On the Origins of Nonradiative Excited State Relaxation in Aryl Sulfoxides Relevant to Fluorescent Chemosensing

Article abstract of DOI:10.1021/jacs.6b00572

We provide herein a mechanistic analysis of aryl sulfoxide excited state processes, inspired by our recent report of aryl sulfoxide based fluorescent chemosensors. The use of aryl sulfoxides as reporting elements in chemosensor development is a significan

Full text of DOI:10.1021/jacs.6b00572

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Article
On the origins of non-radiative excited state relaxation
in aryl sulfoxides relevant to fluorescent chemosensing.
Rahul S. Kathayat, Lijun Yang, Tosaporn Sattasathuchana, Laura
Zoppi, Kim K. Baldridge, Anthony Linden, and Nathaniel S. Finney
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b00572 • Publication Date (Web): 03 Nov 2016
Downloaded from http://pubs.acs.org on November 3, 2016
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Journal of the American Chemical Society
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On the origins of non-radiative excited state relaxation in aryl
sulfoxides relevant to fluorescent chemosensing
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Rahul S. Kathayat,1 Lijun Yang,2 Tosaporn Sattasathuchana,1 Laura Zoppi,1 Kim K. Baldridge,1,2 Anthony
Linden,1 and Nathaniel S. Finney*,1,2
1Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
2School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, Chi-
na.
ABSTRACT: We provide herein a mechanistic analysis of aryl sulfoxide excited state processes, inspired by our recent report of
aryl sulfoxide-based fluorescent chemosensors. The use of aryl sulfoxides as reporting elements in chemosensor development is a
significant deviation from previous approaches, and thus warrants closer examination. We demonstrate that metal ion binding
suppresses non-radiative excited state decay by blocking formation of a previously unrecognized charge transfer excited state,
leading to fluorescence enhancement. This charge transfer state derives from the initially-formed locally excited state followed by
intramolecular charge transfer to form a sulfoxide radical cation/aryl radical anion pair. With the aid of computational studies, we
map out ground and excited state potential energy surface details for aryl sulfoxides, revealing that ground state effects are also
important in fluorescence enhancement. This work expands previous proposals that excited state pyramidal inversion is the major
non-radiative decay pathway for aryl sulfoxides. We show that pyramidal inversion is indeed relevant, but that an additional and
dominant non-radiative pathway must also exist. These conclusions have implications for the design of next generation sulfoxide
based fluorescent chemosensors.
O
INTRODUCTION
NH2
O
S
R =
N
O
O
O
Fluorescent chemosensors – small molecule probes that re-
spond to reversible analyte binding by undergoing changes in
fluorescence – are now widely used in the detection of non-
fluorescent analytes in biological, medical and environmental
assays.1 These probes are chiefly based on modulation of
photoinduced electron transfer (PET) or internal charge trans-
fer (ICT), induced by nitrogen atom coordination.2 Less com-
mon for small molecule probes are other signaling mecha-
nisms, such as fluorescence resonance energy transfer (FRET),
binding-induced conformational restriction, excited-state
proton transfer, and excimer formation.2 The heavy reliance
on nitrogen binding, while efficient and widely employed,
suffers from drawbacks such as pH sensitivity and requisite
placement of recognition domain at anilinic or benzylic amine
positions. These limitations provide motivation to discover
alternative motifs for signaling, in order to broaden the range
of strategies and structures for development of fluorescent
chemosensors.3-6
1b
R
O
1d
O
N
N
N
1a R = CH3
O
1c
1e
To this end, we have reported a new approach employing aryl
sulfoxides as the chemosensor signaling motif (1a-e; Chart
1).7 Remarkable gains in fluorescence emission from pyrenyl
sulfoxides were demonstrated to occur upon metal ion coor-
dination (Figure 1), despite sulfoxides’ very weak intrinsic
metal ion affinity.7,8,9
1.2E+05!
0.045 M!
1.0E+05!
8.0E+04!
Chart 1. Sulfoxide-based fluorescent chemosensors 1a-e.
6.0E+04!
4.0E+04!
2.0E+04!
0.0E+00!
0.0 M!
350!
400!
450!
500!
wavelength / nm!
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aAll measurements made in CH3CN. Emission spectra acquired
at 10 ꢀM, with excitation at the longest absorption maximum.
bLongest
absorption/emission maxima for pyrene: 335nm/381
nm.13 Longest
Figure 1. Titration of 1a (10 ꢀM in CH3CN) with ZnCl2.
