determination of the stability constants in alkanol/α-cyclodextrin mixed system

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Page 1: Determination of the Stability Constants in Alkanol/α-Cyclodextrin Mixed System

Drug Development and Industrial Pharmacy 26(10) 1111ndash1114 (2000)

COMMUNICATION

Determination of the Stability Constantsin Alkanola-Cyclodextrin Mixed System

Yoshihiro Saito Kaname Hashizaki Hiroyuki TaguchiKazuo Tomono Hiroko Goto and Naotake Ogawa

College of Pharmacy Nihon University 7-7-1 Narashinodai Funabashi-shi Chiba 274-8555 Japan

ABSTRACT

The simultaneous determination of the stability constants for inclusion of alkanolswith α-cyclodextrin (α-CD) was investigated in a mixed alkanol system using statichead-space gas chromatography (SHSGC) The 11 stability constants obtainedwere in fair agreement with those obtained previously using other methods Thetime required for determination of the stability constant was markedly reduced usingthis simultaneous SHSGC methodKey Words Alkanols Complexes α-Cyclodextrin Mixed system Stability constant

INTRODUCTION

We recently proposed new methods using static head-space gas chromatography (SHSGC) for determination ofthe stability constant for the cyclodextrin (CD) complex(12) Those methods have been applied successfullyto determine the stability constants for the benzenederivativesα-CD and alkanediolsα-CD complexesFurthermore we applied this SHSGC technique to fra-grance material2-hydroxypropyl-β-CD complexes in amixed fragrance materials system and succeeded in thesimultaneous determination of the stability constants (3)This method is called the simultaneous SHSGC methodHowever the accumulation of additional information is

To whom correspondence should be addressed Fax 181-47-465-5865 E-mail ysaitophanihon-uacjp

1111

Copyright 2000 by Marcel Dekker Inc wwwdekkercom

required for further corroboration of the simultaneousSHSGC method

In the present study we investigated the determinationof the stability constants for alkanolα-CD complexes ina mixed alkanol system using the simultaneous SHSGCmethod

EXPERIMENTAL

Materials

Reagent-grade 1- and 2-alkanols were purchased fromTokyo Kasei Kogyo Company Limited and used with-out further purification The α-CD was provided by Ni-

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ORDER REPRINTS

1112 Saito et al

hon Shokuhin Kako Company Limited and was usedafter vacuum drying Distilled water per injection JP wasobtained from Ohtsuka Pharmacy Company Limited

Sample Preparation

Various amounts of an equimolar mixture of 1- and2-alkanols were added to aqueous solution (10 g) withand without 10 mmol kg21 α-CD weighed into 195-mlhead-space vials The sample solutions were sealed usingsilicone septa and aluminum foil The vials were thenthermostated at 25degC 6 01degC and shaken overnight priorto analysis

Gas Chromatographic Analysis

After equilibrium was established 400 microl of the alka-nol vapor from above the solution was drawn from thevial using a gas-tight syringe This sample was then ana-lyzed using a gas chromatograph (GC GC-14B Shi-madzu Co Kyoto Japan) equipped with a flame-ioniza-

Figure 1 Schematic illustration of the simultaneous SHSGCmethod

Figure 2 Plots based on Henryrsquos law for mixed alkanols inaqueous solution s 1-pentanol (r 5 09902) h 1-hexanol(r 5 09828) n 1-heptanol (r 5 09620) d 2-hexanol (r 509916) 2-heptanol (r 5 09870) m 2-octanol (r 5 09873)

tion detector with a 1 m 3 3 mm id glass column packedwith polyethylene glycol 20M (PEG-20M) The injectionand detection temperatures were maintained at 200degCand the column temperature was 80degC Nitrogen wasused as the carrier gas and the flow rate was kept at 20

Figure 3 Best-fit curves for alkanolα-CD complexes basedon Eq 4 s 1-pentanol h 1-hexanol n 1-heptanol d 2-hexanol 2-heptanol m 2-octanol

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ORDER REPRINTS

Stability Constants in Alkanolα-CD 1113

mlmin The area of each peak was measured using aShimadzu Chromatopac C-R 6A integrator

