Spectroscopic investigations of molecular association of cyclophanes with anthracene

We report an improved synthesis method for the production of cyclophanes 5 , 6 , and 7 in higher yields of 71, 98, and 99%, respectively, compared to the previously reported 40, 30, and 70% yields, respectively. Cyclophanes C 5 , C 6 , and C 7, called corrals, have different cavity sizes determined by the number of methylene spacers varying from three to five; they form inclusion complexes with neutral aromatic molecules. Therefore, we have studied their interactions with anthracene (A) using absorption, fluorescence, and Fourier transform infrared spectroscopies. The average association constants of each cyclophane with anthracene in dichloromethane were determined to be (log K) 4.24 + 0.10, 4.81 + 0.05, and 4.25 + 0.03 for the C 5 /A, C 6 /A, and C 7 /A systems, respectively. The binding of anthracene is favored by C 6 over C 5 and C 7 in solution, possibly due to increased stability of the equilibrium geometry of the C 6 /A complex. Upon complexation low frequency spectral shifts for several transitions associated with anthracene and corral molecules were observed. The slight spectral shifts are in accord with weak intermolecular forces prevalent in the studied corral/anthracene complexes.


Introduction
][3][4][5][6] Host/guest interactions play an important role in biochemical systems and the environment.The study of host/guest interaction of cyclophane/neutral compounds spanned the past three decades 5,7 ; however, the structure-function of noncovalently bound interactions is still not yet completely understood.
In this paper, we report host/guest interactions of recently synthesized cyclophanes-corrals 5, 6, and 7-with anthracene.Corrals 5-7 have different cavity sizes determined by the number of methylene groups in the spacers (n) varying from three to five (Figure 1).A crystal structure of the complex of corral 7 with anthracene indicating inclusion complexation in the solid phase has been reported. 3Selective binding of an aromatic molecule by a corral molecule to form an inclusion host/guest complex, Figure 2, is governed by the nature of the interacting species. 4orral cavity size, the medium, and the temperature play vital roles in the binding capabilities of corrals.Anthracene interacts with corrals 5-7 and forms 1:1 host/guest complexes that are characterized in solution and in the solid phase.
In the current investigation, absorption and fluorescence titrations are employed in the study of solution phase systems.Attenuated Total Reflection Fourier-infrared (ATR-FTIR) spectroscopy is used to investigate the solid phase systems.Equilibrium constants, K, for the binding of corrals and anthracene in CH2Cl2, and vibrational frequencies of the solid phase corral/anthracene complexes are presented.

Fluorescence titrations
In all three systems-C5/A, C6/A, and C7/A-the anthracene fluorescence is quenched by the presence of the corral molecule (Figure 5).Isostilbic points were observed in all three systems suggesting the presence of only two absorbing species in equilibrium, in accordance with 1:1 complexation between each corral and anthracene.Fitting of the fluorescence spectral data at specific wavelengths to the equation of Bourson, et al. 8 (Figure 6) yielded average association constants (log K) of 4.24 + 0.10, 4.81 + 0.05, and 4.25 + 0.03 for the C5/A, C6/A, and C7/A systems, respectively (Table 2).The concentration of anthracene was kept contant at 2.5 x 10 -5 M in all systems.The results indicate that inclusion complexation of anthracene by corral 6 is favored over inclusion complexation of anthracene by corrals 5 and 7.  b Absorption data for C6/A could not be determined as the absorption peaks of the spectra in the region of interest 320-400 nm coalesced, Figure 5. c Data taken from reference 4.

