Unraveling the Photodeprotection Mechanism of Anthraquinon-2-ylmethoxycarbonyl-Caged Alcohols Using Time-Resolved Spectroscopy

Article abstract of DOI:10.1021/acs.joc.8b02252

Anthraquinone (AQ) compounds have been used as photolabile protecting groups (PPGs) to protect alcohols, ketones, and carboxylic acids. However, because of the lack of direct spectroscopic information for the transient species and intermediates related with the deprotection reaction(s), the photorelease mechanism(s) of these systems are still largely unknown. In this contribution, we detail a time-resolved spectroscopic investigation using anthraquinone-protected galactose (1) and adenosine (2) to investigate the photodeprotection reaction mechanism(s) of these kinds of AQ-PPGs. It was found that, in THF-H₂O solvents, the ketyl radical species generated for 1 and 2 was found to be a reactive intermediate that then formed a dihydroxyanthracene species. The photodeprotection then occurred with the accompaniment of a decarboxylation process. These results provide an improved understanding for how AQ-PPGs work and will help assist in the design and applications of selected anthraquinone derivatives as a PPG platform, especially in aqueous environments more relevant for use in biological systems.

Full text of DOI:10.1021/acs.joc.8b02252

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Article
Unraveling the Photodeprotection Mechanism of Anthraquinon-2-
ylmethoxycarbonyl Caged Alcohols Using Time-Resolved Spectroscopy
Yan Guo, Qingqing Song, Jialin Wang, Jiani Ma, Xiting Zhang, and David Lee Phillips
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02252 • Publication Date (Web): 10 Oct 2018
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Unraveling the Photodeprotection Mechanism of
Anthraquinon-2-ylmethoxycarbonyl Caged Alcohols Using
Time-Resolved Spectroscopy
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Yan Guo1, Qingqing Song1,Jialin Wang,1Jiani Ma*,1, Xiting Zhang2 and David Lee Phillips*,2
[1] Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education,
College of Chemistry and Materials Science, Northwest University, Xi’an, P. R. China
[2] Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, P. R. China
Abstract: Anthraquinone (AQ) compounds have been used as photolabile protecting groups
(PPGs) to protect alcohols, ketones and carboxylic acids. However, due to the lack of direct
spectroscopic information for the transient species and intermediates related with the
deprotection reaction(s), the photorelease mechanism(s) of these systems are still largely
unknown. In this contribution, we detail a time-resolved spectroscopic investigation using
anthraquinone protected galactose (1) and adenosine (2) to investigate the photodeprotection
reaction mechanism(s) of these kinds of AQ-PPGs. It was found that in THF-H2O solvents, the
ketyl radical species generated for 1 and 2was found to be a reactive intermediate that then
formed a dihydroxyanthracene species. The photodeprotection then occurred with the
accompaniment of a decarboxylation process. These results provide an improved
understanding for how AQ-PPGs work and will help assist in the design and applications of
selected anthraquinone derivatives as a PPG platform, especially in aqueous environments
more relevant for use in biological systems.
Introduction
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Photolabile protecting groups (PPGs) for different functional moieties have wide applications in
synthetic chemistry and in the study of biology.123 The more popular PPG platforms are based
on arylcarbonylmethyl, coumarin-4-ylmethyl, arylmethyl and nitroaryl groups. To complement
these existing platforms, there is increasing interest and continuous efforts to exploit new PPGs
based on other types of functional groups.2
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Anthraquinone compounds (AQs) can be very effective cancer therapy drugs. Among them,
daunorubicin,3 idarubicin,4epirubicin,5 aclarubicin,6 pirarubicin,7 and valrubicin8 have earned
clinical approval. In this research area, the photophysics and photochemistry activities of AQs
have been deeply examined.9 A commonly studied reaction is the intermolecular hydrogen
atom transfer (HAT) in a hydrogen donor like isopropanol (IPA). Previously, we performed
mechanistic studies10 on an unusual and efficient photoredox reaction of AQs such as
2-(p-hydroxymethyl) phenylanthraquinone (PPAQ) and 2-hydroxyethyl anthraquinone
(2-HEAQ) in aqueous solutions first discovered by Wan and coworkers.11 Due to their excellent
photosensitivity, AQs have been utilized as a PPG plat-form and several AQ-PPGs were
developed. The first example was reported by Kemp and coworkers using
(2-anthraquinonyl)-methyl to protect a carboxylic moiety.12 Furuta and coworkers utilized
anthraquinon-2-ylmethoxy-carbonyl (Aqmoc) to protect some primary alcohols like galactose
(1) and adenosine (2) due to their wide use in the biological areas of research such as
solid-phase oligonucleotide array synthesis, nucleotide synthesis and saccharide modification.
