Solvent effects on the formation of cross-linking microspheres in γ-irridiated solutions

Radiat. Phys. Chem. Vol. 40, No. 2, pp. 83-88, 1992 Int. J. Radiat. Appl. Instrum., Part C

0146-5724/92 $5.00+0.00 Copyright © 1992Pergamon Press Lid

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SOLVENT EFFECTS ON THE FORMATION OF CROSS-LINKING MICROSPHERES IN 3,-IRRADIATED SOLUTIONS YUKIHIKO NAKAIt, YUKIO YAMAMOTO2 and KOICHIROHAYASH!2 IResearch Institute for Science and Technology, Kinki University, 3-4-1 Kowakae, Higashi-Osaka, Osaka 577, Japan and 2The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567, Japan (Received 1 November 1991; in revised form 16 January 1992)

Abstract--Solvent effects on the formation of cross-linking microspheres by the radiation-induced polymerization are described. Polymerization of some bi- and tri-vinyl monomers in several organic solvents was tested. Diethylene glycol dimethacrylate (2G) is the unique monomer that gives microspheres. The distance between two vinyl groups of monomer molecules is one of the important factors for the formation of microspheres. The comparison of the solvent properties for the preparation of microspheres suggests that the forms of the monomer molecules in the solutions are also important, that is, the stretched form is favorable. Alcohols, except t-butanol, are not favorable as the solvents for the preparation of microspheres because of not only solubility but also an occurrence of the chain transfer reaction. The chain transfer reactions to the solvents and additives interfere with the formation of microspheres.

phase separation, but the low affinity of the surface of the particles to the solvents causes the aggregation of the particles. The use of poly-functional monomers is also characteristic of the method. That is to say, the cross-linking promotes the formation of particles (Naka and Yamamoto, 1992a). We prepare microspheres with other 2G type di-vinyl monomers, such as diacrylates with different numbers of the ethylene oxide units, (--C2H40---),, in various solvents. The selection of solvent is important for the present method. We have previously reported that the solubility and the viscosity affect the formation of microspheres (Naka et al., 1991). The solubility parameter and the viscosity are convenient factors to select the solvents, although there are some exceptions. We have studied the relationship between monomer and solvent for the formation of microspheres in the radiation-induced polymerization.

INTRODUCTION

Radiation-induced polymerization of diethylene glycol dimethacrylate (2G) in the organic solvents gives polymer monodisperse microspheres (Yoshida et al., 1987). The irradiation with ~, rays contributes to the monodisperse microsphere formation (Naka et al., 1991). The ~,rays give the homogeneous initiation due to their strong transmission ability. The photoinitiation also gives microspheres, but the size distribution is wide because of the heterogeneous initiation in the course of the polymerization. Heating of the solutions gives homogeneous initiation, when the solutions are stirred. The stirring causes contact between growing particles and gives aggregated particles. It is a characteristic of the method that the simple mixtures of only monomer and solvents give monodisperse microspheres. Since the polymerization is carried out in an organic solvent, the method described in this paper may be regarded as a kind of dispersion polymerization. But the mechanism is considered to be completely different from the conventional dispersion polymerization (Barrett, 1975; Guo et al., 1989) because the preparation of the microspheres can be carded out in the absence of the stabilizer and the polymer microspheres are obtained in good solvents. Many kinds of solvents can be used for the preparation of microspheres. The good solvents seem to make growing microspheres stable in the solution and able to avoid the aggregation of the microspheres. The poor solvents seem to help the

EXPERIMENTAL

Reagents

Ethylene glycol dimethacrylate (IG), 2G, tfiethylene glycol dimethacrylate (3G), tetraethylene glycol dimethacrylate (4G) and trimethylolpropane trimethacrylate [TMPT, 2-ethyl-2-(hydroxymethyl)1,3-propanediol trimethacrylate], supplied by Shin Nakamura Kagaku, were purified by passing through active alumina. 2-Hydroxyethyl methacrylate (HEMA), purchased from Wako Pure Chemicals, was used after distillation. Reagent grade solvents and carbon tetrabromide, purchased from

tTo whom all correspondence should be addressed. apc 4oa-s

83

84

YUKIHIKO NAKA et al.