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λ
The sensitivity to metal ions was shown to increase many-fold
upon replacing the methyl group of 1a with more strongly
coordinating receptor units as in 1b-e.7 In addition, sulfoxide-
based fluorophores were shown to function in aqueous me-
dia. Sulfoxides as a signaling motif, therefore, have potential
for the development of useful metal-ion responsive
chemosensors.
λ
λ
absorption/emission maxima for 1a-e: 349-350
nm/377-378 nm. Units: 103 M-1cm-1. Literature quantum yield
c
d
for pyrene;13 absolute quantum yields for 1a-e.
Established excited state deactivation pathways
The alkyl aryl sulfoxide non-radiative decay mechanism is
dependent on the nature of the alkyl group attached to the
sulfur atom. It is well-established that for alkyl aryl sulfoxides
bearing 2°/3° alkyl groups, the excited states deactivate by
Before further expansion of this approach, it is essential to
understand the mechanistic basis for fluorescence enhance-
ment. Based on a combination of experimental and theoreti-
cal work we provide insight into the excited state processes
of aryl sulfoxides, with particular emphasis on how these pro-
cesses are perturbed by metal ion coordination.
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undergoing reversible fragmentation to form
a sulfi-
nyl/carbinyl radical pair.12 It is accepted that aryl sulfoxides
possessing a 1° alkyl group, such as 1a-e, primarily deactivate
via excited-state photostereomutation at the tetrahedral
sulfoxide center.12,14,15 That is, the excited state energy is dis-
sipated by pyramidal inversion of the sulfoxide. This has most
convincingly been shown through labeling studies (Figure
2),12e where major photochemical was that of pyramidal in-
version in the singlet excited state, with negligible radical
fragmentation. (The involvement of triplet states in this pro-
cess has been excluded.)12c. 14
RESULTS AND DISCUSSION
Structural and optical properties
The general optical properties of 1a and the related mole-
cules 1b-e are very similar to those of pyrene. The longer-
wavelength absorption maxima of 1a-e are slightly red-
shifted, indicating variation of the π/π* energetic separation
as the result of the sulfoxide substituent (Figure S1).
As our fluorescent probes are all aryl sulfoxides bearing a 1°
alkyl group, our studies have focused on the origin of excited
state sulfoxide pyramidal inversion.
The crystal structure of 1a reveals that the S-O bond lies co-
planar with the pyrene ring in the solid state (Figure S5). This
could be taken as reflecting a favorable alignment of the py-
rene π system with the bond formed between an O atom lone
pair and an empty d-orbital on S. (This S-O bonding is often –
incorrectly – taken as being the “second bond” of a π bond
between S and O.) In fact, while our optimized structure does
not show perfect pyrene/S-O coplanarity, the dihedral angle
between the S-O bond and the pyrene π system is quite small
(ca. 20°; Figure S6), still consistent with conjugation, as evi-
dent from the molecular orbitals. Previous computational,
and experimental gas-phase and solution-phase studies, indi-
cate that, regardless of the minimum energy configuration,
the barrier to rotation of the Caryl-S(O) bond is very low, pos-
sibly <1 kcal/mol.10 The conjugative interaction between the
pyrene and the sulfoxide is thus weak enough that variation
in the π/π* energy gap could just as well result from inductive
effects.11
Figure 2. Photostereomutation of a labeled 1° alkyl/aryl sul-
foxide.
Racemization studies
To begin, it was necessary to see whether enhanced fluores-
cence in the presence of metal ions was correlated with re-
duced pyramidal inversion. We studied the photoracemiza-
tion of sulfoxide (S)-1a (Scheme 1), and observed that added
metal ions do indeed influence this process (Figure 3).
Enantiomerically enriched (S)-1a was obtained in 94% ee
(97% (S)-1a) and acceptable yield by oxidative kinetic resolu-
tion of racemic 1a using a chiral catalyst generated in situ
from VO(acac)2 and ligand 2 (Scheme 1).16 The absolute con-
figuration of (S)-1a was confirmed by single crystal XRD (Fig-
ure S5).17
The quantum yields of 1a-e (Table 1) are very low, consistent
with the previous reports for alky aryl sulfoxides.7,12 These
reports have shown that the low emission in aromatic sulfox-
ides is a consequence of non-radiative deactivation of the
excited state, rather than variation in the rate of radiative
decay.
