[12]Annulene gemini surfactants: Structure and self-assembly

Article abstract of DOI:10.1002/anie.200702140

(Chemical Equation Presented) The long and short of it: Gemini surfactants with a non-Hueckel diaza[12]annulene core have been synthesized (see picture). DFT computations give a minimum-energy conformation with alternate shorter and longer bonds, and with the two N substituents pointing away from each other. Studies on the aggregation of the molecules in water show they encounter packing difficulties, with no evidence for ring/ring interactions at the micelle surfaces.

Full text of DOI:10.1002/anie.200702140

Angewandte
Chemie
DOI: 10.1002/anie.200702140
Self-Assembly
[12]Annulene Gemini Surfactants: Structure and Self-Assembly**
Lei Shi, Dan Lundberg, Djamaladdin G. Musaev, and Fredric M. Menger*
Enticed by a 2006 report of the first N-substituted dia-
za[12]annulenes,[1] we shifted the new ring system into the
colloidal domain via the long-chain derivatives A, B, and C
(Scheme 1). The compounds can be classified as “gemini
thereby estimate their size and shape, without the use of
potentially invasive probes.
A, B, and C were synthesized by treating N-(2,4-dinitro-
phenyl)pyridinium chloride with long-chain amines.[1]
1H NMR and 13C NMR spectroscopy, high-resolution mass
spectrometry (HRMS), and elemental analysis left no doubt
as to the structures. For example, the ring moieties showed
only three proton signals [d = 8.1 (4H); 8.5 (2H); and 9.5 ppm
(4H)] and three carbon signals [d = 128.6; 145.1; and
145.5 ppm]. The HR mass spectrum of A, for example, gave
a mass of 531.44353 (calcd for [MÀCl]+ = 531.44395).
The first task, after the pure annulene gemini surfactants
were in hand, was to obtain the geometry of the N-methyl
derivative using density functional theory with a large basis
set [B3LYP/6-311 + G(2d,p)]. All calculations were per-
formed by using the Gaussian03 program.[12] The normal
mode analysis (1 atm, 298.15 K) confirms that structures I and
II (Figure 1) are the minimum-energy conformers for the N-
methyl derivative. Conformer I was found to be slightly more
stable. In contrast, conformer II is a few kcalmolÀ1 more
Scheme 1. Structure of [12]annulene gemini surfactants.
surfactants” because of their double-chain, double-cation
structures.[2–4] In more recent years, particularly after the term
“gemini surfactant” had been christened as such,[5] investiga-
tion of the compounds has flourished. Both academic and
industrial laboratories have sought and found useful members
of the family (with potential applications ranging from gene
transfection,[6] to oil recovery,[7] styrene polymerization,[8] and
the synthesis of mesoporous materials[9]). Inserting
a
[12]annulene moiety into the gemini format represents an
unorthodox approach from which we hoped to learn how a
large electronically active core affects self-assembly.
Work on the annulene gemini surfactants had origins over
and above the general curiosity surrounding most new and
interesting molecules. First, we wanted to determine the
geometric parameters (planarity, bond-order, etc.) for the
non-Hückel ring system—a system that is remarkably stable
compared to the ephemeral all-carbon analogue.[10] Second,
the annulene core gave us an opportunity to detect by NMR
spectroscopy any possible interactions between the head
group and the termini of the two hydrocarbon tails. The
presence of a “looping disorder” in self-assembled systems
has been a contentious issue over the years.[11] Third, a
recently installed capability in pulse-gradient-spin-echo NMR
(PGSE NMR) spectroscopy allowed us to measure the
diffusion constants of the self-assembled structures, and
Figure 1. Optimized conformations. Blue: N; gray: C; and white: H.
Values in parentheses are derived from PCM computations (see text).
Bond lengths (Š) are shown.
favorable than the N-hydrogen derivative. Natural population
analysis indicated that about half of the total positive charge is
borne by the hydrogens on the “spacer” carbons.[13] The
analysis also provided a 2s(1.22)2p(4.10) configuration for the
N atoms. Steric factors force the two N-methyl groups in I to
point away from each other, a feature that we presume would
likewise hold true for our long-chain gemini surfactants.
