Structural peculiarities of block copolyurethanes with peptide links as rigid block extenders

Structural peculiarities of block copolyurethaneswith peptide links as rigid block extenders T.E.Upatova,GA Pkhakadze,D.V.Vasil’chenko,V.V.Voronaand V.V.Shilov lnstrtute of Organic Chemistry, Academy of Sciences, Sciences, Ukrainian SSR. Kiev, USSR. (Received 26 March 1982; revised 26 June 1982)

Ukrainian SSR, Institute of Macromolecular

X-ray crystal analysis was performed on block copolyurethanes

Chemistry, Academy

of

with peptide links as rigid block extenders. The

increase in peptide link length was shown to improve the microphase separation of flexible and rigid segments. The influence of the isocyanate nature on phase separation conditions in the block copolyurethanes established.

The correlation

microphase between

structure

medicine

of successful

according time

was

to a hydrolysis

controlled links

in a polymeric

sensitive

ments serving introduced

to specific

as substrates

the

properties

chains

tion6.

A

properties

and

established solving subject study taining pursues 0 1983

but also

to

by the type

implants

specific

amino

are

on the

physical represented

of preparing enzymatic peculiarities

acid and dipeptide

their

organizachemical should

be

by purpose-

new temporary

& Co (Publishers)

analysis

as

Tab/e and

6.2-0.35

dimethylformamide

under vacuum

= 2-4

1.

mechanical

mm

solution.

atp

1000,

acids and dipeptide

extenders.

structural

from

mass

or diphenylmethane

amino

block

prepared

from

was distilled 333

for

(HMDI)

Various

used as rigid

were synthesized molecular

thick The

films solvent

hPa and T =

313-

K. Mechanical

tensile

tester.

&p, were

testing

Tensile

determined.

was

was

stress,

performed

Softening

determined

using

ob, and residual

a ZM-40

elongation,

temperature

using

a

Koefler

interval, hot

stage

X-ray Copper was

analyses

anode

used.

The

X-ray diffraction

out using a KPM-1

placed

packets

into

used’

of widethe

unit.

by a nickel

procedure

measurement

for the same sample

were

1.5 mm thick

carried

monochromated

experimental

the simultaneous examined

were

radiation

permitted

and small-angle

area. Samples X-ray

filter

unit

being

holder

as

of films.

for

implants,

The

present

of polyurethanes, links in the main

conchain

this aim. Butterworth

diisocyanate

were

obtained

with

microscope.

nature

is a prerequisite

hydrolysis.

testing

for the fact

and

EXPERIMENTAL

studied

glycol

(DPMDI).

Samples

T,-T,

component5.

characteristics This

and

of hydrolysable

on

AND

samples

hexamethylene

links

copolyure-

supermolecular

polymers

a

of

based

organization.

SAMPLE CHARACTERISTICS PROCEDURE

are

be

Physical

existing

X-ray scattermg

diisocyanate

frag-

not only on the chemical

copolyurethanes.

of structural

be

Polymers

are conspicuous

structural

the problem

synthesized.

between

for these

block

and their superrnolecular

The polyurethane

should

acid and dipeptide

of the rigid chain

type of

relationship

of enzymes, enzymes

of the

because of the dependence

polytetramethylene

To make

of this class of block

and depend

of the

can

polymers

of the polymer.

both

of the above

degradability

made

action

studied was

and peculiarities

in

mainly

hydrolysable

hydrolysis.

for certain

recently

and by the nature

Polymers

of easily

of synthetic

amino

characteristics are determined

blocks that

bonds enzymatic

in the main chain were thanes

degradation

chain”‘.

type containing

chemical

in

of their

organism

important

links were

in the main chain

the above

implants

proceed

characteristics

Imks, biodegradation,

Thus, the residence

in the

the amount

by specific

polymer

to

mechanism.

As a rule, chemical unaffected

earlier’

implant

by changing

peptide

the time

Polyurethane

shown

of a polymeric

and temperature

of the polyurethanes

use of temporary of controlling

in an organism.

organism

tendency

block copolyurethanes,

is the possiblity

degradation the

Polymer,

mechanical

was found. The latter seems especially

the biodegradation

Keywords:

A prerequisite

between

EXPERIMENTAL

RESULTS

Figure

7 shows

of the

polyurethanes

small-

and wide-angle being

studied.