Scheme 1. Synthesis of sulfoxide (S)-1a.
Table 1. Optical properties of 1a-e.a,b
d
εc
φf
Compound
pyrene
1a
54.0
34.7
31.1
27.6
28.5
27.5
0.32
0.012
0.009
0.004
0.003
0.015
1b
1c
1d
1e
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The resulting reduction in electron density at the sulfur cen-
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ter should lower the barrier to pyramidal inversion (Figure 3,
right). This CT state would bear similarity to a sulfoxide radical
cation, although: 1) the molecule as a whole remains neutral;
and, 2) the CT state formation does not necessarily involve
complete transfer of an electron from the sulfoxide fragment
to the pyrene ring. However, for convenience, we will discuss
the proposed CT state as being a paired sulfoxide radical cati-
on and pyrenyl radical anion.
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Figure 3. Photoracemization of (S)-1a (2.5 mM, CH3CN), with
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and without added Mg(ClO4)2.
Irradiation of 2.5 mM (S)-1a in CH3CN was carried out, with
and without excess (100 eq.) Mg(ClO4)2, in quartz cuvettes,
irradiating with a TLC lamp.17 Small samples were withdrawn
at periodic intervals and the enantiomeric composition was
determined by HPLC on a chiral column (Figure S2). The two
enantiomers of 1a were found to be the major products by
HPLC, confirming the absence of any significant side
reactions. Without added Mg2+, the composition of the (S)-1a
sample declined from 94% to 69% (S)-1a upon irradiation for
1 hour (black circles; Figure 3). In contrast, in the presence of
Mg2+, racemization was significantly inhibited, and the enan-
tiomeric composition changed relatively little over the same
time period (red squares; Figure 3).18 This demonstrates that
metal coordination correlates with suppression of pho-
tostereomutation in this aryl sulfoxide. As φf for 1a increases
from 0.01 to 0.35 in the presence of excess Mg2+, this is con-
sistent with metal ion coordination increasing fluorescence
emission by suppressing excited state deactivation via pyram-
idal inversion.
Figure 4. Origin of the inversion barriers in S0 and S1.
In this CT model, pyramidal inversion would lead to enhanced
non-radiative decay in the form of enhanced internal conver-
sion (IC; Figure 4). Since the rate of IC scales with the negative
exponent of ∆E,19 the smaller S0–S1 separation in the planar
transition state should lead to enhanced non-radiative decay.
An ICT model for excited state pyramidal inversion
Figure 5. Enhanced internal conversion (IC) during pyramidal
inversion in an intramolecular charge transfer (ICT) excited
state (pyr = pyrene).
Having shown that metal ion-mediated fluorescence en-
hancement correlates with suppression of photostereomuta-
tion, the next task was to explain why this should be so. It has
long been known that photoracemization of aryl sulfoxides is
far faster than thermal racemization,12a,b and that the barrier
to excited state inversion must therefore be lower than the
ground state barrier. As noted above, this reduction in inver-
sion barrier is a singlet excited state process. However, a
complete descriptive model has not previously been provid-
ed.14
Fast S1→S0 IC at planar geometry would be followed by the
return to either of the enantiomers, resulting in the observed
rapid photostereomutation.
Existing support for this hypothesis comes in two forms. First,
it has been established by pulse radiolysis and computational
study that the methyl phenyl sulfoxide radical cation has the
positive charge localized on S.20a Second, reversible 1e– oxida-
tion of enantiomerically-enriched methyl phenyl sulfoxide
leads to rapid racemization at room temperature, indicating
low-barrier pyramidal inversion of the radical cation.20b
The barrier to pyramidal inversion in sulfoxides is electrostatic
in origin (Figure 3, left).15 Increased repulsion between the
lone pair electrons on S and O accounts for the higher energy
of the planar configuration relative to the pyramidal configu-
ration.
Additional support is provided by simulated photoelectron
spectroscopy (PES) of phenyl pyrenyl sulfoxide in the gas
phase (Figures S3, S4)17 via accurate GW-BSE calculations.21
The calculated optical absorption spectrum reveals a long
wavelength electronic transition at 2.4 eV (~515 nm) that
must be an n→π* transition. Because it is symmetry-
forbidden, it would be too weak to be observed directly in the
UV spectrum, but would still represent direct transfer of an
electron from a sulfoxide lone pair to the π* orbital of pyrene.