(see Scheme 1).13 Aqmoc exhibits promising and intriguing photoreactivity that can be useful
for many kinds of applications, especially to be potentially used to protect biologically related
molecules.13 Song and coworkers developed 2-(1,2-dihydroxyethyl)-AQ to protect aldehydes
and ketones,14 and used 2-(1-hydroxyethyl)-AQ as a PPG for several carboxylic acids.15 Jones
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and coworkers demonstrated that 1-alkoxy-9,10-AQ can be used to cage 4-hydroxy-2-nonenal
and the photorelease gave 4-hydroxy-2-nonenal in excellent yields.16 Herrmann and coworkers
employed 1-alkoxy-9,10-AQ to release fragrances like volatile aldehydes or ketones, which may
have promisein body care and household applications of functional perfumery.17 Since the AQ
carboxyl moiety is a photo-oxidant which may facilitate single electron oxidation from an
attached arene, Floreancig and coworkers used this to develop a PPG using AQ carboxylates
to release some protected carbonyl and carboxyl compounds.18
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Reaction mechanism studies for PPGs are crucial so as to not only better understand how
PPGs work under different conditions but also aid in the design of new PPGs for applications.
For AQ-PPGs, although some effort has been devoted to study the photodeprotection
mechanisms by using traditional steady-state methods, there appears to be little if any direct
observation and characterization of the reactive intermediates and transient species from
time-resolved spectroscopic investigations. Several issues are still left to be addressed. First,
what is the precursor that reacts to give the photodeprotection? Second, it is noted that the
different AQ-PPGs liberate the caged compounds in different solvents, like Aqmoc works well in
THF-H2O while Aqe and Aqe-diol work well in MeOH. What is the role of the solvent and its
effect on the deprotection reaction of AQ-PPGs? Third, whether the photoredox reaction
observed for 2-HEAQ and PPAQ will be involved in the photodeprotection of AQ-PPGs? Fourth,
what is the effect of the photoreduction reaction?
In this work Aqmoc protected galactose (1) and adenosine (2) were selected to start
time-resolved spectroscopy investigations for photodeprotection mechanisms of AQ-PPGs. The
state-of-art time-resolved spectroscopic techniques of nanosecond transient absorption (ns-TA),
femtosecond transient absorption (fs-TA) and nanosecond time-resolved resonance Raman
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(ns-TR3) spectroscopies were utilized to directly probe the electronic absorption and vibrational
spectra of the reactive intermediates of 1 and 2 in different solvent systems. Density functional
theory (DFT) computations were also conducted to aid in the assignments and interpretation of
the experimental spectra so as to improve knowledge of the reaction pathway(s) and
deprotection mechanism(s) under varying conditions.
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O
O
hv
THF/H2O
OR
O
ROH + side-product
H2N
O
O
N
N
O
OH
N
N
O
O
HO
ROH =
O
O
OHOH
1
2
Scheme 1. The photodeprotection of 1 and 2 in THF-H2O.[13]
Results and Discussion
A. Time-resolved spectroscopic studies of 1 and 2 in ACN, IPA and THF
To gain representative spectra and help in the investigating of the photochemical reactions of 1
and 2 in THF-H2O, time-resolved spectroscopic experiments were first performed for 1and 2 in
the organic solvents of acetonitrile (ACN), IPA and THF, respectively.