X-ray

photographs

Small-angle

diffrac-

Ltd. 0142-9612/83/040201GO4$03.00 Biomaterials

1983,

Vol 4 July

201

Copolyurethanes

with peptide

links: T E. Lipatova

Figure 1. Wide-and small-angle (b) L-tyrosine; (c) L-alanyl-L-alanine:

X-ray diffraction patterns of copolyurethanes containing in the main chain the blocks of (a) L-phenylalanine; (d) L-phenylalanyl-L-phenylalanine; (e) L-phenylalanyl-0 acetyl-L-serine: (f) r-phenylalanine; (g) L-phenylalanyl-L-

phenylalanine

tion patterns have been positioned in the central area of wide-angle photographs to assist comparison. Comparison of wide-angle patterns shows no qualitative differences. Each of the above patterns shows diffraction rings of the diffuse type. The outer ring is more diffuse and has much greater intensity than the inner one. It may be noted, that the outer diffraction ring is typical for the majority of flexible chain polymers having an amorphous structure. The inner ring, from the point of view of its diameter and intensity, may be regarded as typical for many segmented polyurethanesa-“. Small-angle diffraction patterns are characterized by one diffuse ring. The degree of blackening and the diameter of the ring change occuring during the transition from one polymer to the other were studied. The interplanar spacings corresponding to observed diffraction rings were calculated using X-ray diffraction patterns shown in Figure 1. The results in Table 1, show that Table 1.

Characteristics

Sample No.

Amino acid or dipeptide in a rigid segment

1.

of studied block copolyurethane Diisocyanate

Polymer mol. mass x1osg

systems

interplanar spacings corresponding to the diffraction ring of wide-angle X-rays were within the range 0.46-0.48 nm for all the polymers studied. Periods corresponding to the inner rings vary within the interval of 0.93-I .12 nm, depending on the nature of the diisocyanate group and the extender. Changes of macrolattice periods, corresponding to small-angle reflections (from 8.0 to 13.6 nm), were even more pronounced. Tab/e 7 also gives the results of mechanical testing and temperature analysis of the polymers studied. These characteristics vary within a very broad range depending on the molecular structure of the rigid block. Minimum softening temperature was observed for the polymer prepared on the basis of HMDI and L-phenylalanine, whereas the polymer from DPMDI and t_-phenylalanyl-tphenylalanine showed the maximum softening point. The above results suggest that, as a whole, the mechanical characteristics were better for DPMDI-based systems.

(The glycol was polytetramethylene

Interplanar spacing wide-angle X-ray

outer ring

inner ring

Macrolattice period, nm

Small-angle maximum intensity in rel. units

glycol in all cases) Tensile stress (ultimate)

Rel. rupture elongation, %

Softening range, “C

MN/m,

L-phenylalanine

HMDI

15.0

0.47

1.12

11.3

2

5.57

140

106-l

30

2.

L-tyrosine

DPMDI

17.2

0.48

1.12

9.7

9

5.67

1050

179-l

85

3.

L-alanyl-Lalanine

HMDI

18.7

0.46

0.93

9.7

5

8.64

120

193-l

97

4.

L-phenylalanylL-phenylalanine

HMDI

9.6

0.47

1.12

13.6

3

5.69

130

167-171

5.

L-phenyalalanylL-acetyl-L-serine

DPMDI

11.6

0.48

0.99

8.0

8

4.79

390

115-141

6.

L-phenylalanine

DPMDI

22.6

0.48

1.12

9.0

6

11.13

1340

138-l

7.

L-phenylalnylL-phenylalanine

DPMDI

21.0

0.48

1.12

8.0

10

16.04

1150

200-201

202

Biomaterials

1983,

Vol4

July

40

temp.

Copolyurethanes

DISCUSSION

degree

of phase

remaining The data from X-ray crystal analysis of amorphous

structure,

characterized

order of the fragments long-range

order,

diffraction given

rings

of adjacent

i.e.

fragments.