This is further confirmed by the theoretical analysis, which
A simple explanation for rapid excited state pyramidal inver-
sion would be that the planar sulfoxide transition state lead-
ing to inversion is a charge transfer (CT) state, in which elec-
tron density is shifted from the sulfoxide to the pyrene ring.
This would presume initial excitation to a locally excited (LE)
state, followed by intramolecular charge transfer (ICT) to
form a lower-energy CT state.
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Br
SCH3
reveals the molecular states mainly contributing to this elec-
1. BuLi, THF,
–78 °C
1. BuLi, THF,
1
2
3
4
tronic excitation (Figure S4). The product of this excitation
(sulfoxide radical cation/pyrenyl radical anion) would be the
proposed CT state.
–78 °C
RO
RO
RO
RO
2. (H3C)2S2,
–78 °C to RT
83%
2. CH3OH
–78 °C to RT
93%
Br
Br
Substituent effects
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As a further test of the CT state hypothesis, we evaluated
substituent effects on the spectroscopic properties of aryl
sulfoxides by two approaches: first, exchanging the methyl
group in 1a for a phenyl group (3a; Chart 2), which facilitated
electronic variation by substitution (3b,c); and, second, incor-
porating electron donating groups on the pyrene ring (4).7
O
S
SCH3
CH3
mCPBA,
CH2Cl2, 0 °C
RO
RO
RO
RO
9
86%
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Fluorophores with p-substituted phenyl groups were synthe-
sized from bromopyrene (Scheme 2).17 Lithiation of 5 fol-
lowed by reaction with appropriate disulfides gave the corre-
sponding p-substituted phenyl pyrenyl sulfides 6a-c. The sul-
fides were then oxidized to the sulfoxides (3a-c) with mCPBA
in acceptable yield.
9
4
Spectroscopic properties such as extinction coefficients and
excitation/emission maxima for 3a-c were similar, and very
similar to those of 1a-e. However, fluorescence quantum
yields (φf) varied significantly with para substitution: there is a
10-fold difference in φf between the p-OCH3 and p-CF3-
substituted derivatives (3b vs. 3c). In parallel, the lifetimes (τ)
of 3a-c were observed to follow the same trend: a 10-fold
change in τ is observed between 3b and 3c.
Chart 2. Substituted aryl sulfoxides.
O
S
O
S
3a X = H
3b X = CF3
3c X = OCH3
n-H13C6O
n-H13C6O
The extracted rates of radiative and non-radiative decay (kr,
knr; kr = φf/τ ; knr = (1/τ)-kr) are explanatory (Table 2). kr re-
mains virtually independent of the p-substituent, although it
is worth noting that the kr are quite slow – on the order of 107
s–1. In contrast, knr varies with substitution. The change from
p-CF3 to p-OCH3 (3b vs. 3c) increases the rate of non-radiative
decay by an order of magnitude, with the p-H (3a) value lying
in-between. As would be expected with near-invariant kr,, the
knr values match the trends observed for φf and τ.
X
4
Scheme 2. Synthesis of 3a-c.
Br
S
1. n-BuLi
6a X = H, 78%
6b X = CF3, 80%
6c X = OCH3, 43%
THF, –78 °C
X
2. Ar2S2
Table 2. Optical properties of 3a-c.a
–78 °C to RT
5
3a (p-H)
3b (p-CF3)
3c (p-OCH3)
λex/nmb
λem/nmb
O
351
380
35.5
352
381
35.9
352
379
39.7
S
3a 91%
3b 83%
3c 83%
mCPBA
ε/103 M-1cm-
X
1
CH2Cl2, 0 °C
φfc
0.011
0.42
0.24
21.5
0.053
1.84
0.29
5.15
0.006
0.19
0.32
53.7
τ/ns
kr/108 s-1
knr/108 s-1
Sulfoxide 4 was synthesized from the dibromopyrene deriva-
tive 7 (Scheme 3).17 Monolithiation of 7 followed by quench-
ing with dimethyl disulfide provided intermediate 8 in 83%
yield. Subsequent lithium-halogen exchange and quenching
with CH3OH gave compound 9 in 93% yield. Partial oxidation
of this sulfide was carried out with mCPBA, furnishing sulfox-
ide 4 in 86% yield.
aAll measurements made in CH3CN. Excitation/emission spec-
tra acquired at 10-5 M. bLongest λ excitation/emission maxima.
cAbsolute quantum yields.
