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Diffusion ordered spectroscopy for resolution of double bonded cis, trans-isomers
Journal of Molecular Structure 1017 (2012) 106–108
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc
Diffusion ordered spectroscopy for resolution of double bonded cis, trans-isomers Sachin Rama Chaudhari a,b, N. Suryaprakash b,⇑ a b
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India NMR Research Centre, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e
i n f o
Article history: Received 7 January 2012 Accepted 2 March 2012 Available online 12 March 2012 Keywords: DOSY Cis, trans-isomers Micelles SDS AOT NMR spectroscopy
a b s t r a c t NMR spectroscopic separation of double bonded cis- and trans-isomers, that have different molecular shapes but identical mass have been carried out using Diffusion Ordered Spectroscopy (DOSY). The mixtures of fumaric acid and maleic acid, that have similar hydrodynamic radii, have resolved been ‘on the basis of their diffusion coefficients arising due to their different tendencies to associate with micelles or reverse micelles. Sodium dodecyl sulfate (SDS) and Dioctyl sulfosuccinate sodium salt (AOT) have been used as the media to mimic the chromatographic conditions, modify the average mobility and to achieve differential diffusion rates. The best separation of the components has been achieved by Dioctyl sulfosuccinate sodium salt (AOT) in D2O solution. Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction NMR spectroscopy, being a versatile and sensitive tool, is extensively employed by chemists for determining the molecular structure and conformation of compounds. The most challenging problems experienced by synthetic chemists and in industries is the separation of individual components of combinatorial mixtures. In the studies involving separation of the individual components of the mixtures, such as identification of metabolites, characterization of aggregates and hydrogen bonding, host–guest complexes, ion pairing in organometallic chemistry and supramolecular assemblies [1,2], the Diffusion Ordered Spectroscopy (DOSY) [3–7] has been employed as a non-invasive tool. The diffusion coefficient is a measure of the mean square displacement of the diffusing molecules during a certain time. The DOSY also mimics a chromatographic process in that the molecular average mobilities in mixture are modified according to the individual affinities for stationary phase and referred as ‘‘in tube chromatography or NMR chromatography’’ [8–12]. The two dimensional DOSY spectrum, which represents chemical shifts and diffusion coefficients in two orthogonal directions, effectively separates out the NMR signals according to the diffusion coefficients of the components differing by less than 1%. This approach is very effective only if the NMR spectrum of the mixture is well-resolved and the components of the mixtures exhibit different rates of diffusion, arising because of different molecular masses. The conventional DOSY ⇑ Corresponding author. Tel.: +91 80 22933300; fax: +91 80 23601550. E-mail address: [email protected] (N. Suryaprakash). 0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.molstruc.2012.03.009
methodology generally fails to resolve isomeric species (species of similar size and structure) which have similar diffusion coefficients, possessing nearly the same hydrodynamic radii. In circumventing such situations, an excellent technique has been reported by the group of Morris, cited as matrix-assisted DOSY [13], where the separation of the isomeric mixtures has been achieved by the utilization of micelles or reverse micelles within which the embedded solute molecules diffuse. The substantial difference in their diffusion rates have been achieved by the introduction of co-solvent, which permitted the resolution of mixture, exploiting the idea that these structural isomers binds differently with the surfactant micelles. The effect of the concentration of the solute and conditions under which the separations can be achieved is also discussed [14]. A similar separation has also been demonstrated using reverse micelles [13,14]. In the present study, we have utilized this idea for the separation of another class of isomers, such as, double bonded cis- and trans-isomers which is very important in the field of retinoid chemistry [15,16]. The isomers, fumaric and maleic acids, have nearly equal hydrodynamic radii and exhibit no difference in their diffusion coefficients in commonly employed solvents for NMR spectroscopy have been chosen as test samples for the study. We have employed the technique of matrix assisted DOSY using micelles or reverse micelles as co-solvents to resolve such mixtures by their differential diffusion rates [13]. Substantial change in the diffusion rates compared to those in the solvent D2O and significant difference in the diffusion rates between the isomers both in micelles and reverse micelles, the large differential value especially in reverse micelles has been detected.
