Photorelease of carboxylic acids mediated by visible-light-absorbing gold-nanoparticles

Article abstract of DOI:10.1021/ol702813w

Visible-light-absorbing citrate-stabilized gold nanoparticles and tryptophan-dithiane-conjugate-stabilized gold nanoparticles have been used to mediate electron transfer between dithiothreitol (DTT), a good electron donor, and an N-methylpicolinium ester in aqueous solution. Quantitative yield of the free carboxylate has been obtained with quantum yields of release, Φ_rel, ranging from 0.5 to 4.5.

Full text of DOI:10.1021/ol702813w

ORGANIC
LETTERS
2
008
Vol. 10, No. 3
57-460
Photorelease of Carboxylic Acids
Mediated by Visible-Light-Absorbing
Gold-Nanoparticles
4
J. Brian Borak, Susana L o´ pez-Sola, and Daniel E. Falvey*
Department of Chemistry and Biochemistry, UniVersity of Maryland,
College Park, Maryland 20742
falVey@umd.edu
Received November 20, 2007
ABSTRACT
Visible-light-absorbing citrate-stabilized gold nanoparticles and tryptophan
to mediate electron transfer between dithiothreitol (DTT), a good electron donor, and an N-methylpicolinium ester in aqueous solution. Quantitative
yield of the free carboxylate has been obtained with quantum yields of release, rel, ranging from 0.5 to 4.5.
−dithiane-conjugate-stabilized gold nanoparticles have been used
Φ
The use of photoremovable protecting groups (PRPGs) has
become an established technique for modulating the reactivity
of a variety of functional groups. A large majority of PRPG
strategies have been designed to take advantage of a
rearrangement and/or radical mechanism that occurs within
cal reactions within the system. As such, many studies have
focused on using new chromophores that absorb at higher
5
wavelengths or modifying existing PRPG chromophores to
6
,7
red-shift their absorption profiles. Unfortunately, while
modification of existing chromophore moieties can lead to
a favorable change in the absorption properties, this often
comes at the cost of the diminishment in other desirable
qualities in the PRPG (i.e., high quantum yield, solubility,
background stability, etc.)
1
the chromophore upon light absorption. Nitrobenzyl alcohol,
2
3
4
benzoin, phenacyl ester, and coumarinyl derivatives are
examples of some of the more highly studied systems in this
category. One significant limitation of the aforementioned
groups is that ultraviolet (UV) light is required to initiate
deprotection which can initiate other unwanted photochemi-
In attempts to sidestep this delicate balance, our group
has focused on a more recent class of PRPG that relies on
8
sensitized photoinduced electron transfer (PET). In these
(
1) (a) Kaplan, J. H.; Forbush, B.; Hoffman, J. F. Biochemistry 1978,
systems, an excited-state sensitizer initiates an electron-
1
7, 1929-1935. (b) Il’ichev, Y. V.; Schwoerer, M. A.; Wirz, J. J. Am.
Chem. Soc. 2004, 126, 4581-4595. (c) Patchornik, A.; Amit, B.; Woodward,
R. B. J. Am. Chem. Soc. 1970, 92, 6333-6335. (d) Pirrung, M. C.; Lee, Y.
R.; Park, K.; Springer, J. B. J. Org. Chem. 1999, 64, 5042-5047. (e)
Cameron, J. F.; Frechet, J. M. J. J. Am. Chem. Soc. 1991, 113, 4303-
(4) (a) Furuta, T.; Torigai, H.; Sugimoto, M.; Iwamura, M. J. Org. Chem.
1995, 60, 3953-3956. (b) Schade, B.; Hagen, V.; Schmidt, R.; Herbrich,
R.; Krause, E.; Eckardt, T.; Bendig, J. J. Org. Chem. 1999, 64, 9109-
9117. (c) Suzuki, A. Z.; Watanabe, T.; Kawamoto, M.; Nishiyama, K.;
Yamashita, H.; Ishii, M.; Iwamura, M.; Furuta, T. Org. Lett. 2003, 5, 4867-
4870.
