Photorelease of carboxylic acids, amino acids, and phosphates from N-alkylpicolinium esters using photosensitization by high wavelength laser dyes

Article abstract of DOI:10.1021/ja050760f

Visible light (>450 nm) is used to efficiently cleave carboxylic acids, amino acids, and phosphates from their N-methyl picolinium esters. Photolysis using pyrromethene dyes PM 546 and PM 597 and also coumarin 6 as photosensitizers effects release of carboxylic acids, N-protected amino acids, and phosphates in quantitative yields. The effective rate of photorelease by the dyes, Φε, was found to be as high as 4500 M^-1 cm^-1. The photorelease proceeds through photoinduced electron transfer from the dye sensitizers to the N-methyl picolinium group. Fluorescence quenching and laser flash photolysis experiments support the photoinduced electron-transfer mechanism. Copyright

Full text of DOI:10.1021/ja050760f

Published on Web 05/12/2005
Photorelease of Carboxylic Acids, Amino Acids, and Phosphates from
N-Alkylpicolinium Esters Using Photosensitization by High Wavelength Laser
Dyes
Chitra Sundararajan and Daniel E. Falvey*
Department of Chemistry and Biochemistry, UniVersity of Maryland, College Park, Maryland 20742
Received February 4, 2005; E-mail: falvey@umd.edu
The development of selective bond-breaking reactions that are
triggered by the absorption of a photon is a fundamental goal of
photochemistry. These reactions also have many practical applica-
tions. For example, photolithographic techniques create nanometer-
scale images on a surface by selectively breaking bonds in a
photoinitiator molecule, creating free radicals or cations. These
intermediates, in turn, react in a way to modify the solubility of a
photoresist coating.1 The photochemical generation of free radicals
has also been exploited in synthetic chemistry.2,3 An additional
family of applications utilizes photochemical bond breaking with
the goal of releasing stable molecules, rather than reactive
intermediates. In synthetic chemistry, such systems are referred to
as “photoreleasable protecting groups” (PRPGs),4 and in biophysical
applications they are referred to as “caged molecules” (e.g., caged
ATP or caged neurotransmitters).5,6
of the NAP esters (CH3CN solution), the radical scavenger 1,4-
cyclohexadiene (CHD, 1.7 M),17 and a visible light-absorbing
photosensitizer. These solutions were purged with N2, irradiated
1
for the prescribed periods of time, and then analyzed by H NMR
spectroscopy. The protected substrates are released in good, and
in most cases nearly quantitative, yields, based on converted 1.
Chart 1 illustrates the photosensitizers employed in these reac-
tions. The dyes, PM 546 and PM 597, are pyrromethene dyes that
Chart 1. Structures of PM 546, PM 597, and Coumarin 6
Widely used PRPGs, including ortho-nitrobenzyl alcohol deriva-
tives,7 benzoin esters,8 phenacyl groups,9 and aryl ketones,10-12
generally require ultraviolet (UV) light (<420 nm) for activation.
This requirement has both practical and fundamental limitations.
As a practical matter, photolysis with UV light requires expensive
glassware, specialized light sources, and additional safety precau-
tions. As a fundamental matter, UV light is limiting, because these
wavelengths are often absorbed by the protected molecule and/or
the matrix. Thus, one challenge is to develop wavelength-tunable
PRPGs and, specifically, to develop photorelease technology that
utilizes visible light.13 In a series of articles we have advocated the
design of PRPGs that are activated through an electron transfer
from a photosensitizer molecule14,15 or tethered chromophore.16 In
this way, it is possible to decouple the light absorption step from
the photorelease chemistry, making it possible to independently
optimize both. Our most recent efforts involved electron-transfer
reactions from either a photosensitizer or a reduced mediator to
N-alkyl-4-picolinium esters (1) (Scheme 1). Herein we are pleased
to report a system capable of efficiently releasing carboxylic acids,
amino acids, and phosphates using high wavelength visible light.
were originally developed for use in lasers.18,19 Consequently, these
chromophores have strong, sharp absorption bands in the visible
region of the spectrum (Table 1). Coumarin 6 is also a laser dye.20