W a k o Pure Chemicals, were used without further purification. Polymerization Screening tests were carried out with 2 m l of 5 v o l % solutions deoxygenated by nitrogen bubbling. The samples were irradiated with 6°Co y rays at r o o m temperature (ca 25°C). The total dose was about 2 kGy. Solutions of 2G (10 vol%) in organic solvents were degassed and sealed in 20 ml glass vessels. The degassing was carried out by five-times freeze-melt repeating. The samples were irradiated with ~°Co rays at r o o m temperature. The dose rate and the irradiation time were 4 k G h - l and 2 h, respectively. Teflon filters of 0.2/~m pore size (Advantest) were used for the separation of the microspheres from the irradiated solutions. The soluble polymer was deposited by adding methanol to the residual solutions and then separated. The microspheres and the soluble polymer were washed with the solvents and dried under vacuum. Measurements The microspheres were photographed by using a scanning electron micrograph (SEM) (JELO, JST300). The sizes of the microspheres were measured from the SEM photographs by a digitizer ( N E C MG-10) connected to a personal computer. The diameters were calculated from three points on the outer circles of 20 microspheres. RESULTS

AND

DISCUSSION

Screening tests The radiation-induced polymerization of 2G m o n o m e r gives microspheres from various solvents. Since cross-linking is considered to cause the microsphere formation of 2G, we tested with other bi- and Table

1. Screening test

tri-methacrylates. The results of the screening tests for the combination of various monomers and solvents are presented in Table 1. The irradiation resulted in particles, aggregated particles, gel and polymer solutions. The monomers except 2G did not give fine particles. The polymer obtained from 3G seemed not to be fine particles but somewhat aggregated particles. The difference among IG, 2G, 3G and 4G is the number of ethylene oxide units (--C2 H4 O---) between two methacrylate groups. This result suggests that the distance or the three dimensional positions of two vinyl groups in the solutions is an important factor. Esters as solvents gave good results, but alcohols and hydrocarbons gave poor results in general. No monomers except 2G gave fine particles in various ester solvents examined. These suggest that the effect of the solvents is attributed to the interaction with methacrylate groups, not with ethylene oxide units. Microspheres obtained in ester solvents The results of the microsphere formation in various esters are shown in Table 2. The microspheres are obtained from esters listed above ethyl propionate. The esters in Table 2 can be classified into three groups according to their sizes, i.e. the small, middle and large sized esters. The small esters, such as formates, are good to obtain large microspheres, but some aggregated particles are observed in the SEM photograph (Fig. 1). There are some basins suggesting a contact with another particle. The soluble polymer is a by-product of polymerization (Naka and Y a m a m o t o , 1992a). The percentage of the soluble polymer in the total recovered polymer for the small esters are higher than for the other esters. The small esters also give a wide distribution in size of microspheres (standard deviation divided by the average size). The conditions for

for the combinations of monomers and solvents~ Monomers

2G 3G 4G TMPT IG Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Gel Particles Gel Agg. Gel Liq. Liq. + gel Liq. + gel Liq. Liq. Liq. Liq. Liq. + gel Liq. + gel Liq. Gel Gel Gel Gel Gel Gel Particles Liq. Liq. Gel Gel Particles Agg. Liq. Gel Gel Particles Agg. Agg. Gel Gel Particles Agg. Agg. Gel Gel Particles Agg. Liq. Gel Gel Particles Agg. Agg. Gel Gel Particles Liq. Liq. Gel Gel Particles Liq. Liq. Gel Gel Liq. Liq. Liq. Gel Gel Liq. Liq. Liq. Gel ' M o n o m e r concentration was 5 vol%. Solutions were deoxygenated by nitrogen bubbling. Total dose was 2 kGy.: Liq. and Agg. mean the polymer solution and aggregated particles, respectively.

Solvents Methanol Ethanol Propanol 2-Propanol t-Butyl alcohol Benzene Toluene Hexane Methyl formate Methyl acetate Ethyl acetate Propyl acetate Methyl propionate Methyl butylate Methyl succinate Ethyl succinate Methyl malonate Ethyl malonate

Formation of cross-linking microspheres in ~/-irradiated solutions

Number 273 284 285 286 297 289 288 291 290 292 293 296 68 295 67

Table 2. Solvent effecton the formation of the microspheres" Yield Loss Size Distributionb Solvents Result (%) (%) (#m) (%) Methylformate Ethyl f o r m a t e Propylformate Methylacetate Ethyl a c e t e t e Propylacetete Butyl a c e t e t e Methylpropionate Ethyl propionate Methylbutylate Ethyl caprylate Dimethylmalonate Diethylmalonate Diethylsuccinate Diethylphthalate

Ms + Agga Microspheres Aggregatedparticles Microspheres Microspberes Microspheres Microspheres Microspheres Microspberes Gel Gel Gel Gel Ms + Aggd Gel