Although there can be no assurance that conformer I is
maintained when the gemini surfactants self-assemble in
water, it is clear that substantial intramolecular chain/chain
contact would necessitate major ring distortions. In this
regard, polarizable-continuum-model (PCM) calculations
show that conformer I is further stabilized by 0.5 kcalmolÀ1
relative to conformer II. Bond distances, which are interesting
[*] L. Shi, Dr. D. Lundberg, Prof. Dr. F. M. Menger
Department of Chemistry
Emory University
1515 Dickey Drive, Atlanta, GA 30322 (USA)
Fax: (+1)404-727-6586
E-mail: menger@emory.edu
Dr. D. G. Musaev
Cherry L. Emerson Center for Scientific Computation
Emory University
1515 Dickey Drive, Atlanta, GA 30322 (USA)
[**] This work was supported by the National Institutes of Health. We
thank Dr. Shaoxiong Wu for help with the PGSE NMR experiments.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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Communications
in their own right for this non-Hückel conjugated ring
NMR chemical shifts, being weighted averages arising
from monomeric and micellar species, are linearly related to
the reciprocal of the total surfactant concentration below and
above the CMC value. A striking difference was seen between
system,[14] are also given in Figure 1. The twelve C N/C C
bonds of I alternately shift from shorter (dav = 1.33 Š) to
longer (dav = 1.44 Š), with the former bonds being all
cisoid.[15]
À
À
1
the H NMR chemical shift behavior of the terminal methyl
Plots of surface tension, conductivity, 1H NMR shifts, and
13C NMR shifts versus gemini concentration show “breaks”
corresponding to critical micelle concentrations (CMCs). The
surface tension plot for B and conductivity plot for C shown
Figure 2 are typical. CMC values, which are in satisfactory
agreement among the different methods, are A: 7.7 mm; B:
2.0 mm; and C: 0.55 mm. These values are much higher than
those of conventional gemini surfactants of identical chain
groups of C and those of DTAB (Figure 3). Whereas a
downfield shift of the signals takes place for DTAB upon
micellization, C shows an upfield shift. The most likely
explanation is that the p electrons of the annulene core shield
Figure 3. 1H NMR chemical shifts of the terminal methyl groups
plotted against the inverse normalized concentrations of C and DTAB.
the methyl protons of C. This, then, demands transient
proximity between the head groups and the mobile chain
termini, a result compatible with flexible chains and consid-
erable “chain looping”.[11]
The translational mobility of surfactants in solution
diminishes upon formation of aggregates; thus self-diffusion
coefficients (Dobs) supply important information about the
assembly process. Dobs values were obtained using a Hahn-
echo sequence and the Stejskal–Tanner equation in what is
generally termed the PGSE NMR method.[20,21] A plot of Dobs
versus ([gemini]/CMC)À1 is expected to give two straight lines
intersecting at unity, and Figure 4 bears this out for gemini A.
When normalized to adjust for differences in the CMC values,
A and DTAB have virtually superimposable plots from which
we conclude that A forms micelles of roughly the same size
and spherelike shape (radius ca. 20 Š)[22] as those of DTAB.
We surmise that the slight curvature at the CMC for A in
Figure 2. a) Surface tension versus log(concentration) of B; b) conduc-
tivity versus the concentration of C.
lengths (for example, 1 mm for “12–4–12”, and 0.009 mm for
“16–5–16”).[16,17] Indeed, the annulene gemini surfactants
have CMC values approaching those of single-chain surfac-
tants (for example, the CMC value of C12H25N+Me3BrÀ,
abbreviated “DTAB”, is 13 mm).[18] The [12]annulene gemini
surfactants clearly encounter difficulties packing within
micelles. So-called a parameters (the fraction of dissociated
counterions obtained from the ratio of the slopes in the
conductivity plots) are all 0.4 for A, B, and C as compared to
the more usual 0.20–0.26 for DTAB and conventional gemini
surfactants.[19] High a values might be related in part to the
positive charge in the annulene head group being distributed
over multiple atoms. Inspection of the gemini surfactants by
UV spectroscopy (394.5 nm) at concentrations encompassing
the CMCs gave no evidence (for example, non-Beerꢀs law
behavior) of ring/ring interactions.[13]
Figure 4. Difffusion coeffecients plotted against the inverse normalized
concentrations of A and DTAB.
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Figure 4 likely arises from a reduced cooperativity in the self-
assembly of the gemini surfactant as a consequence, in part,
ofthe previously mentioned packing constraints.
[1] I. Yamaguchi, Y. Gobara, M. Sato, Org. Lett. 2006, 8, 4279.
[2] F. M. Menger, J. S. Keiper, Angew. Chem. 2000, 112, 1980;
Angew. Chem. Int. Ed. 2000, 39, 1906.
To summarize: three gemini surfactants with a non-
Hückel diaza[12]annulene core were synthesized and exam-
ined by density functional theory, surface tension, conductiv-
ity, and UV measurements as well as 1H NMR, 13C NMR, and
PGSE NMR spectroscopy. The computations give a mini-
mum-energy conformation in which shorter bonds alternate
with longer bonds, and with the two N substituents pointing
away from each other. The latter feature renders intra-
molecular chain/chain contact in self-assemblies difficult.