(5) (a) Chen, Y.; Steinmetz, M. G. J. Org. Chem. 2006, 71, 6053-6060.
(b) Chen, Y.; Steinmetz, M. G. Org. Lett. 2005, 7, 3729-3732. (c)
Shembekar, V. R.; Chen, Y.; Carpenter, B. K.; Hess, G. P. Biochemistry
2005, 44, 7107-7114. (d) Senda, N.; Momotake, A.; Nishimura, Y.; Arai,
T. Bull. Chem. Soc. Jpn. 2006, 79, 1753-1757.
4
313. (f) Dussy, A.; Meyer, C.; Quennet, E.; Bickle, T. A.; Giese, B.; Marx,
A. ChemBioChem 2002, 3, 54-60.
2) (a) Corrie, J. E. T.; Trentham, D. R. J. Chem. Soc., Perkin Trans. 1
992, 2409-2417. (b) Cameron, J. F.; Willson, C. G.; Frechet, J. M. J. J.
(
1
Chem. Soc., Perkin Trans. 1 1997, 2429-2442. (c) Sheehan, J. C.; Wilson,
R. M. J. Am. Chem. Soc. 1964, 86, 5277-5281. (d) Baldwin, J. E.;
McConnaughie, A. W.; Moloney, M. G.; Pratt, A. J.; Shim, S. B.
Tetrahedron 1990, 46, 6879-6884.
(3) (a) Givens, R. S.; Athey, P. S.; Matuszewski, B.; Kueper, L. W.;
(6) Conrad, P. G.; Givens, R. S.; Weber, J. F. W.; Kandler, K. Org.
Lett. 2000, 2, 1545-1547.
(7) Aujard, I.; Benbrahim, C.; Gouget, M.; Ruel, O.; Baudin, J.-B.; Neveu,
P.; Jullien, L. Chem. Eur. J. 2006, 12, 6865-6879.
Xue, J. Y.; Fister, T. J. Am. Chem. Soc. 1993, 115, 6001-6012. (b) Sheehan,
J. C.; Umezawa, K. J. Org. Chem. 1973, 38, 3771-3774. (c) Anderson, J.
C.; Reese, C. B. Tetrahedron Lett. 1962, 1-4.
1
0.1021/ol702813w CCC: $40.75
© 2008 American Chemical Society
Published on Web 12/29/2007

transfer reaction that reduces a protecting group which
subsequently initiates release of the attached compound. The
light absorption step is, in essence, uncoupled from the
deprotection step since reduction of the protecting group,
from any source, causes deprotection. This allows for the
individual optimization of each step in the deprotection
process with relatively little consequence to other steps.
However, the introduction of another component into the
system does complicate the deprotection scheme to a certain
extent. Our group has developed the N-alkylpicolinium
would offer an improvement over delicate organic chro-
mophores that decompose over time. AuNPs can be synthe-
sized in a variety of sizes, from one to several hundred
nanometers in diameter, and with various organic stabilizing
ligand shells surrounding them. AuNPs with core diameters
greater than 5 nm exhibit a characteristic strong visible
absorption band centered at approximately 520 nm (for 15
nm AuNPs), respresentative of the suface plasmon band
1
2
(SPB) electron cloud. The position of the λmax of the
plasmon resonance band (PRB) is largely dependent on the
size of the AuNPs, their shape, and the nature of the
(NAP) group for use as a PET-PRPG in order to take
11,13,14
advantage of the benefits of PET-based deprotection to
stabilizing ligands surrounding them.
In addition to the
9
protect carboxylates and carbamates. Simple one-electron
favorable absorption characteristics, several AuNP systems
appear to have favorable reduction potentials as evidenced
by electrochemical experiments performed by Murray et al.
on smaller AuNP systems (1.1 nm diameter). For those
systems, Murray suggests the nanoparticles have one-electron
reduction potentials at ca. -1.5 to -1.7 V, potentials
sufficiently negative to reduce our NAP-esters in a mediated-
reduction by thermal or photochemical means (Ered ) -1.1
V) using a photoexcited donor results in release of the
protected compound. (Scheme 1).