68.3 77.3 84.9 75.8 84.9 90.7 90.1 86.1 88.2

14.9 6.8 6.7 4.1 2.0 0.8 1.0 2.4 0.2

4.59 1.98 2.89 i.85 1.28 1.11 0.76 1.48 1.11

9.6 10.3

92.6

6.5

0.48

10.2

4. I 4.0 5.3 6.2 2.9 3.8

85

6c 10.2 9.4 9.2 9.6 9.1 8.8 8.5 8.9 8.4 8.9 7.3 11.0 9.9 9.5c 10.0

280 Acetone Microspheres 73.3 10.8 2.38 30.6 10.0 294 Methylethyl ketone Microspheres 75.0 12.5 2.49 6.8 9.3 283 Diethylk e t o n e Microspheres 66.4 8.1 1.95 27.0 8.8 330 DMSO Gel 12.0 329 Acetonitrile Microspheres 81.8 NDf 1.96 5.6 12.1 246 Propanol Gel I 1.9 357 t-Butylalcohol Particles 92.3 2.3 0.51 12.0 10.6 251 Benzene Gel 9.2 aConcentration of 2G was 10 vol%. Dose rate and irradiation time were 4 kGy h ~ and 2 h, respectively. bCoelficientof size variation. Standard deviation divided by the size. CSolubilityparameter(cal t/2cm 3/2)from the reference(Brandrup and lmmergut, 1989;Riddicketal., 1986). dMicrosphereswith aggregated particles. ¢Calculated value. tThe soluble polymer was observed, but could not be recovered. the higher soluble polymer yields also give p o o r results in shape and monodispersity. The middle-sized esters, such as acetates and p r o p i o n a t e s gave the best results a m o n g the esters. The size o f the microspheres varies with the size o f the solvent molecules. The shape o f the microspheres is a complete sphere as shown in Fig. 2. The loss in the microsphere formation due to the soluble polymer formation is low and the size distributions are narrow. Propyl acetate, butyl acetate and ethyl p r o p i o n a t e especially gave good results, i.e. high yield and low loss. The size o f propyl acetate, butyl acetate and ethyl p r o p i o n a t e are almost similar to the half o f 2G. The form o f the m o n o m e r molecules in the solvents seems to be an i m p o r t a n t factor.

The large-sized esters resulted in gelation. Methyl butylate and ethyl caprylate gave microspheres for the 5 vol% solution (Naka et al., 1991), but not for the l0 vol% solution. Since ethyl acetate gives microspheres for wide range o f 2G concentration (2-24 vol%), the large esters are not favorable for the preparation o f microspheres. The characteristic o f the large-sized esters becomes close to that o f h y d r o c a r b o n s with an increase in their size. The g o o d solvents for 2G m o n o m e r are favorable to prepare microspheres. The solubility parameter, (Brandrup and Immergut, 1989; Riddick et al., 1986), is convenient to discuss the solubility. A l t h o u g h the use o f the solubility p a r a m e t e r o f the growing poly 2G particles is preferred, we used the solubility parameter o f 2G, which is calculated to be 8.9. The

Fig. I. SEM photograph of particles obtained in methyl formate,

Fig. 2. SEM photograph of microspheres obtained in propyl acetate.

86

YUKIHIKO NAKA el a/,

On the other hand, the two methacrylate groups of the 2G molecule may be close to each other in nonpolar hydrocarbon solvents. The 2G m o n o m e r is considered to take a bent form m hydrocarbons.

CH3 H2C~ d

H2C~c/CH3

O=C I O t H2

/C~ O O

/

I

C\c..O.. C/CH2 H2

Fig. 3. SEM photograph of microspheres obtained in acetonitrilc.

solvent of which the solubility parameter is close to 8.9 is considered to be a good solvent for the 2G monomer, and is favorable for the preparation of microspheres. Esters and ketones seem to satisfy this requirement. Since the monomer, 2G, is an ester, esters are good solvents for 2G and give good results for the microsphere preparations. There is no doubt that a good solvent is essential for preparing microspheres by this method. The solubility parameter is one of the indicators to know the solubility of the solute in the solvent. The problem of the solubility parameter is that it is an average of a whole molecule, but it does not express any local affinity of m o n o m e r molecules to solvent. Thus, it is not appropriate to apply it to other types of solvents. In spite of the solubility parameter not being close to 8.9, acetonitrile (~5 = 11.9) gave microspheres (Fig. 3). Benzene, toluene and hexane (~ = 0.91, 8.9 and 7.3, respectively) did not give particles. The solubility parameter is not an absolute factor. The difference in effect on the microsphere preparation between the hydrocarbons and the esters may be attributed to the polarity of the solvents. Both the hydrocarbons and the esters are good solvents for 2G, but the forms of 2G molecules in the solvents may be different. The structure of 2G can be divided into two parts, i.e. methacrylate and ethyleneoxide moieties. The two methacrylate groups of the 2G molecule may be solvated independently and separated from each other in the ester solvents. So the 2G m o n o m e r takes a stretched form in the esters.

