PRODAN: PICT or TICT?
Introduction
Sensors. The development of sensors for organic and biological compounds in water is an
important area of research. Sensors must respond to the presence of an organic substance
with a signal that can be used to quantify the substance.1 Compounds that possess an ICT
(intramolecular charge transfer) state are particularly useful as sensors. Their fluorescence is
modulated by the nature of their immediate environment. The environment can affect not only
the fluorescence intensity, but also the emission wavelength maximum and the lifetime. Our
interest in these fluorophores stems from their use in the construction of fluorescent
cyclodextrin chemosensors.2-4
These systems can sense the presence of small organic
substrates that are difficult to quantify otherwise.
Intramolecular Charge Transfer States. Of the many fluorophores that have been attached to
cyclodextrins, those that have a twisted intramolecular charge transfer state (TICT) 5-8 are
especially noteworthy.
The fluorophores that fall under this category are derivatives of
dimethylaminobenzonitrile (DMABN) and 5-dimethylaminonaphthalene-1-sulfonic acid (DNS,
Figure 1).
The lowest energy absorption band in DMABN is a 1Lb transition, and it is
sometimes termed the normal planar (NP) state.
Twisting 90 about the N-C(aryl) bond
generates the TICT state through a surface crossing. The TICT state exhibits nearly complete
electron transfer from the amino N to the cyanophenyl group. Fluorescence from the TICT
state often shows substantial Stokes shifts in contrast with the normal Stokes shift of the NP
emission.
The large charge transfer character of the TICT state leads to high sensitivity
1
towards certain environmental factors, especially solvent polarity.
H3C
N
CH 3
CN
H3C
N
CH 3
O S O
OH
DMABN
DNS
Figure 1. Structures of DMABN and DNS
TICT emission is enhanced and red-shifted as solvent polarity increases.
A polar
solvent stabilizes the charged separated state more so than does a non-polar solvent. The redshift in the emission occurs because lowering the TICT potential well places it nearer to the
ground state surface. It turns out that in DMABN the energies of the NP and TICT states are so
close that solvent polarity determines whether the TICT is formed. Formation of the TICT state
is also sensitive to viscosity and free volume effects. In highly cross-linked polymers, for
example, the free volume can be reduced to the point where twisting becomes impossible.
Despite the large volume of literature probing on the topic, the TICT model is still not
universally accepted.
Zaccharaise and coworkers have cited numerous results that are
seemingly inconsistent with the TICT model.9-13 They propose that the intramolecular chargetransfer state (ICT) of DMABN does not involve complete electronic decoupling of the donor
2
and acceptor portions.
They assert that twisting is not required, and the adiabatic state
crossing can be achieved by nitrogen inversion. However, the strongest evidence for the TICT
model has been the behavior of related model compounds that either force the nitrogen lone
pair to be parallel or perpendicular to the aromatic pi-system (Figure 2).14-18 Compound 1a
shows only NP emission, whereas 1b and 1c show only red-shifted CT emission.
H3C
CN
H3C
N
N
CN
H3C
N
H3C
1a
CN
H3C
1c
1b
Figure 2. Model Compounds for Planar and Twisted DMABN
A similar controversy exists for PRODAN (6-propionyl-2-dimethylaminonaphthalene),
another widely used polarity probe.19 Unlike DMABN, PRODAN exhibits only CT emission.
Also unlike DMABN, the acceptor substituent is able to twist out of conjugation with the
aromatic portion. Theoretical studies on PRODAN excited states have supported the aminotwisted geometry (TICT) as the lowest energy.20-22
However, it was noted that this
assignment was greatly dependent on the choice of the Onsager radius.
The solvent
stabilization by a radius of 4.6  favored the TICT state, whereas a slightly higher value (5.6 )
gave the PICT (planar ICT) state as the lowest.20 The synthesis of appropriate models is
proposed here to clear up this controversy.
O
N
PRODAN
3
Proposed Research.
We propose to synthesize several model compounds (Figure 3) for the twisted and
planar forms of PRODAN and to investigate their photophysical properties.
O
O
O
R
N
N
2a, R = Et
2b, R = t-Bu
O
R
N
N
2c
2d, R = Et
2e, R = t-Bu
6f
Figure 3. Model Compounds for Twisted and Planar PRODAN.
Compounds 2a-c have the quinuclidine nucleus, and they are models for PRODAN with
a twisted dimethylamino group. In 2c the carbonyl group pi-system is forced to be parallel to
the aromatic pi-system. In 2a the carbonyl group can be parallel, whereas in 2b the t-butyl
group forces the carbonyl group to twist.
Molecular mechanics calculations (PCMODEL)
indicate that twisting to 90 relieves 6 kcal/mol of strain. Compounds 2d-f are models for
PRODAN with a planar dimethylamino group. The orientation of the carbonyl group is the
same as with 2a-c.
The proposed synthesis of these targets is based on literature precedents for PRODAN
and the DMABN models. The preparation of 2a-c is shown in Figure 4. The synthesis starts
with 6-bromo-2-aminonaphthalene, which is prepared from 6-bromo-2-naphthol.23
condensation/cyclization step is known for 2-aminonaphthalene.24
4
The
Cyclization proceeds
preferentially at C1 and not at C3 of the naphthyl ring. Chain extension with formaldehyde,
Birch reduction, and cyclization with HI are all known steps for benzoquinuclidine synthesis. 25
The Rosenmund von Braun cyanation step is one with which we have extensive expertise. 26,27
Reaction of the nitrile with Grignard reagents gives 2a and 2b directly. The synthesis of 2c
requires acylation of the aryl methyl ketone followed by cyclization and hydrogenation.
OMe
OMe
MeO
Br
Br
Br
H2CO
N
FeCl3
ZnCl2
NH2
N
HO
Nao
N
C
Br
Br
CuCN
HI
N
NH
N
HO
RMgX
R = Et, t-Bu, Me
O
R
N
HCO2Et
EtO-
O
N
FeCl3, H2
ZnCl2 Pd/C
O
EtOH
2a, R = Et
2b, R = t-Bu
N
2c
Figure 4. Proposed Syntheses of 2a-c.
The syntheses of 2d-f are shown in Figure 5. The transformations are analogous with the
syntheses of 2a-c.
5
OMe
OMe
MeO
Br
Nao
Br
FeCl3
ZnCl2
NH2
Br
NH
N
H2CO
H2SO4
N
O
C
Br
RMgX
R
CuCN
N
N
R = Et, t-Bu, Me
N
2d, R = Et
2e, R = t-Bu
HCO2Et
EtO-
O
N
FeCl3, H2
ZnCl2 Pd/C
O
EtOH
N
2f
Figure 5. Syntheses of 2d-f.
The absorption and fluorescence spectra of 2a-f will be determined in a variety of
solvents with a range of polarities. These results will be compared with those of PRODAN.
Excited-state dipole moment changes will be determined by the dependence of the
fluorescence band on the solvent polarity.28 If the emitting state of PRODAN is a TICT state,
then 2a-c should behave like PRODAN. But if the excited state of PRODAN is a PICT state,
then 2d-f should behave like PRODAN. The effect of the carbonyl orientation will also be
determined by the similarity of the model compounds with PRODAN.
Compound 2c is
predicted to be the best model for the geometry of the emitting state of PRODAN.
6
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