Synthesis and properties of hydrophilicpolymers. Part 7. Preparation, characterizationand metal complexation of carboxy-functionalpolyesters based on poly(ethylene glycol)M Tulu1 and KE Geckeler1,2*1Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Tubingen, Auf der Morgenstelle 18, D-72076 Tubingen,Germany2Laboratory of Applied Macromolecular Chemistry, Department of Materials Science and Engineering, Kwangju Institute of Science andTechnology, 1 Olyong-dong, Puk-gu, Kwangju 500-712, South Korea

Abstract: Novel water-soluble polyesters with pendant carboxylic groups were synthesized by

polycondensation of ethylenediaminetetra-acetic acid (EDTA) dianhydride and diethylenetriamine-

penta-acetic acid (DTPA) dianhydride with poly(ethylene glycol)s of different chain-lengths. Two

experimental approaches (polycondensation using various solvents and in the melt) were studied, and

melt condensation was found to give higher yields of polyesters. The polymeric products were soluble

in water, acetone, chloroform and toluene, and were characterized by elemental analysis, IR and NMR

spectroscopy. In addition, the carboxyl functionalities were determined by titration and the hydrolytic

stability studied as a function of pH. The complexing capacity of the functional polyesters was

determined in dependence of pH for copper in aqueous solution using the Liquid-Phase Polymer-

Based Retention (LPR) technique and found to be 257mggÿ1 for the EDTA-based copolymer at pH5

and 230mggÿ1 for the DTPA-based copolymer, respectively.

# 1999 Society of Chemical Industry

Keywords: aqueous solution; diethylenetriaminepenta-acetic acid; ethylenediaminetetra-acetic acid; metalcomplexation; polyester; poly(ethylene glycol)

INTRODUCTIONTelechelic polymers have found considerable interest

as versatile intermediates in many ®elds.1 Among

those, poly(oxyethylene)-based telechelic compounds

are dominant for many applications because of their

salient properties, especially their strong solubilizing

power in many solvents.2±5 They have been used for

peptide synthesis,4,6 enzyme modi®cation,7 chelating

molecules and for the development of drug

derivatives.8±10 Recently, they have also been em-

ployed as building blocks for dendrimers.11 Many of

these applications require certain end-groups, and

telechelic modi®cation is therefore an important

prerequisite for the practical use of such basic

telechelics as poly(ethylene glycol). Consequently, a

number of functionalization reactions have been

proposed and investigated,3,10,12±16 because poly-

(ethylene glycol)s with varying molecular masses ®nd

numerous applications in the pharmaceutical, cos-

metic and rubber industries.

During recent decades, ultra®ltration has been

shown to be a promising way for removing trace

metals from industrial ef¯uents, provided that metal

ions were primarily bound to water-soluble poly-

mers.17,18 This technology uses water-soluble poly-

mers designed to bind selectively with metals to

recover valuable metals from process or waste waters.

The system can tackle many elements (such as copper,

silver, nickel and other valuable metals) in industrial

wastes, and consists of water-soluble polymers and a

compact, pumping and ultra®ltration apparatus that

mixes the polymers with liquid wastes. The polymers

bind with metal ions in the liquid waste stream which

then is pumped through an ultra®ltration system. The

metal-bound polymers are too large to pass through

the ®lter. Water and smaller, unbound components of

the solution pass through the membrane. The poly-

mers can be reused by changing the solution condi-

tions to release the metal ions. The metals then are

recovered in concentrated form for recycling or

disposal.

To combine the outstanding properties of poly-

(oxyethylene) telechelics with those of polymeric

complexing agents suitable for this technological

application, it seems to be advantageous to employ

the polycondensation of poly(ethylene glycol) (PEG)

Polymer International Polym Int 48:909±914 (1999)

* Correspondence to: KE Geckeler, Laboratory of Applied Macromolecular Chemistry, Department of Materials Science and Engineering,Kwangju Institute of Science and Technology, 1 Olyong-dong, Puk-gu, Kwangju 500-712, South Korea(Received 21 December 1998; revised version received 29 March 1999; accepted 20 May 1999)

# 1999 Society of Chemical Industry. Polym Int 0959±8103/99/$17.50 909

with appropriate chelating building blocks. Because a

number of organic ligands containing amino-acetic

acid groups (ÐNHCH2COOH) or iminodiacetic acid

groups [ÐN(CH2COOH)2] are known to form stable

complexes with a variety of metal ions,19 oligofunc-

tional carboxylic acids (such as ethylenediaminetetra-

acetic acid and diethylenetriaminepenta-acetic acid)

represent promising candidates for the preparation of

environmentally-degradable polycondensates.