H2

.,C.c_c° _

C H2

c,

o/C-,. C,, O, C IC'-- O_C/C --CHa ~l H2 H2 O Stretched form of 2G

H2

Bended form of 2G

In this lk~rm, the distance between two vinyl groups of the same molecule is short. The approaching of two vinyl groups of the same 2G molecule makes the two vinyl groups contained in the same preparation chain. Consequently, this causes the reduction in the cross-linking probability of 2G as no cross-linking microspheres were obtained in benzene. Even if the solubility of 2(3 is the same in esters and hydrocarbons, the forms of the m o n o m e r molecules in the solvents may be different. The solvent properties appropriate 1"o1 the microspherc preparation are not only good solubility of 2G but also making the 2G molecule expanded in the solution to take the stretched f o r m Propyl acetate, butyl acetate and ethyl propionate gave good results. This is probably related to the spread of 2G m o n o m e r in the solvents. In order to obtain the microspheres. the solvent must make the two vinyl groups of the 2G molecule separated.

Solvent qff~'ct 01 ethyl succinate amt ethyl malonate In spite of the resembling structures, ethyl succinate and ethyl malonate gave different results as shown in Tables 1 and 2, Ethyl succinate gave microsphercs but ethyl malonate did not. Both ethyl succinate and ethyl malonate have two ester groups. The solubilities of these solvents are almost the same (ethyl succinate 6 = 9.1; ethyl malonate 6 =9.0). The difference between those two solvents in their structures is the length between the ester groups. Since the size of ethyl malonate is smaller than that of ethyl succinate, ethyl malonate was expected to give microspheres. An occurrence of the hydrogen abstraction from the solvent may inhibit the formation of microspheres. The hydrogens of the methylene (--CH_,--) of the ethyl malonate are easily abstracted compared with those of the ethyl succinate. The active hydrogens of the methylene interposed by the two ester moieties of ethyl malonate cause the termination of the propagation of the polymer chain and interfere with the formation of microspheres.

Formation of cross-linking microspheres in 7-irradiated solutions

OC2H5

OC2 H5

I

CH 3 CO

I

I

---CH2---C" + HCH ~

I

I

I

CH 3

CO

I

I

--CH2---CH + "CH

I

CO

87

I

CO

CO

I

I

OC2 H5

I

CO

I

OC2 H5

On the other hand, the effect of ester moieties on the hydrogens of the methylene chain of ethyl succinate is considered to be weaker than that of ethyl malonate. Thus the hydrogen abstraction is less probable in ethyl succinate.

¢

OC2 H5

I

CH 3

CO

J

I

I

I

--CH2--C" + HCH

Fig. 4. SEM photograph of microspheres obtained in t-butyl alcohol. , No Reaction hydrogen abstraction of ct carbon interferes with the microsphere formation. The particles obtained are partially aggregated. The aggregation may occur after the irradiation.

CO HCH

I

I r

CO OC2 H5

The chain transfer reaction due to the hydrogen abstraction from the solvents causes the reduction of the chain length of the polymer. This is considered to be the reason for causing the gelation instead of the microsphere formation.

Solvent effect o f alcohols Although alcohols are used commonly in the preparation of microspheres by the dispersion polymerization, no particles were obtained by the method described in this paper as shown in Table 1. We have reported that alcoholic solvents are not favorable for the microsphere preparation by this method because of their solubilities and viscosities (Naka et al., 1991). Furthermore, it has been found that the chain transfer reaction caused by the hydrogen abstraction from alcohols interferes with the formation of microspheres. For example, ethanol has two ~ hydrogens. The hydrogens on the ~ carbon are easily abstracted by the radicals. The chain transfer reaction terminates the propagation reaction, and interferes with the formation of microspheres CH3

I

The reactivity of 2G is considered to be the same as MMA. Some monomers are expected to form copolymer microspheres with 2G (Naka and Yamamoto, 1992b). The copolymerization with hydroxy ethyl methacrylate (HEMA) provides the hydrophilicity to the microspheres. The copolymerizations of 2 G - H E M A do not give microspheres as shown in Table 3. All of the feed solutions containing HEMA result in gelation. That is, the presence of HEMA leads to the gelation. This is considered to be the same as the alcohols having ~ hydrogen. The hydrogens of the hydroxy ethyl group can be easily abstracted by the propagating radical similar to the case of alcohols. HEMA is not favorable as the comonomer for the preparation of microspheres.

