hemicb articol.pdf

8/17/2019 HemiCB articol.pdf

http://slidepdf.com/reader/full/hemicb-articolpdf 1/16

F o r P

e e r R e v

i e w O n l y

Hemicucurbiturils as receptors in extraction and transport

of some amino acids

Journal: Supramolecular Chemistry

Manuscript ID: GSCH-2015-0154

Manuscript Type: Special Issue Paper

Date Submitted by the Author: 30-Aug-2015

Complete List of Authors: Mutihac, Lucia; University of Bucharest, analytical ChemistryCucolea, Elena Iulia; University of Bucharest, Analytical ChemistryBuschmann, Hans-Jurgen; University Duisburg-Essen,

Keywords:hemicucurbit[6]uril, hemicucurbit[12]uril, amino acids, liquid-liquidextraction, amino acid transport

URL: http:/mc.manuscriptcentral.com/tandf/gsch Email: [email protected]

Supramolecular Chemistry



F o r P

e e r R e v

i e w O n l y

Hemicucurbiturils as receptors in extraction and transport through liquid membrane of amino acids38x45mm (300 x 300 DPI)

ge 1 of 15





F o r P

e e r R e v

i e w O n l y

1

Hemicucurbiturils as receptors in extraction and transport of some amino

acids

Elena Iulia Cucoleaa, Hans-Jürgen Buschmann b, Lucia Mutihaca*

aUniversity of Bucharest, Department of Analytical Chemistry, 4-12 Blvd. Regina Elisabeta,

030018 Bucharest, Romania ; b

University Duisburg-Essen, NETZ / DTNW gGmbH, Carl-

Benz-Strase 199, D-47057, Duisburg, Germany

Abstract

The molecular recognition properties of hemicucurbit[6]uril (HemiCB[6]) and

hemicucurbit[12]uril (HemiCB[12]) towards a series of amino acid native and methyl esters

(L-phenylalanine, L-leucine, L-valine, L-cysteine, L-tryptophan, L-isoleucine, L-

phenylalanine methyl ester hydrochloride (L-PheOMe), L-tyrosine methyl ester hydrochloride

(L-TyrOMe), L-valine methyl ester hydrochloride (L-ValOMe), L-leucine methyl ester

hydrochloride (L-LeuOMe), L-serine methyl ester hydrochloride (L-SerOMe), and L-cysteine

methyl ester hydrochloride (L-CysOMe) were investigated. In this respect, by means of

liquid-liquid extraction, a series of amino acid native and methyl esters were extracted from

an aqueous phase (pH = 5.5) into a chloroform phase as ion pairs in the presence of tropaeolin

00 as counter ion. Based on results obtained in extraction experiments, the active transport

assisted by pH gradient of amino acids as ion pairs through chloroform liquid membrane

employing HemiCB[6] as carrier was performed. Both receptors used in experiments

exhibited extractability towards amino acids under study. From the results obtained, one can

observed the good affinity of both receptors, hemiCB[6, 12], towards hydrophobic amino

acids (L-PheOMe, L-LeuOMe, and L-ValOMe)). It was emphasized that the structure of

hemicucurbiturils and amino acids together with the anion nature, and pH have influenced the

experimental results.

Keywords: hemicucurbit[6]uril, hemicucurbit[12]uril, amino acids, liquid-liquid extraction,

amino acid transport

*Corresponding author. E-mail: [email protected]

Page 2





F o r P

e e r R e v

i e w O n l y

2

Introduction

Cucurbit[n]urils (n = 5, 6, 7, 10, 14) as a new receptors in supramolecular chemistry

are intensively studied especially for a large area of applications in molecular recognition,

catalysis, supramolecular vesicles, fluorescence sensing, drug delivery, nanoscience, as well

as in separation science (1-8). It is known that molecular recognition is one of the most

important issue in supramolecular chemistry concerning the supramolecular design,

supramolecular catalysis, molecular machines, and mechanisms of biological systems (9-17).