Table 1. Deprotection Yields of NAP Esters
time
(min)a
% acid
formedb,c
% ester
consumedb,c
dye
ester
R
4
4
4
4
4
5
5
5
5
5
6
6
6
6
6
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
1a
1b
1c
1d
1e
CH2C6H5
5
5
92 (80)d
100 (96)d
77
90 (100)d
100 (100)d
78
CH(C6H5)2
N-cbz-glycine
N-cbz-serine
PO(OCH2CH3)2
CH2C6H5
5
5
100
97
100
20
20
20
20
20
60
20
20
20
20
60
100
87
96
CH(C6H5)2
84
80
N-cbz-glycine
N-cbz-serine
PO(OCH2CH3)2
CH2C6H5
87
87
100
100
100
100
76
100
100
100
CH(C6H5)2
100
N-cbz-glycine
N-cbz-serine
PO(OCH2CH3)2
75
97
100
100
100
a Photolysis solution was 2.5-3.0 mL of a 3.5 mM solution of ester and
1
sensitizer, 1.7 M CHD in CH3CN. b Yields were determined by H NMR
Scheme 1. Photofragmentation of N-Alkyl-4-picolinium Esters
integration of the R-C-H protons relative to an internal standard. c Estimated
error (5%. d Isolated yields from preparative experiments.
The visible light photorelease follows the same mechanism we
characterized earlier for several UV-absorbing sensitizers (Scheme
2). This is supported by three observations. First, the oxidation
potentials (Eox) and the singlet state energies of the three sensitizers
(Eoo, in electron volts) along with the reduction potential for the
picolinium esters (Ered ) -1.1 V) can be applied to eq 1 to estimate
the driving force (∆GCT, in kilocalories per mole) for the charge-
transfer step (Table 2). In each case, an exergonic electron-transfer
reaction is predicted in CH3CN.
The properties of the N-alkyl-4-picolinium (NAP) protecting
group have been described earlier.17 The corresponding alcohol can
be coupled to carboxylic acids, protected amino acids, and
phosphates using standard ester synthesis techniques, which are
described in detail in the Supporting Information. High-wavelength
photorelease of carboxylic acids (1a, 1b), N-carbonylbenzyloxy
(cbz)-protected amino acids (1c, 1d), and diethyl phosphate (1e)
was effected through tungsten lamp (>400 nm, 300 W) irradiation
∆GCT ) 23.06(Eox - Ered - Eoo + 0.06)
(1)
9
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J. AM. CHEM. SOC. 2005, 127, 8000-8001
10.1021/ja050760f CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
triplet sensitizers.25 We carried out preliminary quantum yield
measurements for the present system using 1a at 3.5 mM in CH3-
CN with 1.5 M CHD. These solutions were illuminated, using a
Xe-lamp/monochromator/radiometer system, at the absorption
maximum of the dye. The Φꢀ values derived from these experi-
ments (630-4500 M-1 cm-1, depending on the dye) are comparable
to, and in the case of PM 546 exceed, those previously reported. It
should be emphasized that these values were obtained at a single
concentration of the acceptor and are thus limited by the efficiency
of singlet quenching by 1. We anticipate that a substantial increase
in these rates can be obtained if the dyes were covalently tethered
to the NAP group or if the photolyses were carried out in
constrained media where the effective concentration of the quencher
is higher. These approaches are currently being explored.
Scheme 2. Photorelease Mechanism
Table 2. Photophysical Parameters of the Photosenstizers21-24
Eox
(V)
Eoo
(V)
λmax
(nm)
ꢀ
τ
(ns)
kq
Φꢀ
1
1
1
dye
(M-1 cm-
)
(109 M-1 s-
)
(M-1 cm-
)
4
5
6
1.22 2.50 493
1.01 2.32 525
1.02 2.65 467
81 000
68 000
54 000
5.6
4.2
3.1
2.8
1.3
7.6
4500
1700
630
Acknowledgment. We would like to thank the National Science
Foundation for their financial support of this work and Prof. N.
Blough for assistance with the quantum yield determinations.
Second, the NAP esters react rapidly with the singlet states of
the three sensitizers. This was established by fluorescence quenching
experiments using NAP ester 1a. Stern-Volmer analysis of these
data, along with literature values for the singlet lifetimes of the
dyes, gives rate constants kq > 109 M-1 s-1 (Table 2).
Supporting Information Available: Transient absorption spectra,
fluorescence data, synthesis, and characterization data for esters 1a-e
data. This material is available free of charge via the Internet at http://
pubs.acs.org.
Third, laser flash photolysis (LFP) experiments show the
formation of the expected radical intermediates. Figure 1 illustrates
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