RESULTS AND DISCUSSION

Theoretical

Figure 1 shows the proposed mechanism of the simul-taneous SHSGC method There are two equilibria in thevolatile guests (Gn n 5 1 2 )CDwater system (a)Each guest included in CD was in equilibrium with eachfree guest in the solution and (b) each free guest was inequilibrium with each monomeric guest in the vaporabove the solution The guests shared the CD correspond-ing to their stability constants K based on the assumptionthat no complexes are formed except binary complexesthat do not interfere with one another in the solution Ifeach guest in the vapor is separated and determined byGC in principle the stability constants can be evaluatedusing this method The assumption was that the equilib-rium between a guest component Gi and CD involved a11 complex as shown in Eq 1

Gi 1 CD harrKi

Gi 2 CD (1)

Stability constant Ki for a 11 complex is defined byEq 2

Ki 5[Gi 2 CD][Gi][CD]

(2)

where [Gi] and [CD] denote the concentrations of the freesolutes

[Gi 2 CD] denotes the complex concentration Themass balance of Gi in aqueous solution is represented byEq 3

Table 1

Comparison of Stability Constants for Alkanolα-Cyclodextrin Complexes

This Worka Ref 5 Ref 6Alkanols K (kgmol) K (Lmol) K (kgmol)

1-Pentanol 188 6 28 324 275 6 151-Hexanol 509 6 68 891 379 6 511-Heptanol 1586 6 174 2291 mdash2-Hexanol 331 6 34 355 285 6 132-Heptanol 1215 6 104 mdash mdash2-Octanol 2153 6 197 1413 mdash

a The values represent the mean 6 SD

[Gi] t 5 [Gi] 1 [Gi 2 CD] (3)

where [Gi]t is the total concentration of Gi in aqueoussolution The [Gi] t after equilibrium was determined bysubtracting the number of moles of Gi in the vapor calcu-lated using the ideal gas equation from the total amountof Gi added to the vial Substituting Eq 2 into Eq 3

[Gi] 5[Gi] t

1 1 Ki [CD](4)

[Gi] t is known and [Gi] can be obtained from a linearrelationship according to Henryrsquos law (Eq 5) for the so-lution in the absence of CD (4)

Pi 5 Hi xi (5)

where Pi is the partial pressure of Gi over the solutionHi is Henryrsquos constant of Gi and xi is the molar fractionof Gi in the solution Then Eq 5 becomes

PiP0i 5 γinfin

i xi (6)

where

Hi 5 γinfini P0

i (7)

in which γ infini is the limiting activity coefficient and P0

i isthe vapor pressure of Gi in the pure state The ratio of Pi

and P0i is equal to the ratio of the integrated GC peak

areas corresponding to the GC peaks obtained from thehead space of Gi in the solution and of its pure state

The [CD] in Eq 4 can also be determined from themass balance of CD by Eq 8

[CD] 5 [CD]t 2 [G 2 CD] t (8)

where [CD]t is the total concentration of CD that isknown [G 2 CD] t is the total concentration of the com-

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ORDER REPRINTS

1114 Saito et al

Figure 4 Effects of carbon number on stability constants foralkanolα-CD complexes d 1-alkanols (r 5 09995) s 2-alkanols (r 5 09624)

plex for all guests and is also calculated from the sum ofeach complex obtained from Eq 3

[G 2 CD] t 5 ^n

i51

[Gi 2 CD] (9)

Therefore the stability constants for each guest can beestimated by a nonlinear least-squares fit using Eq 4

Stability Constant

We were able to make a quantitative separation of al-kanol vapor above the solution containing the mixed al-kanols by GC Figure 2 shows the relationship betweenPP0 and concentrations of each alkanol for a mixed alka-nol solution in the absence of α-CD based on Eq 6 Theplots gave straight lines in accordance with Henryrsquos lawfor each alkanol These straight lines were used to evalu-ate [Gi] in the presence of α-CD

Figure 3 shows the plots according to Eq 4 for each1-alkanolα-CD and 2-alkanolα-CD system togetherwith the calculated curves that gave the best fit of theexperimental data The theoretical values agreed wellwith the experimental values (data points) for each alka-nol The findings shown in Fig 3 also suggest that thestoichiometry of the complexes between alkanol and α-