In this study we report the one-step preparation,

characterization and metal complexing properties of

polymer derivatives of PEG with ethylenediamine-

tetra-acetic acid and diethylenetriaminepenta-acetic

acid for potential environmentally-relevant applica-

tions.

EXPERIMENTALMaterials and instrumentsEthylenediaminetetra-acetic acid (EDTA), diethyle-

netriaminepenta-acetic acid (DTPA) and poly(ethy-

lene glycol) (PEG) were obtained from Fluka

(Deisenhofen, Germany) and silica gel plates (F254

TLC) from Merck (Darmstadt, Germany). PEG was

puri®ed by repeated precipitation from dichloro-

methane solution into diethylether before use.

Infrared (IR) spectra were recorded on a Perkin-

Elmer spectrophotometer model 281 B (KBr pellets)

(Perkin-Elmer, UÈ berlingen, Germany). 1HNMR

(250MHz) and 13CNMR (62.9MHz) spectra were

recorded on a Bruker AC 250 spectrometer (Bruker,

Karlsruhe, Germany).

Preparation of EDTA dianhydride 20

10.0g of EDTA (34mmol) was suspended in 16ml of

pyridine; then 14.0g of acetic anhydride (0.14mmol)

was added and the mixture was stirred at 65°C for

24h. The product was ®ltered, washed with acetic

anhydride and diethylether, and dried in vacuo for

24h. The compound was characterized by thin layer

chromatography, elemental analysis and IR spectro-

scopy. Yield 90%, mp 193°C (Lit.20 192°C).

C10H12N2O6 (calc C 46.74, H 4.70, N 10.85; found:

C 46.88, H 4.72, N 10.93). IR (cmÿ1) 1810, 1760,

1130.

Preparation of DTPA dianhydride10.0g of DTPA (25mmol) was suspended in 20ml of

pyridine; then 18g of acetic anhydride (0.18mol) was

added, and the mixture was stirred at 65°C for 24h.

The product was ®ltered, washed with acetic anhy-

dride and diethylether, and dried in vacuo for 24h. The

compound was characterized by thin layer chroma-

tography, elemental analysis, and IR spectroscopy.

Yield 80%; mp 182±183°C. C14H19N3O8 (calc C

46.94, H 5.24, N 11.75; found: C 47.06, H 5.36, N

11.76). IR (cmÿ1) 2940, 1820, 1770, 1630.

Preparation of polyestersSynthesis of poly[ethylenediaminetetra-acetic acid±poly(ethy-

lene glycol) ester] in solution

1.5g of PEG1500 (1mmol) was dissolved in 10ml of

freshly dried toluene, and a suspension of 0.256g of

EDTA dianhydride (EDTA-DA, 1mmol) in 10ml of

freshly dried toluene was added. To this suspension,

the PEG1500 solution was added dropwise and the

mixture was heated to 130°C under re¯ux for 6h.

After a slight change of the colour, the mixture was

cooled and the remaining toluene was evaporated by

reduced pressure. The product was ®rst dissolved in

20ml of toluene, then ®ltered and precipitated into

Table 1. Molar masses and solvents used for polycon-densation of PEG with EDTA and DTPA

n M (g molÿ1) Solvent

7 400 ±

7 400 Toluene

22 1000 Toluene

33 1500 Toluene

33 1500 Chloroform

33 1500 Dichloromethane

33 1500 Dimethylformamide

33 1500 Acetonitrile

33 1500 In the bulk

44 2000 Toluene

Table 2. Functionality fx (COOH) andnumber of fy of the EDTA/DTPAfunctions of the polyesters at pH 5(determined by titration)

Dianhydride Telechelic Reaction medium

Temperature

(°C)

fx(mmol gÿ1)

fy(mmol gÿ1)

