A non-steroidal facial amphiphile

Article abstract of DOI:10.1021/ja0608747

This paper gives the synthesis of an unusual non-steroidal amphiphile consisting of a large rigid molecule that possesses two water-solubilizing sulfates on one face and an extended hydrophobic surface on the other. The properties of this compound have been examined by X-ray analysis, light and cryo-electron microscopy, surface tension, conductivity, microrheology, and NMR. Aqueous solutions behave quite differently from those of a conventional amphiphile with long linear and flexible chains (e.g., sodium dodecyl sulfate). Thus, there is evidence that the facial amphiphile self-assembles to form viscous networks, but without the traditional critical micelle concentration, as if assembly is a stepwise process. Emulsions of toluene in water promoted by the facial amphiphile are stable for many months. In contrast to conventional surfactants, the NMR peaks are obliterated in aqueous solutions of the facial amphiphile. Both X-ray and cryo-HRSEM data suggest a lamellar morphology. Copyright

Full text of DOI:10.1021/ja0608747

Published on Web 03/28/2006
A Non-Steroidal Facial Amphiphile
Fredric M. Menger* and Jennifer L. Sorrells
Department of Chemistry, Emory UniVersity, Atlanta, Georgia 30322
Received February 13, 2006; E-mail: menger@emory.edu
Synthetic amphiphiles most commonly consist of a polar group
attached to a long hydrocarbon chain. Dissolving such amphiphiles
in water produces micelles and other hydrophobically driven self-
assemblies. Rigid hydrophobic surfaces, like the flexible linear
chains, also induce association, a fact that Nature has exploited to
great advantage. Bile salts (steroids with a hydrophobic R-side and
a hydrophilic â-side)1 and certain helical peptides with hydrophobic
patches2 are common examples. Attempts to synthesize nonpeptidal
“facial amphiphiles” have centered mainly on steroidal systems.
Thus, Kahne et al.3 glycosylated the R-face of cholic acid, while
Marcelis et al.4 and Zhao et al.5 placed three R-ammonium groups
on the same steroid. Savage et al.6 synthesized anionic facial
amphiphiles from cholic acid. Elemans et al.7 departed from the
cholic acid motif with their glycouril-based facial amphiphiles. We
have now synthesized non-steroidal facial amphiphile 1 that
possesses two water-solubilizing sulfates on one face and a rigid
wall of hydrophobicity on the other. As will be shown, the
properties of 1 are markedly different from those of sodium dodecyl
sulfate (SDS), a long-chain counterpart of 1.
Figure 1. Synthesis of 1.
Scheme 1
Synthesis of 1 (Figure 1) followed in part the work of Feldman
et al.8 The Ni-catalyzed cycloaddition reaction of norbornadiene
gave both dimer and trimer that were separated by fractional
sublimation (65 and 127 °C). Diels-Alder reaction of the trimer
with methyl 9-anthracenecarboxylate gave both syn and anti diesters
that were separated by chromatography (see details in the Sup-
porting Information). Proof of isomer structure relied on an X-ray
analysis of the syn diester (Figure 2). Compound 1 had the expected
1H and 13C NMRs and an HRMS molecular weight calcd for
C51H47O8Na2S2 of 897.24997 (M + H)+, found 897.25023. The
anti isomer of 1 was also prepared, but it was too water-insoluble
to warrant further study.
Evidence supporting an affinity of 1 for a hydrocarbon interface
came from the following experiment: 3 mg of 1 was dissolved in
2.5 mL of water and vortexed for 10 min with 2.5 mL of toluene.
This resulted in an o/w emulsion whose photomicrograph (20X) is
given in Figure 3. No change in the size distribution of the droplets
was observed after more than 6 months.
Figure 2. X-ray crystal structure of the syn trimer diester in Scheme 1.
reached 1100 ( 100 mPa‚s after 6 days of aging, aggregation does
not reach full equilibrium instantly as it does with SDS. Aggregation
1
was further indicated by a H NMR spectrum in D2O where, in
contrast to a normal sharp spectrum in CD3OD, the peaks were
obliterated owing to slow intra-aggregate tumbling. Defining
aggregate size by dynamic light scattering was not possible because
of a high polydispersity.
Surface tension versus log [conc] plots of 1 bear little resem-
blance to those of SDS (Figure 4A). Although SDS has a sharp
break corresponding to its critical micelle concentration, 1 displays
no such behavior; aggregation must be stepwise rather than
cooperative. Moreover, 1 is less surface active than SDS (e.g., 63
vs 38 mN/m, respectively, at 15 mM). Consistent with previous
work,9 the larger area/molecule of 1 tends to adversely affect its
surface activity. Additionally, the rigidity of the structure might
impair the packing density at the air/water interface.
A 40.1 mM aqueous solution of 1 is noticeably viscous,
suggesting solute aggregation. Microrheology measurements (ob-
tained by analyzing the Brownian motion of suspended carboxylate-
modified polystyrene particles bearing a fluorescent tag) on a freshly
made solution gave a value of 170 ( 10 mPa‚s. Since this value
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C O M M U N I C A T I O N S
Figure 5. Cryo-HRSEM at 104X instrumental magnification; bar ) 1 µm.
spectroscopy, caution must be exercised before extrapolating cryo-
HRSEM to the solution state with which we have been primarily
concerned.12 Nonetheless, Figures 2 and 4, plus an observed
birefringence under cross polarizers, are all consistent with a
propensity of 1 to form lamellar sheets that grow in a noncoopera-
tive manner while enhancing the solution viscosity.
Figure 3. Photomicrograph (phase contrast, green filter) of an o/w emulsion
stabilized by 1 in which toluene droplets are suspended in water. The
emulsion is stable for many months.
Until just recently, 1 was merely a virgin molecule unaddled by
investigation. Future synthetic organic chemistry will no doubt
bestow upon us additional facial amphiphiles whose solution
properties presently defy prediction and thus pique curiosity.
Acknowledgment. This work was supported by the Petroleum
Research Foundation and the National Institutes of Health. We are
grateful to Dr. Kenneth Hardcastle (Department of Chemistry) and
Dr. Vikram Prasad (Emory Department of Physics) for the X-ray
and microrheology data, respectively. The cryo-HRSEM picture
was taken by the late Dr. Robert P. Apkarian whose friendship
and masterful electron microscopy over the years will be deeply
missed.
Note Added after ASAP Publication. After this paper was
published ASAP on March 28, 2006, a production error in the text
of the third sentence of the first paragraph was corrected to restore
the authors’ intended meaning. The corrected version was published
ASAP on March 30, 2006.
Supporting Information Available: Analytical and synthetic
procedures including spectroscopic data and instrumentation. This
material is available free of charge via the Internet at http://pubs.acs.org.
Figure 4. (A) Surface tension versus log [conc]. (B) Conductivity versus
[conc] for 1 in water at room temperature.
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Conductivity versus [conc] plots for 1 likewise do not show the
abrupt change in slope accompanying micellization as seen with
SDS (Figure 4B). The slope decrease at the CMC of SDS has been
attributed to 63% of the sodium counterions binding tightly to the
micelles.10 Linearity with 1’s conductivity plot thus indicates full
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