Since the synthesis of cucurbit[6]uril, the first member of cucurbituril family reported

in 1905 by Behrend and coworkers (18) by acid-catalyzed condensation of glycoluril and

formaldehyde, several studies of its involvement as receptor in host-guest chemistry have

been reported. Moreover, the synthesis of functionalized derivatives of cucurbituril by

enhancing their cavity and their solubility opens the possibility of large perspectives of these

molecular containers (2) to be use in fundamental areas. It should be noted that their

remarkable potential as high affinity binding in their hydrophobic cavity and two polar portals

towards various guests such as amino acids, peptides, nucleobases, dyes, drug molecules, and

even proteins attracted considerable attention of many research groups (2, 4, 19-21). Even

diastereoselectivity of cucurbiturils was reported by Kim et al. (22) and Masson et al. (23).

Recently, another members of cucurbiturils family, namely hemicucurbit[n]urils (n = 6, 12)

and bambusurils based on glycoluril building blocks similarly to cucurbiturils were

synthetized (24-27). They are interesting receptors in host-guest chemistry forming stable

complexes with inorganic and organic compounds. It was mentioned that hemicucurbiturils

form complexes with selected anions, cations, and small molecules. A few studies were

reported so far highlighting the possibility of molecular recognition of biological compounds

by hemicucurbiturils. As such, Buschmann et al. (26) reported the complex formation of

hemiCB[6] with various salts in aqueous solution. The characterization of the complex

behavior was performed by quantum mechanical chemical calculations. The study of nature

of bonding between halides and three related host molecules (CB[6], hemiCB[6], and

bambus[6]uril) using density functional theory reveals the role of solvation and the role of

cations. The results show that the binding of halides in CB[6] is assisted by a cation and the

binding in hemiCB[6] is assisted by solvents (28). By using1H NMR, UV-vis, IR, mass

spectrometry, and quantum chemistry, Xiang et al. (29) studied the host-guest interactions of

phenazine hydrochloride salt with hemicucurbit[n]uril, (n = 6, 12) in a mixture of methanol

and chloroform. It was established 1:1 stoichiometry for the complex phenazine:hemiCB[6]

ge 3 of 15





F o r P

e e r R e v

i e w O n l y

3

and 2:1 stoichiometry for the complex phenazine:hemiCB[12]. The authors highlighted a

strong hydrogen binding between the protonated nitrogen of phenazine and the oxygen of

carbonyl group of hemiCB[6] (29).

In our previous work, we reported studies on the host-guest complexation of biological

compounds (amino acids, peptides, and nucleobases) with cucurbit[n]urils (n = 6, 7) by

means of calorimetric titrations, UV-vis measurements, fluorescence, and1H NMR

investigations (6, 8, 17, 30). Continuing our research on the recognition and separation of

biomolecules by various macrocyclic receptors, we report herein the liquid-liquid extraction

of a series of amino acid native and methyl esters with new receptors, hemiCB[6] and

hemiCB[12] respectively, and their transport through liquid membrane using hemiCB[6] as

carrier. To our best knowledge, it is for the first time when these macrocyclic receptors have

been used in separation processes.

Results and discussion

In Figure 1, there are given the values of the extraction yield of some amino acid

native and methyl esters as ion pairs by using hemiCB[6] and hemiCB[12] as extractants in

the presence of tropaeolin 00 from aqueous phase into chloroform phase. The extractability of

the receptor hemiCB[6] towards amino acids as ion pairs is between 27% (L-CysOMe) and

3 % (L-Leu), respectively, and between 25% (L-PheOMe) and 3% (L-Leu) respectively, for

receptor hemiCB[12]. One can observe that the extraction yields of native amino acids under

study (L-Leu and L-Cys) with both receptors is lower compared with the values of extraction

concentration obtained for amino acid methyl esters. It is obviously that both hemiCB[6] and

hemiCB[12] exhibit poor extraction properties towards native amino acids.

We also studied the extraction of L-Trp, L-Phe, L-Ile, and L-Val in the same

conditions without any relevant results. One explanation could be given by the electrostatic

repulsion between the carboxylic groups of amino acids and the carbonyl groups of

hemicucurbiturils.

