Makromol. Chem., Theory Simul.

1,375-385 (1992)

375

Intramolecular phase separation of a copolymer chain with mobile primary structure

Elena E. Dormidontova, Alexander Yu. Grosberga),AIexei R. Khokhlov*
Physics Department, Moscow State University, Moscow 117234, Russia (Date of receipt: May 18, 1992) SUMMARY The phenomenon of intramolecular phase separation of a single copolymer chain with mobile primary structure (i. e., a polymer chain with reversibly adsorbable ligands) in dilute solution is investigated on the basis of a Flory-type interpolation theory of the coil-globule phase transition. It is shown that under certain critical conditions the stability of the homogeneous primary structure is violated and intramolecular phase separation takes place. Phase diagrams for the cases of rigid and flexible chains are calculated. The main characteristics of a polymer chain in the twophase state (such as fraction of monomeric units, swelling coefficient and fraction of units with ligands for coexisting intramolecular phases) are investigated.

Introduction
Reversible adsorption of low-molecular-weight compounds (ligands) on monomeric units of polymer chains is a well known phenomenon of physics and chemistry of polymers and biopolymers Due to the reversibility of adsorption and hence the mobility of primary structure, such polymer-ligand complexes have a number of various specific properties. One of the most interesting of these properties is the possibility of intramolecular phase separation within the chain. The detailed investigation of this phenomenon is just the aim of the present paper. Below we will study the stability of the homogeneous state of a macromolecule (when the ligands are uniformly distributed along the chain) and determine the conditions under which intramolecular phase separation can take place. In addition to this we will analyze several properties of the intramolecularly separated state of a polymer chain (e. g. characteristics of coexisting phases). All consideration is concerned with a single polymer chain with mobile ligands in dilute solution. From the physical point of view such a polymer chain is a heteropolymer (copolymer) with two kinds of monomeric units - with and without ligands. Interaction constants of these two kinds of units can be different. In addition to this, due to the reversibility of adsorption of ligands the primary structure of the chain (i. e. the sequence of monomeric units along the chain) is not fixed. It is due to this reason that intramolecular phase separation can occur in such a polymer chain. In the course of this phase separation both primary and spatial structures of the chain are simultaneously affected. An example of the phase-separated state of a chain is schematically depicted in Fig. 1. This picture corresponds to the case when the monomeric units with ligands attract each other, while the interaction of free
Institute of Chemical Physics, Russian Academy of Sciences, Moscow 117977, Russia. CCC 1018-5054/92/$03.O0

a)

@ 1992, Hiithig & Wepf Verlag, Basel

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E. E. Dormidontova, A. Yu. Grosberg, A. R. Khokhlov

'd i

Fig. 1. Intramolecular phase separation in a copolymer chain with mobile ligands (0 free : monomeric unit; 0 : monomeric unit with adsorbed ligand)

units is repulsive, i. e. the solvent is selective. Then ligands will tend to concentrate on some section of the chain with simultaneous contraction (globulization) of this section, while the other part of the chain, which includes only few monomeric units with ligands, will remain in the state of a coil. For other interaction constants another case is possible when concentrating of ligands on some section of the globular chain leads to the formation of a polymer coil in this section, while the main part of the chain is in the globular state. This coil formation of a polymer section, which otherwise would precipitate, may allow a chain to remain in solution under certain conditions. As it was noted above, the main reason for the possibility of intramolecular phase separation is the mobility of the one-dimensional primary structure of the chain. On the other hand, according to the so-called Landau theorem '), phase separation in onedimensional systems with short-range interactions is impossible. However, in the present case, due to the interrelation between primary and spatial structure the system is not purely one-dimensional and the intramolecular phase separation becomes possible. The phenomenon of intramolecular phase separation of a copolymer with mobile primary structure has already been discussed in the literature'). However in ref. ') too crude assumptions were used. It was supposed that the coil phase is ideal, i. e. volume interactions are absent at all in this phase, while the globule phase is very dense. Below we will present a theory of intramolecular phase separation without using these assumptions. We will apply a Flory-type interpolation theory which is approximately valid over the whole range of the swelling coefficient a of a polymer chain: from the dense globule (a Q 1 ) to the swollen coil (a S l)93'0). Free energy of a copolymer chain Within the framework of a Flory-type interpolation theory the free energy of a copolymer chain with mobile primary structure can be written in the following form:
F = F,,

+ Fin,+ F ,

(2.1)

Intramolecular phase separation of a copolymer chain with . . .