CD was 11 The apparent stability constants K deter-mined by this method are summarized together with stan-dard deviations and are compared with the previously re-ported values in Table 1 The K values determined in thisstudy are in reasonable agreement with those obtainedfrom previous reports (56) The K values were plottedas log K against total number of carbon atoms of the alka-nols in Fig 4 The plots for a homologous series of thestraight-chain alkanols gave approximately straight lineswhich increased with the increasing carbon number ofthe alkanols Accordingly this supports the idea that thecavity of α-CD accommodates the hydrophobic moietyof alkanols In addition it was also shown that the affinityof the 1-alkanols toward α-CD was higher than that of2-alkanols which suggests that the hydroxyl group of al-kanols becomes a hindrance factor with their inclusion

CONCLUSIONS

In this study the stability constants for inclusion com-plexes of alkanols with α-CD were determined simulta-neously using the simultaneous SHSGC method It isvery important to determine the K value for the 11 inclu-sion complex because most guests form 11 inclusioncomplexes with CD This method is suggested as usefulfor the determination of the stability constant particu-larly in the case of 11 stoichiometry In addition it ismore advantageous than the conventional method be-cause the experimental time required for the determina-tion of the stability constant can be drastically shortened

REFERENCES

1 Y Saito K Yoshihara I Tanemura H Ueda and TSato Chem Pharm Bull 45 1711 (1997)

2 K Yoshihara I Tanemura Y Saito H Ueda and TSato Chem Pharm Bull 45 2076 (1997)

3 Y Saito I Tanemura H Ueda and T Sato ChemPharm Bull 46 1777 (1998)

4 B V Ioffe and A G Vitenberg Head-Space Analysisand Related Methods in Gas Chromatography John Wi-ley and Sons New York 1984 p 13

5 Y Matui and K Mochida Bull Chem Soc Jpn 522808 (1979)

6 S Andini G Castronuovo V Elia and E Gallotta Car-bohydr Res 217 87 (1991)

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Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081DDC100100276

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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Page 2: Determination of the Stability Constants in Alkanol/α-Cyclodextrin Mixed System

ORDER REPRINTS

1112 Saito et al

hon Shokuhin Kako Company Limited and was usedafter vacuum drying Distilled water per injection JP wasobtained from Ohtsuka Pharmacy Company Limited

Sample Preparation

Various amounts of an equimolar mixture of 1- and2-alkanols were added to aqueous solution (10 g) withand without 10 mmol kg21 α-CD weighed into 195-mlhead-space vials The sample solutions were sealed usingsilicone septa and aluminum foil The vials were thenthermostated at 25degC 6 01degC and shaken overnight priorto analysis

Gas Chromatographic Analysis

After equilibrium was established 400 microl of the alka-nol vapor from above the solution was drawn from thevial using a gas-tight syringe This sample was then ana-lyzed using a gas chromatograph (GC GC-14B Shi-madzu Co Kyoto Japan) equipped with a flame-ioniza-

Figure 1 Schematic illustration of the simultaneous SHSGCmethod

Figure 2 Plots based on Henryrsquos law for mixed alkanols inaqueous solution s 1-pentanol (r 5 09902) h 1-hexanol(r 5 09828) n 1-heptanol (r 5 09620) d 2-hexanol (r 509916) 2-heptanol (r 5 09870) m 2-octanol (r 5 09873)

tion detector with a 1 m 3 3 mm id glass column packedwith polyethylene glycol 20M (PEG-20M) The injectionand detection temperatures were maintained at 200degCand the column temperature was 80degC Nitrogen wasused as the carrier gas and the flow rate was kept at 20

Figure 3 Best-fit curves for alkanolα-CD complexes basedon Eq 4 s 1-pentanol h 1-hexanol n 1-heptanol d 2-hexanol 2-heptanol m 2-octanol

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ORDER REPRINTS

Stability Constants in Alkanolα-CD 1113

mlmin The area of each peak was measured using aShimadzu Chromatopac C-R 6A integrator

RESULTS AND DISCUSSION

Theoretical

Figure 1 shows the proposed mechanism of the simul-taneous SHSGC method There are two equilibria in thevolatile guests (Gn n 5 1 2 )CDwater system (a)Each guest included in CD was in equilibrium with eachfree guest in the solution and (b) each free guest was inequilibrium with each monomeric guest in the vaporabove the solution The guests shared the CD correspond-ing to their stability constants K based on the assumptionthat no complexes are formed except binary complexesthat do not interfere with one another in the solution Ifeach guest in the vapor is separated and determined byGC in principle the stability constants can be evaluatedusing this method The assumption was that the equilib-rium between a guest component Gi and CD involved a11 complex as shown in Eq 1