Scheme 1. Reduction of the N-Methyl-picolinium Group
1
5
PET mechanism. Given the aforementioned qualities,
AuNPs seemed to be an interesting candidate for mediated
deprotection experimentation.
The scheme designed for these experiments incorporates
the nanoparticles in the presence of a large excess of a good
electron donor and a NAP-protected ester. Upon absorption
of incident radiation, the AuNPs are expected to act as net
electron shuttles, transferring an electron between the electron
The chromophore or sensitizer often represents a signifi-
cant expense in the deprotection scheme as a stoichiometric
amount or greater (relative to the amount of protected
compound) is needed to fully deprotect a particular system.
However, if a sensitizer is in the presence of a “sacrificial”
electron donor with the appropriate oxidation/reduction
potentials, the sensitizer can act as a mediator or electron
shuttle between the donor and the PRPG. The net effect is
to preserve the original state of the chromophore so that it
can be recycled in multiple deprotection events. Initial
experiments with this system were performed using UV-light-
absorbing sensitizers;10 however, it would be convenient to
use visible light instead. It should even be possible to use a
substoichiometric amount of sensitizer in these systems,
greatly reducing the cost and waste associated with a
deprotection photolysis experiment. This is the focus of the
current work being discussed.
1
6
donor (D) and the NAP ester. (Scheme 2)
Although a staggering variety of AuNPs can be prepared,
our studies began with citrate-stabilized AuNPs (cit-AuNP)
due to their ease of preparation, narrow size distribution, and
aqueous solubility. Synthesis of 16 nm citrate-stabilized
AuNPs (cit-AuNP) was easily achieved using the modified
1
7
citrate reduction method by Frens. The nanoparticles were
prepared in D O to facilitate analysis by proton NMR. Size
2
was confirmed by comparison to reference UV-vis absorp-
tion spectra and by transmission electron microscopy (TEM)
analysis. Although oxidation/reduction potentials of the
cit-AuNPs could not be determined, several aqueous-soluble
donor molecules were surveyed, and dithiothreitol (DTT) was
chosen since irreversible aggregation of the cit-AuNPs was
not observed immediately after addition as it was with other
donors (e.g., ascorbic acid and EDTA). N-Methyl-picolin-
iumphenylacetate (mPPA) was chosen as a representative
NAP-ester to include in these experiments. A major limitation
of the cit-AuNPs is their susceptibility to irreversible
aggregation by a variety of sources. This aggregation is
accompanied by a red-shifting and reduction in intensity of
the PRB, effectively limiting photochemical processes.
Given the success of the mediated systems previously
studied, we are interested in finding new robust high-
wavelength absorbing sensitizers to incorporate into this
design. Gold nanoparticles (AuNPs) have recently attracted
a great amount of attention due to their unique optoelectronic
properties that are dissimilar from those of bulk metal
11
materials or molecular compounds. Additionally, they have
proven to be robust under illumination in many cases and
(
12) Mie, G. Ann. Phys. 1908, 25, 377-445.
(13) Brust, M.; Kiely, C. J. Colloids Surf., A 2002, 202, 175-186.
(
8) (a) Banerjee, A.; Falvey, D. E. J. Org. Chem. 1997, 62, 6245-6251.
b) Banerjee, A.; Lee, K.; Falvey, D. E. Tetrahedron 1999, 55, 12699-
2710. (c) Banerjee, A.; Lee, K.; Yu, Q.; Fang, A. G.; Falvey, D. E.
Tetrahedron Lett. 1998, 39, 4635-4638.
(14) Hostetler, M. J.; Wingate, J. E.; Zhong, C.-J.; Harris, J. E.; Vachet,
R. W.; Clark, M. R.; Londono, J. D.; Green, S. J.; Stokes, J. J.; Wignall,
G. D.; Glish, G. L.; Porter, M. D.; Evans, N. D.; Murray, R. W. Langmuir
1998, 14, 17-30.