EDTA PEG400 Bulk reaction 20 2.84 1.42

EDTA PEG400 Bulk reaction 60 3.00 1.50

EDTA PEG1000 Bulk reaction 60 1.40 0.70

EDTA PEG1500 Bulk reaction 60 0.98 0.49

EDTA PEG1500 Toluene 111 0.90 0.45

EDTA PEG1500 DMF 153 0.82 0.41

EDTA PEG1500 Chloroform 61 0.98 0.49

EDTA PEG1500 Dichloromethane 40 0.98 0.49

DTPA PEG400 Bulk reaction 20 2.56 0.85

DTPA PEG400 Bulk reaction 60 2.70 0.90

DTPA PEG1000 Bulk reaction 60 0.56 0.18

DTPA PEG1500 Bulk reaction 60 0.55 0.18

910 Polym Int 48:909±914 (1999)

M TuÈluÈ, KE Geckeler

diethylether using a 10-fold excess. After the pre-

cipitation, the polymer was ®ltered and dried under

vacuum. Yield 100%. The product was then dissolved

in 20ml of water, ultra®ltered using a membrane ®lter

with a nominal molar mass exclusion limit of

10000gmolÿ1. For the membrane ®ltration process,

as described previously,17 at least 200ml (10-fold

excess) of water was used to wash the cell solutions

(pressure 300kPa). The retained substance was

lyophilized and a retention value of more than 83%

(molar mass>10000gmolÿ1) was obtained. mp 45±

50°C. Solubility: water, acetone, chloroform, toluene.

C28H50N2O17 (calc C48.98, H7.29, N4.08; found

C45.83, H8.05, N4.59).

IR (cmÿ1) 3540, 2880, 1735, 1635, 1100.

The synthesis described was repeated several times

using other solvents such as chloroform, dichloro-

methane, acetonitrile and dimethylformamide (Table

1). All the reactions were carried out in the hetero-

genous phase, except for dimethylformamide where

the reaction was performed homogeneously because

EDTA-DA/DTPA-DA and PEG are soluble in DMF.

Poly[ethylenediaminetetra-acetic acid±poly(oxyethylene)

ester] in the melt

1.5g of poly(ethylene glycol) (PEG1500; 1mmol) was

puri®ed by dissolution in 10ml of dried toluene and

precipitating the solution with 100ml of dried diethy-

lether; after precipitation the solution was ®ltered and

dried in vacuo. The puri®ed PEG1500 was melted in an

oil bath at 50°C and to the molten glycol 0.256g of

well-powdered, dry ethylenediaminetetra-acetic acid

dianhydride (EDTA-DA, 1mmol; 10% excess) was

slowly added, after which the mixture was stirred at

50°C for 4h. The product was cooled, dissolved in

20ml of water and then ®ltered. Yield 100%. The

®ltrate was transferred to a membrane ®ltration system

where it was puri®ed.

The same approach was used for diethylenetriami-

nepenta-acetic acid dianyhdride (DTPA-DA) with

PEG of different chain lengths. For the DTPA-PEG,

retention values greater than 82% (molar mass

>10000gmolÿ1) were obtained.

C32H56N3O19 (calc C48.85, H7.12, N5.34 found

C43.20, H7.80, N4.48).

IR (cmÿ1) 3460, 2800, 1740, 1630, 1100.

Table 3. Degree of hydrolysis of EDTA-PEG400 andDTPA-PEG400 at different pH and at room tempera-ture

Degree of hydrolysisa (%)

pH EDTA-PEG400 DTPA-PEG400

1 41.5 38

3 9.5 10

5 7 6

a After 10h, referred to a molecular mass of

10000gmolÿ1 (nominal molar mass exclusion limit

of membrane).

Scheme 1

Scheme 2

Table 4. Characterization of the EDTA-PEG and DTPA-PEG polyesters by1H NMR and 13C NMR (in D2O and CDCl3, respectively)

M

Chemical shift (ppm)

Polyester (g molÿ1) 1H NMR 13C NMR

EDTA-PEG400 674 a: 3.80 a: 54.73

b: 3.30 b: 51.42

c: 4.35 c: 63.88, cOH: 61.24

d: 4.05 d: 68.54, dOH: 72.40

e: 3.60 e: 69.94

f: 169.64

g: 171.98

DTPA-PEG400 775 a: 3.80 a: 55.39

b: 3.40 b: 52.53

b': 3.30 b': 49.42

c: 4.35 c: 63.84, cOH: 61.72

d: 3.90 d: 68.93, dOH: 72.65

e: 3.70 e: 70.35

h: 3.70 f: 174.31

g: 173.75

h: 55.39

Polym Int 48:909±914 (1999) 911

Carboxy-functional PEs based on PEG

Asurveyof PEG chain lengths and solvents employed

for the polycondensation is presented in Table 1.

