Synthesis of highly fluorescent BODIPY-based nanocars

Article abstract of DOI:10.1021/ol100108r

(Figure Presented) The convergent synthesis of inherently highly fluorescent nanocars incorporating 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-containing axles and p-carborane wheels Is reported. These nanocars are expected to exhibit rolling motion with predetermined patterns over smooth surfaces, depending on their chassis. Their quantum yields of fluorescence (Φ_F > 0.7) make them excellent candidates for imaging and tracking by single-molecule fluorescence microscopy. An analogue as a stationary control with tert-butyl groups Instead of p-carborane wheels was also synthesized.

Full text of DOI:10.1021/ol100108r

ORGANIC
LETTERS
2010
Vol. 12, No. 7
1464-1467
Synthesis of Highly Fluorescent
BODIPY-Based Nanocars
Jazmin Godoy, Guillaume Vives, and James M. Tour*
Department of Chemistry, Department of Mechanical Engineering and Materials
Science, Smalley Institute for Nanoscale Science and Technology, Rice UniVersity,
MS 222, 6100 Main Street, Houston, Texas 77005
tour@rice.edu
Received January 15, 2010
ABSTRACT
The convergent synthesis of inherently highly fluorescent nanocars incorporating 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-containing
axles and p-carborane wheels is reported. These nanocars are expected to exhibit rolling motion with predetermined patterns over smooth
surfaces, depending on their chassis. Their quantum yields of fluorescence (ΦF > 0.7) make them excellent candidates for imaging and
tracking by single-molecule fluorescence microscopy. An analogue as a stationary control with tert-butyl groups instead of p-carborane wheels
was also synthesized.
The control of motion at the molecular level stands as a
challenge for scientists. Nature gives the supreme example
of such control when the synchronization of motion of
individual molecules leads to intricate biological functions.1
Unfortunately, the use of natural molecular machines for ex
ViVo applications is intrinsically limited due to unfavorable
environmental perturbations.2 Much effort has been devoted
toward the design, synthesis and operation of synthetic
molecular machines. As a consequence, a large variety of
nanostructures have been made to operate either in solution,
in the solid state or mounted on surfaces.3
ular wheels in a flexible oligo(phenylene ethynylene) (OPE)
chassis has afforded a collection of molecular vehicles termed
nanocars.7
Most nanocars were designed to be observed and tracked
using scanning tunneling microscopy (STM) since it offers
unparalleled atomic resolution.8 Exploration of other single-
molecule imaging tools, however, is essential in order to observe
movement of nanomachines on nonconductive surfaces. Single-
molecule fluorescence microscopy (SMFM) is a good alterna-
tive. Even though its resolution is limited by diffraction,
nanometer localization of individual fluorophores has become
possible.9 Indeed, we recently reported the use of SMFM to
monitor the motion of fluorescently tagged nanocars on a glass
surface under ambient conditions.10 The nanocars were func-
tionalized with a tetramethylrhodamine fluorescent tag to allow
excitation with a Nd:Vn laser (532 nm) and to have good
Our group has focused on the study of restricted rolling
motion to control the translation of individual molecules
along atomically flat surfaces. Incorporation of either C60-
fullerene,4 p-carborane5 or a ruthenium complex6 as molec-
(1) Schliwa, M., Ed. Molecular Motors; Wiley-VCH: Germany, 2003.
(2) Huang, T. J.; Juluri, B. K. Nanomedicine 2008, 3, 107.
(3) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007,
46, 72.
(5) Morin, J.-F.; Sasaki, T.; Shirai, Y.; Guerrero, J. M.; Tour, J. M. J.
Org. Chem. 2007, 72, 9481.
(6) Vives, G.; Tour, J. M. Tetrahedron Lett. 2009, 50, 1427.
(7) Vives, G.; Tour, J. M. Acc. Chem. Res. 2009, 42, 473.
(8) Grill, L. J. Phys.: Condens. Matter 2008, 20, 053001.
(4) Shirai, Y.; Osgood, A. J.; Zhao, Y.; Kelly, K. F.; Tour, J. M. Nano
Lett. 2005, 5, 2330.
10.1021/ol100108r  2010 American Chemical Society
Published on Web 03/08/2010