The sequence of decreasing extraction yield of amino acids in the case of receptor

hemiCB[6] is the following: L-CysOMe (27 %) > L-PheOMe (25 %) ≅ L-LeuOMe (25) > L-

ValOMe (15 %) > L-SerOMe (12 %) > L-Cys (5 %) > L-Leu (3 %) and for the receptor

hemiCB[12] is the following: L-PheOMe (25 %) > L-LeuOMe (23) > L-ValOMe (12 %) > L-

CysOMe (8 %) > L-SerOMe (7 %) > L-Leu (3 %). The good extractability is observed for the

amino acid methyl esters: L-CysOMe, L-PheOMe, L-ValOMe, and L-SerOMe. Except L-

Page 4





F o r P

e e r R e v

i e w O n l y

4

CysOMe, the amino acids L-PheOMe, L-LeuOMe, and L-ValOMe have aproximatively

close values of extraction yields with the both receptors. In the case of L-CysOMe were

obtained better extraction yields with receptor hemiCB[6]. The structure of Cys could be

responsible for these results. Our previous experiments concerning the thermodynamic study

of some amino acid complexes with CB[6] in aqueous formic acid solutions (50 %)

suggested the formation of exclusion complexes (8) by interactions between protonated amino

acid and carbonyl group of CB[6].

Figure 1

The extraction efficiency depends on parameters like structural properties of amino

acids, the structure of the receptor, the nature of the counter ion, the pH of aqueous solution,

the nature of the solvent, and the thermodynamic equilibrium. From the results displayed in

Figure 1 one can observed the good affinity of both hemiCB[6, 12] towards hydrophobic

amino acids (L-PheOMe, L-LeuOMe, L-ValOMe) (31).

The transport of amino acid methyl esters as ion pairs in the presence of tropaeolin 00

as counter ion through chloroform liquid membrane using hemiCB[6] as carrier was also

studied. The results of transport are given in Figure 2 together with the extraction yields of a

series of amino acid methyl esters. As can be seen from Table 1 and Figure 2, the receptor

hemiCB[6] exhibited good transport ability towards L-LeuOMe, L-PheOMe, L-CysOMe. The

sequence of decreasing transport yields of amino acids was the following: L-LeuOMe (25%)

> L-PheOMe (20%) > L-CysOMe (12%) > L-ValOMe (9%) > L-SerOMe (5%) > L-TyrOMe

(1%). In the membrane system, the values of the transport yields of amino acids are smaller

than that extraction yields of amino acids with receptor hemiCB[6]. In Table 1, the fluxes of

amino acids through chloroform liquid membrane with hemiCB[6] as carrier are presented.

The receptor exhibited lower fluxes towards L-TyrOMe and L-SerOMe.

Figure 2

Table 1

It was realized an active transport from aqueous source phase into aqueous receiving phase

assisted by the pH gradient. The transport experiments were carried out using a device

presented in Figure 3. Like in extraction experiments, the receptor hemiCB[6] showed

transport ability towards L-PheOMe and L-LeuOMe. Similarly, hemiCB[12] exhibited

affinity for the same amino acids in extraction experiments. A large difference in extraction

ability of L-CysOMe was observed in the case of hemiCB[6] and hemiCB[12], respectively.

ge 5 of 15





F o r P

e e r R e v

i e w O n l y

5

The recognition behavior of the both receptors in respect to the amino acids studied is quite

good especially for the some amino acids methyl esters compared with the native amino

acids. There are need more experiments to elucidate all aspects involved in host-guest

properties of hemicucurbiturils.