Gi 1 CD harrKi

Gi 2 CD (1)

Stability constant Ki for a 11 complex is defined byEq 2

Ki 5[Gi 2 CD][Gi][CD]

(2)

where [Gi] and [CD] denote the concentrations of the freesolutes

[Gi 2 CD] denotes the complex concentration Themass balance of Gi in aqueous solution is represented byEq 3

Table 1

Comparison of Stability Constants for Alkanolα-Cyclodextrin Complexes

This Worka Ref 5 Ref 6Alkanols K (kgmol) K (Lmol) K (kgmol)

1-Pentanol 188 6 28 324 275 6 151-Hexanol 509 6 68 891 379 6 511-Heptanol 1586 6 174 2291 mdash2-Hexanol 331 6 34 355 285 6 132-Heptanol 1215 6 104 mdash mdash2-Octanol 2153 6 197 1413 mdash

a The values represent the mean 6 SD

[Gi] t 5 [Gi] 1 [Gi 2 CD] (3)

where [Gi]t is the total concentration of Gi in aqueoussolution The [Gi] t after equilibrium was determined bysubtracting the number of moles of Gi in the vapor calcu-lated using the ideal gas equation from the total amountof Gi added to the vial Substituting Eq 2 into Eq 3

[Gi] 5[Gi] t

1 1 Ki [CD](4)

[Gi] t is known and [Gi] can be obtained from a linearrelationship according to Henryrsquos law (Eq 5) for the so-lution in the absence of CD (4)

Pi 5 Hi xi (5)

where Pi is the partial pressure of Gi over the solutionHi is Henryrsquos constant of Gi and xi is the molar fractionof Gi in the solution Then Eq 5 becomes

PiP0i 5 γinfin

i xi (6)

where

Hi 5 γinfini P0

i (7)

in which γ infini is the limiting activity coefficient and P0

i isthe vapor pressure of Gi in the pure state The ratio of Pi

and P0i is equal to the ratio of the integrated GC peak

areas corresponding to the GC peaks obtained from thehead space of Gi in the solution and of its pure state

The [CD] in Eq 4 can also be determined from themass balance of CD by Eq 8

[CD] 5 [CD]t 2 [G 2 CD] t (8)

where [CD]t is the total concentration of CD that isknown [G 2 CD] t is the total concentration of the com-

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ORDER REPRINTS

1114 Saito et al

Figure 4 Effects of carbon number on stability constants foralkanolα-CD complexes d 1-alkanols (r 5 09995) s 2-alkanols (r 5 09624)

plex for all guests and is also calculated from the sum ofeach complex obtained from Eq 3

[G 2 CD] t 5 ^n

i51

[Gi 2 CD] (9)

Therefore the stability constants for each guest can beestimated by a nonlinear least-squares fit using Eq 4

Stability Constant

We were able to make a quantitative separation of al-kanol vapor above the solution containing the mixed al-kanols by GC Figure 2 shows the relationship betweenPP0 and concentrations of each alkanol for a mixed alka-nol solution in the absence of α-CD based on Eq 6 Theplots gave straight lines in accordance with Henryrsquos lawfor each alkanol These straight lines were used to evalu-ate [Gi] in the presence of α-CD

Figure 3 shows the plots according to Eq 4 for each1-alkanolα-CD and 2-alkanolα-CD system togetherwith the calculated curves that gave the best fit of theexperimental data The theoretical values agreed wellwith the experimental values (data points) for each alka-nol The findings shown in Fig 3 also suggest that thestoichiometry of the complexes between alkanol and α-

CD was 11 The apparent stability constants K deter-mined by this method are summarized together with stan-dard deviations and are compared with the previously re-ported values in Table 1 The K values determined in thisstudy are in reasonable agreement with those obtainedfrom previous reports (56) The K values were plottedas log K against total number of carbon atoms of the alka-nols in Fig 4 The plots for a homologous series of thestraight-chain alkanols gave approximately straight lineswhich increased with the increasing carbon number ofthe alkanols Accordingly this supports the idea that thecavity of α-CD accommodates the hydrophobic moietyof alkanols In addition it was also shown that the affinityof the 1-alkanols toward α-CD was higher than that of2-alkanols which suggests that the hydroxyl group of al-kanols becomes a hindrance factor with their inclusion

