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 towards certain environmental factors, especially solvent polarity.

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 red-shift 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 charge-transfer state (ICT) of DMABN does not involve complete electronic decoupling of the donor 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.

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 amino-twisted 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.

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.

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 The condensation/cyclization step is known for 2-aminonaphthalene.24 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.

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.

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.

References.

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