377

The first term F,, characterizes the contribution which comes from the entropic elasticity of the polymer chain. It is expressed by93I0)

where a denotes the swelling coefficient of the polymer chain, a2 = (S2)/(S2),;(S2)is the actual mean-square radius of gyration of the macromolecule, and (S2), is the radius of gyration in the absence of interaction of units. The first term in Eq. (2.2) is responsible for the entropy loss in the course of the chain swelling while the second term describes the entropy loss from the chain contraction. The second term Fin,in the expression (2.1) is the free energy of volume interactions in the polymer chain. In the case of a small average concentration of monomeric units the virial expansion can be used. In refs. l r , 1 2 ) it was shown that for the description of the coil-globule transition it is sufficient to take into account the second and third virial terms. We will adopt the same approach in the present paper. Let us denote the monomeric units with adsorbed ligands by the index 1and free units by the index f. There will be three second virial coefficients B,,,B,,, B,,, and third virial coefficients C,,,, C,,,, and Cfff.For simplicity let us suppose that all third virial C,, coefficients are identical

As to the second virial coefficients we will consider the case which is most interesting from the practical point of view when there are strong forces of attraction between the monomeric units with adsorbed ligands, while all other interactions are determined mainly by repulsion forces. Thus we will assume that
B,, = - k B B,,
=

Bff = B > 0

(2.4)

where k denotes the coefficient which characterizes the relative strength of the forces of attraction between units with ligands. In Eq. (2.4) we assumed that B,, = B , just to simplify the subsequent analysis (analogously to the supposition (2.3)). In this case the expression for the free energy of volume interaction Fin, can be written as

where N is the number of units in the chain, p the fraction of units with adsorbed ligands, V , = B/a3, V, = C1I2/a3; is the average distance between neighboring a monomeric units of the polymer chain. In ref. lo) it was shown that the parameters V , and V, characterize, as a matter of fact, the chain stiffness. For flexible chains, V i= 1, V , t 1 , while for stiff enough chains these parameters are much smaller than unity. :

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E. E. Dormidontova, A. Yu. Grosberg, A. R. Khokhlov

Finally, the third term F in Eq. (2.1) is connected with the entropy of redistribu, tion of ligands on the polymer chain (i. e. with the mobility of the primary structure)

F,

-TS = -TlnW = T N . f J l n p + (1

P)ln(l

p))

(2.6)
-

where W is the number of all possible primary structures (W = N ! / [ ( P N )( N . (1 !

P))!II.
Phase-uniform states of a polymer chain

To analyze phase-uniform states of the polymer chain, let us determine at first the value of the swelling coefficient a for such states. It is given by the free energy Fdefined in the previous section. The equilibrium value of a corresponds simply to the minimum of E From the minimization condition dF/da = 0 we obtain
a5
-

VS/a3 = V , .N/. (1 - ( k

+ 1)p)

(3.1)

As it can be seen from this equation, the values of the parameters V , and V, determine the qualitative form of the dependence a (P, k , N ) . For the case of rather large values of V2 (V2 > 1/60) which corresponds to flexible chainsI0) the functional dependence of @ ( a )= as - a - Vi/a3o n the swelling coefficient a is a monotonously increasing function (Fig. 2a), while for the case of rigid chains (V, < 1/60) lo) the corresponding curve is not monotone (Fig. 2 b) and the plot of the function @ ( a ) contains a region, where (dqVda) < 0, i.e. (dF/da) < 0. In this region the uniform state of the macromolecule is unstable and the jump-like coilglobule transition from high to low values of a is performed in order to avoid this region.

Fig. 2. Plot of @ ( a )= a5 a - v$/a3as a function of the swelling coefficient a for flexible (curve a) and rigid (curve b) chains

Intramolecular phase separation of a copolymer chain with . . .

319

Thus, for a chain with statistically uniform distribution of ligands the macromolecular collapse occurs as a standard coil-globule transition, where the role of a relative temperature deviation from the 6-point in the usual transition (see ref. lo)) is played by the value
Teff =

1 -(k

I)/.?*

(3.2)

Let us now address to the investigation of the problem of stability of phase-uniform states. To obtain stability conditions, let us determine the chemical potential p of monomeric units with ligands.