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S.R. Chaudhari, N. Suryaprakash / Journal of Molecular Structure 1017 (2012) 106–108
2. Experimental methods For the demonstration of experimental methodology, fumaric acid and maleic acid, which are double bonded cis and trans isomers were chosen. A model binary component mixture was prepared by taking fumaric acid and maleic acid (all purchased from Sigma–Aldrich) at 15 mM concentration of each in 99% D2O solution (sample 1). Another solution was prepared containing 30 mM fumaric acid and maleic acid and 200 mM of Sodium dodecyl sulfate (SDS) in D2O (sample 2). Similarly a third sample was prepared in D2O containing 35 mM of fumaric acid, maleic acid and 200 mM of Dioctyl sulfosuccinate sodium salt (AOT) (sample 3). All the NMR measurements were carried out at 400 MHz using Bruker Avance NMR Spectrometer with a total sample volume of nearly 500 lL taken in a 5 mm NMR tube. The sample temperature was maintained at 298 K using BVT3000 temperature controller. The DOSY experiments were performed using the pulse sequence available in the Bruker library (ledbpgp2s), with stimulated echo, longitudinal eddy current compensation, bipolar gradient pulses, and two spoil gradients using 16 different gradient values varying from 2% to 95% of the maximum gradient strength. Diffusion times ranging from 100 to 1000 ms and the maximum bipolar gradient pulse length of 2.2 ms were used for all the experiments. The longitudinal eddy current delay was kept constant at 5 ms in all the experiments whereas, gradient pulse recovery time was set to 200 ls. The data was processed using 4096 points in the F2 dimension and 256 points in F1 dimension. The line-width factor (LWF) set to 1 permitted the measurement of peak width in the diffusion dimension. 3. Results and discussion The conventional DOSY spectrum of fumaric acid and maleic acid mixture in D2O solution (sample 1) is given in Fig. 1. The assignment of peaks to fumaric and maleic acids are carried out based on the reported chemical shifts [17]. It is clearly evident from the figure that it is not possible to achieve any resolution or separation of the two isomers. The diffusion coefficients (D) measured for the individual components of the mixtures are reported in Table 1. The rates of diffusion for both fumaric acid and maleic acid are identical preventing their separation. The SDS micelle was then added to the mixture of fumaric acid and maleic acid (sample 2) in order to explore the possibility of the separation of the binary component mixture. The DOSY spectrum of this sample is reported in Fig. 2. The remarkable change is seen
Table 1 Measured diffusion coefficients for fumaric acid and maleic acid from the different DOSY experiments carried out on samples 1–3. Compound
Df/10 10 m2 s (sample 1)
Maleic acid Fumaric acid
9.14 ± 3.2 9.14 ± 1.9
1
Dm/10 10 m2 s (sample 2) 8.10 ± 0.90 6.92 ± 0.74
1
Drm/10 10 m2 s (sample 3)
1
2.82 ± 1.41 4.49 ± 1.47
f – free, m – micelles, rm – reverse micelles.
Fig. 2. The 400 MHz 1H DOSY spectrum of a sample 2 containing 30 mM fumaric and maleic acids and 200 mM of Sodium dodecyl sulfate (SDS) in D2O, obtained at 298 K. The experimental parameters same as those utilized for obtaining spectrum shown in Fig. 1. The projection on the top pertains to 1D spectrum. The region of the spectrum marked with rectangle is expanded to provide clarity of their separation. The spectrum display large difference between the diffusion coefficients between the isomers. The uncertainty in the measurement of diffusion coefficients is reflected in the line broadening in the diffusion dimension. The F1 dimension pertains to diffusion and F2 dimension represents the conventional one dimensional spectrum.
Fig. 3. The 400 MHz 1H DOSY spectrum of mixture of fumaric acid and maleic acid in D2O with 200 mM Dioctyl sulfosuccinate sodium salt (AOT) (sample 3). The region of the spectrum marked with solid rectangle is expanded below to provide clarity of their separation. The projection on the top pertains to 1D spectrum.