TitrationThe content of free carboxylic acid in the polycon-

densates was determined by titration using 0.01N

NaOH (see Table 2).

Metal capacity studiesThe pH of a solution of 500mg of Cu(NO3)2

.3H2O in

5ml of water was adjusted to the de®ned value by

adding a small volume of 0.1N KOH or 0.1N HCl.

Then a solution of 100mg polymer in 5ml of water

was added. The complexation was performed at a pH

range of 1±5. The volume of the solution was made up

to 20ml by adding distilled water at the de®ned pH.

The addition of Cu(II) to the EDTA-PEG solutions

led to a colour change from blue to green; however, no

precipitation was observed. Therefore the complexa-

Scheme 3

Scheme 4

Figure 1. 1H NMR spectrum of EDTA-PEG400.

Figure 2. 1H NMR spectrum of DTPA-PEG400.

Figure 3. 13C NMR spectrum of EDTA-PEG400.

912 Polym Int 48:909±914 (1999)

M TuÈluÈ, KE Geckeler

tion process was controlled using membrane ®ltration

by measuring the amount of Cu(II) ions in the ®ltrate

and those bound to the polymer.17

The hydrolysis of the polymer was determined at

different pH values by measuring the mass loss after

membrane ®ltration (10h) at room temperature

(Table 3).

RESULTS AND DISCUSSIONSynthesisPolyesters were prepared from poly(ethylene glycol)

(PEG) and activated oligocarboxy-functional acids

such as ethylenediaminetetra-acetic acid (EDTA) and

diethylenetriaminepenta-acetic acid (DTPA) in a one-

step polycondensation. Both the tetracarboxylic and

the pentacarboxylic acid represent well-known ligands

for a variety of metal ions, and their incorporation into

a polymer chain with a high solubilizing power such as

a polyether should yield effective polymeric complex-

ants. To this end, the dianhydrides of EDTA (Scheme

1) and DTPA anhydride (Scheme 2) were synthesized

according to the method of Eckelman20 at 65°C with

80±90% yield and characterized by various techniques

(Tables 1±4).

The polycondensations of the two carboxylic acids

with PEG were investigated by applying both methods

in solution and in the melt. The solution condensa-

tions were performed using a variety of solvents such

as toluene, chloroform and dimethylformamide

(Table 1). The reaction in DMF which was carried

out in the homogenous phase, required high tempera-

tures because the educts were not soluble at lower

temperatures. However, with respect to the product

yield, elevated reaction temperatures seemed to be less

advantageous. This is in accordance with earlier work

reporting that an increase of the temperature involves a

reactivity decrease of alcohol and amine functions

towards anhydride functions which favours the con-

current hydrolysis of these groups.6 However, the best

results were obtained from the polycondensation in

the melt, giving yields of about 100%. Thus the

polycondensation in the melt is more ef®cient and also

rapid.

During polycondensation, the average molecular

mass of polymer increased from 400, 1000 or 1500 to

over 10000gmolÿ1 as demonstrated by retention

experiments using membrane ®ltration (exclusion

limit 10000gmolÿ1), with retention values of more

than 83% and 82%, respectively. The EDTA and

DTPA groups in the polycondensates were deter-

mined by titration using 0.01N NaOH (see Table 2).

Because of the relatively high molecular masses of the

building blocks PEG1000 and PEG1500, the mass

content of EDTA and DTPA is relatively low (eg

Figure 4. 13C NMR spectrum of DTPA-PEG400.

Figure 5. Metal binding capacity of EDTA-PEG400 for copper(II) as afunction of pH.

Figure 6. Metal binding capacity of DTPA-PEG400 for copper(II) as afunction of pH.

Polym Int 48:909±914 (1999) 913

Carboxy-functional PEs based on PEG

1500:256gmolÿ1 for a 1:1 mole fraction). In contrast,

for the polymer using PEG400 as the hydroxy building

block, this ratio is 400:256gmolÿ1. To assess the

purity of the polycondensates, thin-layer chromatogra-

phy was used. The polyelectrolytes were soluble in

water, acetone, chloroform and toluene.