Scheme 3. Synthesis of 4 (R = n-C6H13).
Substituent effects are consistent with deactivation via py-
ramidal inversion in a CT excited state
The observed substituent effects are consistent with excited
state deactivation by pyramidal inversion (Figures 4, 5). Pre-
vious studies have shown that the barrier for S0 sulfoxide
inversion is minimally perturbed by electronic effects.22 In
contrast, the variation (ca. 10 fold) in knr between 3b and 3c
indicates stronger electronic effects for excited state stere-
omutation. This is reasonable, in that substituents on the
phenyl ring are expected to influence the S1 planar sulfoxide
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an energy maximum at planar geometry (Tables 3, S1, S2;
radical cation transition state more strongly than the un-
charged S0 planar sulfoxide transition state.23 The electron
withdrawing p-CF3 group in 3b should destabilize the fully-
conjugated, planar configuration of the sulfoxide radical cati-
on (blue curve; Figure 5), whereas the electron donating p-
OCH3 group in 3c should lead to stabilization (green curve;
Figure 5). Therefore, the S0-S1 ∆E at planar geometry should
vary with p-substituent as follows: OCH3 < H < CF3. This vari-
ance should be reflected in the rate of non-radiative IC be-
tween the planar S0 and S1 configurations, where the S0-S1
energy gap is the smallest, with IC being fastest for 3c and
slowest for 3b. The measured quantum yields are in agree-
ment with this analysis.
Figures 6, S6, S7a). However, the energy required to reach the
planar geometry in S1 is far lower than in S0 (6 vs. 36
kcal/mol).17,24 At Ea = 6 kcal/mol, , the rate for inversion
should be on the order of 1011s–1, similar to the inversion bar-
rier of an amine.15 This reinforces the idea that the S0-S1 ener-
gy gap for the planar geometry should lead allows a rate of IC
that is fast on the timescale of radiative decay.
1
2
3
4
5
6
7
8
Table 3. Calculated ground and excited state inversion barriers
for 3a in gas and solution phase. a,b,17
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Gas Phase
CH3CN
3a (S0) 36.2 (32.9) 36.0 (33.1)
3a (S1) 5.04 (5.11) 5.56 (5.70)
The high φf (0.43) of 4 relative to 1a (0.012) can be rational-
ized by considering that the pyrene ring bearing OC6H13
groups is electron rich in comparison to that of 1a. Thus, for-
mation of the CT sulfoxide radical cation/pyrenyl radical anion
pair should be less favorable. This inhibition of CT state for-
mation, and IC via pyramidal inversion, would lead to a higher
φf.
b
aErel/kcal•mol–1. Ground state calculations using B3LYP/Def2-
TZVP (B97-D/Def2-TZVP); excited state calculations using TD-
B3LYP/Def2-TZVP (TD-B97-D/Def2-TZVP//TD-B3LYP/Def2-TZVP).
Figure 7. Simple potential energy diagram derived from cal-
culated energetic data (in CH3CN) for S0 and S1 of 3a (pyr =
pyrene).15 See Table 3.
Upon further investigation (Table 4, Figure 8), it was
determined that ground state effects play a only a minimal
role in altering IC during pyramidal inversion. In CH3CN, the
ground state barrier to inversion of 3a•MgCl2 drops from 36.0
kcal/mol (3a) to 33.9 kcal/mol (∆Erel = 2 kcal/mol).17 Thus, the
observed increase in quantum yield induced by MgCl2
addition (0.01 vs. 0.35) is almost entirely an excited state
effect.
Figure 6. Qualitative potential energy (PE) diagram for elec-
tronic effects in 3a-c (pyr = pyrene).
Computational characterization of the S1 and S0 potential
energy surfaces for 3a, with and without Mg2+
The above indirect arguments are consistent with pyramidal
inversion in a CT excited state determining the efficiency of
non-radiative relaxation in S1 of aryl sulfoxides. While com-
plete energetic parameterization would be desirable, it is
experimentally inaccessible. However, computational meth-
ods allow a quantitative analysis of the potential energy (PE)
surfaces associated with 3a (Table 3; Figures 6, 7).17 Calcula-
tions were performed for the gas phase and with a CH3CN
continuum model. Discussion will focus on the CH3CN calcula-
tions.17
Table 4. Calculated ground state inversion barriers for 3a•MgCl2
in gas and solution phase. a,b,17
gas phase CH3CN
3a•MgCl2 (S0)
34.5
33.9
aErel/kcal•mol–1. bCalculated using B3LYP/Def2-TZVP.