Figure 3

Experimental

Reagents

The following amino acids native and methylesters: L-phenylalanine, L-leucine, L-valine, L-

cysteine, L-tryptophan, L-isoleucine, L-phenylalanine methyl ester hydrochloride (L-

PheOMe), L-tyrosine methyl ester hydrochloride (L-TyrOMe), L-valine methyl ester

hydrochloride (L-ValOMe), L-leucine methyl ester hydrochloride (L-LeuOMe), L-serine

methyl ester hydrochloride (L-SerOMe), and L-cysteine methyl ester hydrochloride (L-

CysOMe) were purchased from Fluka (purity > 99.5 %) and were employed without further

purification (Chart 1). [4-(4’-Anilinophenylazo) benzenesulfonic acid] (tropaeolin 00) as

counter ion was obtained from Fluka at the analytical grade. The organic solvent chloroform

(dielectric constant) εr = 4.81 (32) was distilled before usage. Distilled (Millipore) water was

used througout the experiments. Hemicucurbit[6]uril (HemiCB[6]) and Hemicucurbit[12]uril

(HemiCB[12] were synthesized according to Miyahara’s method (24).

Chart 1

Solvent extraction of amino acid native and methyl esters

Equal volumes (5 mL) of 5.0 x 10-4

M of amino acid and 8.0 x 10-5

M tropaeolin 00 at pH =

5.5 were mixed with chloroform solution (5 mL) of hemiCB[6] and hemiCB[12] (1.0 x 10-4

M), respectively, and shaken for 30 minutes at T = 298.15 K to attend equilibrium. The

extractability was calculated according to Pedersen’s procedure (33) [ ] ( )

100 A

A A E

0

0×

−=% ,

where 0 A and are the absorbance of the aqueous phases before and after the extraction

with the receptor, respectively, at λ = 444 nm (33). The absorbance was determined by

spectrophotometric measurements carried out by means of an UV-Vis Spectrometer JASCO

V-530. Each experiment was repeated five times.

Page 6





F o r P

e e r R e v

i e w O n l y

6

The pH of the aqueous solutions was adjusted by the hydrochloric acid. Chloroform and water

were saturated with each other to prevent volume change during extraction.

Liquid membrane transport

The transport experiments were run by using a U-shaped glass tube for 24 h (Figure 3). The

source phase contains 5 mL of aqueous solution of amino acid 5 x 10-4

M, and 8.0 x 10-5

M

tropaeolin 00 as counter ion at pH = 5.5. The receiving phase contains 5 mL of aqueous

solution (pH = 1.5). The pH of the aqueous solutions was adjusted by the hydrochloric acid.

The membrane phase, 10 mL of hemiCB[6] (1.0 x 10-4

M) in chloroform was introduced in

the tube. The transport experiments were carried out by stirring the aqueous and organic

phases at 200 rpm at room temperature. The concentration of amino acids in both aqueous

phases (source and receiving phase) was assessed by UV-Vis measurements. Each experiment

was repeated three times and reproducibility was < 6%. Blank experiments were performed

for reference in the absence of carrier. The transport flux was calculated according to the

following eq. r r C V J

At

∆ ×= where ∆Cr is the concentration difference of receiving phase, Vr

the volume of receiving phase, A is the effective membrane area, and t is the time.

Conclusion

The ability of hemicucurbit[6]uril and hemicucurbit[12] to act as extractants for a

series of native and derivatives amino acids in the presence of tropaeolin 00 as counter ion

was studied. The obtained results suggested that hemiCB[6] and hemiCB[12] can act as

extractant and carrier for amino acid native and methyl esters under study (L-Leu, L-Cys, L-

PheOMe, L-TyrOMe, L-ValOMe, L-LeuOMe, L-SerOMe, and L-CysOMe) aiming at their

separation. The experimental results showed that the extraction and the transport through

liquid membrane of amino acids are strongly influenced by the nature of the anion used as

counter ion, the structure of the amino acid, and the structure of the receptor. Thus, the

hydrophobicity of the amino acid is an important parameter in extraction and transport

experiments. Further studies in the field are in progress concerning the finding of optimal

conditions of these separation processes.

ge 7 of 15





F o r P

e e r R e v

i e w O n l y

7

Acknowledgements

Elena Iulia Cucolea is grateful for financial support to strategic grant POSDRU

159/1.5/S/133652, Project “Support for Doctoral students and Postdoctoral researchers”

cofinanced by the European Social Found within the Sectorial Operational Program HumanResources Development 2007 – 2013.