The

alternation groups

reason

capable

bonding. diffraction

patterns

approachg.

true for the systems wide-angle

studied

diffraction

polymers

studied,

chain

data has

on the basis of

nature

observed

in multi-block diffraction

in small-angle phase

microareas form

a so-called these

present

it

the

seems

periods

interpreted

1 -

chain of

diffraction

extender

the

intensity

diffuse

As shown

rings

only.

be

maxima

in

characteristics

All

of

the

diffraction

rings

with

of the above

whole, segments

their

may

be arranged

extent

of

blocks:

type

that

extender

is of

These

sequence

from L-phenylalanine

For samples

period

1 and 4 the change

correlates

correlation

with

is distorted

DPMDI-based greater area.

intensity

The

the

rigid

when

passing

polyurethanes of diffraction

substitution

in the macrolattice

block

size.

of the aromatic

should

above

over to sample

3.

characterized

by

are rings

The

in the

small-angle

substituent

in the

sample intensity

by -

II

0 -

7 to sample

and

amino

Thus,

temperature

CH,

group

(the transition

5) brings

about

the decrease

of small-angle

reflection

(and,

accordingly

from

only

6 to sample stress,

in the

tendency

the

siderable

to the

depends

the of

material

studied

as

rigid

and

the

mechanical peculiarities of the

characteristics,

a and

of their

their

7983,

fact

that

not

but also the

biodegradation

upon

peptide

extenders

of such a relationship

because

Biomaterials

hardness

with

block

between

to

that

network

temperature.

The existence

of polyurethanes

chemical

fact

the

7)

increas-

thermoelastoplastics,

polyurethanes

important

the con-

(Table the

of different

of polymeric

and mechanical

in

causes

with

forming

in

1 to sample

to the increase

and

of blocks

and

increase

temperatures

of its softening

established

the

decrease

mentioned

polyurethane

was

extent

the

rupture

in

fragments

urethane

mechanical

7) leads to

blocks,

acid

especially

of

sample

be attributed

characteristics

physical

the

separation

their

from

rigid

structure.

on the of

of poly-block

of softening

the

is The

influence

phase

with

transition

may

are

extent

increase

In particular,

separation

for

correlation

seems C -

peculiarities

as already

growth

microphase

0 extender

to the

the

were rest

diisocynate.

the

of rigid

polyurethanes.

lead to the increase

and

the

has smaller

during

latter

polymers

of the

improves

tensile

increase

three

separation

nature

agreement

sample

nodes

studied

whereas

However,

elongation

physical

segrega-

phase

size (the

of component

first

the

the extender

of

on small-

copolyurethanes

basis

structural

The

the

and

in these

ing microphase

Based

is

of

flexible

characteristics.

nature.

nature

extenders.

fragment

corresponds

the

(mani-

patterns)

between

are in good

siderable

X-ray

in

HMDI

of

insignificant

however,

separation

by the

ultimate

shows

structure,

block

pattern

by the peculiar-

patterns

changes

temperature

the

arrangement

rigid

increase

as a rule

4 or that from

as a of

to the

an

components

systems

This

(the

characterized

block

Thus,

size

copolyurethanes composition

of small-angle

characteristics.

facilitates tion.

on

to

according

affected

segregation

extent

phase

in

as opposed

diisocyanate. of block

the

used. As

decreases

as follows

of extending

relative

be

rigid

separation,

being

period

chemical

data

diffrac-

leads

phase

polyurethanes,

1, 4, 3, 6, 5, 2, 7. The

above

may

Thus, to the

diffraction

and

diffraction

these

probably,

supermolecular

angle

For

of the isocyanate

the

com-

size is observed.

most

structure

to

Such

extender

fragments)

Their

as rigid block extenders

increasing

fine

block differ-

6 and 7 (DPMDI-

4 (HMDI-based).

aliphatic

ities of wide-angle

fragment.

of component

changing

for

of small-angle

the series

with

insignifi-

extenders,

the macrolattice

containing

Regarding

with

intensity

of DPMI-based

to L-phenylalanyl-L-phenylalanine the

degree

show 2 in the

compared

samples

blocks,

of the nature

systems

of

7 the intensity sample

7)

above

separation

increasing

in the

case

rings on

of phase

in the

of rigid

irrespective

be

of diisocyanate

samples

increase

used

in Figure in the

1 and

the

(i.e. on amino

which

the transition

and

primarily

these.

