Clarification of a misconception in the BINOL-based fluorescent sensors: Synthesis and study of major-groove BINOL-amino alcohols

Article abstract of DOI:10.1039/c0cc05514j

The major-groove BINOL-amino alcohol (S)-6 shows greatly enhanced fluorescence over the minor-groove one (S)-3. The study of a series of the major-groove BINOL-amino alcohol compounds demonstrates that the commonly accepted acid inhibition of the PET fluo

Full text of DOI:10.1039/c0cc05514j

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Clarification of a misconception in the BINOL-based fluorescent sensors:
synthesis and study of major-groove BINOL-amino alcoholsw
Hai-Lin Liu,a Qiao-Ling Zhao,b Xue-Long Hou*a and Lin Pu*c
Received 11th December 2010, Accepted 27th January 2011
DOI: 10.1039/c0cc05514j
The major-groove BINOL-amino alcohol (S)-6 shows greatly
enhanced fluorescence over the minor-groove one (S)-3. The
study of a series of the major-groove BINOL-amino alcohol
compounds demonstrates that the commonly accepted acid
inhibition of the PET fluorescence quenching of aryl-amine
compounds is not involved in the BINOL-amine sensors.
(BINOL)-amine-based fluorescent sensors such as (S)-25a and
(S)-35b in the presence of various substrates. Because of the
The photo-induced electron transfer (PET) from a nitrogen
atom to an adjacent aromatic fluorophore has been extensively
extensive activity in the development of the BINOL-based
used in the design of fluorescent sensors for metal cations,
fluorescent sensors, this misconception propagates continuously.
pH, carbohydrates, carboxylic acids and other species.1 As
Herein, we present an experimental study on a series of
represented by compounds 1a and 1b, the attachment of the
BINOL-amino alcohol derivatives to clarify the role of PET
azacrown ether unit to the anthracene and naphthalene rings
in the fluorescent recognition conducted by the BINOL
has quenched their fluorescence via PET. Binding of the
derivatives.
azacrown ether rings with an alkaline metal cation or an acid
proton makes the lone pair electron of the nitrogen unavailable
for PET, generating significant fluorescence enhancement.2
The fluorescence quenching via the electron transfer process
can be determined by the oxidation potentials of the donor
and acceptor.3 For a tertiary amine donor [E(D/D+) E 0.9 V
vs. SCE, 1.1 V vs. NHE]4a or a secondary amine donor
[E(D/D+) E 1.1 V vs. SCE, 1.3 vs. NHE]4a in the presence
of an alkyl naphthalene acceptor [E(A/A+) E 1.5 V vs.
Recently, we reported that when a solution of (S)-3 was
Ag/AgCl, 1.7 V vs. NHE],4b the reaction is thus exothermic
treated with (S)-mandelic acid (MA), a white precipitate was
produced accompanied with a large fluorescence enhancement.5b
In contrast, no precipitate formed in the presence of (R)-MA
and also only very small change in fluorescence was observed.
In order to probe the origin of the unusually large fluorescence
enhancement observed for the interaction of (S)-3 with (S)-MA
and to develop new enantioselective fluorescent sensors,6 the
structural analogs of (S)-3 are prepared and studied. As shown
in Scheme 1, compound (S)-6 was obtained by moving the
minor groove 3,30-amino alcohol units of (S)-3 to the major
groove. Bromination of (S)-BINOL followed by protection of
the hydroxyl groups with MOM gave (S)-4.7a Treatment of
(S)-4 with nBuLi followed by addition of DMF and then
hydrolysis generated the 6,60-diformylBINOL (S)-5.7b Reductive
amination of (S)-5 by reaction with (1R,2S)-2-amino-1,2-
and favorable. However, if 1-naphthol [E(A/A+) E 0.8 V vs.
Ag/AgCl, 1.0 V vs. NHE]4b or 2-naphthol [E(A/A+) E 0.9 V
vs. Ag/AgCl, 1.1 V vs. NHE]4b is used as the acceptor, the
electron transfer from amines should be endothermic and
unfavorable.
In spite of the above thermodynamic argument, the
acid-suppressed PET was proposed previously to account
for the fluorescence enhancement of the 1,10-bi-2-naphthol
a State Key Laboratory of Organometallic Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Ling Ling Rd, Shanghai 200032, China.