When the gemini surfactants aggregate in water, they form
micelles with CMC values that are substantially higher than
those of conventional gemini surfactants, a fact that indicates
that the annulene molecules encounter packing difficulties.
The UV spectra of the gemini surfactants at concentrations
encompassing the CMC values show no evidence for ring/ring
[3] M. J. Rosen, CHEMTECH 1993, 23, 30.
[4] R. Zana, Curr. Opin. Colloid Interface Sci. 1996, 1, 566.
[5] F. M. Menger, C. A. Littau, J. Am. Chem. Soc. 1991, 113, 1451.
[6] A. J. Kirby, P. Camilleri, J. B. F. N. Engberts, M. C. Feiters,
R. J. M. Nolte, O. Sꢁderman, M. Bergsma, P. C. Bell, M. L.
Fielden, C. L. Garcꢂa Rodrꢂguez, P. Guꢃdat, A. Kremer, C.
McGregor, C. Perrin, G. Ronsin, M. C. P. J. van Eijk, Angew.
Chem. 2003, 115, 1486; Angew. Chem. Int. Ed. 2003, 42, 1448.
[7] H. Chen, L. Han, P. Luo, Z. Ye, Surf. Sci. 2004, 552, L53.
[8] M. Dreja, B. Tieke, Langmuir 1998, 14, 800.
[9] M. Benjelloun, P. Van Der Voort, P. Cool, O. Collart, E. F.
Vansant, Phys. Chem. Chem. Phys. 2001, 3, 127.
[10] a) J. F. M. Oth, J.-M. Gilles, G. Schrꢁder, Tetrahedron Lett. 1970,
11, 61; b) J. F. M. Oth, H. Rꢁttele, G. Schrꢁder, Tetrahedron Lett.
1970, 11, 67.
[11] F. M. Menger, R. Zana, B. Lindman, J. Chem. Educ. 1998, 75,
115.
[12] Gaussian03 (RevisionC1): M. J. Frisch et al., see the Supporting
Information
[13] See the Supporting Information.
[14] K. B. Wiberg, Chem. Rev. 2001, 101, 1317.
[15] For optimized geometries of the all-carbon analogue without
substituents (tri-trans-[12]annulene), see C. Castro, W. L.
Karney, M. A. Valencia, C. M. H. Vu, R. P. Pemberton, J. Am.
Chem. Soc. 2005, 127, 9704. In this molecule, where there are no
alkyl groups to perturb the conformation, the double bonds
alternate cis and trans.
[16] E. Alami, G. Beinert, P. Marie, R. Zana, Langmuir 1993, 9, 1465.
[17] F. Devꢂnsky, I. Lacko, F. Bittererovꢄ, L. Tomeꢅkovꢄ, J. Colloid
Interface Sci. 1986, 114, 314.
[18] S. S. Berr, E. Caponetti, J. S. Johnson, Jr., R. R. M. Jones, L. J.
Magid, J. Phys. Chem. 1986, 90, 5766.
[19] Y. Geng, L. S. Romsted, F. M. Menger, J. Am. Chem. Soc. 2006,
128, 492.
1
interactions at the micelle surface. Plots of H NMR shifts
versus ([gemini]/CMC)À1 for the terminal methyl group of the
chains suggest the presence of transient proximity between
the methyl group and the annulene ring system. Diffusion
coefficients from PGSE NMR experiments reveal that the
annulene gemini micelles are similar in size and shape to
those of simple monochained surfactants.
Over the past few years cationic gemini surfactants have
been used in vitro gene transfection investigations.[6,23] Invar-
iably, these gemini surfactants have flexible spacers separat-
ing their cationic nitrogen atoms (as do other DNA binders
such as spermidine and spermine). How our more rigid
annulene gemini surfactants (with an N···N distance of 4.8 Š
approximating the N(CH2)3N distance in spermidine) behave
toward DNA is as not yet known.
[20] F. M. Menger, H. Lu, D. Lundberg, J. Am. Chem. Soc. 2007, 129,
272.
[21] W. S. Price, Concepts Magn. Reson. 1997, 9, 299; W. S. Price,
Concepts Magn. Reson. 1998, 10, 197.
Received: May 15, 2007
Published online: July 6, 2007
[22] V. K. Aswal, P. S. Goyal, Chem. Phys. Lett. 2003, 368, 59.
[23] M. Castro, D. Griffiths, A. Patel, N. Pattrick, C. Kitson, M.
Ladlow, Org. Biomol. Chem. 2004, 2, 2814.
Keywords: annulenes · density functional calculations ·
gemini surfactants · micelles · self-assembly
.
Angew. Chem. Int. Ed. 2007, 46, 5889 –5891
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
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