hexadecyl-/3-maltoside(M-16), ndodecyltrimethylammonium bromide (DTAB), lauroyl monoglyceride (MG-121, sodium laurate, decanol, and hexadecane. p-Nitrophenyl hexadocanoate (C16) is used as the kinetic probe: and hydrolytic rate constants of C16 were measured a t 35 "C in 4060 (v/v) (4 = 0.40) and 4555 (v/v) (4 = 0.45) dioxane (DX)-H20 mixtures. It has been firmly (4) (a) Menger, F. M.; Portnoy, C. E. J.Am. Chem. SOC.1968,90,1876. (b) Blyth, C. A.; Knowles, J. R. J. Am. Chem. SOC.1971,93,3021. (c) Murakami, Y.; Aoyama, Y.;Kida, M. J. Chem. SOC., Perkin Tram. 2 1977, 194.
0 1994 American Chemical Society
Langmuir, Vol. 10, No. 1, 1994 123
Effective Neutral Deaggregators established that aggregated C16, hereafter designated as C16-Ag, hydrolyzes more slowly than monomeric C16;49s therefore, one crucial test for the true deAgr behavior is that it will accelerate the hydrolysis of the C16-Ag but will not affect the hydrolysis of the monomeric C16.2b In likeness to the concepts of cmc and CAgC (critical aggregate concentration),' in this paper, the "critical deaggregator concentration" or deCAgC of a deAgr is defined as the deAgr concentration a t which the deAgr will start to break up the Ag of a probe, e.g., the kinetic probe C16, a t a specified concentration of the probe. Again, e.g., in analogy to the measurement of CAgC's and C ~ C ' S , the deCAgC values can be obtained from the break point of ak,dk,versus [deAgrl plot, where kobandk, represent hydrolytic rate constants of C16 in the presence and absence of a deAgr. Obviously, a smaller deCAgC value signifies a greater deaggregating ability. In the present work, both the deCAgC values and k o b / k , ratios are used to assess the effectiveness of an additive as a deAgr. l-(a-Naphthyl)-3-oxapentadecane (Np-12) is used as the fluorescence probe in the 4 = 0.40 DX-H20 system a t 25 "C. The excimer of Np-12 is easily formed inside aggregated Np-12 (Np-12-Ag);therefore, an added effective deAgr is expected to reduce the fluorescence emission of the Np-12 excimer and simultaneously increase the Np12 monomer emission.
Experimental Section Instruments. Boiling and melting points were not corrected. 'H-NMR spectra were obtained at 60 MHz on a Varian EM360, at 90 MHz on a FX-gOQ, or at 200 MHz on a Varian XL-200. IR spectra were recorded on a Shimadzu IR-440. MS were taken on a Finnigan 4021 or Shimadzu QPlO00 in E1 or FAB mode. Kinetic experiments were performed on a Perkin-Elmer 559UV/ vis spectrophotometer. Fluorescence spectra were run on a Perkin-Elmer LS-50 luminescence spectrometer. Materials. All prepared compounds were identified by melting points, 1H-NMR,IR, MS, and elemental analysis. M-0, decanol, and DTAB were purchased. M-0 (A.R.) was used without further purification; decanol (c.P.) was distilled twice before use; DTAB was recrystallizedfrom ethanol. Sodium laurate was recrystallized from EtOAcether twice before use. C16,Np-12, and MG-12 were prepared according to ref 6: C16, mp 63-64 OC; MG-12, mp 62-63 "C; Np-12, mp 132-133.5 "C. Alkyl glycosides (a-G-2, a-G-8, a-G-12, 0-G-12, M-12, M-16, M-2-12,M-2-16)were synthesized according to refs 7 and 8.The general procedure is given in the following paragraphs: The monosaccharide or disaccharide (10 mmol) was treated with anhydrous sodium acetate (10 or 16 mmol) and acetic anhydride (12.5 or 20 mmol) heated to 100 "C (or 120 "C) for 4 hand worked up as usual to give the 0-anomerof the peracetylated