References

(1) Lagona, J.; Mukhopadhyay, P.; Chakrabarti, S.; Isaacs, L. Angew. Chem. Int. Ed. 2005,

44, 4844-4870.

(2) Assaf, K.I.; Nau, W.M. Chem.Soc.Rev. 2015, 44, 394-418.

(3) Florea, M.; Nau, W. M. Angew. Chem. Int. Ed. 2011, 50, 9338-9342.

(4) Cao, L.; Isaacs, L. Supramol. Chem. 2014, 26 , 251-258.

(5) Buschmann, H.-J.; Cleve, E.; Mutihac, L.; Schollmeyer, E. Microchem. J . 2000, 64,

99-103.

(6) Buschmann, H.-J.; Mutihac, L.; Mutihac, R.-C.; Schollmeyer, E. Thermochim. Acta

2005, 430, 79-82.

(7) Masson, E.; Ling, X. X.; Joseph, R.; Kyeremeh-Mensah, L.; Lu, X. Y. RSC Adv. 2012,

2, 1213-1247.

(8) Buschmann, H.-J.; Schollmeyer, E.; Mutihac, L. Thermochim. Acta. 2003, 399, 203-

208.

(9) Lehn, J.-M. Supramolecular Chemistry: Concepts and Perspective; Wiley-VCH:

Weinheim, 1995.

(10) Mutihac, R.-C.; Riegler, H. Langmuir 2010, 26 , 6394-6399.

(11) Harrowfield, J. Chem. Comm. 2013, 49, 1578-1580.

(12) Buschmann, H.-J.; Mutihac, R.-C.; Schollmeyer, E. J. Solution Chem. 2010, 39, 291-

299.(13) Popeney, C.S.; Setaro, A.; Mutihac, R.-C.; Blummel, P.; Trappman, B.; Vonnem, J.;

Reich, S.; Haag, R. ChemPhysChem 2012, 13, 203-211.

(14) Buschmann, H.-J.; Mutihac, L.; Mutihac, R. Sep. Sci. Technol . 1999, 34, 331-341.

(15) Mutihac, L.; Mutihac, R.; Buschmann, H.-J. J. Incl. Phenom. Macrocycl. Chem. 1995,

23, 167-174.

Page 8





F o r P

e e r R e v

i e w O n l y

8

(16) Kim, H. J.; Lee, M. H.; Mutihac, L.; Vicens, J.; Kim, J. S. Chem. Soc. Rev. 2012, 41,

1173-1190.

(17) Buschmann, H.-J.; Mutihac, L.; Schollmeyer, E. J. Incl. Phenom. Macrocycl. Chem.

2005, 3, 85-88.

(18) Behrend, R.; Meyer, E.; Rusche, F. Liebigs Ann. Chem. 1905, 339, 1-37.

(19) Kim, K.; Selvapalam, N.; Ko, Y.H.; Park, K.M.; Kim, D.; Kim, J. Chem. Soc.Rev.

2007, 36 , 267–279.

(20) Li, C.; Rowland, M.J.; Shao, Y.; Cao, C.; Chen, C.; Jia, H.; Zhou, X.; Yang, Z.;

Scherman, O.A.; Liu, D. Adv. Mater . 2015, 27 , 3298-3304.

(21) Logsdon, L. A.; Urbach, A.R. J. Am. Chem. Soc. 2013, 135, 11414-11416.

(22) Rekharsky, M.V.; Yamamura, H.; Inoue, C.; Kawai, M.; Osaka, I.; Arakawa, R.;

Shiba, K.; Sata, A.; Ko, Y.H.; Selvapalam, N.; Kim, K.; Inoue, Y. J. Am. Chem. Soc.

2006, 128, 14871-14880.

(23) Joseph, R.; Masson, E. Supramol Chem. 2014, 26 , 632-641.

(24) Miyahara, Y.; Goto, K.; Oka, M.; Inazu, T. Angew. Chem. Int. Ed., 2004, 43, 5019–5022.