quantum yields of fluorescence. The nanocars moved at an
average speed of 4 nm/s at room temperature. However, the
results suggested that the fluorophore might interfere with the
nanocar motion by blocking some of the molecules. In addition,
the synthesis of the tagged nanocars presented some drawbacks
such as lengthy routes and low-yielding attachment of the
fluorescent label. Consequently, a new set of intrinsically
fluorescent nanocars was designed to obviate the need for a
pendant fluorescent tag.
two units of a BODIPY-containing axle with the appropriate
inner portion or via a homocoupling. By incorporating the
fluorophore in the axle, a modular synthesis of nanocars with
various chassis is accessible. The tert-butyl-substituted
analogue 4 could be analogously assembled using a different
axle. Both axles were synthesized from known BODIPY 514
using the 2,6-acetylenic functionalization first explored by
Ziessel.15
The synthesis of axle 10 (Scheme 1) started with a
Sonogashira coupling reaction between BODIPY 5 and
We report a modular and convergent synthesis of fluo-
rescent nanocars 1-3 and the analogue 4 that incorporate a
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) core11
in their axles. The BODIPY moiety is a versatile fluorophore;
BODIPY-based chromophores tend to exhibit good thermal
and photochemical stability, high fluorescence quantum
yields, intense absorption profiles, tunability of absorption
range, and good solubility in most organic solvents.12
Furthermore, the geometry of the core yields nanocars where
the chassis is perpendicular to the axles, leading to fewer
conformations on the surface, in contrast to the previous ‘Z-
shaped’ chassis obtained from OPE-axle-based nanocars.5
Nanocars 1 and 2 were designed to move in a straight
line on surfaces while nanocar 3 is expected to exhibit
circular surface motion that could be detected by measuring
the polarization anisotropy distribution.13 In order to confirm
the importance of the p-carborane wheels in translational
motion, nanocar analogue 4, bearing tert-butyl groups instead
of the p-carborane clusters, was also designed and synthe-
sized.
Scheme 1. Synthesis of Axle 10
trimethylsilylacetylene (TMSA) that afforded 6. Double
iodination of the BODIPY core in 6 using N-iodosuccinimide
(NIS) gave 7. Diiodide 7 was then subjected to a double
Sonogashira coupling with 1-ethynyl-p-carborane 816 to give
9, which upon TMS deprotection afforded axle 10. Fluoride
sources were avoided for deprotection since they are known
to give lower yields due to partial destruction of the BODIPY
core.17 It is noteworthy that, in our experience, reaction times
longer than 1.5 h with the K2CO3/MeOH system also reduce
the yield and lead to formation of unknown byproducts. In
summary, axle 10 was prepared in four steps from BODIPY
5 with an overall yield of 58%.
Our synthetic strategy was based upon the realization that
nanocars 1-3 (Figure 1) could be assembled by coupling
Nanocar 1 was assembled by palladium-catalyzed homo-
coupling of axle 10 in the presence of air (Scheme 2). The
(9) (a) Yildiz, A.; Forkey, J. N.; McKinney, S. A.; Ha, T.; Goldman,
Y. E.; Selvin, P. R. Science 2003, 300, 2061. (b) Yildiz, A.; Tomishige,
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A. B.; Tour, J. M.; Link, S. ACS Nano 2009, 3, 351. (b) Claytor, K.; Khatua,
S.; Guerrero, J.; Tcherniak, A.; Tour, J. M.; Link, S. J. Chem. Phys. 2009,
130, 164710.
(11) Treibs, A.; Kreuzer, F.- H. Liebigs Ann. Chem. 1968, 718, 208.
(12) (a) Ulrich, G.; Ziessel, R.; Harriman, A. Angew. Chem., Int. Ed.
2008, 47, 1184. (b) Loudet, A.; Burgess, K. Chem. ReV. 2007, 107, 4891.
(13) Ha, T.; Laurence, T. A.; Chemla, D. S.; Weiss, S. J. Phys. Chem.
B 1999, 103, 6839.
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J.; Burgess, K.; Bergstroem, F.; Johansson, L. B.-A. J. Org. Chem. 1999,
64, 7813.
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Batsanov, A. S.; Goeta, A. E.; Rankin, D. W. H.; Robertson, H. E.; Schirlin,
J. T. Dalton Trans. 2006, 29, 3544.
Figure 1. Structure of BODIPY-based nanocars 1-3 and analogue
4. Every vertex of the carborane wheel is BH except the darkened
sites, where the outer (para) is CH and the inner (ipso) is alkynyl-
substituted C.
(17) Wan, C.- W.; Burghart, A.; Chen, J. M.; Bergstro¨m, F.; Johansson,
L. B.-Å.; Wolford, M. F.; GyumKim, T.; Topp, M. R.; Hochstrasser, R. M.;
Burgess, K. Chem.sEur. J. 2003, 9, 4430.
Org. Lett., Vol. 12, No. 7, 2010
1465