Addition o f CBr 4 Carbon tetrabromide (CBr4) is known as a strong chain transfer reagent in radical polymerization (Pryor, 1966). It is expected that the addition of CBr 4 interferes with the microsphere formation by the chain transfer reaction. CH 3

--CH2--C" + CH3CH2OH --~

I

I

CH3

/

--CH2--C" + CBr4 --~ - - C H 2 - - ~ B r + "CBr 3

CO

I

Copolymerization o f 2G and HEMA

I

CH 3

I I

I

CO

CO

I

t

- - C H 2 - - C H + CH3(~HOH CO

I This effect, interference by the hydrogen abstraction, can be confirmed by using t-butyl alcohol (TBA) as a solvent having no ct hydrogen. Figure 4 shows the SEM photograph of the particles obtained from the TBA solution. The results indicate that the

Table 3. Copolymerizationof 2G and HEMA" Number Mole fraction of HEMA Result 219 0 Microspheres 220 0.1 Gel 221 0.2 Gel 224 0.5 Gel 233 1.0 Gel aConcentrationof monomermixture was 10vol%. Dose rate was 4 kGy h t and irradiationtimewas 2 h. Temperaturewas 23"C.

88

YUKIH1KO NAKA et al.

formation. The chain transfer reaction interferes with the f o r m a t i o n o f microspheres, i.e. the gelation occurs a n d the yield of the microspheres is decreased by the chain transfers to the solvents a n d the additive like CBr4.

lOO

~A

o-.... __~ ~ >-

Acknowledgements--The authors thank the Shin Nakamura Kagaku, Co. Ltd for supplying the monomers and the members of the Radiation Laboratory of ISIR of Osaka university for help with 7 ray irradiation.

Gel

O 40

20 REFERENCES

[] 0 .0001

i

.001

i

.01

.1

1

10

Concentration of CBr 4 / xlOa tool dm a Fig. 5. Addition effect of CBr 4 on the yield of microspheres. Concentrations of 2G were (©) 5 vol%, (V7) 10 vol% and (A) 15vo1%, respectively. Dose rate was 4kGy h ~ and irradiation time was 2 h. Its addition results in a decrease in the microsphere yield and in an occurrence of the gelation. The yield decreased with increasing CBr4 c o n c e n t r a t i o n as s h o w n in Fig. 5. G e l a t i o n is observed for the 15 vol% 2G solution by the e q u i m o l a r addition of CBr 4. The p r o p a g a t i o n chain length becomes short by the chain transfer to CBr4. The use of h a l o g e n a t e d solvents, such as CC14, CHzCI 2 a n d so on, was not favorable for the p r e p a r a t i o n of microspheres. Conclusion The c o n f o r m a t i o n of the m o n o m e r in the solvents is i m p o r t a n t for the p r e p a r a t i o n of the microspheres because the cross-linking p r o m o t e s the microsphere

Barrett K. E. J. (1975)Dispersion Polymerization in Organic Media. Wiley, New York. Brandrup J. and ]mmergut E. H. (1989) Polymer Handbook, 3rd Edn. Wiley, New York. Guo J. S., El-Aasser M. S. and Vanderhoff J. W. (1990) Microemulsion polymerization of styrene. J. Polvm. Sci. Polym. Chem. Edn 27, 691. Naka Y. and Yamamoto Y. (1992a) Preparation of microspheres by radiation-induced polymerization. 2. Mechanism of microspheres growth. J. Polym. St'i. Polym. Chem. Edn (in press). Naka Y. and Yamamoto Y. (1992b) Preparation of copolymer microspheres of diethylene glycol dimethacrylate. J. Polym. Sci. Polym. Chem. Edn (in press). Naka Y., Kaetsu I., Yamamoto Y. and Hayashi K. (1991) Preparation of microspheres by radiation-induced polymerization. I. Mechanism for the formation of monodisperse poly(diethylene glycol dimethacrylate) microspheres. J. Polym. Sci. Po(ym. Chem. Edn 29, 1197. Pryor W. A. (1966) Free Radicals. McGraw-Hill, New York. Riddick J. A., Bunger W. B. and Sakano T. K. (1986) Organic Solvents. Wiley, New York. Yoshida M., Asano M., Kaetsu I. and Morita Y. (1987) Characteristics of polymer microspheres prepared by radiation-induced polymerization in the presence of organic solvents. Radiat. Phys. Chem. 30, 39.