(25) Buschmann, H.-J.; Cleve, E.; Schollmeyer, E. Inorg. Chem. Commun. 2005, 8, 125-

127.

(26) Buschmann, H.-J.; Zielesny, A.; Schollmeyer, E. J. Incl. Phenom. Macrocycl. Chem.

2006, 54, 181-185.

(27) Svec, J.; Necas, M.; Sindelar, V. Angew. Chem., Int. Ed . 2010, 49, 2378–2381.

(28) Sundararajan, M.; Solomon, R.V.; Ghosh, S.K.; Venuvanalingam, P. RSC Advances,

2011, 1, 1333-1341.

(29) Xiang, D.-D.; Geng, Q.-X.; Cong, H.; Tao, Z.; Yamato, T. Supramol. Chem. 2015, 27 ,

37-43.

(30) Cucolea, E.I.; Tablet, C.; Buschmann, H.-J.; Mutihac, L. J. Incl. Phenom. Macrocycl.

Chem. 2015, DOI 10.1007/s10847-015-0544-5.

(31) Tayar, N. El; Tsai, R. S.; Carrupt, P. A.; Testa, B. J. Chem. Soc., Perkin Trans. 1992, 2,

79-84.

(32) Marcus, Y. Ion Solvation; Wiley: Chichester, 1985.

(33) Pedersen, C. J. J. Fed. Proc. Fed. Am. Soc. Exp. Biol . 1968, 27 , 1305-1309.

ge 9 of 15





F o r P

e e r R e v

i e w O n l y

9

Caption of Figures

Figure 1 Extraction (%) of amino acids from aqueous phase (pH = 5.5) into chloroform

phase by receptors hemiCB[6] and hemiCB[12].

Figure 2 Transport and extraction yields (%) of amino acids methyl esters through

liquid membrane by hemiCB[6] as carrier and extractant.

Figure 3 Schematic representation of the device employed in the transport experiments

of amino acids.

Chart 1 Chemical structure of amino acids, macrocyclic receptors, and counter ions

used throughout the experiments.

Page 10





F o r P

e e r R e v

i e w O n l y

10

Table 1. Transport data of amino acid methyl esters through liquid membrane by

hemiCB[6] (1.0 x 10-4

M) as carrier in the presence of tropaeolin 00

J 24 = flux of transported amino acid methyl esters after 24 h (mol m-2

s-1

)

Amino acid Concentration of

mino acid in

source phase

x 10-4

Concentration of

amino acid in

receiving phase

M x 10-4

η (%) J 24 x 108

(mol m-2

s-1

)

L-LeuOMe 5.0 1.23 25 7.50

L-PheOMe 5.0 0.98 20 5.95

L-CysOMe 5.0 0.62 12 3.76

L-ValOMe 5.0 0.47 9 2.87

L-SerOMe 5.0 0.27 5 1.66

L-TyrOMe 5.0 0.03 1 0.18

ge 11 of 15





F o r P

e e r R e v

i e w O n l y

Extraction (%) of amino acids from aqueous phase (pH = 5.5) into chloroform phase by receptorshemiCB[6] and hemiCB[12].

165x59mm (300 x 300 DPI)

Page 12





F o r P

e e r R e v

i e w O n l y

Transport and extraction yields (%) of amino acids methyl esters through liquid membrane by hemiCB[6] ascarrier and extractant.

106x56mm (300 x 300 DPI)

ge 13 of 15





F o r P

e e r R e v

i e w O n l y

Schematic representation of the device employed in the transport experiments of amino acids.

74x76mm (300 x 300 DPI)

Page 14





F o r P

e e r R e v

i e w O n l y

Chemical structure of amino acids, macrocyclic receptors, and counter ions used throughout theexperiments.

152x91mm (300 x 300 DPI)

ge 15 of 15

URL: http:/mc manuscriptcentral com/tandf/gsch Email: gsch peerreview@tandf co uk


hemicb articol.pdf

Documents