Fig. 1. The 400 MHz 1H DOSY spectrum of the sample 1 recorded at 298 K. The experimental parameters are discussed in the text. The contours correlate the 1H chemical shift with the negative log of the diffusion coefficient. The projection plotted at the top of the contour map pertains to the one-dimensional 1H NMR spectrum. The diffusion coefficients of the cis and trans isomers are equivalent in this spectrum. The assignments to fumaric acid and maleic acids were using the literature [17]. The F1 dimension pertains to diffusion and F2 dimension represents the conventional one dimensional spectrum.
in the spectrum and the signals are separated due to different association of the molecules with SDS micelles. This effect and the variation of mobility are similar to the earlier reported work [13]. It is clearly evident from Fig. 2 that the diffusion of fumaric acid is considerably slowed compared to maleic acid because of its stronger association with micelles. The calculated diffusion coefficients indicate that there is nearly 15% difference in the diffusion coefficients between the two isomers. Consequent to the
108
S.R. Chaudhari, N. Suryaprakash / Journal of Molecular Structure 1017 (2012) 106–108
embedding of the molecules in the micelle matrix, the small changes in line widths and chemical shifts compared to the sample in pure D2O are also observed. However, this does not prevent the precise estimation of diffusion coefficients. Subsequently the effect of differential association of the isomers with reverse micelles was also explored. The addition of Dioctyl sulfosuccinate sodium salt (AOT) to D2O creates reverse micelles. Thus the DOSY spectrum of the sample 3 prepared in AOT was recorded and is reported in Fig. 3. The significant changes in the diffusion coefficients (Table 1) are observed both for fumaric and maleic acids indicating their association with AOT micelles are stronger compared to SDS. The visual inspection of Fig. 3 brings out the fact that diffusion trend is now reversed and it is relatively strongly affected for the maleic acid compared to fumaric acid. The measured diffusion coefficients are reduced by nearly 69% and 51% for maleic acid and fumaric acid respectively compared to those in the solvent D2O. Furthermore the difference in their coefficients is also larger in AOT compared to SDS. The study thus confirms significant advantage of AOT micelles over SDS micelles in separating double bonded cis, trans-isomers. It is evident from the study that micellar SDS and AOT solutions can be utilized in matrix-assisted DOSY experiment to impose the competition between solute molecules in the free aqueous and the micellar environment to resolve the NMR spectra of mixtures of cis- and trans-isomers, whose spectra are impossible to resolve by conventional DOSY technique. The significant resolution of isomers is seen in the spectra obtained in both micelles and reverse micelles. A possible mechanism for the lowering diffusion of the both isomers in the presence of micelles is the hydrophobic interactions providing the driving force for their interactions. 4. Conclusions The matrix assisted diffusion-order spectroscopy has been employed as a tool for achieving resolution in double bonded cis, trans-isomers. The influence of micelles on the mixture of double bonded isomeric organic acids provided high-resolution DOSY spectra. The diffusion rates are not only substantially altered