(
1
(
9) (a) Sundararajan, C.; Falvey, D. E. J. Org. Chem. 2004, 69, 5547-
(15) Lee, D.; Donkers, R. L.; Wang, G.; Harper, A. S.; Murray, R. W.
J. Am. Chem. Soc. 2004, 126, 6193-6199.
(16) While our proposed mechanism shows all components free in
solution, it is unclear whether the donor or the NAP-esters are bound to
the surface of the nanoparticle.
5
8
554. (b) Sundararajan, C.; Falvey, D. E. J. Am. Chem. Soc. 2005, 127,
000-8001.
(10) Sundararajan, C.; Falvey, D. E. Photochem. Photobiol. Sci. 2006,
5
, 116-121.
(
11) Daniel, M.-C.; Astruc, D. Chem. ReV. 2004, 104, 293-346.
(17) Frens, G. Nature Phys. Sci. 1973, 241, 20-22.
458
Org. Lett., Vol. 10, No. 3, 2008

Scheme 2. Proposed Mechanism for Nanoparticle-Based Deprotection
(
Figure 1). Careful adjustment of the concentrations of the
photolysis experiments that lacked either cit-AuNP or DTT
or both resulted in an insignificant amount of deprotected
ester (within experimental error). It should be noted that the
effective concentration of cit-AuNPs in the photolysis
mixture was actually lower than reported due to a particularly
peculiar source of aggregation. It appears that the nitrogen
purging can trigger partial aggregation through a mechanism
that is not clear. Absorbance at the PRB λmax was reduced
by an average of 29% after the 10-min nitrogen purge.
Solutions containing only cit-AuNPs of identical concentra-
tion were unaffected by purging. Purging with argon using
identical conditions resulted in a similar reduction in absor-
bance. Quantum yields of release, Φrel, of the free carboxylate
three components in our experiments identified an optimal
ratio in which the solutions were stable. In general, higher
concentrations of DTT and lower concentrations of mPPA
lead to more stable solutions. Photolysis solutions containing
mPPA, DTT, and cit-AuNP were prepared in D O with a
2
minimal amount of acetonitrile as cosolvent for mPPA. The
on the aforementioned system were determined to be Φrel
.4 using monochromatic irradiation at 525 nm ( 10 nm
compared to a dark control solution.
)
0
Due to the high instability of the cit-AuNP system, a
different NP system was explored. DeShong et al. have
prepared 4 nm AuNPs stabilized by a L-tryptophan-dithiane
18
derivative (TRP-AuNP). (Figure 2) These NPs are signifi-
Figure 1. UV-vis spectra of cit-AuNPs with varying concentration
of mPPA.
2
solutions were purged with N for 10 min and irradiated with
a 300 W broad-band tungsten-filament lamp for a predeter-
mined amount of time. Free carboxylic acid yields were
determined by integration of the aromatic protons of the free
picolinium group in the proton NMR spectrum. Yields of
phenylacetic acid (PAA) were confirmed by HPLC analysis
of the final mixtures. A representative sampling of the data
is found in Table 1.
Table 1. Selected Data for the Cit-AuNP Deprotection
Experiment
[
mPPA] [DTT] [cit-AuNP] irradiation % yield of
entry
(mM)
(mM)
(nM)a
time (min)
PAAb
Figure 2. Tryptophan-dithiane ligand used for TRP-AuNP system.
1
2
3
1.24
1.24
1.24
12.5
62.2
62.2
1.9
0.95
1.9
60
60
60
64
80
95
a
cantly more robust to different environments including a wide
range of solution pH values (∼6-14). Additionally, the
formation of aggregates or the restoration of free nanopar-
Theoretical concentrations assuming perfectly spherical 16 nm nano-
b
particles generated in 100% yield in the synthesis reaction Determined
by HPLC, relative to [mPPA] in dark control, error ( 10%
Quantitative yield of PAA was observed after 1 h of
(18) Unpublished work: Park, J.-H.; DeShong, P. University of Mary-
irradiation (within the error of integration, ∼10%). Control
Org. Lett., Vol. 10, No. 3, 2008
land, College Park, MD.