Ns-TA spectra for 1 and 2 in ACN are displayed in Figure S3. The spectra have absorbance
features at 325, 372, 462, 620 and 670 nm and these profiles resemble those of the triplet state
for other AQ containing systems.9d The ns-TA spectra of 1 was compared with a DFT calculated
ultraviolet-visible triplet spectrum of 1 (Figure S4) and the close resemblance implies the triplet
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species is the predominant one formed after photoexcitation of 1 and 2 in ACN. Additional
evidence for this triplet assignment results from ns-TR3 spectra (Figure S5), where the Raman
signals at 1557, 1572, 1590 and 1616 cm-1 closely resemble those for the computed triplet
species Raman spectrum.
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HAT is typical for aromatic ketone compounds in hydrogen donor solvents like IPA and has
been studied for a number of AQ derivatives.19 The ns-TA spectra for 1 (Figure S6) and 2
(Figure S7) in IPA have characteristic absorbance features at 383 and 426 nm with a negative
feature near 320 nm. A similar known negative feature near 320 nm was attributed to the
fluorescence signal of the dihydroxyanthracene species, demonstrating occurrence of an HAT
process of the substrate (1 and 2) so the transient detected at 383 and 426 nm is accordingly
assigned to be a ketyl radical species.
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Figure 1.(Left) Ns-TR3 spectra for 1 in IPA acquired at different delay times displayed adjacent
to the spectra. (Right) Comparison of (a) the experimental 50 ns Raman spectrum to (b) the
computed Raman spectrum for the 1ketyl radical species.
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The ns-TR3 experiments were performed for 1 in IPA (Figure 1). Mainly one species was
probed in the ns-TR3 spectra for both 1 and 2 in IPA with Raman peaks at 1551, 1572, 1590
and 1616 cm-1. Based on the ns-TA study, the experimental Raman spectrum recorded at 50 ns
was selected to compare with the simulated Raman spectrum of the ketyl radical in Figure 1
(right). The good agreement between the two supports that the main photochemical reaction of
1 and 2 in IPA is the intermolecular HAT. This is consistent with our previous studies that the
triplet nπ* configuration of AQs act as the reactive species for a HAT reaction to produce a ketyl
radical intermediate in IPA.10
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Figure 2.(a)The fs-TA; (b) ns-TA spectra of 1 in THF.
Figure 2 presents the fs-TA and ns-TA spectra for 1 in THF. To be concise, only the fs-TA
spectra recorded at a later delay time region are presented. The first species at 372 and 462 nm
decayed to form a new intermediate that absorbs at 380 and 426 nm with an isosbestic feature
near 405 nm. Based on the time-resolved spectroscopic studies in ACN and IPA, the first
species is the triplet species and the second is the ketyl radical species of 1. For the ns-TA
spectra recorded in THF, a ketyl radical species was also probed for 1 and 2 (Figure S8). That
is, the HAT takes place for 1 and 2 in THF. On the other hand, it is noted that in THF the triplet
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species was still observable with its typical signal at 462 nm for both 1 and 2 while the bleaching
band observed in IPA was absent for 1 and was less intense for 2.
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Figure 3. Ns-TR3 results of (a) 1 and (b) 2 in THF obtained with different time delays displayed
adjacent to the spectra.
The ns-TR3 spectra for 1 and 2 in THF are displayed in Figure3. The spectra have Raman
peaks at 1551, 1557, 1572, 1590 and 1616 cm-1 and therefore is proposed to gain combined
contributions from the triplet and the ketyl radical species. It can be concluded that the HAT
reaction takes place for both 1 and 2 in THF but that it occurred with a slower rate compared to
that seen in IPA. This is reasonable as the HAT process for the substrates from the 3° C −H
bond of IPA is easier to take place than that from the 2° C-H of THF.