compared to solvent D2O but also differs significantly between the isomers in both micelles and reverse micelles. It is also convincingly established that the rates of diffusion and their differential values are several times larger in reverse micelles (AOT) compared to micelles (SDS). The results provide further evidence for the flexibility and robustness of matrix-assisted methods in the analysis of combinatorial mixtures. The method has certain limitations. The two essential requirements are; the isomers must possess interactive groups to form complex with the micelles, such as –COOH and since the solutions are prepared in micelles, the isomers must be soluble in water. Acknowledgements N.S. gratefully acknowledges the financial aid for this work by the Board of Research in Nuclear Sciences, Mumbai (Grant No. 2009/37/38/BRNS). S.R.C. thanks UGC, India for Senior Research Fellowship. References [1] Y. Cohen, L. Avram, L. Frish, Angew. Chem., Int. Ed. 44 (2005) 520 (and reference therein). [2] Claridge, T.D.W., 2009. High-Resolution NMR Techniques in Organic, Chemistry. [3] E.O. Stejskal, J.E. Tanner, J. Chem. Phys. 42 (1965) 288. [4] K.F. Morris, C.S. Johnson Jr., J. Am. Chem. Soc. 115 (1993) 4291. [5] A. Chen, D.H. Wu, C.S. Jonson, J. Am. Chem. Soc. 117 (1995) 7965. [6] K.F. Morris, C.S. Johnson Jr., J. Am. Chem. Soc. 114 (1992) 3139. [7] S.J. Gibbs, C.S. Johnson Jr., J. Magn. Reson. 93 (1991) 395. [8] S. Viel, F. Ziarelli, S. Caldarelli, Proc. Natl. Acad. Sci. USA 100 (2003) 9696. [9] C. Pemberton, R. Hoffman, A. Aserin, N. Garti, J. Magn. Reson 208 (2011) 262. [10] S. Caldarelli, Magn. Reson. Chem. 45 (2007) S48. [11] J.S. Kavakka, I. Kilpeläinen, S. Heikkinen, Org. Lett. 11 (2009) 1349. [12] C. Carrara, S. Viel, F. Ziarelli, G. Excoffier, C. Delaurent, S. Caldarelli, J. Magn. Reson. 194 (2008) 303. [13] R. Evans, S. Haiber, M. Nilsson, G.A. Morris, Anal. Chem. 81 (2009) 4548. [14] C.F. Tormena, R. Evans, S. Haiber, M. Nilsson, G.A. Morris, Magn. Reson. Chem. 48 (2010) 550. [15] M. Maden, Curr. Biol. 8 (1998) R846. [16] L. Jong, J.M. Lehmann, P.D. Hobbs, E. Harlev, J.C. Huffman, M. Pfahl, M.I. Dawson, J. Med. Chem. 36 (1993) 2605. [17] P. Nolis, A. Roglans, T. Parella, J. Magn. Reson. 173 (2005) 305.
Contents lists available at SciVerse ScienceDirect
Journal of Molecular Structure journal homepage: www.elsevier.com/locate/molstruc
Diffusion ordered spectroscopy for resolution of double bonded cis, trans-isomers Sachin Rama Chaudhari a,b, N. Suryaprakash b,⇑ a b
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560 012, India NMR Research Centre, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e
i n f o
Article history: Received 7 January 2012 Accepted 2 March 2012 Available online 12 March 2012 Keywords: DOSY Cis, trans-isomers Micelles SDS AOT NMR spectroscopy
a b s t r a c t NMR spectroscopic separation of double bonded cis- and trans-isomers, that have different molecular shapes but identical mass have been carried out using Diffusion Ordered Spectroscopy (DOSY). The mixtures of fumaric acid and maleic acid, that have similar hydrodynamic radii, have resolved been ‘on the basis of their diffusion coefficients arising due to their different tendencies to associate with micelles or reverse micelles. Sodium dodecyl sulfate (SDS) and Dioctyl sulfosuccinate sodium salt (AOT) have been used as the media to mimic the chromatographic conditions, modify the average mobility and to achieve differential diffusion rates. The best separation of the components has been achieved by Dioctyl sulfosuccinate sodium salt (AOT) in D2O solution. Ó 2012 Elsevier B.V. All rights reserved.