saccharide. The peracetylated 8-saccharide (1.0 &mol) was dissolved in anhydrous CHZC1, (80 mL) and stirred with molecular sieves 4A (4g) under Nz atmosphere. The solution was treated with SnC4 (1.0 mmol) and then with the alcohol component (1.2 mmol) dissolved in anhydrous CHzClz (20 mmol). a-G-n(n = 2,8,12) and 8-G-12. The preparation of 0-G-12 according to the above-mentioned general procedure required a reaction time of 4 h, and that of the a-G-n (n = 2, 8, 12) approximately 15 h. After that time the mixture was poured into saturated NaHCOs solution (100 mL). The organic layer was separated, and the aqueous phase extracted with CHzClz (40 mL). The combined organic phase was washed twice with water (40mL), dried over anhydrous Na2S04,and evaporatedtodryness. Purification was achieved by chromatography on silica gel with 100:5 petroleum ether-ethyl acetate as the developer. The (6)Jiang, X.K.; Hui, Y.Z.; Fan, W. Q. J. Am. Chem. SOC.1984,106,
~ ~
resulting material was deacetylated by treatment with NaOMe in anhydrous MeOH (40mL) under reflux, the solution was then neutralized with anhydrous acetic acid and evaporated. The crude product was purified by chromatography: a-G-2, mp 112114 "c, [ a I D = +148O (CHsOH); a-G-8, mp 72-73 OC, [U]D = +156O (CHIOH); a-G-12, mp 80-81 "C, [ a [ = ~ + 9 6 O (CHsOH); 8-G-12, mp 77-78 OC, [ah = -24' (CHsOH). (B)M-nand(B)M-2-n(n= 12,16). Treatmentofanequimolar mixture of peracetylated disaccharides and ROH in CH&lZ with an equivalent amount of Me3SiOSOzCFs in the presence of powdered molecular sieve 4A for 4 hat room temperature afforded the 8-anomer. The procedure for purification and deacetylation were the same as that for 8-G-n. M-12, mp 78-80 OC, = +48 OC (CHIOH). M-16, [ a ] D = +57.1° (CHaOH). M-2-12,mp 222c, 224 OC, [ a ] D = +35.2O (CHsOH). Anal. Calcd for C&7&: 62.20; H, 10.10. Found: C, 61.82; H, 10.16. 1H NMR S 0.88 (6H,m),1.25(40H,m),3.4-3.8(m),4.00(1H,d, J=7.8Hz),4.45 (1H, d, J = 3.8 Hz). IR (KBr): 3380 cm-l. MS (FAB):776 (M + 23), 100%. M-2-16, mp 212-214 OC. [ a ] D = +38O (CHsOH). Anal. Calcd for C47Hm013: C, 65.24; H, 10.72. Found: C, 64.85; H, 10.64. lH NMR S 0.90 (6 H, m), 1.28 (56 H, m), 3.4-3.8 (m), 4 . 0 5 ( 1 H , d , J = 7 . 8 ) , 4 . 5 0 ( 1 H , d , J = 3 . 8 H z ) .IR(KBr): 3380 cm-l. MS (FAB): 888 (M+ 23), 100%. Solvent. Dioxane and water were purified by standard procedures. The kinetic experimentawere performed in mixtures of DX and NaOH-NaHCOs (0.01 M each) buffer solution containing 0.34 M of NaCl (pH 11.70). The pH value of the final mixture is 13.00 for the 4 = 0.40 solvent and 13.11 for 4 = 0.45. The fluorescencespectra were taken in the mixture of DX and H20 with 4 = 0.40. Kinetics. Kinetic measurements weremade by using a PerkinElmer 559UV/vis spectrohotometer witha constant-temperature bath connected to a cell holder. A 1.0-cm cell was filled with 3.00 mL of solution and thermally equilibrated for 15 min. A DX solution of C16 (30 pL) was injected into the cell with a microsyringe. The increase in absorbance of p-nitrophenolate at 410 nm was then traced as a function of time. Pseudo-firstorder rate constants were obtained in the usual manner." All the rate constants are accurate to within *lo%. Fluorescence Measurement. Fluorescence spectra of Np12 in the absence and presence of d e w s and other additives were run on a Perkin-Elmer LS-50 luminescence spectrometer in the = 0.40 DX-HzO system at 25 OC, by using the excitation wavelength of 283 nm.