B. Time-resolved spectroscopic studies of 1 and 2 in THF/H2O and THF/KMOPS
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After clarifying the photophysical and photochemical reactions of 1 and 2 in organic solvents,
we now focus on the photochemical reactions of Aqmoc-PPG in THF-H2O, where
photodeprotection was found to take place.13 Photolysis experiments were performed for 1 and
2 in THF-H2O and the products were isolated by thick layer chromatography. It was determined
that the predominant product after photolysis is 2-methylAQ (Figure S9). This is consistent with
the studies by Kemp and coworkers on AQ protected carbonic acids that the predominant
deprotection product is 2-methylAQ. It is noted that the major deprotection byproduct of 1 was
anthraquinon-2-ylmethanol tetrahydrofuranyl ether as reported earlier by Furuta. This is not
surprising because THF is known to be easily oxidized and the ether product could be formed
from 2-methylAQ by several pathways.
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Figure 4.Shown are the fs-TA (a, b, c and d) and ns-TA (e and f) results for 1 in THF-H2O (1:1).
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Figure 4 presents ns-TA and fs-TA results observed of 1 in THF-H2O. The very early changes
seen within 1 ps (Figure 4a) are attributed to an internal conversion transformation of Sn to S1.
Then, S1 decayed with the production of the triplet having the specific absorption features near
382 and 452 nm (see Figure 4b, 4c). Finally, the triplet species reacts to produce a ketyl radical
species (Figure 4d). This is similar to the transformations observed for 1 in pure THF solvent. In
the subsequent times revealed by the ns-TA spectra (Figure 4e and Figure 4f), the observation
of an isobestic point at 410 nm for both 1 and 2 suggests a kinetic transformation from the ketyl
radical species (382 and 426 nm) to another transient species having its typical absorbance at
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505 nm, that was not seen in the organic solvent systems we studied and this species is
denoted as IM1. It is noted that the radical anion species of some AQ compounds absorbs in
the 500-620 nm region.[20] To discern whether IM1 is the radical anion intermediate of an AQ
species, the ns-TA experiment was performed for 1 in the electron donor solvent
dimethylsulfoxide (DMSO) (Figure S10). The spectra profile in Figure S10 resembles well with
the spectrum of the reported radical anion species of an AQ compound,9 while the spectrum
was distinctly different from that observed in THF-H2O, suggesting that IM1 is not the radical
anion species of an AQ species. After 2 μs, IM1 decayed and a second new species (denoted
as IM2) that has a shoulder band at 370 and 400 nm, and a band at 400 nm formed around 16
μs.
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Figure 5.The ns-TA results for(a, b)1, (c, d) 2in THF-KMOPS (1:1) solutions.
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Since the final product analysis suggested that the deprotection occurs more efficiently for 2
in a THF-KMOPS solutions (with quantum yields up to 98%), ns-TA spectra of 1 and 2 were
also obtained in THF-KMOPS (Figure 5). Upon 266 nm irradiation, IM1 was produced and then
transferred to IM2 faster and more efficiently as compared to the analogous species seen in
THF-H2O. In addition, a third species (IM3) was observed at 330 nm for1 and 2that coexisted
with IM1 in THF-H2O and THF-KMOPS. To assist in the identification of the three intermediates
IM1, IM2 and IM3, ns-TR3 experiments were performed for 1 and 2 in THF-H2O and
THF-KMOPS, and these results are respectively shown in Figure 6 and Figure S11.
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Figure 6.Thens-TR3 results obtained for 2 in (a) THF-H2O (1:1) and (b) THF-KMOPS (1:1)
solutions recorded at varying time delays displayed adjacent to the spectra.
In THF-H2O, the ns-TR3 spectral profile of the first species (Figure 6a) exhibits an apparent
similarity with that of a ketyl radical species (see the comparison of the spectra observed in IPA
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and THF-H2O in Figure S12). It was shown earlier that the HAT reaction for 1 and 2 can take
place between the substrates and the solvent THF with the generation of the ketyl radical
species. At 10 μs, a new transient emerged with diagnostic Raman features at 1585 and 1612
cm-1 along with a weak while still noticeable feature at 1635 cm-1.