In terms of chemical potential the stability condition assumes the form

The plots of the chemical potentialp as a function of the fraction of monomeric units with ligands p a r e shown in Fig. 3 (for flexible chains) and in Fig. 4 (for rigid chains). Fig. 3 demonstrates that the value k (see Eq. (2.4)) essentially influences the form of

2.0

1.5

1.0

0.5

Fig. 3. Chemical potential of monomeric units with ligands as a function of B for a flexible copolymer chain (v, = V, = 1; N = lo4) for different values of k (the values of k are shown near the corresponding curves)

-0.5

-1.0

-1.5

\i

3 80
.I

E. E. Dormidontova, A. Yu. Grosberg, A. R . Khokhlov

2.5

2.0

1.5

1.0

0.5

0
-0.5

-1.0

-1.5

Fig. 4. Chemical potential of monomeric units with ligands as a function of 3 for / a rigid copolymer chain ( V , = vz = O,OI; N = lo4) for different values of k (the values of k are shown near the corresponding curves)

this dependence and plays an important role in the determination of the stability conditions for the phase-uniform state of a macromolecule. For the case of flexible chains (i. e. Vz > 1/602), the situation is the following. When k < k,, the curves of dependence of the chemical potentialp on the fraction of monomeric units with ligands / are monotonously increasing. This means that phase-uniform states of polymer 3 chains are stable. When k 2 k,, the corresponding curves contain a region where

($)N

< 0). In this region phase-uniform the state of a polymer chain loses

stability and intramolecular phase separation takes place. The larger the attractive forces in the system (i.e. the larger k ) , the wider the range of values of p at which intramolecular separation occurs. For the case of rigid chains ( V 2 < 1/602, i.e. not all the values of a can be realized) the instability region corresponds to the interval where the following two inequalities are fulfilled: (d@/da2)lr,N < 0, (d2F/d/32),,N < 0. As it follows from Fig. 2 b for the case of rigid chains a range of p values for which (d2F/da2)lr,N 0 < exists at all the values of attraction forces in the polymer system. However this range of fl values can partially or completely lie outside the interval of physically reasonable values of /3 (0 I p I 1). Thus, it is natural to regard the largest value of the parameter k , at which the corresponding instable region of j turns out to lie completely outside ?

Intramolecular phase separation of a copolymer chain with

. ..

381

the interval 0 5 fl . 1, as the critical point, k,,, for the case V , < 1/601'2under conI sideration (i. e. the critical point has coordinates (kc,;p,, = 1) in the phase diagram). In other respects.the qualitative behavior of the chemical potential depending on the values of the parameters (k;p) is analogous to the case of flexible chains.

Region of absolute instability, spinodal for intramolecular phase separation

Now, let us consider in detail the spinodal for intramolecular phase separation. This curve is the boundary of absolute instability of the phase-uniform state of the polymer. For the case of flexible chains the spinodal equation is defined from the condition (d2F/dP2) = 0. Taking into consideration Eq. (3.1) this condition can be written as
2 v

k + 1 , 7 u N"'

12(k

1)2p

5a8 -

ad,+ 3 V i

v: +

B.(l - 8 )

=o

(4.1)

The solution of this equation (spinodal) for the case of flexible chains is shown in Fig. 5 (the dashed curve).

0.66

0.61

0.62

Fig. 5 . Phase diagram for a flexible copolymer chain (v, = v, = 1 N = 103. ; The regions of the phase diagram labeled 1, 2 and 3 correspond to a uniform coil, the intramolecular phase separation region and a uniform globule, respectively. The dashed curve is the spinodal of the phase separation region. The dotand-dash line indicates the coil-globule transition

0.60

0.58

0.56

\
0.51 0.75 0.80

0.85

0.90

382

E. E. Dormidontova, A. Yu. Grosberg, A. R. Khokhlov

0.6 -

0.5 -

0.3 1

0.2 -

0.1 -

0 k/

for a rigid copolymer chain ( V , = 0,06; V2 = 0,05; N = lo4). The regions of the phase diagram labeled 1, 2 and 3 and the dot-and-dash line have the same meaning as in Fig. 5. The dashed curve is the spinodal curve corresponding to the loss of stability of the spatial structure of the chain as a whole. The line (- o -) is the spinodal curve corresponding to the loss of stability of uniform distribution along the chain
I I
I

0.80

0.85

0.90

0.95

1.00

For the case of rigid chains the boundary of the instability region is defined from the conditions (d2F/da2)8,N= 0, (d2F/d/3),,., = 0. As we can see from Fig. 4, the left branch of the spinodal, corresponding to the transition from the phase of uniform coil to the instability region can be determined in fact from the equation (d2F/da2)8,N = 0. Since this equation has two solutions for the case of rigid chains (see previous section, Fig. 2 b), there are two different spinodal curves (Fig. 6). One of these spinodal curves is connected with the loss of stability of the uniform distribution of ligands along the chain. Another spinodal curve corresponds to the loss of stability of the spatial structure of the chain as a whole. After the determination of the boundaries of absolute instability of the uniform state of a polymer chain, we proceed now to the investigation of the conditions of phase separation. The conditions of phase separation

To determine the boundaries of the separation region (i.e. the binodal curve) ordinary conditions of phase equilibrium should be considered

Intramolecular phase separation of a copolymer chain with

...