Vibrational structure analysis of solid phase C/A complexes
Crystals of corral/anthracene complexes were prepared by dissolving 1:1 corral:anthracene mole ratio in a minimal amount of heated 1:1 (by volume) solution of CHCl3-CH2Cl2.All corral/anthracene KBr pellet vibrational spectra were acquired from crystals grown using the initial samples 2 of corrals 5-7 and a 1:1 corral/anthracene mole ratio.The ATR-FTIR spectra were obtained from samples that were prepared with the newly synthesized corrals 5-7, described in this paper.The C/A complexes used to acquire the ATR spectra were prepared with 1:2 corral/anthracene mole ratio in a heated solution of 1:1:2 (by volume) solution of CHCl3-CH2Cl2-MeCN.The acquired spectrum of unbound anthracene (Figure 7) demonstrates that the ATR-FTIR technique can provide repeatable data that match literature values 9,10 and are comparable to the KBr pellet data.The FTIR spectra of the newly synthesized and previous 2 corrals are identical suggesting that the compounds are the same.The vibrational spectra of the three C/A systems-C5/A, C6/A, and C7/A-in Figures 8-10 indicate different spectra for the isolated anthracene, corral, and corral/anthracene complexes.Peak positions of the C/A complexes include peaks associated with individual units-anthracene and each corral-with minimal or no spectral shift.Spectral shifts upon complexation were in the range of 2-10 cm -1 because of weak intermolecular forces prevalent in the studied corral/anthracene complexes.The largest spectral shifts observed were associated with the out-of-plane C-H bending modes of anthracene at 726 and 884 cm -1 , and corrals 5-7 at 826 cm -1 .Decreased intensities were observed for the complexes possibly due to changes in the dipole moment upon complexation.Vibrational spectra-KBr pellet data-suggest that structures of C5/A and C7/A are similar in the solid phase based on spectral similarities.This observation is in agreement with absorption and fluorescence results in Table 2, where the binding of C5/A and C7/A are similar (log K ~ 4.2) and that of C6/A is favored (log K~ 4.8).
The ATR vibrational spectra were acquired with newly synthesized corrals.Observed similarities in the ATR spectra of C6/A and C7/A are unexpected.Single crystal X-ray structural analyses of these complexes to determine their geometries in the solid phase are in progress.  .ATR-FTIR vibrational spectra of anthracene, C7 and C7/A in the solid phase and FTIR spectrum of C7/A complex obtained using a KBr pellet.

Molecular modeling
The calculated vibrational spectra (Figure 11) of the of the gas phase anthracene, corrals 5-7, C5/A, C6/A, and C7/A systems using the Gaussian 03W PM3MM semi-empirical method 11 yielded vibrational spectra similar to the solid phase experimental spectra.Moreover, the predicted gas phase geometries (Figure 12) of C5/A and C7/A are similar with the anthracene guest molecule coplanar with the corral molecule in agreement with experimental observations in the liquid and solid phases.
An improved method for the synthesis of corrals 5-7 with high yields in the range of 70-99 % is reported.Binding studies of these corrals with anthracene reveal that corral 6 forms the most stable complex.Molecular modeling and experimental observations suggest that the structures of C5/A and C7/A are similar, possibly with the anthracene molecule in the same plane as the corral molecule.Molecular modeling predicts that the anthracene guest lies perpendicular to the plane of corral 6, in the gas phase C6/A complex (Figure 12).

Electronic and vibrational spectroscopy
The following chemicals were purchased from Sigma-Aldrich and used as received: anthracene and spectrophotometric grade CH2Cl2.Stock solutions in CH2Cl2 were prepared: 110 -5 to 110 -3 M for each corral and 510 -5 M for anthracene.The absorbances of the prepared stock solutions were measured using Agilent 8453 UV-vis photodiode array.Beer-Lambert's law was used to determine the molar extinction coefficients and these parameters are tabulated in Table 1.Solution phase complexes were prepared by mixing stock solutions of each corral (1:1, by volume) with a constant final concentration-2.510-5 M-of anthracene solution.The final concentration of each corral was varied from 0 to 510 -4 M. UV-vis absorption spectra of prepared solutions were acquired.Variation of anthracene absorption intensity was monitored as a function of the corral concentration in CH2Cl2 at 25 o C. The same procedures were followed for solutions prepared for fluorescence measurements.Fluorescence spectra were measured with a LS-55 Perkin-Elmer spectrofluorimeter.For data analysis, wavelengths were chosen where only one of the reactants-anthracene-absorbs or fluoresces and where the variations as a function of the concentration of cyclophane were the largest.A Perkin-Elmer Spectrum One spectrometer was used to record KBr pellet vibrational spectra 12 and solid phase ATR-FTIR spectra were recorded with the Perkin-Elmer Spectrum 100 spectrometer.

Figure 8 .
Figure8.ATR-FTIR vibrational spectra of anthracene, C5 and C5/A in the solid phase and FTIR spectrum of C5/A complex obtained using a KBr pellet.

Figure 12 .
Figure 12.Optimized gas phase structures (from left to right) of C5/A, C6/A, and C7/A complexes using Gaussian 03W semi-empirical PM3MM method.

Table 1 .
Molar absorptivities of anthracene and corrals in CH2Cl2 at 25 C ARKAT USA, Inc.

Table 2 .
8on-linear regression analysis (line) of the fluorescence spectral data (symbols) for C4/A complex CH2Cl2 at 302, 382, and 402 nm according to the Bourson equation.8Emissionintensitiesobtainedfrom Figure5.Stability constants, log K, of corral/anthracene systems in CH2Cl2 at 25 o C a Excitation wavelength for the C/A systems was at 278 nm.
ATR-FTIR vibrational spectra of anthracene, C6 and C6/A in the solid phase and FTIR spectrum of C6/A complex obtained using a KBr pellet.