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For the ns-TR3 results for 2 in THF-KMOPS (Figure 6b) the species having Raman peaks at
1585, 1612 and 1635 cm-1 was produced earlier at around 100 ns and completely formed by
300 ns (indicated by the blue line) and appears to be produced more efficiently with more
intense Raman signals accompanying the decay of the ketyl radical species. On one hand, as
the deprotection of 2 occurs more efficiently in a THF-KMOPS solution,[13] the preceding
behavior suggests that IM1 is formed from the decay of ketyl radical species and IM1 that has
specific electronic absorption bands at 372 and 505 nm and vibrational peaks at 1585, 1612
and 1635 cm-1 could be produced from the photodeprotection reaction. On the other hand, the
predominant product after photolysis for 1 and 2 is 2-methyl AQ.
a
O
O
OH
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O
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e
300
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Raman Shift (cm-1)
Wavelength (nm)
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Figure 7.(Left) Comparison of (a) the ns-TA spectrum of 2 obtained in THF-H2O at 2 μs to the
(b) calculated xylylidene species of 2-methylAQ (utilizing a 1.0 scale factor with a 2500 cm-1
half-width) with its structure shown in the figure, and comparison of (d) the ns-TA spectrum of 2
in THF-KMOPS recorded at 2 μs to (c) the UV-vis spectra of 2-methyl AQ acquired in THF-H2O
and (e) computed ultraviolet-visible spectrum of triplet couple-reaction product between the
ketyl radical and THF (using a 1.1 scale factor with a 1400 cm-1half-width)with its structure
shown in the figure. (Right) Comparison of (black) the ns-TR3 spectrum of 2 in THF-KMOPS at
10 μs to (red) the computed Raman spectrum for the xylylideneform for 2-methyl AQ.
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We compared the experimental ns-TA spectra of the species IM1 recorded for 2 in THF-H2O
at 2 μs with an UV-vis spectrum of an authentic sample of 2-methyl AQ in THF-H2O and a
calculated one for its xylylidene form (Figure 7, Left), and compared the experimental
resonance Raman spectrum for the intermediate IM1 at 10 μs was respectively correlated with
the computed ones for 2-methyl AQ (Figure S13) and its xylylidene species (Figure 7, Right). It
is found the ns-TA spectra have joint inputs due to the two species, that is, the absorbance at
372 and 505 nm (IM1) are from a more conjugated xylylidene structure of 2-methylAQ and the
330 nm (IM3) band gains a contribution from 2-methylAQ. This assignment is consistent with
the ns-TA study on naphthoquinone by Wirz and coworkers showing the quinone form absorbs
in the lower wavelength region while its corresponding enol has a specific absorption at longer
wavelength from 500 nm.21To make the assignment of the species IM2 generated at late delay
time with a shoulder band spectrum (372, 400 and 500 nm), TD-DFT calculations were
performed for several possible species and the experiment spectrum is more similar to the
simulated ultraviolet-visible spectrum for the triplet of the couple-reaction product between the
ketyl radical of 2-methylAQ and THF (see its chemical structure in Figure 7e). The ns-TR3
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results for the species (1585, 1612 cm and 1635 cm-1) seen subsequent to the decay of the
ketyl radical resembles more with the xylylidene species while it is different from 2-methylAQ
and the couple-reaction product. This could be due to the fact that 2-methylAQ has a strong 330
nm absorbance so it is not easy to be observed under our ns-TR3 experimental condition using
the probe wavelength of 368.9 nm. The absence of signal from the couple-reaction product in
ns-TR3 could be accounted for by the ns-TA experiments being done for the sample solutions
stored in a quartz cell, which allows for the detection of the byproduct, while the ns-TR3
experiments use a flowing system which makes sure the species are generated from fresh
sample solutions with little build-up of photoproducts in the bulk solution.
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After generation of dihydroxyanthracene species, the cleavage process was proposed to be
accompanied by a decarboxylation, which resembles the cleavage of 2-nitrobenzyl carbonate
esters,22 coumarin esters,23 N-methylpicolinium carbamates24 and thiochromone S,S-dioxide
esters.25As suggested by the ns-TA and ns-TR3 results, the photodeprotection takes place
during the nanosecond time region and thus the singlet excited state reaction pathway is
therefore excluded. We first simulated this reaction on the excited triplet surface using DFT
calculations and these results are presented in Figure 8 and suggest the triplet
dihydroxyanthracene overcomes a barrier of 10.05 kcal/mol to release the protected alcohol as
well as undergoes a decarboxylation process. We also simulated the deprotection via the
ground state surface (Figure S14), while the endothermic product and the energy barrier of
24.17 kcal/mol excluded this pathway.
