Polymer International 42 (1997) 22È24

Synthesis and Evaluation ofb-Cyclodextrin–2-Hydroxyethyl

Methacrylate Copolymer as a NovelAdsorbent

K. Sreenivasan

Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Poojapura,Trivandrum 695 012, India

(Received 13 March 1996 ; revised version received 9 July 1996 ; accepted 13 July 1996)

Abstract : 2-Hydroxyethyl methacrylate (0É01 mol) was allowed to react with0É01 mol of hexamethylene di-isocyanate and the product was coupled to0É01 mol of b-cyclodextrin to form a new cyclodextrin-based copolymer. Theinteraction of the polymer with di†erent steroids was investigated and the extentof adsorption was in the order cholesterol [ progesterone [ testosterone. Theresults indicate that the new polymer matrix could be used for the removal ofsteroids, particularly cholesterol, from a given medium. The polymer could alsobe used for sample puriÐcation, such as the removal of progesterone from amixture prior to its analysis by other analytical techniques. The preliminaryresults show that the polymer may have interesting clinical and analytical appli-cations.

Key words : b-cyclodextrin, 2-hydroxyethyl methacrylate, hexamethylene di-isocyanate, steroid adsorption.

INTRODUCTION

Polymeric systems capable of recognising speciÐc com-ponents can be used as selective sorbents having appli-cation in puriÐcation and separation. Polymericmatrices in affinity chromatography are well knownexamples.

Cyclodextrins (CDs) are well known for their abilityto form inclusion complexes with a variety of com-pounds.1h3 CDs can be incorporated in ordinary poly-mers with the aim of developing membranes with acertain degree of selectivity.4h8

Coupling of CDs to common polymers can beachieved by introducing polymerisable groups to CDs.Recently, we have modiÐed b-cyclodextrin (BCD) bybridging 2-hydroxyethyl methacrylate (HEMA) to oneof the hydroxyl groups of BCD using diisocyanate.9The presence of the double bond in the modiÐed BCDenables its grafting to common polymers such as poly-

urethanes and polyvinyl chloride. Additionally, themodiÐed BCD can be polymerised by free radical initi-ation and the resulting polymer can be used as anadsorbent, which may have a certain degree of selec-tivity owing to the presence of BCD. This communica-tion addresses the preparation of poly(HEMAÈBCD)and its preliminary evaluation as an adsorbent bystudying its interaction with some steroids.

EXPERIMENTAL

2-Hydroxyethyl methacrylate (HEMA) and b-cyclodextrin (BCD) were obtained from Sigma Chemi-cals (St. Louis, USA). Hexamethylene di-isocyanate,ethylene glycol dimethacrylate (EDA) and azobisiso-butyronitrile (AIBN) were procured from Fluka,Germany. Cholesterol, testosterone and progesteronewere from Sigma Chemicals (St. Louis, USA). All otherchemicals, such as methanol and dimethylacetamide

22Polymer International 0959-8103/97/$09.00 1997 SCI. Printed in Great Britain(

Synthesis of a novel adsorbent 23

(chromatographic grade), were obtained from Sisco(Bombay, India).

A model 597 Perkin-Elmer infrared spectrophotom-eter was used for recording the infrared spectra. AWaters Associates Inc. HPLC system, consisting of amodel 6000A solvent delivery pump, model U6K injec-tor and model 486 tunable absorbance detector, wasused for the chromatographic studies. A k-Bondapak

column in conjunction with methanol orC18methanol : water (70 : 30 v/v) as mobile phase at a Ñowrate of 1 ml min~1 was employed for the chromato-graphic estimation. The column effluents were moni-tored at 206 nm (for cholesterol) and at 241 nm (fortestosterone and progesterone) and the chromatogramswere obtained on an Ominiscribe strip chart recorder(Texas Instruments, Houston, USA).

Synthesis of the polymer

The coupling of BCD to HEMA was carried out byreacting hexamethylene di-isocyanate with the wOHgroup of HEMA and one of the wOH groups of BCDas detailed elsewhere.9 BrieÑy, 0É01 mol of hexa-methylene di-isocyanate was allowed to react with0É01 mol of HEMA at elevated temperature (45¡C) for30 min in the presence of catalyst (dibutyltin dilaurate)in dimethylacetamide. Dried BCD (0É01 mol) was dis-solved in dimethylacetamide and added to the solution.The temperature was raised further to about 55¡C andthe matrix stirred magnetically for about 2 h.

To this solution (10 g), was added 14 mg AIBN and0É001 mol EDA. The mixture was stirred and heated to70¡C. The polymer, in the form of white Ñakes, waswashed several times with methanol and vacuum dried.The dried polymer was powdered.

Methanolic solutions of cholesterol, testosterone andprogesterone were prepared by dissolving separatelyabout 12 mg of the components in 10 ml of methanol.To these solutions, 50 mg of the polymer was added andkept for 150 min under static conditions. The solutionswere subjected to chromatographic analysis before andafter addition of the polymer. The di†erence in peakheights at the respective wavelengths (206 nm for choles-terol and 241 nm for testosterone and progesterone)were used for estimating the extent of uptake of thecomponents by the polymer.