1. Introduction NMR spectroscopy, being a versatile and sensitive tool, is extensively employed by chemists for determining the molecular structure and conformation of compounds. The most challenging problems experienced by synthetic chemists and in industries is the separation of individual components of combinatorial mixtures. In the studies involving separation of the individual components of the mixtures, such as identification of metabolites, characterization of aggregates and hydrogen bonding, host–guest complexes, ion pairing in organometallic chemistry and supramolecular assemblies [1,2], the Diffusion Ordered Spectroscopy (DOSY) [3–7] has been employed as a non-invasive tool. The diffusion coefficient is a measure of the mean square displacement of the diffusing molecules during a certain time. The DOSY also mimics a chromatographic process in that the molecular average mobilities in mixture are modified according to the individual affinities for stationary phase and referred as ‘‘in tube chromatography or NMR chromatography’’ [8–12]. The two dimensional DOSY spectrum, which represents chemical shifts and diffusion coefficients in two orthogonal directions, effectively separates out the NMR signals according to the diffusion coefficients of the components differing by less than 1%. This approach is very effective only if the NMR spectrum of the mixture is well-resolved and the components of the mixtures exhibit different rates of diffusion, arising because of different molecular masses. The conventional DOSY ⇑ Corresponding author. Tel.: +91 80 22933300; fax: +91 80 23601550. E-mail address: [email protected] (N. Suryaprakash). 0022-2860/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.molstruc.2012.03.009
methodology generally fails to resolve isomeric species (species of similar size and structure) which have similar diffusion coefficients, possessing nearly the same hydrodynamic radii. In circumventing such situations, an excellent technique has been reported by the group of Morris, cited as matrix-assisted DOSY [13], where the separation of the isomeric mixtures has been achieved by the utilization of micelles or reverse micelles within which the embedded solute molecules diffuse. The substantial difference in their diffusion rates have been achieved by the introduction of co-solvent, which permitted the resolution of mixture, exploiting the idea that these structural isomers binds differently with the surfactant micelles. The effect of the concentration of the solute and conditions under which the separations can be achieved is also discussed [14]. A similar separation has also been demonstrated using reverse micelles [13,14]. In the present study, we have utilized this idea for the separation of another class of isomers, such as, double bonded cis- and trans-isomers which is very important in the field of retinoid chemistry [15,16]. The isomers, fumaric and maleic acids, have nearly equal hydrodynamic radii and exhibit no difference in their diffusion coefficients in commonly employed solvents for NMR spectroscopy have been chosen as test samples for the study. We have employed the technique of matrix assisted DOSY using micelles or reverse micelles as co-solvents to resolve such mixtures by their differential diffusion rates [13]. Substantial change in the diffusion rates compared to those in the solvent D2O and significant difference in the diffusion rates between the isomers both in micelles and reverse micelles, the large differential value especially in reverse micelles has been detected.
107
S.R. Chaudhari, N. Suryaprakash / Journal of Molecular Structure 1017 (2012) 106–108
2. Experimental methods For the demonstration of experimental methodology, fumaric acid and maleic acid, which are double bonded cis and trans isomers were chosen. A model binary component mixture was prepared by taking fumaric acid and maleic acid (all purchased from Sigma–Aldrich) at 15 mM concentration of each in 99% D2O solution (sample 1). Another solution was prepared containing 30 mM fumaric acid and maleic acid and 200 mM of Sodium dodecyl sulfate (SDS) in D2O (sample 2). Similarly a third sample was prepared in D2O containing 35 mM of fumaric acid, maleic acid and 200 mM of Dioctyl sulfosuccinate sodium salt (AOT) (sample 3). All the NMR measurements were carried out at 400 MHz using Bruker Avance NMR Spectrometer with a total sample volume of nearly 500 lL taken in a 5 mm NMR tube. The sample temperature was maintained at 298 K using BVT3000 temperature controller. The DOSY experiments were performed using the pulse sequence available in the Bruker library (ledbpgp2s), with stimulated echo, longitudinal eddy current compensation, bipolar gradient pulses, and two spoil gradients using 16 different gradient values varying from 2% to 95% of the maximum gradient strength. Diffusion times ranging from 100 to 1000 ms and the maximum bipolar gradient pulse length of 2.2 ms were used for all the experiments. The longitudinal eddy current delay was kept constant at 5 ms in all the experiments whereas, gradient pulse recovery time was set to 200 ls. The data was processed using 4096 points in the F2 dimension and 256 points in F1 dimension. The line-width factor (LWF) set to 1 permitted the measurement of peak width in the diffusion dimension. 3. Results and discussion The conventional DOSY spectrum of fumaric acid and maleic acid mixture in D2O solution (sample 1) is given in Fig. 1. The assignment of peaks to fumaric and maleic acids are carried out based on the reported chemical shifts [17]. It is clearly evident from the figure that it is not possible to achieve any resolution or separation of the two isomers. The diffusion coefficients (D) measured for the individual components of the mixtures are reported in Table 1. The rates of diffusion for both fumaric acid and maleic acid are identical preventing their separation. The SDS micelle was then added to the mixture of fumaric acid and maleic acid (sample 2) in order to explore the possibility of the separation of the binary component mixture. The DOSY spectrum of this sample is reported in Fig. 2. The remarkable change is seen
Table 1 Measured diffusion coefficients for fumaric acid and maleic acid from the different DOSY experiments carried out on samples 1–3. Compound
Df/10 10 m2 s (sample 1)
Maleic acid Fumaric acid
9.14 ± 3.2 9.14 ± 1.9
1
Dm/10 10 m2 s (sample 2) 8.10 ± 0.90 6.92 ± 0.74
1
Drm/10 10 m2 s (sample 3)
1
2.82 ± 1.41 4.49 ± 1.47
f – free, m – micelles, rm – reverse micelles.