Scheme 2. Synthesis of Nanocars 1-3
reaction was complete in 10 min, and the product was
obtained in high yield. In contrast, Eglinton-Glaser condi-
tions18 led only to decomposition of 10, probably due to
substitution of the boron by the Cu(II) required in the
process.19
Scheme 3. Synthesis of Nanocar Analogue 4
Axle 10 was also used in the final assembly of nanocars
2 and 3 (Scheme 2). Synthesis of nanocar 2 was ac-
complished through Sonogashira coupling between 1,4-
diiodo-2,5-dimethoxybenzene (11)20 and 3 equiv of 10 to
give 2 using typical coupling conditions. A methoxy-
substituted benzene was used as the inner portion to allow
easier purification away from the byproduct nanocar 1.
Similarly, to obtain nanocar 3, 9-butyl-3,6-diiodo-9H-car-
bazole (12)21 was coupled with 3 equiv of axle 10 to give
the desired nanocar 3.
The efficiency of the coupling reactions to obtain 1-3
suggests that the BODIPY-containing axle 10 is a versatile
building block to prepare even more complex nanocars by
varying the inner portion.
In order to address the importance of the carborane wheels
in translational motion, their replacement by a nonwheel-
like group was desired. Introduction of small alkyl chains
was considered since they are not expected to significantly
modify the fluorescence of the BODIPY core. Lacking the
wheel-like structure of p-carborane, an alkyl-substituted
analogue would also enable us to evaluate the influence of
the p-carborane on the absorption and emission properties
of the BODIPY core. To prepare analogue 4, bisiodide 7
was coupled with 3,3-dimethyl-1-butyne to give the TMS-
protected axle 13. After nearly quantitative deprotection, the
free alkyne 14 was subjected to the final coupling with 11
to give the nanocar analogue 4 in excellent yield (Scheme
3).
The optical properties of the nanocars and some precursors
were investigated by UV-vis and fluorescence spectroscopy
Table 1. Optical Properties of all Compoundsa
b
compd
λabs (nm)
ε (M-1 cm-1
)
λem (nm)
ΦF
1
2
3
4
6
7
9
10
13
14
554
552
552
564
504
538
552
552
564
564
123 000
181 000
191 000
144 000
70 000
571
569
567
586
514
552
567
567
586
586
0.69
0.70
0.79
0.59
0.46
0.04
0.82
0.85
0.58
0.62
90 000
109 000
116 000
59 000
(18) Eglinton, G.; McCrae, W. AdV. Org. Chem. 1963, 4, 225.
(19) Maeda, H.; Hasegawa, M.; Hashimoto, T.; Kakimoto, T.; Nishio,
S.; Nakanishi, T. J. Am. Chem. Soc. 2006, 128, 10024.
(20) Waybright, S. M.; Singleton, C. P.; Wachter, K.; Murphy, C. J.;
Bunz, U. H. F. J. Am. Chem. Soc. 2001, 123, 1828.
69 000
a Determined in chloroform solution, ca. 1 × 10-7 M. b Using rhodamine
6G as reference, ΦF ) 0.95 in EtOH, λexc 488 nm. Excitation was done at
the corresponding λmax -30 nm..
(21) Zhao, T.; Liu, Z.; Song, Y.; Xu, W.; Zhang, D.; Zhu, D. J. Org.
Chem. 2006, 71, 7422.
1466
Org. Lett., Vol. 12, No. 7, 2010