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10.05
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Figure 8. Profile of the reaction energy derived by (U)B3LYP/6-311G** computations for the
photodeprotection of 1 via triplet surface accompanied by the decarboxylation process with
assistance of two H2O molecules.
Combing these DFT computational results to final product analysis data and the time-resolved
spectroscopic data, a photorelease reaction mechanism is proposed for the Aqmoc caged
alcohol compounds (Scheme 2). Briefly, the caged AQs are excited to Sn and undergo an
efficient ISC process to produce the triplet species, which starts the photorelease reaction.
Then, a process occurs that generates the ketyl radical species and that then further formed the
dihydroxyanthracene species, which undergoes the deprotection reaction along with a
decarboxylation.
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*
3
*
O
O
O
O
O
O
O
O
OR
O
ORhv
ISC
O
OR
O
THF
OHketyl radical
382, 426 nm
1551, 1572, 1590 & 1616 cm-1
O
H
O
O
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O
OR
hv
O
tautomerize
-CO2
-ROH
OH
OH
O
IM1
372, 505 nm
dihydroxyanthraquinone
bleaching at 320 nm
IM3
330 nm
1585, 1612 & 1635 cm-1
Scheme 2.The proposed photodeprotection mechanism of alcohols from Aqmoc-PPG in
aqueous solutions. a
a Letters below the structures are the corresponding labels used in the text. And the absorbance
for the transient species detected from fs-TA and/or ns-TA spectra, and the Raman bands from
ns-TR3 are given.
Conclusions
To conclude, the investigation here found that in THF-H2O solvents, the ketyl radical species of
1
and
2
is active intermediate on the way to deprotection. After the
dihydroxyanthraceneintermediate was formed from the ketyl radical, the deprotection of
alcohols from the AQ-PPGs 1 and 2 occurred with the accompaniment of a decarboxylation.
The release of the protected alcohol as well as the carbon dioxide might have potential
applications as a probe and maybe useful in the photodynamic therapy area for suitably
designed molecules.
Even though the ketyl radical species can be efficiently produced for 1 and 2 in IPA, no
photorelease was observed for the two Aqmoc-PPG compounds under this solvent system.
That is because the recombination reaction between the ketyl radical species and IPA radical
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competed effectively relative to the photodeprotection of 1 and 2. This is also the case for the
experimental fact that the photodeprotection product was detected for 1 and 2 in THF-H2O
while not in pure THF. In addition, the photodeprotection occurs more efficiently in a
THF-KMOPS solution than in THF-H2O for both1 and2. This is because the buffered solution
facilitates the decarboxylation reaction as observed for ketoprofen PPGs.[26] We note that
studies on AQ-PPGs using the Aqe and Aqe-diol platforms that do not contain the ether group
were reported to release the carbonyl group efficiently in methanol and the use of a buffered
aqueous solution is not required which supports that the decarboxylation is likely involved in the
Aqmoc-PPG deprotection as well. It is noted that the photorelease occurs more efficiently for 2
than 1 under analogous experimental conditions (in both THF-H2O and THF-KMOPS). This can
be accounted for by the adenosine moiety in 2 being a more effective leaving moiety compared
to that of galactose in 1, resulting from the less basic character of adenosine as the leaving
group than galactose which makes it is easier to accept electrons and facilitate its cleavage,
also the two electron-withdrawing hydroxyl groups attached can stabilize the O- of the
adenosine after cleavage.
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The key intermediates related with photoredox reactions and photohydration reactions were
not detected during the photodeprotection process for 1 and 2,suggesting that the
photodeprotection will not be effected by the photoredox process or the photohydration
process.It is noted that photoredox and photohydration of AQs are respectively triggered by
proton coupled electron transfer (PCET) and proton transfer (PT) via ππ* configuration of the
triplet states, while photodeprotection starts from HAT via nπ* triplet in neutral aqueous
conditions. The PCET, PT and HAT are general topics in photochemical and photobiological
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areas, therefore, this work supplies important information on the solvent-related
configuration-controlled photochemical reactions of aromatic carbonyls.