Results The CAgC values of C16 in the 4 = 0.40 and 0.45 DXH2O systems were determined to be 0.87 X 106 and 3.72 X 104 M, respectively, in our previous works.Q The effect of concentration of a-G-12 and other additives on the kob of the C16-Ag for 4 = 0.40 DX-H20 system are listed in Table 1,in which the data for a-G-8,@-G-12,M-12, M-16, M-2-12, and M-2-16, are not included because the concentration range studied differed greatly and because they are available from Figure 1. Systematic and similar data have also been obtained for the 4 = 0.45 DX-H20 system. Figure 1 illustrates the effects of added deAgr's and other additives on the hydrolysis of the C16-Ag (IC161 = 4.0 X 10-6 M)in the 4 = 0.40 DX-H20 system, by plotting k&,/k, vs [deAgr]. Similar results were obtained for the 4 = 0.45 DX-H20 system. Figure 1 shows that a-G-12 and other deAgr's can speed up the hydrolysis of the C16Ag, whereas M-12 and M-16 fail to do so. Table 2 lists the deCAgC values of the deAgr's obtained from the kob/k, vs [deAgrl plots for both 4 = 0.40 and 0.45 DX-H20 systems. Figure 2 illustrates the effect of a-G-12 concentration on the hydrolysis of the C16-Ag a t different specified concentrations of C16 in the 4 = 0.40 DX-H20 system, by
7202.
(6) Hui, Y.Z.; Wang, S. J.; Jiang, X. K. Acta Chim. Sin. 1982,40,1148. (7) Vill, V.; Bocker, T.; Thiem, J.; Fisher, F., Lip. Cryst. 1989,6, 349. (8) Paulaen, H.Carbohydr. Res. 1984, 131, C1.
(9) Jiang, X. K.; Ji, G. Z.; Nie, J.; Zhang, J. T. Chin. J. Chem. 1991, 9, 559.
(10)Jiang, X. K.; Shi, J. L.; Chen, X. To be submitted for publication.
124 Langmuir, Vol. 10, No. 1,1994
Jiang et al.
Table 1. Dependence of Hydrolytic Rate Constants, k;b ( l e s-l), of C16-Ag on the Concentration of deAgr's and Other Additives in the g5 = 0.40 D X - H B System at 35 OC, [C16] = 4.0 X 1od M [additivelb (106 M) de& or additive 0 1.0 10 50 100 150 200 250 300 350 400 a-G-12 a-G-12" a-G-2
2.61 11.4 2.95 2.71 2.66
CiaHzsOH MG-12
a
2.58 10.9 3.06 2.81 2.78
2.67 11.2 2.82 2.58 2.83
2.76 11.2 2.98 2.49 2.70
2.92 11.1 2.89 2.66 2.67
3.06
3.34 10.9 2.95
3.53
3.70 11.2 2.95
3.86
3.96 11.9 3.11 2.55
[ClS] = 0.6 X 106 M, Le., C16 is in ita monomeric form. The maximum concentration of the additives used is close to ita solubility limit. 1. M-2-12
I
2. no additive
2.00 A
1.00
4 . hexadecane
3 v1
E' U
C
0
X
9
4.0
8.0
12.0
16.0
3
1.40
m 1.20
Figure 3. Effects of M-2-12 (8.0 X 1od M), hexadecane (8.0 X 106 M) and M-0 (1.0 X 10-9 M) on the fluorescence spectra of the aggregated Np-12 (8.0x 1 0 6 M) in the 4 = 0.40 DX-H20 system at 25 "C.
1.00
I 0
:
500
1000
1500
2000
u----t
4000
[deAgr] (lO%I)
1. M-2-12
Figure 1. Plots of kdk, VB [deAgrl. The effect of deAgr concentration on the hydrolytic rate constants of C16-Ag in the 4 = 0.40 DX-HaO mixture at 35 OC. [C16] = 4.0 X 1od M.
2. no additive 3. hexadecane
Table 2. The deCAgC (lod M) Values of dehgr's in DX-Ha0 Systems at 35 OC, for g5 = 0.40, [CN] = 4.0 X 104 M for 4 = 0.45, [C16] = 10 X lo4 M* 9 a-G-8 a-G-12 8-G-12 M-2-12 M-2-16 DTAB M-12 M-16 0.40 80.9 9.3 41.5 4 . 0
