• Journal of Pharmaceutical Investigation
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• v.18 no.3
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• pp.113-123
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• 1988

A series of water-soluble polyparacyclophanes bearing two diphenylmethane or two diphenyl ether skeletons were investigated to develop useful host compounds by using 1-anilinonaphthalene-6-sulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) as fluorescent hydrophobic substrates in aqueous solution. It was noteworthy that remarkable fluorescent enhancements and blue shifts of ANS and TNS were observed only in the presence of 1,6,20,25-tetraaza[6.1.6.1] paracyclophane (CPM 44) and 1,6,21,27-tetraaza [7.1.7.1] paracyclophane (CPM 55) for diphenylmethane skeleton, and 1,7,21,27-tetraaza-14,34-dioxa [7.1.7.1] paracyclophane (CPE 55) and 1,8,22,29-tetraaza-15,36-dioxa [8.1.8.1] paracyclophane (CPE 66) for diphenyl ether skeleton, comparing with ${\alpha}-\;and\;{\beta}-cyclodextrins$. However, their acyclic analogues such as 4,4'-dimethylaminodiphenylmethane and 4,4'-dimethylaminodiphenyl ether, and paracyclophanes whose cavities were smaller showed only small effects under the same conditions. These facts suggested that hosts and substrates were in an intimate contact which would not occur without larger structures, and thus that guest molecules were strongly incorporated in the hydrophobic cavities of these larger paracyclophanes. The effects of pH on the fluorescent intensity of ANS-CPM 44, ANS-CPM 55, ANS-CPE 55, ANS-CPE 66, TNS-CPM 44, TNS-CPM 55, TNS-CPE 55 and TNS-CPE 66 systems were not significant below pH 2.0, but their fluorescent intensities were markedly reduced with increasing ionic strength.

• Journal of Pharmaceutical Investigation
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• v.21 no.3
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• pp.133-141
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• 1991

The fluorescence characteristics of l-anilinonaphthalene-8-sulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) made the dyes useful probes for the determination of the polarity at the binding sites of several water-soluble polyparacyclophanes. Polyparacyclophanes used were 1,6,20,25-tetraaza[ 6.1.6.1]paracyclophane (CPM 44), 1,7,21,27 -tetraaza[7.1.7.1]paracyclophane (CPM 55). 1,7,21,27 -tetraaza-14,34-dioxa[7.1.7.1]paracyclophane (CPE 55) and 1,8,22,29-tetraaza-15,36-dioxa[8.1.8.1] paracyclophane (CPE 66). The fluorescence quantum yield, emission maximum, and half bandwidth of ANS or TNS obtained in a variety of solvent systems were plotted as a function of four kinds of empirical solvent polarity scales such as dielectric constant (D), (D-l)/(2D+1). Y and Z values. It was found that the Z-value-emission maximum $(\overline}V_F,\;cm^{-1})$ profile showed the most reliable linearity. ANS and TNS interacted with CPM 44, CPM 55, CPE 55. CPE 66. ${\alpha}-cyclodextrin$ (CyD) and ${\beta}-CyD$ in the aqueous solution, and from the emission maxima the polarities (Z-value) of their binding sites were calculated to be 92.65, 87.50, 93.35, 84.52, 94.36, and 90.48 for ANS, respectively. and 91.07, 89.68, 85.44, 86.74 and 87.6 for TNS except for ${\alpha}-CyD$, respectively.

• Journal of Pharmaceutical Investigation
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• v.19 no.2
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• pp.71-79
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• 1989

Complex formation of water-soluble polyparacyclophanes bearing two diphenylmethane or two diphenyl ether skeletons with l-anilinonaphthalene-8-sulfonate (ANS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) was investigated quantitatively to develop useful host compounds comparing with ${\alpha}\;-\;and\;{\beta}-cyc1odextrins$$({\alpha}-\;and\;{\beta}-CyDs$) in aqueous solution. Benesi-Hildebrand type analysis of the fluorescent intensity showed that the dissociation constants (Kd) of paracyclophane-ANS complexes were $1.55\;{\times}\;10^{-4}M$ for 1,6,20,25-tetraaza[6.1.6.1]paracyclophane(CPM 44) and $1.23\;{\times}\;10^{-4}M$ for 1,7,21,27-tetraaza[7.1.7.1]paracyclophane (CPM 55), and those of paracyclophane-TNS complexes were $6.99\;{\times}\;10^{-6}M$ for CPM 44 and $6.23\;{\times}\;10^{-5}M$ for CPM 55, in 1:1 molar ratio. On the other hand, the Kd values of 1,7,21,27-tetraaza-14,34-dioxa[7.1.7.1]paracyclophane (CPE 55)-ANS, 1,8,22,29-tetraaza-15,36-dioxa[8.1.8.1]paracyclophane (CPE 66)-ANS, CPE 55-TNS, CPE 66-TNS complexes were $1.75\;{\times}\;10^{-3}M$, $3.07\;{\times}\;10^{-3}M$, $3.75\;{\times}\;10^{-3}M$ and $2.15\;{\times}\;10^{-3}M$, respectively. On the contrary, the Kd values of ${\alpha}-CyD-ANS$, ${\beta}-CyD-ANS$, ${\alpha}-CyD-TNS$ and ${\beta}-CyD-TNS$ complexes were found to be $3.98\;{\times}\;10^{-2}M$, $1.05\;{\times}\;10^{-2}M$, $1.38\;{\times}\;10^{-2}M$ and $3.52\;{\times}\;10^{-4}M$, respectively. These results mean that the complexation of CPMs with ANS or TNS is by 5.6-1,975 fold stronger than that for ${\alpha}-or\;{\beta}-CyDs$, and the complex formation of CPEs with ANS or TNS is nearly same as or somewhat stronger than that for ${\alpha}-or\;{\beta}-CyDs$. From the Kd values determined at different temperatures, thermodynamic parameters were calculated and the complexation was found to be a spontaneous exothermic reaction. The effects of pH on Kd values of CPM 44-ANS, and CPM 55-ANS complexes were negligible in the range of pH 1.2-1.8. However, the Kd values of these complexes increased significantly with increasing ionic strength.

• Archives of Pharmacal Research
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• v.9 no.3
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• pp.139-144
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• 1986

The solubilization sites of aniline and its derivatives in micelles were investigated with fluorescence probe technique. The fluorescence probes employed in this study are 12-(9-anthroyl) stearic acid (AS) and 2-p-toluidinylnaphthalene-6-sulfonate (TNS) which are incorporated in the interior of the micelle and attaced to its surface, respectively. As these two probes were effectively quenched by aniline and its surface, respectively. As these two probes were effectively quenched by aniline and its derivatives, the modified Stern-Volmer relationship in micellar system could be applicable to estimate the partition coefficient, $K_{p}$ of the solubilizate between aqueous and micellar phase. Because $K_{p}$ derived by this method reflects the relative proximity of the fluorophore to the quencher, the ratio of $K_{p}$ in the surface area to that in the interior of the micelle is interpreted in terms of the relative location of the solubilizate in micellar aggregate. The results show that the solubilizates are not located in a definite position but distributed in the multiple-sites of the micelle. The solubilization sites of the solubilizates in the icelle are dependent on their structures. As the solubilizate has more numbers of N-substituents of aniline and more numbers, of carbon in the substituent, it tends to incorporate in the interior of the micelle more effectively.