CONCLUSIONS

In this study the stability constants for inclusion com-plexes of alkanols with α-CD were determined simulta-neously using the simultaneous SHSGC method It isvery important to determine the K value for the 11 inclu-sion complex because most guests form 11 inclusioncomplexes with CD This method is suggested as usefulfor the determination of the stability constant particu-larly in the case of 11 stoichiometry In addition it ismore advantageous than the conventional method be-cause the experimental time required for the determina-tion of the stability constant can be drastically shortened

REFERENCES

1 Y Saito K Yoshihara I Tanemura H Ueda and TSato Chem Pharm Bull 45 1711 (1997)

2 K Yoshihara I Tanemura Y Saito H Ueda and TSato Chem Pharm Bull 45 2076 (1997)

3 Y Saito I Tanemura H Ueda and T Sato ChemPharm Bull 46 1777 (1998)

4 B V Ioffe and A G Vitenberg Head-Space Analysisand Related Methods in Gas Chromatography John Wi-ley and Sons New York 1984 p 13

5 Y Matui and K Mochida Bull Chem Soc Jpn 522808 (1979)

6 S Andini G Castronuovo V Elia and E Gallotta Car-bohydr Res 217 87 (1991)

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Uni

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itat d

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031

4Fo

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rson

al u

se o

nly

Order now

Reprints of this article can also be ordered at

httpwwwdekkercomservletproductDOI101081DDC100100276

Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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Page 3: Determination of the Stability Constants in Alkanol/α-Cyclodextrin Mixed System

ORDER REPRINTS

Stability Constants in Alkanolα-CD 1113

mlmin The area of each peak was measured using aShimadzu Chromatopac C-R 6A integrator

RESULTS AND DISCUSSION

Theoretical

Figure 1 shows the proposed mechanism of the simul-taneous SHSGC method There are two equilibria in thevolatile guests (Gn n 5 1 2 )CDwater system (a)Each guest included in CD was in equilibrium with eachfree guest in the solution and (b) each free guest was inequilibrium with each monomeric guest in the vaporabove the solution The guests shared the CD correspond-ing to their stability constants K based on the assumptionthat no complexes are formed except binary complexesthat do not interfere with one another in the solution Ifeach guest in the vapor is separated and determined byGC in principle the stability constants can be evaluatedusing this method The assumption was that the equilib-rium between a guest component Gi and CD involved a11 complex as shown in Eq 1

Gi 1 CD harrKi

Gi 2 CD (1)

Stability constant Ki for a 11 complex is defined byEq 2

Ki 5[Gi 2 CD][Gi][CD]

(2)

where [Gi] and [CD] denote the concentrations of the freesolutes

[Gi 2 CD] denotes the complex concentration Themass balance of Gi in aqueous solution is represented byEq 3

Table 1

Comparison of Stability Constants for Alkanolα-Cyclodextrin Complexes

This Worka Ref 5 Ref 6Alkanols K (kgmol) K (Lmol) K (kgmol)

1-Pentanol 188 6 28 324 275 6 151-Hexanol 509 6 68 891 379 6 511-Heptanol 1586 6 174 2291 mdash2-Hexanol 331 6 34 355 285 6 132-Heptanol 1215 6 104 mdash mdash2-Octanol 2153 6 197 1413 mdash

a The values represent the mean 6 SD

[Gi] t 5 [Gi] 1 [Gi 2 CD] (3)

where [Gi]t is the total concentration of Gi in aqueoussolution The [Gi] t after equilibrium was determined bysubtracting the number of moles of Gi in the vapor calcu-lated using the ideal gas equation from the total amountof Gi added to the vial Substituting Eq 2 into Eq 3

[Gi] 5[Gi] t

1 1 Ki [CD](4)

[Gi] t is known and [Gi] can be obtained from a linearrelationship according to Henryrsquos law (Eq 5) for the so-lution in the absence of CD (4)

Pi 5 Hi xi (5)

where Pi is the partial pressure of Gi over the solutionHi is Henryrsquos constant of Gi and xi is the molar fractionof Gi in the solution Then Eq 5 becomes