Fig. 2. The 400 MHz 1H DOSY spectrum of a sample 2 containing 30 mM fumaric and maleic acids and 200 mM of Sodium dodecyl sulfate (SDS) in D2O, obtained at 298 K. The experimental parameters same as those utilized for obtaining spectrum shown in Fig. 1. The projection on the top pertains to 1D spectrum. The region of the spectrum marked with rectangle is expanded to provide clarity of their separation. The spectrum display large difference between the diffusion coefficients between the isomers. The uncertainty in the measurement of diffusion coefficients is reflected in the line broadening in the diffusion dimension. The F1 dimension pertains to diffusion and F2 dimension represents the conventional one dimensional spectrum.
Fig. 3. The 400 MHz 1H DOSY spectrum of mixture of fumaric acid and maleic acid in D2O with 200 mM Dioctyl sulfosuccinate sodium salt (AOT) (sample 3). The region of the spectrum marked with solid rectangle is expanded below to provide clarity of their separation. The projection on the top pertains to 1D spectrum.
Fig. 1. The 400 MHz 1H DOSY spectrum of the sample 1 recorded at 298 K. The experimental parameters are discussed in the text. The contours correlate the 1H chemical shift with the negative log of the diffusion coefficient. The projection plotted at the top of the contour map pertains to the one-dimensional 1H NMR spectrum. The diffusion coefficients of the cis and trans isomers are equivalent in this spectrum. The assignments to fumaric acid and maleic acids were using the literature [17]. The F1 dimension pertains to diffusion and F2 dimension represents the conventional one dimensional spectrum.
in the spectrum and the signals are separated due to different association of the molecules with SDS micelles. This effect and the variation of mobility are similar to the earlier reported work [13]. It is clearly evident from Fig. 2 that the diffusion of fumaric acid is considerably slowed compared to maleic acid because of its stronger association with micelles. The calculated diffusion coefficients indicate that there is nearly 15% difference in the diffusion coefficients between the two isomers. Consequent to the
108
S.R. Chaudhari, N. Suryaprakash / Journal of Molecular Structure 1017 (2012) 106–108
embedding of the molecules in the micelle matrix, the small changes in line widths and chemical shifts compared to the sample in pure D2O are also observed. However, this does not prevent the precise estimation of diffusion coefficients. Subsequently the effect of differential association of the isomers with reverse micelles was also explored. The addition of Dioctyl sulfosuccinate sodium salt (AOT) to D2O creates reverse micelles. Thus the DOSY spectrum of the sample 3 prepared in AOT was recorded and is reported in Fig. 3. The significant changes in the diffusion coefficients (Table 1) are observed both for fumaric and maleic acids indicating their association with AOT micelles are stronger compared to SDS. The visual inspection of Fig. 3 brings out the fact that diffusion trend is now reversed and it is relatively strongly affected for the maleic acid compared to fumaric acid. The measured diffusion coefficients are reduced by nearly 69% and 51% for maleic acid and fumaric acid respectively compared to those in the solvent D2O. Furthermore the difference in their coefficients is also