459

ticles can be cycled a limited number of times (∼2-4)
through protonation or deprotonation of the carboxylate
group. While deprotection reactions can be carried out in
unbuffered solution, the experiments reported here were
performed in 50 mM phosphate buffer at pH 7. Yields were
determined by HPLC analysis. Quantitative yield of PAA
was observed after 1 h of broad-band visible-light irradiation
from 1.4 to 4.5 for this system. This may be indicative of a
radical chain mechanism since these processes typically have
quantum yields greater than unity.
1
9
In conclusion, these experiments demonstrate the success-
ful deprotection of a photoinduced electron transfer-based
PRPG using gold nanoparticles. To the best of our knowl-
edge, this is the first account of the application of AuNPs
for a photodeprotection strategy. The most attractive aspects
of both of the explored systems used to initiate deprotection
include: (1) the use of visible light, (2) the use of very
substoichiometric amounts of the chromophore, and (3)
compatibility with aqueous media. Limitations do exist in
using cit-AuNPs since irreversible aggregation is triggered
by a variety of environmental factors, many of which have
yet to be fully described. TRP-AuNPs seem to offer a more
stable and easier to control system. It may be possible to
identify a larger set of NP ligands that are even more stable
to different environments and/or better suited for these
reactions. Future work will focus on ellucidating the mech-
anism of deprotection, kinetics, and identifying other nano-
particle systems for use in this application.
(Table 2, entry 1). Increasing concentrations of DTT (Table
Table 2. Selected Data for the TRP-AuNP Deprotection
Experiment
[
mPPA] [DTT] [TRP-AuNP] irradiation % yield of
entry
(mM)
(mM)
(nM)a
time (min)
PAAb
1
2
3
4
5
6
7
8
9
1
1
1
1
1.25
1.25
1.25
1.25
1.25
1.25
1.25
1.25
1.25
1.25
1.25
1.25
1.25
31.3
1.25
2.5
5
10
20
40
80
31.3
31.3
31.3
31.3
31.3
15
15
15
15
15
15
15
15
0.75
15
30
37.5
75
60
30
30
30
30
30
30
30
20
20
20
20
20
100
4.2
14.4
15.7
20.2
24.3
24.9
14.2
30.2
40.3
44.4
49.4
56.2
Acknowledgment. We are grateful to Dr. Philip DeShong
and Ju-Hee Park at the University of Maryland for their
assistance with the nanoparticle synthesis. This work was
supported by the National Science Foundation chemistry
division and the Spanish MEC.
0
1
2
3
a
Theoretical concentrations assuming perfectly spherical 2.6 nm nano-
b
Supporting Information Available: Experimental pro-
cedures, syntheses, and spectral data. This material is
available free of charge via the Internet at http://pubs.acs.org
particles generated in 100% yield in the synthesis reaction Determined
by HPLC, relative to [mPPA] in dark control, error ( 10%
OL702813W
2, entries 2-8) or TRP-AuNP (Table 2, entries 9-13)
subsequently increase the deprotection yield of PAA for a
given photolysis period. However, the data seem to indicate
a maximum in deprotection yield at about 1:25 mPPA/DTT
molar ratio. Control photolysis experiments lacking TRP-
AuNP, DTT, light, or any combination of the three resulted
in an insignificant yield of PAA (within experimental error).
Surprisingly, quantum yields of release, Φrel, of PAA range
(
19) Although speculative, it is conceivable that the methylpicolinium
radical generated in the reaction can oxidze the tryptophan moiety to trigger
a radical decarboxylation resulting in the production of a tryptophan radical
species. (see Mehta, L. K.; Porssa, M.; Parrick, J.; Candeias, L. P.; Wardman,
P. J. Chem. Soc., Perkin Trans. 2. 1997, 8, 1487-1491.) This radical could
potentially promote further deprotection events by reducing the nanoparticle.
Since there are a large number of tryptophan moieties on the surface of the
nanoparticles, this would effectively amplify the number of deprotection
events per absorbed photon, resulting in a larger than unity Φrel.
460
Org. Lett., Vol. 10, No. 3, 2008