Spectroscopic characterizationIn comparison to those of EDTA-DA and DTPA-DA,

the IR spectra of EDTA-PEG400 and DTPA-PEG400

show a wavenumber shift of 25±30cmÿ1. In addition,

the formation of new bands at 1630cmÿ1 and

1635cmÿ1, respectively, was observed, resulting from

the ring-opening reaction of the dianhydrides EDTA-

DA and DTPA-DA.

The NMR spectra of the polycondensates were

measured using two solvents (D2O and chloroform)

because it was not possible to measure the 1H NMR

values of the products in CDCl3. The 1H NMR and13C NMR spectra of the polymers are shown in Figs.

1±4 including the signal assignments in the corre-

sponding formulae.

Metal binding capacityThe results of the metal binding capacity studies of the

polyesters EDTA-PEG and DTPA-PEG as a function

of pH are presented in Fig 5 and Fig 6, respectively.

Both pH pro®les show a similar shape, and it is clear

that at lower pH the metal binding capacity is directed

toward zero. In contrast, at higher pH (5), maximum

values of 257mggÿ1 for EDTA-PEG and 230mggÿ1

for DTPA-PEG were attained. The difference be-

tween the two polyesters cannot currently be ex-

plained. However, further studies on the metal binding

ability of PEG polycondensates and other polyelec-

trolytes are underway.

CONCLUSIONSThe results show that soluble polycondensates of PEG

and EDTA and DTPA can be conveniently and

quickly prepared in a one-step reaction from PEG

and the corresponding dianhydrides by polycondensa-

tion in the melt or in solution. The linear polyesters

with pendant carboxyl groups are able to bind metal

ions, such as copper, in aqueous solutions, and this

property was found to be strongly pH dependent.

Additionally, a number of further applications of these

biodegradable polyesters, eg in the biomedical area,

can be envisaged.

REFERENCES1 Goethals E, Telechelic Polymers ± Synthesis and Applications, CRC

Press, Boca Raton, Florida (1989).

2 Geckeler KE, Pillai VNR and Mutter M, Adv Polym Sci 39:217

(1981).

3 Geckeler KE, Terminal transformation of telechelics, in Telechelic

Polymers ± Synthesis and Applications, Ed by Goethals E, CRC

Press, Boca Raton, Florida, p 229 (1989).

4 Geckeler KE, Adv Polym Sci 31:121 (1995).

5 Rivas BL and Geckeler KE, Bol Soc Chil Quim 39:107 (1994).

6 Montembault V, Soutif JC and Brosse JC, React Funct Polym

29:29 (1996).

7 Abuchowski A, Mccoy J, Palczuk N, van EsT and Davis F, J Biol

Chem 52:3582 (1977).

8 Geckeler K and Mutter MZ Naturforsch Teil B, 34:1024 (1979).

9 Zalipsky S, Gilon C and Zilkha A, Eur Polym J 19:1177 (1983).

10 Harris JM, J Macromol Sci Rev Macromol Chem Phys C25:325

(1985).

11 Wooley KL, Hawker CJ and Frechet JM, Angew Chem 106:123

(1994).

12 Geckeler K, Polym Bull (Berlin) 1:691 (1979).

13 Bayer E, Zheng H, Albert K and Geckeler K, Polym Bull (Berlin)

10:231 (1983).

14 De Vos R and Goethals EJ, Polym Bull (Berlin) 15:547 (1986).

15 Rivas BL and Geckeler K, Polym Bull (Berlin) 8:585 (1982).

16 Geckeler KE and Arsalani N, J Macromol Sci Pure Appl Chem

A33:1165 (1996).

17 Spivakov BYa, Geckeler KE and Bayer E, Nature 315:313

(1985).

18 Geckeler KE and Volchek K, Env Sci Technol 30:725 (1996).

19 Schwarzenbach G, Kampitsch E and Steiner R, Helv Chim Acta

28:1133 (1945).

20 Eckelman WC, J Pharm Sci 64:704 (1975).

914 Polym Int 48:909±914 (1999)

M TuÈluÈ, KE Geckeler