PiP0i 5 γinfin

i xi (6)

where

Hi 5 γinfini P0

i (7)

in which γ infini is the limiting activity coefficient and P0

i isthe vapor pressure of Gi in the pure state The ratio of Pi

and P0i is equal to the ratio of the integrated GC peak

areas corresponding to the GC peaks obtained from thehead space of Gi in the solution and of its pure state

The [CD] in Eq 4 can also be determined from themass balance of CD by Eq 8

[CD] 5 [CD]t 2 [G 2 CD] t (8)

where [CD]t is the total concentration of CD that isknown [G 2 CD] t is the total concentration of the com-

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ORDER REPRINTS

1114 Saito et al

Figure 4 Effects of carbon number on stability constants foralkanolα-CD complexes d 1-alkanols (r 5 09995) s 2-alkanols (r 5 09624)

plex for all guests and is also calculated from the sum ofeach complex obtained from Eq 3

[G 2 CD] t 5 ^n

i51

[Gi 2 CD] (9)

Therefore the stability constants for each guest can beestimated by a nonlinear least-squares fit using Eq 4

Stability Constant

We were able to make a quantitative separation of al-kanol vapor above the solution containing the mixed al-kanols by GC Figure 2 shows the relationship betweenPP0 and concentrations of each alkanol for a mixed alka-nol solution in the absence of α-CD based on Eq 6 Theplots gave straight lines in accordance with Henryrsquos lawfor each alkanol These straight lines were used to evalu-ate [Gi] in the presence of α-CD

Figure 3 shows the plots according to Eq 4 for each1-alkanolα-CD and 2-alkanolα-CD system togetherwith the calculated curves that gave the best fit of theexperimental data The theoretical values agreed wellwith the experimental values (data points) for each alka-nol The findings shown in Fig 3 also suggest that thestoichiometry of the complexes between alkanol and α-

CD was 11 The apparent stability constants K deter-mined by this method are summarized together with stan-dard deviations and are compared with the previously re-ported values in Table 1 The K values determined in thisstudy are in reasonable agreement with those obtainedfrom previous reports (56) The K values were plottedas log K against total number of carbon atoms of the alka-nols in Fig 4 The plots for a homologous series of thestraight-chain alkanols gave approximately straight lineswhich increased with the increasing carbon number ofthe alkanols Accordingly this supports the idea that thecavity of α-CD accommodates the hydrophobic moietyof alkanols In addition it was also shown that the affinityof the 1-alkanols toward α-CD was higher than that of2-alkanols which suggests that the hydroxyl group of al-kanols becomes a hindrance factor with their inclusion

CONCLUSIONS

In this study the stability constants for inclusion com-plexes of alkanols with α-CD were determined simulta-neously using the simultaneous SHSGC method It isvery important to determine the K value for the 11 inclu-sion complex because most guests form 11 inclusioncomplexes with CD This method is suggested as usefulfor the determination of the stability constant particu-larly in the case of 11 stoichiometry In addition it ismore advantageous than the conventional method be-cause the experimental time required for the determina-tion of the stability constant can be drastically shortened

REFERENCES

1 Y Saito K Yoshihara I Tanemura H Ueda and TSato Chem Pharm Bull 45 1711 (1997)

2 K Yoshihara I Tanemura Y Saito H Ueda and TSato Chem Pharm Bull 45 2076 (1997)

3 Y Saito I Tanemura H Ueda and T Sato ChemPharm Bull 46 1777 (1998)

4 B V Ioffe and A G Vitenberg Head-Space Analysisand Related Methods in Gas Chromatography John Wi-ley and Sons New York 1984 p 13

5 Y Matui and K Mochida Bull Chem Soc Jpn 522808 (1979)

6 S Andini G Castronuovo V Elia and E Gallotta Car-bohydr Res 217 87 (1991)

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The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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Page 4: Determination of the Stability Constants in Alkanol/α-Cyclodextrin Mixed System

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1114 Saito et al

Figure 4 Effects of carbon number on stability constants foralkanolα-CD complexes d 1-alkanols (r 5 09995) s 2-alkanols (r 5 09624)

plex for all guests and is also calculated from the sum ofeach complex obtained from Eq 3