diffraction,

increases

3. Therefore,

based)

obtained

6 to sample

identical

between

the

data

both

identical

period.

may

in the nature

are

increases

entirely

may be drawn

DPMDI-based.

may

group

data

ing only

tion

The

sample

parison

increase

L-tyrosine)

intensity

with

polymers

function.

and

macrolattice

diffraction

synthesized

1, 3 and 4 in Table

low intensity

as a consequence

complete.

4 -

extenders

relatively

background

far from the

the show

The

diisocyanate

microphase

to

of the

sensitive

in the

separation

diffraction

growth

more for

that

of blackening

(Nos

cant

by the peculiarities

as by different

of the diisocyanate

polymers

small-angle

fested

links).

HMDI-based by

note

by different

as well

of the chain

from

and

observed

corresponding

intensity

structure.

transition

changes.

typical

of

In this case the above

acid and dipeptide

the

rings

molecular

in the

the

link into the main

pattern

of microphase

the

X-rays.

to

peptide

as to their that

macromolecule

of two-

ordered

most

interest the

both on the nature

polymers

evidence

but also that

ones

is manifested

large

and on the character

differ

of

affects

degree

with

small-angle

at very low

rings appearing

For the compounds

diffraction

the

connected depend

the

If not that,

has a triple

(L-phenylalanine

the

systems

that the characteristics are

The above

for

Roughly,

character

are relatively

of one or another

of small-angle values

polymer

polymers,

extender

extenders

a result

area

into account

diffraction

separation

considerably

separation.

small-angle

phase

polyurethanes’b’7.

introduction

chemical

poly-

the chain

the

taking

are not only direct

be noted

work

chain

of

period

between

in the latter case

increase

is evidence

different

in the

is of diffuse

polymers

segmented

in the

macrolattice.

It should for

rings

of the studied

of phase

that,

polymers.

Characteristic

X-rays

nature

to be

copolyurethane

This

having

single

diffraction

level of intensity.

Thus,

of block

the above conclusion,

small-angle

of as a

as well.

appeared.

for amorphous

is thought

one may suggest

of segments

that

hydrogen

polyurethane

the macrolattice

difference

No. 6 and 2 lies in the fact that

copolyurethanes

is likely

separation

fact

interchain

with

The

links: T. E. Lipatova

urethanes

is the regular

interpretation

phase

Intensive

chain

proton-donating

via

the structure

domains

also confirm

periodicity

by Bonart

This

by

of rigid

of segmented

proposed

of the

determined

electron-and

interpretation

traditional

rigid

are positions

of associating

Such

Internal

X-rays

in the of

no signs of

ordering.

in wide-angle

for such

pattern

with

systems

periodicity

the presence

only by short-range

chains

of crystal-type

appearing

polyurethane

longitudinal

revealed

separation)

unchanged.

with peptide

to a con-

supermolecular

I/o/ 4 Julv

203

Copolyurethanes

with peptide

links: T. E. Lipatova

organization. One more fact is worth noting specialiy: the systems studied posess, in principle, all properties typical for segmented polyurethanes, but at the same time they show the tendency to specific enzymatic hydrolysis which is not typical for the latter.

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204

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T.E. Lipatova, sb. Polimery v meditsinie, Kiev, ‘Naukova dumka’. B. Mazar, P. Cefelin, T.E. Lipatova, L.A. Bakalo, G.G. Lugovskaja, J. Polym. SC;.: Polym. Symp., 1979, 66, 259-268 M.M. Lynn, V.T. Stanmett and RD. Gilbert, J. Poiym. Sci.: Chem. Ed, 1980,18, 1967-1977. K. Kurita, N. Hirakawa. Y. Iwakura, J. Po/ym. Sci.: Pofym. Chem. Ed, 1980, 18. No. 1. T.E. lipatova, G.A. Phakadze, D.V. Vasil’chenko. Doklady AN SSR. I980.251. 368.

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