Figure 8. B3LYP/Def2-TZVP calculated S0 inversion barriers (in
CH3CN) for 3a and 3a•MgCl2 (pyr = pyrene; see also Table
4).15
For ground state 3a, the characteristic pyramidal structure is
determined, with a high barrier to pyramidal inversion via a
planar transition state (Tables 3, S1, S2; Figures 6, S6, S7a). A
pyramidal minimum energy structure for S1 is also found, with
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partitioning to a TICT state once the initial CT state is
generated.
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An alternative interpretation is inspired in part by the
observation that 4, the methyl pyrenyl sulfoxide with two
alkoxy group on the pyrene ring, is quite emissive (φf = 0.43).
For 4, we posited that the enhanced fluorescence was not
caused by reduced pyramidal inversion, but rather by sup-
pression of ICT and thus CT formation.
Actinometry reveals an additional dark relaxation pathway
We believe the simplest explanation for increased sulfoxide
fluorescence in the presence of metal ions is that metal ion
coordination to the sulfoxide oxygen withdraws enough elec-
tron density from the sulfoxide that ICT is suppressed, due to
an increase of Erel for the radical cation-like CT state. Upon
blocking ICT, the two dominant non-radiative decay pathways
(CT pyramidal inversion and TICT state formation) are both
suppressed.
9
As a final direct probe of the role of pyramidal inversion in
the deactivation of S1 for (S)-1a, we carried out chemical
actinometry, using azoxybenzene as a reference,25 in order to
determine the total quantum yield for excited state pyramidal
inversion.17 By measuring the erosion of enantiomeric purity
as a function of time under conditions where >99% of all
photons are absorbed, and comparing this to Φ for the
rearrangement of azoxybenzene under identical conditions,
we find Φinv = 0.04 for (S)-1a (Figures S3, S4).17 The maximum
value for Φinv is 0.5, so pyramidal inversion accounts for only
8% of the excited state relaxation. Because φf for 1a is 1%,
this means that 91% of the absorbed photons remain
unaccounted for. This in turn means that there must be
another non-radiative relaxation pathway in addition to CT
state pyramidal inversion.
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This interpretation is consistent with all of our experimental
observations.
CONCLUSION
Through a combination of experimental and computational
work, we have delineated a plausible mechanism for the
function of aryl sulfoxide fluorescent chemosensors. A central
conclusion is that the primary non-radiative decay pathways
for these sulfoxides require formation of a CT excited state
derived from the initially formed LE state. This CT state has
radical cation character on the sulfoxide S atom, in which the
sulfoxide has donated electron density to the pendant
fluorophore. The addition of metal ions, which withdraw
electron density from the sulfoxide upon coordination,
suppresses formation of the CT state and leads to
fluorescence enhancement.
An alternate process available to the CT excited state is the
formation of a twisted intramolecular charge transfer state
(TICT), in which the radical cation/radical anion pair is twisted
fully out of conjugation.26 TICT states are typically non-
radiative because they lie above very high energetic maxima
on the ground state PE surface, allowing for rapid IC. They are
lower in energy than the parent CT state, primarily for steric
reasons. Partitioning of the CT state between IC via pyramidal
inversion and a TICT state that also undergoes rapid IC would
account for the “missing” excited state energy (Figure 9).
It has previously been hypothesized that excited state
pyramidal inversion is the dominant non-radiative relaxation
pathway for aryl sulfoxides. We find that this pathway is
relevant, and occurs in the CT state. However, the fate of aryl
sulfoxide excited states are more complex than expected, and
we have shown there is an additional, dominant, non-
radiative decay pathway that had not been previously
recognized. We have proposed that this additional pathway is
direct relaxation of a TICT state derived from the parent CT
state.
These conclusions are supported experimentally and
computationally, and this work represents the most complete
model to date for excited state processes in aryl sulfoxides.