larger in AOT compared to SDS. The study thus confirms significant advantage of AOT micelles over SDS micelles in separating double bonded cis, trans-isomers. It is evident from the study that micellar SDS and AOT solutions can be utilized in matrix-assisted DOSY experiment to impose the competition between solute molecules in the free aqueous and the micellar environment to resolve the NMR spectra of mixtures of cis- and trans-isomers, whose spectra are impossible to resolve by conventional DOSY technique. The significant resolution of isomers is seen in the spectra obtained in both micelles and reverse micelles. A possible mechanism for the lowering diffusion of the both isomers in the presence of micelles is the hydrophobic interactions providing the driving force for their interactions. 4. Conclusions The matrix assisted diffusion-order spectroscopy has been employed as a tool for achieving resolution in double bonded cis, trans-isomers. The influence of micelles on the mixture of double bonded isomeric organic acids provided high-resolution DOSY spectra. The diffusion rates are not only substantially altered
compared to solvent D2O but also differs significantly between the isomers in both micelles and reverse micelles. It is also convincingly established that the rates of diffusion and their differential values are several times larger in reverse micelles (AOT) compared to micelles (SDS). The results provide further evidence for the flexibility and robustness of matrix-assisted methods in the analysis of combinatorial mixtures. The method has certain limitations. The two essential requirements are; the isomers must possess interactive groups to form complex with the micelles, such as –COOH and since the solutions are prepared in micelles, the isomers must be soluble in water. Acknowledgements N.S. gratefully acknowledges the financial aid for this work by the Board of Research in Nuclear Sciences, Mumbai (Grant No. 2009/37/38/BRNS). S.R.C. thanks UGC, India for Senior Research Fellowship. References [1] Y. Cohen, L. Avram, L. Frish, Angew. Chem., Int. Ed. 44 (2005) 520 (and reference therein). [2] Claridge, T.D.W., 2009. High-Resolution NMR Techniques in Organic, Chemistry. [3] E.O. Stejskal, J.E. Tanner, J. Chem. Phys. 42 (1965) 288. [4] K.F. Morris, C.S. Johnson Jr., J. Am. Chem. Soc. 115 (1993) 4291. [5] A. Chen, D.H. Wu, C.S. Jonson, J. Am. Chem. Soc. 117 (1995) 7965. [6] K.F. Morris, C.S. Johnson Jr., J. Am. Chem. Soc. 114 (1992) 3139. [7] S.J. Gibbs, C.S. Johnson Jr., J. Magn. Reson. 93 (1991) 395. [8] S. Viel, F. Ziarelli, S. Caldarelli, Proc. Natl. Acad. Sci. USA 100 (2003) 9696. [9] C. Pemberton, R. Hoffman, A. Aserin, N. Garti, J. Magn. Reson 208 (2011) 262. [10] S. Caldarelli, Magn. Reson. Chem. 45 (2007) S48. [11] J.S. Kavakka, I. Kilpeläinen, S. Heikkinen, Org. Lett. 11 (2009) 1349. [12] C. Carrara, S. Viel, F. Ziarelli, G. Excoffier, C. Delaurent, S. Caldarelli, J. Magn. Reson. 194 (2008) 303. [13] R. Evans, S. Haiber, M. Nilsson, G.A. Morris, Anal. Chem. 81 (2009) 4548. [14] C.F. Tormena, R. Evans, S. Haiber, M. Nilsson, G.A. Morris, Magn. Reson. Chem. 48 (2010) 550. [15] M. Maden, Curr. Biol. 8 (1998) R846. [16] L. Jong, J.M. Lehmann, P.D. Hobbs, E. Harlev, J.C. Huffman, M. Pfahl, M.I. Dawson, J. Med. Chem. 36 (1993) 2605. [17] P. Nolis, A. Roglans, T. Parella, J. Magn. Reson. 173 (2005) 305.