[G 2 CD] t 5 ^n

i51

[Gi 2 CD] (9)

Therefore the stability constants for each guest can beestimated by a nonlinear least-squares fit using Eq 4

Stability Constant

We were able to make a quantitative separation of al-kanol vapor above the solution containing the mixed al-kanols by GC Figure 2 shows the relationship betweenPP0 and concentrations of each alkanol for a mixed alka-nol solution in the absence of α-CD based on Eq 6 Theplots gave straight lines in accordance with Henryrsquos lawfor each alkanol These straight lines were used to evalu-ate [Gi] in the presence of α-CD

Figure 3 shows the plots according to Eq 4 for each1-alkanolα-CD and 2-alkanolα-CD system togetherwith the calculated curves that gave the best fit of theexperimental data The theoretical values agreed wellwith the experimental values (data points) for each alka-nol The findings shown in Fig 3 also suggest that thestoichiometry of the complexes between alkanol and α-

CD was 11 The apparent stability constants K deter-mined by this method are summarized together with stan-dard deviations and are compared with the previously re-ported values in Table 1 The K values determined in thisstudy are in reasonable agreement with those obtainedfrom previous reports (56) The K values were plottedas log K against total number of carbon atoms of the alka-nols in Fig 4 The plots for a homologous series of thestraight-chain alkanols gave approximately straight lineswhich increased with the increasing carbon number ofthe alkanols Accordingly this supports the idea that thecavity of α-CD accommodates the hydrophobic moietyof alkanols In addition it was also shown that the affinityof the 1-alkanols toward α-CD was higher than that of2-alkanols which suggests that the hydroxyl group of al-kanols becomes a hindrance factor with their inclusion

CONCLUSIONS

In this study the stability constants for inclusion com-plexes of alkanols with α-CD were determined simulta-neously using the simultaneous SHSGC method It isvery important to determine the K value for the 11 inclu-sion complex because most guests form 11 inclusioncomplexes with CD This method is suggested as usefulfor the determination of the stability constant particu-larly in the case of 11 stoichiometry In addition it ismore advantageous than the conventional method be-cause the experimental time required for the determina-tion of the stability constant can be drastically shortened

REFERENCES

1 Y Saito K Yoshihara I Tanemura H Ueda and TSato Chem Pharm Bull 45 1711 (1997)

2 K Yoshihara I Tanemura Y Saito H Ueda and TSato Chem Pharm Bull 45 2076 (1997)

3 Y Saito I Tanemura H Ueda and T Sato ChemPharm Bull 46 1777 (1998)

4 B V Ioffe and A G Vitenberg Head-Space Analysisand Related Methods in Gas Chromatography John Wi-ley and Sons New York 1984 p 13

5 Y Matui and K Mochida Bull Chem Soc Jpn 522808 (1979)

6 S Andini G Castronuovo V Elia and E Gallotta Car-bohydr Res 217 87 (1991)

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All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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Page 5: Determination of the Stability Constants in Alkanol/α-Cyclodextrin Mixed System

Order now

Reprints of this article can also be ordered at

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Request Permission or Order Reprints Instantly

Interested in copying and sharing this article In most cases US Copyright Law requires that you get permission from the articlersquos rightsholder before using copyrighted content

All information and materials found in this article including but not limited to text trademarks patents logos graphics and images (the Materials) are the copyrighted works and other forms of intellectual property of Marcel Dekker Inc or its licensors All rights not expressly granted are reserved

Get permission to lawfully reproduce and distribute the Materials or order reprints quickly and painlessly Simply click on the Request PermissionReprints Here link below and follow the instructions Visit the US Copyright Office for information on Fair Use limitations of US copyright law Please refer to The Association of American Publishersrsquo (AAP) website for guidelines on Fair Use in the Classroom

The Materials are for your personal use only and cannot be reformatted reposted resold or distributed by electronic means or otherwise without permission from Marcel Dekker Inc Marcel Dekker Inc grants you the limited right to display the Materials only on your personal computer or personal wireless device and to copy and download single copies of such Materials provided that any copyright trademark or other notice appearing on such Materials is also retained by displayed copied or downloaded as part of the Materials and is not removed or obscured and provided you do not edit modify alter or enhance the Materials Please refer to our Website User Agreement for more details

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