These data suggest that for our next generation of
fluorescent probes, electron deficient fluorophores, rather
than the more common electron rich fluorescein-like
fluorophores, e.g., should be explored, as this will facilitate
the formation of the non-radiative CT state. This in turn will
allow fluorescence to be “turned on” by the coordination of
metal ions which block CT state formation. With this guidance
in hand, we anticipate the development of improved
chemosensors with broader application to biological and
environmental problems.
Figure 9. Proposed unifying scheme for excited state process-
es in aryl sulfoxides. Quantum yields used as a measure of krel
for emission and inversion; krel for TICT formation inferred
from these values. (See text.)
An alternate role for metal ions in enhancing fluorescence
Taking together all of the above, we have been forced to
rethink the basis for metal ion-induced fluorescence in
enhancement for aryl sulfoxides. While added metal ion
should clearly suppress IC via pyramidal inversion in the CT
state, it is not obvious how metal ions would suppress
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Journal of the American Chemical Society
nov, A. V.; Dubonosov, A. D.; Bren, V. A.; Minkin, V. I. Chem. Hetero-
Supporting Information. Complete experimental details. UV data
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W.; Ma, H. Chem. Rev. 2014, 114, 590–659.
for 1a and pyrene. Crystallographic data for (±)-1a and (S)-1a.
Details of computational methods. 1H and 13C NMR spectra for all
new compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
2. For overviews of PET-based fluorescent chemosensors, see: a)
Bissell, R. A.; de Silva, A. P.; Gunaratne, H. Q. N.; Lynch, P. L. M.;
Maguire, G. E. M.; McCoy, C. P.; Sandanayake, K. R. A. S. Top. Curr.
Chem. 1993, 168, 223-264. b) de Silva, A. P.; Uchiyama, S. Top. Curr.
Chem. 2011, 300, 1-28. For an overview of ICT signaling, and other
approaches, see: c) Demchenko, A. P. Introduction to Fluorescence
Sensing; Springer Science: London, 2009; Chapter 6; see also ref. 1.
3. For rare examples of oxygen as the reporting element in fluo-
rescent chemosensors, see: a) Sousa, L. R.; Larson, J. M. J. Am. Chem.
Soc. 1977, 99, 307–310. b) De Silva, A. P.; Sandanayake, K. R. A. S. J.
Chem. Soc., Chem. Commun. 1989, 1183-1185. c) Wallace, K. J.;
Fagbemi, R. I.; Folmer-Andersen, F. J.; Morey, J.; Lynth, V. M.; Anslyn,
E. V. Chem. Commun. 2006, 3886–3888.
4. For fluorescent probes based on phosphorus oxidation, see: a)
Akasaka, K.; Suzuki, T.; Ohrui, H.; Meguro, H. Anal. Lett. 1987, 20,
731−745. b) Lemieux, G. A.; de Graffenried, C. L.; Bertozzi, C. R. J. Am.
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Imato, T. Org. Biomol. Chem. 2007, 5, 3762–3768.
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2005, 127,10124–10125. b) Malashikhin, S. A.; Baldridge, K. K.; Fin-
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Vonlanthen, M.; Connelly, C. M.; Deiters, A.; Linden, A.; Finney, N. S.
J. Org. Chem. 2014, 79, 6054–6060. For fluorescent probes relying on
the oxidation state of sulfur, see: h) Malashikhin, S.; Finney, N. S. J.
Am. Chem. Soc. 2008, 130, 12846–12847. i) Dane, E. L.; King, S. B.;
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Popowski, Y.; Antonov, S.; Gozin, M. Org. Lett. 2011, 13, 5532–5535.
6. For fluorescent probes relying on bonding with arsenic, see: a)
Griffin, B. A.; Adams, S. R.; Tsien, R. Y. Science 1998, 281, 269–272. b)
Adams, S. R.; Campbell, R. E.; Gross, L. A.; Martin, B. R.; Walkup, G.
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AUTHOR INFORMATION
Corresponding Author
* Nathaniel S. Finney
School of Pharmaceutical Science and Technology
Tianjin University
92 Weijin Road, Nankai District
Tianjin, China, 300072
nfinney@tju.edu.cn
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Author Contributions
The manuscript was written based on the contributions of all
authors.