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Experimental Section
1 and 2 were made by utilizing procedures detailed in the literature13 and the synthesis route
were shown in Scheme S1 and Scheme S2, respectively. For characterization of the samples
prepared please see the 1H NMR spectra displayed in Figure S1 and Figure S2.
A femtosecond regenerative amplified Ti:sapphire laser seeded by output from a 120 fs
oscillator was utilized to do the fs-TA measurements. Around 5% of the generated amplified
800 nm output was used to prepare (using a CaF2 crystal) the 320 nm to 700 nm whitelight
continuum probe laser beam. One part of the probe passed through the sample (flowing
through a 2 mm pathlength cuvette) that was also excited by a 267 nm pump beam. Ns-TA
experiments were done with a commercial laser flash photolysis system employing 266 nm
laser photoexcitation and a Xenon lamp probe. Sample solutions were prepared to have an
absorbance of 1 at 266 nm and then utilized in the fs-TA and ns-TA measurements. Deionized
water and spectroscopic quality acetonitrile (ACN) were utilized to prepare samples for the
experiments in this study.
Ns-TR3 measurements were done with experimental methods and a system that used 266
nm pump photoexcitation and a 368.9 nm probe derived from the fourth harmonic (266 nm) of
one Nd:YAG laser and the second harmonic (532 nm) second anti-Stokes hydrogen
Raman-shifted laser line (368.9 nm) from a second Nd:YAG laser and a pulse delay generator
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was used to control the relative time delay between the two lasers. The pump pulse excited the
sample to initiate the photochemical reactions and the probe pulse interrogated the sample and
the transient species for the reaction of interest. Deionized water and spectroscopic quality
acetonitrile (ACN) were utilized to prepare samples for the experiments in this study.
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The DFT computations (B3LYP method with 6-311+G** basis set) were performed to find
structures for the ground state, triplet state, the RC, TS, and PC and the connecting reaction
energy pathways Frequency computations (employing the same method and basis set) were
performed to deduce the geometries were at local minima (no imaginary frequency).
TD-B3LYP/6-311+G** calculations were utilized to estimate the UV-vis spectra. The effect of
solvent polarity was estimated by utilizing the integral equation formalism polarizable continuum
model (IEFPCM) in ACN ( = 35.688) on the gas-phase structures for the non-electrostatic
terms and the radii us employed in the universal solvation model (SMD) developed by Truhlar
and co-workers.27 All of the preceding calculations utilized the Gaussian 03 program.28
Supporting Information The synthetic route of compounds with the 1H NMR spectra reactant
and photoproduct species discussed in the text; fs-TA, ns-TA and ns-TR3 spectra for some of
the interested intermediate species; DFT calculated electronic and Raman spectra, RC, TS and
PC optimized geometries and the reaction energy pathway and Cartesian coordinates and
energies for all calculated structures discussed in the text (PDF).
Keywords: Anthraquinone, Photolabile protecting groups, Time-resolved spectroscopy, DFT
calculations
Acknowledgements
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The research was sponsored in part by grants from the National Science Fund of China
(21503167), the China Postdoctoral Science Foundation (2018T111088) and Northwest
University (338031601) to J. M. and the Research Grants Council of Hong Kong
(HKU17301815) to D.L.P. and partial support from the Areas of Excellence Scheme (Grant
AoE/P-03/08), the UGC Special Equipment Grant (SEG-HKU-7) and the University of Hong
Kong Development Fund 2013-2014 project “New Ultrafast Spectroscopy Experiments for
Shared Facilities”. Jiani Ma thanks Dr. Wenjian Tang at School of Pharmacy, Anhui Medical
University, P. R. China for helping to purify compound 1.
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TOC
hv
THF-H2O
IPA/THF

ROH side-product
O
O
O
O
OR
ketyl radical
NH2
N
OH
O
N
N
O
ROH=
O
O
N
O
O
HO
HO OH
2
1
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