E-mail: xlhou@mail.sioc.ac.c
b Division of Material Characterization, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Ling Ling Rd,
Shanghai 200032, China
1
diphenylethanol and NaBH4 produced (S)-6.7c The H NMR
c Department of Chemistry, University of Virginia, Charlottesville,
Virginia 22904, USA. E-mail: lp6n@virginia.edu
spectrum of (S)-6 in CDCl3 shows two doublets at d 3.62
(d, J = 13.6 Hz, 2H) and 3.77 (d, J = 13.6 Hz, 2H) for the
diastereotopic methylene protons on the amino alcohol units
of this compound. The difference between these two signals
(Dd) is 0.15, significantly smaller than that of its minor-groove
w Electronic supplementary information (ESI) available: Preparation
and characterization of the new compounds. Detailed experimental
procedures. Additional UV, Fluorescence and NMR spectra. See
DOI: 10.1039/c0cc05514j
c
3646 Chem. Commun., 2011, 47, 3646–3648
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form the corresponding intramolecular complexes, leading to
its much greater fluorescence than (S)-3.
To further understand the fluorescence property of (S)-6, we
have compared its fluorescence spectrum with that of the
unsubstituted (S)-BINOL. As shown in Fig. 2, very little
difference in fluorescence intensity between these two molecules
is observed. The estimated fluorescence quantum yields (FF) of
(S)-6 and (S)-BINOL in benzene are 6% and 2% respectively
by using quinine sulfate as the standard. That is, the nitrogen
atoms of the amino alcohol units in (S)-6 provide no PET
fluorescence quenching in contrast to that proposed previously.5
To determine the contribution of the intramolecular hydrogen
bonding between the nitrogen atom and the adjacent hydroxyl
proton in each of the amino alcohol units of (S)-6, we
have methylated the amino alcohol hydroxyl groups to give
compound (S)-7 (Fig. 3). No significant difference between the
fluorescence intensity of (S)-7 and (S)-6 was observed (Fig. 2).
The fluorescence quantum yield of (S)-7 is estimated to be 6%.
Therefore, both (S)-6 and (S)-7 do not exhibit the PET
fluorescence quenching by the adjacent nitrogen atoms.
In order to explore the effect of the BINOL hydroxyl groups
of these sensors, the methoxylmethylated compound (S)-8 is
prepared (Fig. 3). This compound shows greatly enhanced
fluorescence over (S)-BINOL, (S)-6 and (S)-7, but very similar
to the methylated (S)-BINOL, (S)-9 (Fig. 2). The much weaker
fluorescence of (S)-BINOL, (S)-6 and (S)-7 than (S)-8 could be
accounted for by the excited state dissociation of their
more acidic BINOL hydroxyl protons to generate the weakly
fluorescent species,8 though this proton dissociation is much
less efficient than that in (S)-3 due to its intramolecular
hydrogen bonds. Alkylation of the BINOL units in (S)-8
and (S)-9 shuts down the excited state proton dissociation,
generating the large fluorescence enhancement. The fluorescence
quantum yields of (S)-8 and (S)-9 in benzene are estimated to
be 49% and 65% respectively. Compound (S)-10 where both
the BINOL hydroxyl groups and the aminoalcohol hydroxyl
groups are alkylated (Fig. 3). Its fluorescence quantum yield is
46%, close to that of (S)-8. Thus, the nitrogen atoms in (S)-8
and (S)-10 do not provide the generally observed large PET
quenching in the naphthalene-amine-based sensors.
Scheme 1 Synthesis of (S)-6.
analog (S)-3 (Dd = 0.32). In (S)-3, there should be intra-
molecular hydrogen bonding between the nitrogens of the
amino alcohol units and the central BINOL hydroxyl protons.
This should restrict the rotation of each methylene group
generating more different environment for the two protons.
Moving the amino alcohol units to the major groove in (S)-6
removes this type of intramolecular hydrogen bonding and
allows the methylene groups to freely rotate around the C–C
single bonds, leading to the much smaller chemical shift
difference for the proton signals. There is also a large difference
in optical rotation between (S)-6 and (S)-3. The specific optical
rotation, [a]D, of (S)-6 is +92.1 (c = 0.36, CH2Cl2) which is
the opposite of that of the specific optical rotation of (S)-3
{[a]D = ꢀ24.5 (c = 1.15, CH2Cl2)}. Thus, these two molecules
should have very different stereo conformation even though
the configurations of their BINOL and amino alcohol units
are the same.