(Table 1). The photophysical behavior of some of the
compounds reported here is particularly interesting, given
that there is no previous report of carborane-BODIPY diads.
The absorption spectrum of all compounds exhibit a strong
S0fS1 (π-π*) transition located between 504 and 564 nm
with variable extinction coefficients depending on the
substitution pattern. The molecules with two BODIPY units
have the largest extinction coefficients due to the extension
in the conjugated system. Interestingly, however, the tert-
butyl-substituted compounds are slightly bathochromically
shifted compared to their carboranyl-susbstituted analogues,
probably due to the stronger electron-donating character of
the tert-butyl groups.
Diiodo BODIPY 7 exhibits very low fluorescence quantum
yield, in part due to efficient intersystem crossing caused by
the heavy iodine atom, leading to a low-lying triplet state.22
The fluorescence was restored, however, upon introduction
of the alkynyl carborane wheels or the alkynyl tert-butyl
groups and was retained after the final assembly. The
presence of the carboranes enhanced the quantum yields
(compare 10 with 14 and 2 with 4). The fluorescence
quantum yields of nanocars 1-3 are slightly smaller than
that of the BODIPY axle 10 possibly due to partial through-
bond energy transfer between the two BODIPY units. Since
our current SMFM setup requires excitation of the molecules
with a 514 nm laser, it was a prerequisite for the nanocars
to exhibit reasonable absorption at this wavelength. As
depicted in Figure 2, both nanocars and analogue (1-4)
absorb in this region. Furthermore, the high fluorescence
quantum yields of 69%, 70%, and 79% for nanocars 1, 2
and 3, respectively, make them particularly well-suited for
imaging by SMFM at the excitation wavelengths.
Figure 2. (A) UV-visible absorption spectra of 1-4 in CHCl3.
(B) Fluorescence spectra of 1-4 in CHCl3. Excitation done at λmax
-30 nm.
In summary, the synthesis of three BODIPY-containing
highly fluorescent nanocars and one analogue was achieved
using a modular approach that involves a versatile BODIPY-
containing axle. The nanocars were prepared in five steps
with overall yields of 49%, 45%, and 46% for 1, 2, and 3,
respectively. Electronic spectroscopic studies revealed that
the nanocars exhibit absorption centered around 550 nm and
have high fluorescence quantum yields which makes them
suitable for SMFM experiments. Investigation of their motion
by SMFM at room temperature on a glass surface is currently
underway.
Acknowledgment. We thank the NSF NIRT (ECCS-
0708765) and the NSF Penn State MRSEC and Center for
Nanoscale Science for financial support. We thank Drs. I.
Chester of FAR Research, Inc., and R. Awartari of Petra
Research, Inc., for providing trimethylsilylacetylene and our
collaborators Dr. Stephan Link and Saumyakanti Khatua
(Rice University) for helpful discussions.
Supporting Information Available: Detailed experimen-
tal procedures and characterization of compounds 1-4, 6,
7, 9, 10, 13, and 14. This material is available free of charge
via the Internet at http://pubs.acs.org.
(22) Yogo, T.; Urano, Y.; Ishitsuka, Y.; Maniwa, F.; Nagano, T. J. Am.
Chem. Soc. 2005, 127, 12162.
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