RESULTS AND DISCUSSION

Table 1 summarises the salient features of the infraredspectrum of the polymer obtained by polymerising theHEMAÈBCD adduct. Peaks centred around 3500 and1040~1 cm~1 are associated with the BCD moiety. Thepresence of HEMA is evident by the prominent CO

TABLE 1. Salient features of the infrared spectrum

of the polymer

Peak position (cmÉ1) Assignment

3 500 wOH stretching of BCD

3 320 wNH stretching

1 680 wCOw stretching of HEMA

1 040 Acetal linkage of BCD

adsorption at 1680~1 cm~1. The infrared spectroscopicresults indicate the formation of the copolymer.

The polymer was found to be insoluble in commonorganic solvents, including dimethylacetamide. It wasstable in acidic and alkaline phases. This stability indi-cates the possibility of using the new polymeric matrixas an adsorbent in a variety of media.

The presence of BCD moeities in the polymer matrixmay be useful in the selective removal of certain entitiesfrom a given medium. We have investigated the inter-action of the polymer with di†erent steroids. Table 2summarises the extent of uptake of the steroids by thepolymer. The extent of adsorption of cholesterol isgreatest, while that of testosterone is least.

Extensive e†orts have been made to understand thefactors governing the complexation of guest moleculeswith BCD.10,11 The hydrophobicity of the guest mol-ecule has been assigned the primary role in deciding thehostÈguest complexation with BCD.

The hydrophobicity of cholesterol is greater than thatof progesterone, which is greater than that of testoster-one. It is reasonable to assume that the ability of choles-terol to form a complex with BCD would therefore behigher. It is interesting to note that the adsorption ofprogesterone is greater than that of testosterone,although both these components have nearly similarstructures. It is felt that the hydrophobic factor is againplaying the major role leading to this increased adsorp-tion.

A typical chromatographic trace of a mixture of pro-gesterone and testosterone using a mixture of water andmethanol (30 : 70 v/v) as mobile phase is shown in Fig.1. Under these chromatographic conditions, testoster-one eluted at 3É1 min, while the retention time of pro-gesterone was 4É3 min. It is well known that in reverse

TABLE 2. Extent of uptake of steroids by the

polymer

Component Percentage adsorption

(amount adsorbed

by 100 mg polymer)

Cholesterol 14·5 À0·08

Progesterone 5·12 À0·06

Testosterone 3·74 À0·1

POLYMER INTERNATIONAL VOL. 42, NO. 1, 1997

24 K. Sreenivasan

Fig. 1. Chromatographic trace of a mixture of testosteroneand progesterone.

phase chromatography, more polar components eluteÐrst. The chromatogram apparently indicates that tes-tosterone is more polar than progesterone. That is, thehydrophobicity of progesterone is higher than that oftestosterone. The variation in the extent of adsorptionof these two compounds, can, therefore, be assigned tothe hydrophobicity factor.

The results summarised in Table 2 show that 100 mgof polymer can adsorb 14É5 mg of cholesterol. Theadsorbed cholesterol can be completely removed fromthe polymer by simply keeping it in organic solvents,such as chloroform, for nearly 30 min. The cholesterol-free polymer matrix can be used to further adsorb cho-lesterol. The possibility of reusing the polymer againand again may be useful for the removal of a consider-able amount of cholesterol from a medium of interest.The polymer matrix can also be used for sample puriÐ-cation, such as the removal of a component (e.g.

progesterone) from a mixture prior to its analysis. Thepreliminary results shown here indicate that thepolymer matrix may have interesting clinical and ana-lytical applications.

CONCLUSIONS

The data clearly show that the new polymer is capableof adsorbing steroids with a certain degree of selectivity,which is primarily determined by the hydrophobicnature of the guest molecules.

The selectivity of BCD towards a speciÐc compoundcan be enhanced by replacing one or two wOH groupsof BCD by other entities such as the methyl group.E†orts in these directions are underway.

The polymer may be investigated for its interactionwith industrially relevant components and its use as asorbent for the selective removal of industrial pol-lutants.

REFERENCES

1 Bender, M. L. & Komiyama, M., Cyclodextrin Chemistry.Springer-Verlag, New York, 1978.

2 Atwood, J. L., Davies, J. E. D. & NacNicole, D., Inclusion Com-pounds. Academic Press, London, Vol. 3, 1984.

3 Szejtli, J., Cyclodextrin and their Inclusion Complexes. Akademia“KiadoÏ, Budapest, 1982.

4 Lee, G. H., J. Appl. Polym. Sci., 26 (1987) 489.5 Yamasaki, A. & Mizoguchi, K., J. Appl. Polym. Sci., 51 (1994)

2057.6 Sreenivasan, K., Polym. Int., 34 (1994) 221.7 Sreenivasan, K., New Polym. Mater., 5 (1996) 73.8 Sreenivasan, K., Ange. Makromol. Chem., 235 (1996) 15.9 Sreenivasan, K., J. Appl. Polym. Sci., 60 (1996) 2245.

10 Szejtli, J., Cyclodextrin T echnology. Kluwer Academic Publishers,Boston, 1988.

11 Song, L. & Purdy, W. C., Chem. Rev., 92 (1992) 1457.

POLYMER INTERNATIONAL VOL. 42, NO. 1, 1997