A dramatic fluorescence enhancement was observed going
from (S)-3 to (S)-6 as shown in Fig. 1 (over 30 fold).
Compound (S)-3 shows dual emission at lem = 439, ca. 370
(sh.) nm, but the major-groove isomer (S)-6 gives only the
short wavelength emission at lem=379 nm with little long
wavelength emission. The dramatic fluorescence enhancement
observed at the short wavelength emission from (S)-3 to (S)-6
could be attributed to the removal of the intramolecular
hydrogen bonding between the BINOL hydroxyl protons of
(S)-3 and the amine nitrogens. According to the study of
Iwanek and Mattay on the fluorescence quenching of BINOL
with amines,8a the greatly quenched fluorescence of (S)-3
could arise from the radiationless decay of the excited intra-
molecularly hydrogen bonded compound as well as the
formation of a weakly fluorescent compound, such as A* shown
in Fig. 1, generated from the excited state intramolecular
proton transfer. The weak emission signals of these species
might overlap with the excimer emission9 of (S)-3 at the long
wavelength. The BINOL hydroxyl groups in (S)-6 cannot
The interaction of (S)-6 with the (R)- and (S)-enantiomers
of MA was studied. When
a clear solution of (S)-6
(2.0 ꢁ 10ꢀ4 M, benzene/0.4% DME) was treated with (S)-MA
(1.0 ꢁ 10ꢀ3–5.0 ꢁ 10ꢀ3 M), a white suspension was generated.
Under the same conditions, when (S)-6 was treated with
(R)-MA, a ‘‘semi-transparent’’ precipitate was generated. Both
precipitates were collected by filtration. 1H NMR analysis
Fig. 2 Fluorescence spectra of compounds (S)-BINOL, (S)-6, (S)-7,
(S)-8, (S)-9 and (S)-10 in benzene at 1.0 ꢁ 10ꢀ4 M (lex = 341 nm,
slit: 5.0/5.0 nm).
Fig. 1 Fluorescence spectra of (S)-6 and (S)-3 in benzene at
1.0 ꢁ 10ꢀ4 M (lex = 341 nm, slit: 5.0/5.0 nm).
c
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the structurally much more rigid fluorephores upon acid
complexation, the suppressed excited state proton transfer
and the isolation of the fluorophores in the solid state. This
work has provided a better understanding for the mechanism
of the fluorescence response of the BINOL-based sensors.
HLL, QLZ and XLH thank the support of this work from
the National Natural Science Foundation of China (20872161,
20821002, 21032007), the Major Basic Research Development
Program (2010CB833300) and Chinese Academy of Sciences.
LP acknowledges the partial support of the US National
Science Foundation (CHE-0717995).
Fig. 3 Structures of various BINOL-derivatives.
Notes and references
showed 1 : 3 ratio between (S)-6 and (S)-MA or (R)-MA in the
precipitate.
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The fluorescence spectra of (S)-6 in the presence of (S)- and
(R)-MA were measured. The suspension of (S)-6 with (R)-MA
exhibited large fluorescence enhancement but that of (S)-6
with (S)-MA showed almost no change in intensity (Fig. 4).
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of MA are highly enantioselective with IR/IS
= 6.8
(Fig. 4a).6,10 The intermolecular complex of (S)-6 + (R)-MA
might be structurally more rigid than that of (S)-6 + (S)-MA,
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not involved in the fluorescent responses of the BINOL-amine
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donors and the naphthol acceptors. The introduction of a
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Fig. 4 (a) Fluorescence spectra of (S)-6 (2.0 ꢁ 10ꢀ4 M) with (R)- and
(S)-MA at 4.0 ꢁ 10ꢀ3 M. (b) Fluorescence responses of (S)-6 (2.0 ꢁ
10ꢀ4 M) at 381 nm toward (R)- and (S)-MA at various concentrations.
(Solvent: benzene containing 0.4% DME. lexc = 341 nm, slit:
5.0/5.0 nm).
c
3648 Chem. Commun., 2011, 47, 3646–3648
This journal is The Royal Society of Chemistry 2011