383

where p i , p i , p2 are chemical potentials of ligands and pressures in both phases, p2, correspondingly. It should be noted that in this case the role of pressure p is played by the value thermodynamically conjugated to the contour length of the chain (more exactly the contour length of the chain section corresponding to a given phase):
P =

(z)
8,N

V, (1

+ 3(k +

l)/12)/(2a3 i l 2 ) + In(1 - p ) N

(5.2)

One would think that for determining characteristics of the phase-separated state of
2

the polymer chain it is possible to use the Maxwell rule in the form: SPdp

0.

However in the present case the free energy of a polymer chain (see Eqs. (2.1), (2.2), (2.5) and (2.6)) is not an additive function of the number of monomeric units in the chain (a change in the number of units in the chain influences both the contour length of the chain and the volume interactions in the whole system). Thus, since the Maxwell rule cannot be applied it is necessary to solve numerically the set of equations (5.1). After determining the values p , , p2, p i , p2 the total system of equations to be solved takes the form

vi

+ 3(k +

1)&

2 a : .N , / ~

+ ln(1

- 8,) = V,

+ 3(k +
1

1)&

2a: Nil2

+ In(1

82)

8 1 . N , + 82.N2 = PN N,

+ N2 = N

where a , ,N , *PI, N 2 .f12 denote the swelling coefficient, degree of polymerization at, and the fraction of monomeric units with ligands in the first and second phase, respectively.

Phase diagram. Analysis of intramolecular phase separation in the polymer chain Based on the numerical solution of the system of equations (5.3) the boundaries of the separation region (binodal curve) were found and phase diagrams were determined (see Fig. 5 for flexible chains and Fig. 6 for rigid chains). These phase diagrams contain

384

E. E. Dormidontova, A. Yu. Grosberg, A. R. Khokhlov

the region of stability of phase-uniform states of a polymer chain - the coil (region 1) and the globule (region 3), which are separated from each other by the line of coilglobule transition and the region of intramolecular phase separation (region 2). Region 2 is separated from regions 1 and 3 by the binodal curves; the corresponding spinodal curves are shown in Figs. 5 and 6 as well. As it is pointed out above the phase behavior of flexible and rigid chains is different - instability and subesequent phase separation arises in the rigid and flexible chains at different conditions and by different reasons. But in spite of this distinction, the change of characteristics of a chain under the transition from the uniform state (e. g. coil phase) to the separated state and then from the separated state to the other uniform state (e. g. globule phase) occurs in the same manner. From the analysis of the variation of the parameters of the chain, we can draw the following picture of structural changes under transition, e. g. from a uniform coil phase to a uniform globule phase through the stage of intramolecular phase separation. These

""1
0.6

r" 0.90

(b)
I

c '
0.86 0,82 0.78
I I I
I

I
I
I

I I
I
I

I I
I

I
I

1
I

I
1

p
I

1.0

2 0.8

<

0.6 0.1
0.2

2 -

0
(

Fig. 7. Main characteristics of the phase-separated state of a flexible copolymer chain with V , = Vz = 1; N = lo4; k = 0,65: swelling coefficients a and a2 (a), fractions of monomeric units with ligands 8,and Pz (b) and fractions of units N l / N and N2/N (c) as functions of

0.80

0.85

0.90

r3

Intramolecular phase separation of a copolymer chain with

. ,.

385

conformational transformations of the copolymer chain are illustrated by Fig. 7. The curves in Fig. 7 correspond to the flexible copolymer chain for which the phase diagram is shown in Fig. 5 . Figs. 7a, 7 b, 7 c are the plots of swelling coefficients, fractions of monomeric units with ligands, and fractions of units in the coexisting phases as functions of fl, respectively. Originally, a small (by length) section of the chain forms the conformation of a weakly contracted globule. The phase state of the greater part of the chain remains almost invariable. With the growth of the fraction of monomeric units occupied by ligands, fl, the length of the globular section increases and an increasing fraction of ligands is concentrated in it. Therefore, the density of the globule becomes considerably higher. The other part of the chain loses an increasing number of ligands and becomes more swollen. This process continues with further increase in fl until the whole chain appears in the globule state. Near the boundary of the uniform globular phase the phase-separated system represents a picture inverse to that which is observed near the boundary of the uniform coil phase, i. e., before the transition into the globule phase the phase-separated polymer chain consists of a small coil section and a much larger section forming a dense globule.

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