Funding Sources
We thank the Department of Chemistry (University of Zurich),
Research Priority Program LightChEC (University of Zurich), the
School of Pharmaceutical Science and Technology (Tianjin Uni-
versity), the National Basic Research Program of China
(2015CB856500), the Qian Ren Scholar Program of China, and the
Synergetic Innovation Center of Chemical Science and Engineer-
ing (Tianjin University) for financial support.
ACKNOWLEDGMENT
We thank Prof. Graham Bodwell (Memorial University of New-
foundland) for the generous gift of compound 7.
ABBREVIATIONS
CT state = charge transfer state
IC = internal conversion
ICT = intramolecular charge transfer
FRET = Förster resonant energy transfer
LE state = locally excited state
PE = potential energy
PES = photoelectron spectroscopy
PET = photoinduced electron transfer
TICT = twisted intramolecular charge transfer state
φf = fluorescence quantum yield
7. Kathayat, R. S.; Finney, N. S. J. Am. Chem. Soc. 2013, 135,
12612−12614.
8. For reviews on sulfoxide metal coordination, see: a) Calligaris,
M.; Carugo, O. Coord. Chem. Rev. 1996, 153, 83-154. b) Calligaris, M.
Coord. Chem. Rev. 2004, 248, 351-375.
9. The crystal structure of Mg2+•(H2O)2(DMSO)6 shows exclusive
coordination through the sulfoxide oxygen. See: Ullström, A.-S.;
Warminska, D.; Persson, I. J. Coord. Chem. 2005, 58, 611–622. In
addition, as noted in ref. 8b, sulfoxide S-coordination has only been
observed for late transition metals, and alkaline and alkaline earth
cation complexes have only been found in O-coordinated form.
10. a) Celebre, G.; Cinacchi, G.; De Luca, G.; Giuliano, B. M.; Iem-
ma, F.; Melandri, S. J. Phys. Chem. B, 2008, 112, 2095–2101. b) Bu-
chanan, G. W.; Reyes-Zamora, C.; Clarke, D. E. Can. J. Chem. 1974, 52,
3895–3904.
Φ
inv = total quantum yield for pyramidal inversion
REFERENCES
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20. a) Baciocchi, E.; Del Giacco, T.; Gerini, M. F.; Lanzalunga, O. J.
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represents a π/π* energy gap change of only 3 kcal/mol.
12. For fundamental studies on the photochemistry of aryl sulfox-
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Coyne, L. M.; Hammond, G. S. J. Am. Chem. Soc. 1965, 87, 4958–
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Phys. Chem. A 2006, 110, 9940–9948. Notably, these calculations
consistently find a pyramidal configuration of the radical cation as
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pyramidal inversion of the ground state radical cation is estimated to
be ~11 kcal/mol, compared to the inversion of the neutral sulfoxide
(~33 kcal/mol). Further, a low reorganization energy is observed for
1e– oxidation of PhS(O)CH3, suggesting a radical cation geometry
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13. Berlman, I. Handbook of Fluorescence Spectra of Aromatic
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21. Hybertsen , M.S.; Louie, S.G. Phys. Rev. B 1986 , 34 , 5390–
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22. The rate of thermal pyramidal inversion of p-substituted aryl
sulfoxides varies by a factor of less than two with variation of the
substituents at the p-position. See: Rayner, D. R.; Gordon, A. J.; Mis-
low, K. J. Am. Chem. Soc. 1968, 90, 4854–4860.
23. At the planar configuration, the S-atom in the excited state can
be described as sp2-hybridized, with a partially filled p orbital. This
hybridization should lead to enhanced π-conjugation with the neigh-
boring aromatic rings compared to the ground state. This explains
the fact that substituent effects in the excited state are larger than
those in the ground state.
24. Although early computational studies suggested that the pla-
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energy surface (ref. 12d), our calculations at more recently-available
levels of theory consistently find that the minimum energy configura-
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17. See Supporting Information for details.
18. We believe that the small amount of photoracemization in the
presence of Mg2+ is the result of inversion in free 1a, as the experi-
ment was carried out in the presence of ~100 eq Mg2+. It takes
~10,000 eq. Mg2+ to saturate formation of Mg2+•1a at [1a] = 10–5 M.
See ref. 7.
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tostereomutation is preferred in this case, as racemization of (S)-1a
is being discussed.
25. Bunce, N. J.; LaMarre, J.; Vaish, S. P. Photochem. Photobiol.
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ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 22 of 22
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44x18mm (600 x 600 DPI)
ACS Paragon Plus Environment